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CONTRIBUTIONS TO EMBRYOLOGY

VotuME XII, No. 56

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PUBLISHED BY THE CARNEGIE INSTITUTION OF WASHINGTON
WASHINGTON, 1921

CARNEGIE INSTITUTION OF WASHINGTON
PusBuicaTion No. 275

PRESS OF A. B. GRAHAM CO.
WASHINGTON

CONTRIBUTIONS TO EMBRYOLOGY, No. 56.

STUDIES ON ABORTUSES: A SURVEY OF PATHOLOGIC OVA
IN THE CARNEGIE EMBRYOLOGICAL COLLECTION.

By FRANKLIN PAINE MALL AND ARTHUR WILLIAM MEYER.

With twenty-four plates, five text-figures, and one chart.

CONTENTS.

PAGE
Prervace, “By A: W. Marae, << fo eee neg tele niclalcle ns cletal cial aleve uelelatelal niece tee eee 5-11
CHAPTER I;.Origin:of, the collection.. By F. P.(Miartie... 0). fccc2cie 00> «seeder oe eee 13-24
II. Care and utilization of the collection. By F. P. MALL..............0.ccceeeeeeeeees 25-40
TH.. Classification. By A.W. Mmyar..). 3.0 220005 sasnctaeiarniech ee eee Eee Eee EEE 41-49
IV. Analysis of abortuses classed as pathologic. By A.W. Meyer. (Plates 1-6.)......... 51-170
Group 1: Specimens composed of ‘villionly <2: 5-°.2.2..5024 see eineaniietee ses 51-59
Group 2: Chorion without amnion or cyema..................esseeeereecescees 60-69
Group 3: Chorion ‘with amnion. .../2. Jo. Jo.cecee bade eee ee EER EERE ERE 69-74
Group 4: Chorionic vesicles with nodular cyemata................00.0eceeeeeeee 74-81
Group 5:' Cylindrical'cyemata.: 5 55.-<..cices1o cee een een ee Ree EEE Eee 81-85
Group 6: ‘Stunted cyemata. <2).soy. wfak dao ae curaced sie One EE Eee 85-92
Group 7: Fetus compressus.i5. cscddakes ones lose at een eee ee 92-102
S01: A mies aries lr es Hon SOON Rasa ooninna aio ahaoe e 102-107
Protocols’ o's. is-sisisvs-cicia svorare,estra’e ayer ete aes Glabier cise eee CE Ee Eee 107-170
V. Relation of cyemic to chorionic size. By A. W. MEYER..................00eceeees 171-176
WI. Sex incidence in abortions. ‘By. Av. H.'Scuurtz.. 4.2... - eee eee eee 177-191
VII. Occurrence of localized anomalies in human embryos and fetuses. By F.P. Mau. (Plate7.) 193-202
VIII. Hydatiform degeneration in uterine pregnancy. By A. W. Mnyer. (Plates 8-12.).... 203-231
IX. Hydatiform degeneration in tubal pregnancy. By A. W. Meyer (Plate 13.)......... 233-242
X. The alleged occurrence of superfetation. By A. W. Mryrer. (Plate 14.).............. 243-250
XI. Ovarian pregnancy. By F. P. Mati and A. W. Meyer. (Plates 15 and 16.)......... 251-266
XII. Lysis and resorption of conceptuses. By A. W. MEYER................c00eceeeeeees 267-279
XIII. Post-mortem intrauterine changes. By A. W. Meyer. (Plates 17-19.).............. 281-300
XIV. Hofbauer cells in normal and pathologic conceptuses. By A. W. Meyer. (Plate 20.) 301-314
XV. The villi in abortuses. By A.W. Muyer. (Plates 21-23.)...............0cc0cceeee 315-326
VI. Villousinodules. By.A. W. Mnymnr. — (Platei24)i5.-.-) eee eee 327-331
XVII. Changes suggestive of lues. By A. W. MEYER.........:0...<0c+00+seuevceeseneseews 333-338
XVIII. Some aspects of abortion. By A. W. MBYmR....... 2.00000 cneereccecs«rerenesesnee 339-356
BIBETOGRAPIY 65005 6.075 0:0js'e.010 v'a.esereis 0's cs oie: o/0/sl ejay eleinje le 6 aver elareeareiere 0 oVSTeVc Er eC EEE ee 357-364

STUDIES ON ABORTUSES: A SURVEY OF PATHOLOGIC OVA
IN THE CARNEGIE EMBRYOLOGICAL COLLECTION.

PREFACE.

The following survey comprises a review and an analysis of conceptuses which
are classed as pathologic in the first 1,000 accessions to the collection of the
Department of Embryology of the Carnegie Institution of Washington. The
majority of these accessions were included in the Johns Hopkins Medical School
collection. They had been collected with untiring effort by Professor Mall, with
the generous codperation of numerous physicians, both at home and abroad,
during the course of two decades. The accompanying studies on special topics
are not, however, so limited, nor are they confined to pathologic conceptuses only.
Although closely related, they aim neither at completeness nor even at unity,
except as individual contributions. Since, with the exception of the tables, the
survey proper is limited to the first 1,200 accessions, with only such references to
the remainder of the collection as time permitted, it is very probable that some of
the results and conclusions drawn from them will not be fully supported by an
extension of this study to the material in the entire collection. This is due not
only to the fact that the abortuses received more recently are better preserved
and that the later histories are fuller, but also to the increasingly closer codperation
with clinicians which often brings us very helpful clinical sidelights. Indeed, it
is this codperation which alone can enable us satisfactorily to develop certain
aspects of the new field of antenatal pathology, and help to bring a final answer
to some of the many unsettled questions. Without the information which the
practitioner alone can furnish one often feels helpless; for although many of the
specimens are eloquent with facts, others remain entirely mute as to their story
because they appear wholly normal.

The much larger series of abortuses composing the entire collection also
includes unique specimens which are the product of some rare experiment on the
part of nature. One is much less likely to find such specimens in a smaller and
hence less representative collection. What is lacking, however, in connection
with many of the specimens, otherwise so valuable, is the decidua. In the absence
of the latter it is often impossible to reach even a tentative conclusion regarding
the genesis of the abnormalities found in a particular specimen. In many instances
this defect could be easily remedied by an appeal to our many coworkers and
benefactors engaged in the practice of medicine. I am certain that they will gladly
save the decidua whenever possible, merely as a matter of codperation, although

Nore—In view of the suggestions made in Science (A. W. Meyer, 1919: A suggestion from Plato, with others, vol.
49, p. 530) some of which have been incorporated in the following pages, the title of this volume demands a word
of explanation. I have retained the word ova because the title had in part been decided upon. Moreover, the word
is still used in this sense in current medical literature, but we are not considering ova but conceptuses. Besides, a
considerable percentage of these undoubtedly are not pathologic or diseased, for surely post-mortem changes in
structure, however profound, can not strictly be regarded as pathologic; and since derangement of function is made

impossible by death, no matter how deformed or how infiltrated the tissues of an abortus may be with the cells of
maternal origin, it can not therefore be said to be diseased.—A. W. M.

5

6 PREFACE.

it need not be forgotten that the assistance we can give to donors when reporting
our findings is very largely contingent upon its preservation. It is true that in the
course of time, and even now to some extent, we shall be able to give a report
suggestive of the possible intrauterine conditions from an examination of the
conceptus alone, and just in proportion as our knowledge of the condition of
the decidua increases this opinion will become more reliable, and hence also of
more practical value.

The chief reason why the decidua, or the membranes, or the placenta are
not preserved oftener is that physicians have not fully realized that they are
needed and wanted. A mere reference to the protocols and summaries will illus-
trate in how large a percentage of the cases it is not included at present. Although
I fully realize that often it is impossible for the physician to secure it, and that in
other cases it is of little value even when secured, I am certain that the percentage
of cases in which it is missing can be greatly reduced in the future with consequent
mutual benefit. The closest codperation with clinicians is necessary, not only
in order to secure the necessary material, but also to obtain further information
through supplementary observations upon the living patient. Only in this way
can the great gap left in human obstetrics and embryology, by the impossibility
of performing experiments, be partly filled. In the case of animals, experimentation
no doubt will eventually determine for us the relationship of teratology to path-
ology, but in the case of man this relationship must be determined very largely
by observation alone, for although every instance of human gestation under
abnormal conditions answers to an experiment, such experiments must always
remain uncontrolled, and the exact conditions which usually obtain must remain
unascertainable. Nevertheless, the practitioner, with the patient’s help, frequently
can bear witness as to the conditions under which nature’s experiment was per-
formed and as to the sequence of crucial events, and it is on the unselfish efforts
of physicians that we must depend for assistance in this matter.

Mall did a very great service in calling attention to the fact that abnormalities
of the fetus are frequently associated with, even if not always or necessarily pro-
duced by, uterine diseases. The relationship between the two is revealed still
further, especially in Chapter 1V, and further investigation of this subject ought
to bring to light facts not only of further scientific interest, but pregnant with
great humanitarian service. It is startling indeed to observe what a monstrous
fetus may accompany an apparently moderately diseased chorion, and it is equally
startling to observe that a chorionic vesicle apparently normal may be wholly devoid
of an embryo. But here we meet one of the obstacles in the way of present
progress, for we do not yet know exactly what a normal ovum or villus looks like
in all stages of development. Both must yet be standardized, and for this standardi-
zation a knowledge of the condition of the decidua and of the probable cause of the
abortion will be extremely helpful. If all early conceptuses were undoubtedly
normal, the problem would be a simple one; but very many are abnormal or
atypical at least,

PREFACE. 7

As our knowledge of the normal becomes more complete, we find that more
and more young embryos which formerly were regarded as normal are not really so.
The literature of human embryology contains many such instances, and it was
impossible, and it remains impossible even at the present time, to determine in all
cases whether we are dealing with a normal or an abnormal specimen, even after .
it has been mounted in serial sections. Hence it happens that abnormal human
embryos and fetuses still are represented as normal in contemporary embryologies.
It has often seemed to me that there is one source of material which could bring
much help in this connection. If the many tragedies with which our coroners
come in contact could always be utilized scientifically, as they rarely have been
in the past, much desired information would soon be in our possession. It seems
that a very promising opportunity for progress lies here. In an intelligent com-
munity public opinion will, I believe, gladly support any one in such utilization of
these chance cases as soon as a broadly humanitarian, even if not a keenly scien-
tific, attitude can be cultivated on the part of our coroners.

What can be accomplished through codperation between public officials and
laboratory workers was illustrated by the fine assistance given Professor Mall
and the Department of Embryology of the Carnegie Institution of Washington by
the department of health of the city of Baltimore. Indeed, one can not recall this
service without feeling the deepest regret that similar codperation, especially with
coroners, has not yet been realized in more American municipalities. Such co-
operation, supplemented by that of the practitioner, especially in obstetrics and
gynecology, can accomplish much in the course of years. But codperation between
laboratory workers also is necessary. Even the chemist, not only the pathologist,
is indispensable. Without him the anatomist often is helpless. Here, for example,
is an unopened, fairly normal looking abortus composed of a clean conceptus.
The periamniotic fluid, to all appearances, is absolutely normal. The interior
of the chorionic vesicle also appears normal. The amniotic vesicle, although
much smaller than one would expect, is normal in all other respects and distended
moderately with perfectly clear and absolutely normal-looking fluid; yet such a
conceptus may contain not even a trace of an embryo, even if the yolk-sac still
looks normal. Such specimens are rare, but they occur, and one of the things
wholly inexplicable to the anatomist is not so much the absence of the embryo as
the fact that its disintegration has not resulted in the least turbidity of or deposit
in the amniotic fluid or the dissolution of the amnion. Even a microscopic examina-
tion of the fluid may fail to reveal any cellular content. The anatomist desires
to know not merely in what respects the composition of the intra-amniotic and
periamniotic fluids has been changed, but what the enzymes are that have caused
the complete lysis of the embryo, from what these arise, and how they become
active. These and many other questions the chemist only can answer. For this
answer fresh material is indispensable, but this the neighboring practitioners or a
closely associated clinic can supply. I am aware of the fact that chemists and
physiologists have not neglected these questions, but at present our knowledge

8 PREFACE.

regarding these matters seems quite insufficient to enable one to formulate satis-
factory hypotheses regarding many of the phenomena encountered in abortuses.
To enable us to do this a much better localization and identification of the
enzymes concerned would seem to be necessary.

“That the dissolution of these early embryos, and undoubtedly also of the
chorionic vesicles, is not due primarily or even very materially to phagocytic
activity, is very evident, even upon cursory examination. In the presence of the
intact chorionic and amniotic vesicles such a process is wholly excluded. Besides,
one never sees any evidence of phagocytosis of the preserved fetal by the maternal
tissues in human conceptuses, although evidences of the contrary processes are
not wanting.

In considering some of the many problems of human antenatal pathology,
it seems very probable that much light can be thrown upon them by comparative
experimental pathology and studies in comparative gestation. A reliable knowledge
of the comparative incidence of abnormalities in man and higher vertebrates
alone would be of great value. The same thing would be true of a knowledge of the
comparative incidence of uterine and ovarian or testicular disease and abnormali-
ties of the uterine mucosa. Indeed, until these and other similar and related
questions have received at least a partial answer, it will always remain rather
venturesome to draw final conclusions regarding many things in human antenatal
pathology, for the first question that always must be answered in connection with
a particular specimen is that of its normality or pathogenicity.

His, Giacomini, and Mall took up this problem with especial devotion and
have done much to lay the basis for the accomplishment of the task set for path-
ologic embryology by Miiller (1847). Miiller stated that it was the task of the
pathological anatomy of prenatal life to show the progressive steps leading from
the slightest deviation from the normal to the most pronounced deformity. This
task is only begun and progress naturally will be slow, especially in connection
with early forms, until we can discriminate better between the normal and the
abnormal and the pathologic.

A comparison of the clinical data relating to infection, with the microscopic
findings, will show that the correspondence is extremely slight. This is not sur-
prising, for physicians themselves often emphasize that the history probably is
quite untrustworthy. Moreover, the clinical diagnosis of infection is usually
based upon the presence of fever, a putrid discharge, or certain symptoms usually
regarded as indicative of fever. If the clinical reports regarding infection were
based upon bacteriologic or even upon histologic examination, they would un-
doubtedly agree better with our findings. These showed the presence of infection,
as indicated by infiltration of the decidua or by abscess formation, in a large
percentage of the cases in which the decidua was present, in the specimens falling
into the first five groups.

The unavoidable confusion resulting from the use of the word ovum to desig-
nate the unfertilized female sex-cell, this cell when fertilized, the chorionic and
amniotic vesicles with or without the embryo, and even the later product of con-

PREFACE. 9

ception in any and all stages of development, even up to birth, has prompted me
to resort to additional terms. It certainly would seem best to restrict the term
ovum to its comparative embryological significance and thus avoid confusion.
But this restriction leaves us without a word to designate the whole product of
conception. For this the word conceptus seemed available. At present the word
embryo is frequently used loosely to designate conceptuses of any age. It is used
still more frequently to designate merely the body of the future individual during
the early stages of its development, in contradistinction to the word fetus, which
usually is restricted to the later months. Hence we have need for still another
term to be used in common for the embryonic disk, the embryo, or the fetus.
Dr. Schultz has kindly suggested kyema, which Professor Foster suggests is prefer-
ably spelled cyema, adding that it is excellent Greek and was used in the proposed
sense by Plato himself. It also has the advantage of being available for compara-
tive embryology and of being easily adapted to meet such needs as are represented
by the terms cyemetric and cyemology. Change may not imply improvement or
progress, but the absence of it certainly never does. I realize fully that the use
of unnecessary terms is to be avoided, but this is equally true of awkward circum-
locution and misunderstanding. When one writes or says at present that no
embryonic remnants were seen, it is impossible to know what is meant. Although
the word embryo could by common consent be used in the proposed sense of cyema,
long usage probably would make such an attempt futile for this reason alone. The
use of this term and of others, presently to be suggested, does not change old mean-
ings or old usage. It abrogates nothing save confusion.

Although the word abortion is available to designate the individual or the
material aborted, it has not been the custom to use it in this inclusive sense. The
word abortion, as now used, is usually restricted to the act itself. To use it ina
double sense would lead to some confusion. Since blood-clot, pus, decidua, and
mucosa usually are not only included with but frequently also surround the entire
conceptus, I have used the word abortus to designate all the material expelled
during an abortion. Only in this way can one avoid the use of such words as ovum,
mole, chorion, and such expressions as the entire mass, embryonic mass, abortion mass,
or (quite inaccurately) the chorionic vesicle, even when the latter is surrounded by a
certain amount of decidua and blood-clot.

Since the term fetus compressus, as customarily used, refers to a twin fetus
which died and was later subjected to pressure from the surviving, growing fetus
during an extended period of time while it was undergoing mummification, the
use of this term in Chapters III and IV requires definition. Practically all the
specimens so designated in this survey are single, not twin. Besides, they have
but rarely been subjected to pressure, and not a single specimen is dehydrated
to the extent of being papyraceous. Rarely, when fetuses so termed have been
subjected to pressure, this was the pressure of the contracted uterus subsequent to
the absorption of the amniotic fluid. In many instances, however, these speci-
mens were contained in a quantity of amniotic fluid sufficient to be protected from
direct pressure of the uterus transmitted through the fetal membranes. More-

10 PREFACE.

over, since all these, as well as the specimens of group 7, are macerated, and since
all manner of gradations are found between the macerated swollen and the macer-
ated wrinkled (fetus compressus) specimen, it may be preferable to restrict this
term to its original usage. Much would also seem to be gained by an abandonment
of such terms as decidua vera and serotina, which, although historical, convey false
suggestions. The occurrence of a psuedo decidua does not seem to be at all estab-
lished, and the sense in which the term vera was first used necessarily has been lost
in the progress of modern embryology. The same thing applies to the term sero-
tina. Hence, as suggested by others, it would seem preferable to speak of a parietal,
a basal, and a capsular decidua, and finally relinquish the older terms.

In order to avoid possible confusion through the introduction of new terms,
I have added the following diagram, which presents their relationship at a glance:

Abortus.
ooo I 0395 I,
Conceptus. Blood-clot.

Decidua.
Chorionic vesicle. Pus, ete.
Amniotic vesicle. { Secundines—placenta and membranes.
Umbilical vesicle. Yolk-sac.
Amniotic fluid—magma. oF Cord.

Periamniotic fluid. | Liquor amnii.
Umbilical cord. )

{Embryonic disk.
Cyema....{Embryo.

(Fetus.

In spite of the fact that some great names have long been associated with the
rising subject of the pathology of human development, a routine examination of
abortuses seems quite worthless to many investigators. This is natural, for, aside
from the poor preservation of many of these abortuses, the conditions under which
nature performs her experiments on man necessarily are uncontrolled and often
also unknown. But there would seem to be no reason for rejecting any testimony
which such experiments may offer, though the search be a long and a disappointing
one and the conditions not standard. To regard all attempts at a study of these
specimens as futile is very largely to abandon man to a cruel fate. He never can
be made the subject of accurately controlled experiment or a wholly satisfying
study. The rigid requirements of scientific investigation must, in the nature of
things, almost always remain unfulfilled. Comparative anatomy, medicine, and
pathology, as well as experiments upon animals, undoubtedly offer greater returns
merely because the subject of experiment can be bred, nurtured, and sacrificed at
the will and by the hand of man. But if it be conceded that in the last analysis
the aim of all human effort must be directed toward the amelioration of the lot of
mankind, then it would be folly to reject even the chance stalk that may spring
from the grain of wheat which lay hidden in a bushel of chaff.

The conception, as well as the general plan, of this volume is that of Professor
Mall himself. It was my happy experience to be invited to share in both. An
unkind fate made it impossible for Professor Mall to complete his own work; for
his part everyone will feel deeply grateful; for the part that might have been his,
others than myself will feel an immeasurable regret.

PREFACE. 11

Although the table of contents had not been prepared, the possible scope of
the volume and the order of the topics had often been considered. It was the
intention not only to read each other’s chapters, but to discuss and revise them
together. With characteristic generosity, Professor Mall suggested that, except
for one chapter not contributed by either one of us (Chapter VI), we share equally
in that part of the undertaking not included in the special studies. Partly in
accordance with this desire, he wrote the introductory chapters in the first person
plural, much against my earnest remonstrance, for my share in them is quite
negligible. However, since they had been considered together they stand as he
wrote them, except for a few footnotes. Unfortunately, only one of my studies
was in final form before his death, but he was familiar with it, although we had
not considered the paper together. Since all the remainder of my part was written
subsequently, it did not seem justifiable to me to charge him with responsibility
for conclusions of my own or for personal opinions which might not have com-
mended themselves to him.

It is with the greatest satisfaction that I record in this connection his decision
to mutually consider all points of difference and, if common ground could not be
found, to state frankly our individual views. It was characteristic of him never
to use the weight of his authority in the discussion of controverted questions—or
to influence anyone’s conclusions. He was ever willing to leave the truth to
the future. It was this attitude that made the completion of this unfinished
work a very satisfying effort, even if lonely and in some respects unsatisfactory.
Chapters I, II, and VIII, and all the protocols at the end of Chapter IV, below
No. 1,000, fortunately had been written by him. However, in accordance with his
intentions, protocols were revised and a number of them entirely rewritten. Since
he himself had requested this in the case of several which we considered together,
I feel that I have merely followed his desire in this matter. In the exercise of this
privilege and duty of revision I have used the greatest care to preserve his descrip-
tions as far as possible. Indeed, in the completion of this volume, it has been my
constant purpose to follow his plan, to preserve his views, and to realize his in-
tentions. Although I feel the deepest scientific interest in this work, it has also
been a labor of love and devotion, and it was a great satisfaction that its continua-
tion was made possible by the Carnegie Institution of Washington, and that its
realization was furthered in every way by my friend and former colleague, Dr.
George L. Streeter.

Since these studies were completed very largely during 1918 and the spring
of 1919, no references are made to the recent literature in a large portion of the

volume.
A. W. MEYER.

CHAPTER I.
ORIGIN OF THE COLLECTION.

The collection of human embryos belonging to the Carnegie Institution of
Washington owes its origin to thirty years of untiring effort on the part of one of
the authors (Mall). The first specimen was obtained while he was a student under
Professor Welch in the Pathological Department of the Johns Hopkins University;
very soon another, in excellent state of preservation, was added. After his (Mall’s)
transfer to Clark University in 1899, embryo No. 2 was studied and modeled in
wax. This was the first reconstruction of a human embryo ever made in America
and at that time the most elaborate one in existence. In 1890 this specimen was
offered to Professor His, who refused to accept the gift, and returned it, together
with several from his own collection, expressing the hope that this small number
of specimens might serve as a nucleus for a much larger collection. With the
subsequent foundation of the University of Chicago, the collection was transferred
there, and during the following year a few additions were made. Now somewhat
augmented, it was returned to Baltimore in 1893, at the opening of the Johns
Hopkins Medical School, and here it grew for a number of years, at first slowly,
then more rapidly, until it was finally taken over by the Carnegie Institution of
Washington in 1915.

In the beginning each specimen was labeled with the name of the physician
who donated it, but it was soon found that this method was not accurate. Bottles
were easily misplaced and notes lost from the files were not missed unless marked
with consecutive numbers. Therefore, after the collection had grown to about 100
specimens, a system of numbering, somewhat in the order of accession, was
adopted. However, a review of the catalogue later disclosed the fact that some of
the specimens collected at Worcester followed in numerical order those collected at
Chicago, so that for the first 100 specimens the sequence of accession can not be
viewed as chronologically reliable. From an examination of table 1, in which the
specimens are arranged in hundreds (or centuries), it will be observed that the
first century includes catalogue numbers 1 to 98, the second century, 99 to 205,
etc. These numerical discrepancies are due to the fact that quite frequently the
same number is given to two or more specimens, as illustrated in the first
century; or, as illustrated in the second century, a number once used may be
discarded subsequently because the specimen is found to contain no remnants of
an ovum. The latter specimens are finally marked on the catalogue card “No
pregnancy.”’ In this way we have been able to retain in the catalogues of the
collection ovaries and uteri from non-pregnant women. The second column of the
table shows the time required to collect each 100 specimens. It took 10 years
for the first, 4 for the second, and 2 for the third 100; but after the collection had
been transferred to the Carnegie Institution, about 400 specimens were collected
in one year. It will be observed also that approximately 60 physicians contributed

13

14 STUDIES ON PATHOLOGIC OVA.

TasLe 1.—Showing gradual growth of collection.

Contributing
: 5 Wh llected Ti No. of
Centuries. Catalogue No. en collected. ime. physicians.
P States and
Hospitals. countries.
yr. mo. day
1 1 to 98 1887, to June 1, 1897 10 57 0 21
2 99 to 205 June 1, 1897, to Apr. 19, 1902 4 8 18 53 6 18
3 206 to 295 May 22, 1902, to Mar. 1, 1905 2 8: 38 59 4 14
4 296 to 380 Mar. 1, 1905, to Jan. 1, 1907 1.20." 70 39 d 13
} 5 381 to 476 Jan. 2, 1907, to Jan. 1, 1911 3 11 29 55 8 17
| 6 477 to 571 Jan. 1, 1911, to Feb. 10, 1912 1 1 9 53 8 17
| 7 572 to 652c Feb. 10, 1912, to Mar. 1, 1913 2. (O22 49 5 16
S 652d to 729 Mar. 1, 1913, to July 19, 1913 0) 56.18 65 14 19
9 730 to 8166 July 19, 1913, to Jan. 9, 1914 0 656 20 62 13 21
10 817 to 900g Jan. 9, 1914, to May 27, 1914 Oo 4 18 66 13 23
ll 900A to 964 May 27, 1914, to Oct. 24, 1914 0 4 27 54 12 14
12 965 to 1028 Oct. 27, 1914, to Dec. 19, 1914 (yal eR} 49 6 11
13 1029 to 1126b Dec. 19, 1914, to Apr. 8, 1915 Os) 18 75 12 17
14 1127a to 1202 Apr. 8, 1915, to June 5, 1915 O27 65 14 21
15 1203 to 1292 June 7, 1915, to Oct. 15, 1915 O48 69 10 18
16 1293 to 1365 Oct. 19, 1915, to Jan. 17, 1916 0 2 28 57 8 19
17 1366 to 1458 Jan. 18, 1916, to May 17, 1916 0 3 2 60 9 15
18 1459 to 1545 May 19, 1916, to Aug. 7, 1916 0 3 «#18 56 12 21
19 1546 to 1641 Aug. 9, 1916, to Dec. 13, 1916 0 4 4 77 10 15
20 1642a to 1728 Dec. 15, 1916, to Mar. 3, 1917 Oo 2 18 60 10 12
21 1729 to 18296 Mar. 5, 1917, to June 15, 1917 0, 3 10 69 7 15
22 1830 to 1900/25 June 15, 1917, to Aug. 27, 1917 0.2 14 40 5 10
23 1900/26 to 1901/76 (?) (?) (?) (?) (?) (?)
24 1901/77 to 1956a Aug. 27, 1917, to Nov. 22, 1917 0 2 25 34 5 1l
25 19565 to 2051 Nov. 22, 1917, to Mar. 18, 1918 0 3 26 54 6 13

to the collection of each 100 specimens, of which number 8 (or about 13 per cent)
resided in hospitals. The last column of the table shows the territorial source
of each century, representing an average of 18 States from which material has been
drawn. Upon comparing columns 2 and 38, it becomes apparent that by far the
largest portion of the collection has come from physicians in private practice. Yet
nearly all of our perfect specimens were obtained from hospitals. This is easily
understood when one considers that only when the operator is near can perfectly
fresh embryos be secured. In several instances these have been brought to the
laboratory still living.

Table 2 gives a list of the contributing hospitals, with the number of specimens
from each. As would be expected, the majority of the specimens came from
hospitals located in Baltimore; second in order is New York, and third Manila,
Philippine Islands. Naturally, the Johns Hopkins Hospital contributes the largest
number, for its work is intimately related to our own and the members of its staff
frequently are interested in embryological studies, both in this laboratory and in
the clinical laboratories of the hospital. Hence we receive all of the embryological
specimens found at operation.

Attention is called to the large number of specimens emanating from a single
hospital in Manila. This is due to the fact that this hospital numbers among
its staff several graduates from the Johns Hopkins Medical School, and these
have responded loyally to our request for Filipino embryos for a study of racial
embryology.

ORIGIN OF THE COLLECTION. 15

TABLE 2.—List of hospitals and laboratories contributing embryological material.

Hospitals and laboratories contributing
embryological material.

Century 1
Century 2.
Century 3
Century 11

Century 12.
Century 13.
Century 14.
Century 15.
Century 16.
Century 17.
Century 18.
Century 19.
Century 20.
Century 21.
Century 22.
Century 23.

Century 24.

Century 25.

Jobns Hopkins, Baltimore
Maryland General, Baltimore
Union Protestant, Baltimore
Church Home, Baltimore
Hebrew, Baltimore

_
. J

University, Baltimore

Franklin Square, Baltimore...............
The Howard A. Kelly, Baltimore

Mercy, Baltimore

DuPont Maternity, Cambridge, Maryland .
Physicians and Surgeons, New York

City, Blackwell’s Island, New York Bo oallSol Solel foal ot ect ford lene Lt Lane (ed lose Fel ee
Society of New York, New York..........|..}..|..]..]..

Brooklyn, New York

Bellevue and Allied, New York...........}..|..|..}..|..|..
Roosevelt, New York

CO OT OT Oe

co

BS.

St. Peters, ieee, New York..
Samaritan, Troy, New York.

~
COW Om Nee

Ontario County, Canandaigua, a York. eelleclodioe
State Inst. for Study of Malig. Diseases, Buf-
falo, New York

Gynecean, Sy 5

Bellefonte, Bellefonte, Pennsylvania...

Woman’s, Philadelphia. .

Christ, Jersey City, New Jersey. .

Orange Memorial, Orange, New Jersey...

Jefferson Surgical, Roanoke, Virginia. . Alea lbal lel eel aol lard) oe

Dr. Tyler’s Surgical, Greenville, S.C...... 651156) ea) len foe lod acl ee

Marine Eye and Ear, Portland, Maine.....|..]..]..]..]..]..]..

New England, Boston, Massachusetts

Boston City, Boston

Union, Fall River, Massachusetts. .

Memorial, Worcester, Massachusetts. . oo lect (eal eral eel a

Bridgeport General, Bridgeport, Connecticut rset ieee 1B

Hartford, Hartford, Connecticut. .

Yale University, New <oidoehes Connecticut .

Lakeside, Cleveland, Ohio. . a5

Post, Fort Wayne, Michigan...

Mercy, Denver, Colorado. .

County, Los Angeles, California, .

University, Berkeley, California. . Sn) Sat Aol IGG Ito! lossl are! I Io) ket As fee

L. D. S., Salt Lake City, Othe, eee calle clocllociico acl (an\ oe tao eal alloel inc
2 Sea cea eae Sollee} allsal ool foal eat fol feral Sctledl (calles
Crouse, El Paso, Texas. .

Augustana, Chicago. .

Clinical and Pathological, Springheld Ti.

St. John’s, Springfield, Illinois

Procter, Peoria, Illinois. .

St. Francis, Peoria, Illinois . atiloalloolloalled alte cl eatlo et foetal acl eotlacl leet aol ladl foe
Laboratory StateBoardof Health, Tampa, Fla. ifort eveid esl ce | Fated nee feel dese olla red callie Hear flens,

=
BUS bat bat 09.09.09 Pet Pat Pet RD CRD at

to

to
RO te ON TR Oe tee

16 STUDIES ON PATHOLOGIC OVA.

TasLe 2.—List of hospitals and laboratories contributing embryological material—Continued.

«-

~iJoi|es||us| 5 |o<| a5] es] oi] oe] $6 lla etl li]
Hospitals and laboratories contributing >
Pi embryological material ) B) 8) 8) 8) 8/8] 8) 5) 3) 2) 2) 2) 2) 5/512 |8/3) 2| lz le lele
AIEEE EE EE EEE ee lee
3813181581318 /3 13/5/5135] 1515 /51513/515/5/515/5|515
|. X cli —|— |---| |---|] -|-|-]-
Walter Reed General, lo eee D. CG. aie
Garfield, Washington, D. C. Br ys hae Be (py ;
Mercy, Arkansas City, Kansas. . ry fry ed Ps ns ey Pe es (seed ed et ei iocian Ita oo oo lias balsas cee
Montreal General, Montreal. pols elecfesfasfs cfc ef ols cfiaa te »iflx mle niittklalallei | ates een Globee eres
Port Simpson, Port Simpson, British Col. afew feel le ef ovef cre] oof oveif ecoifieva {toca ote flovetlfaleipeuelt seet| RieM tape renal an er te Feet
Philippine General, Manila, Philippine Is. sellae fle cde flee fee [ice fiecolflovof MPM] lee cof onail ral pee'l ape! ite Canetl ete| fecal fake etal eel
Imperial University, Tokyo, Japan. . RP (Va Fees (esl IS) (ced (nc (es) eed es es toe! loa oct loa pictlod|salloa}lgaton lnallea'|e aloe
Severance Union, Kores..... Be es ee ey (a sy a ee ot fers siesiesGoscias) ASG ahe ls ike eet:
Sunday School, A. P. M., Changteh, Chinan he oeloneobeclesieelee PH i i P| foe Sil eal Fea lection f= cl ee) ee) fey Is 2
Quaker, Nanking, China. . a) (es (ea Ye eae (ees fees) ee es) (ees fl oes ic fee Bolter Ssiiociiccdieals eieclee js-

Sisidin.wivielvin slew asec bisis'= 0.sinielelea'= 9} 5}13)22/18) 9/22)46)37/42/18/27|46/23)32/25/36/31/35|32/26) 0/21/29) 604

In order to obtain good specimens from hospitals, it is necessary that surgeons
and pathologists connected therewith be sufficiently interested in embryology to
preserve and transmit to this department any valuable specimens obtained at
operations. Only in this way can we secure human embryos in as good preservation
as those from the lower animals. It is very gratifying that in several instances
authorities of hospitals have passed resolutions requesting the members of their
respective staffs to send all of their embryological material to this department.
Upon the receipt of a specimen it is described, the records filed, and a copy
sent to the hospital. These records have in a number of instances enabled us to
give expert information, especially in operations upon the uterine tubes in cases
of doubtful pregnancy

Table 3 is interesting as showing the difficulties encountered by embryologists
in collecting material. In our own experience we found at first that, although
physicians seemed to be entirely willing to send specimens, we rarely received them;
or, at best, only those which had been standing upon the shelves for years. These
were badly preserved and of little scientific value, not only because the tissues were
unfit for microscopic examination, but because histories were entirely lacking.
Nevertheless, we always thankfully receive such specimens, and in return gladly
send fixing fluids, write letters, and also send reprints of embryological studies to
donors. In this way we have learned that a physician who will take the trouble to
send one specimen is always willing to preserve carefully the next that falls into
his hands, and, in the course of time, he naturally becomes a regular contributor.
A number of physicians have been contributors for 30 years, and their unselfish
efforts have been a great encouragement to us.

A glance at table 3 will suffice to show that over half of the specimens came from
Maryland, and most of these necessarily from Baltimore; next in order is New York,
and the third, Pennsylvania. The remainder cover widely scattered points, the
first century being drawn from 21 States, the second from 29 States, the sources
gradually expanding to include practically every State and Territory of the Union.
From the beginning, a few have come regularly from abroad, so that now we have

ORIGIN OF THE COLLECTION. 17

TABLE 3.—Sources of embryological material by states, cities, and countries.

al a | od BLOND AlLS|AlaAlS [HI] Sl SIR | SolalSolalalasalwaiss

—T ec ~ ~ oT nl ~ a — Pel N nN N nN nN N

m| Pb nl rl pala ml | bl] >| ml p| m
BYE E) e) E/E) 2) 2) 2) 2) 2) 2) 8) 8/2) 3) 3) 2/8) 2) 2) 2/8/28) 3) 5
/ 218/88) 2/ 8/8/81 818) 3) 81812) 8] 2] 2) | 8/8] 2| 3] 3/8] 3
O};O/0 ODIOIOLOLOJSOLOILOISLOLOlLOlOsSOsSOJSOlLO;/OLOLOoOIJoO] &
Baltimore..... 49| 43) 62] 43) 47| 49) 41) 36) 34) 41] 34) 44] 53) 32] 44) 33) 54] 39] 67] 58] 54! 28/...| 20] 56/1061
Maryland..... 3 9}...| 6} 7| 19) 13) 10] 8} 11] 12) 20] 10} 6) 13] 10) 15) 8} 10} 20) 10 7| 16) 246
New York..... 3) 16] 3] 15] 8] 10) 9} 5) 18] 5) 9) 2) 7| 25) 12) 27|...) 7] 2] 9) 4) 1 9} 5) 211
Pennsylvania ..} 7| 2) 2) 1) 8 2) 2) 2) 3) 1) 6 1] 2} 3] 4) 5] 5| 5) 5] 56 5) 9j...]... 3] 88
Virginia....... Li) 2. Spal | 203) (SE fore) (cova Sey RE] VAS Vis § Ps | eS TO Pre) i | Ve | 3 ie | 3 Wael Ray)
Sven aranyiae | lliimeh |e eri |erclciller=:-[le- | 2] SO] Qh. [ic orl ero SIRS B yy. | O21 k | orevs ed | tarerell evel areal 23
Kentucky..... Weel LS yal PS Meno! UW eaaliaiac| kage bc Beer (eae Wigetlosallomel oct) 24} ola sal lasa laos 1) 16
Tennessee..... Be Deere | rca eters ort bcovavaltchcevs [fevolsiflaxsiss| sisve\iterevs||| X'lleyone!ll | levecil Gis a]'a\eve'| ara ail ecetal|fateell evavell o, orcil levers 6
Misscuri...... Teal Saal lead ?-|lo59|1) 324 loo.0| bas) bee feo acl (Og lee] lobed lane loos) laces lone Inet roses Gees | (SiSes| few 4 eae 8

Rieerenrenirce en eee le fool calcg [> Mocclecc|ecsfeosleeclcccleccles-lecdecsdees
Wisconsin..... PA rs | eas GIS Meets]! vallnmalctarel ceca sts Wea} Heae?4 weet acl ease Weal aoa) lord aaa) ers

3

28

Connecticut ...]... ea val vers Lees | Oe ean teye:<ifiAlvets [ie Die 2) beveccl] eiGleicicler « Ble S | Git F412 28 rere aretal ota ce 50
West Virginia. .|... eeal Beret eae Nees liSeal [barn is. <:c\[tsreis L Mevelcte tl ciere| variernafiere<|i cel 16
Rhode Island. .}... Ds Jide! Stig] oo led! lo bee) lace) (elo! evar cee ler] eters ere ie (cited iteest Iai 3
Louisiana......]...]... BD leraiseciianc| oo 5

@
Peete
_

_
_
_
NW aR WWOnNK PRAT

(]
_
oO
_

Germany... 3, sce el eel cel Bab ond ee ea Fae te ace Paget Pace el gl cate Peg pal ll ee a

E
iz
1
5
o
lol
=
~~
-_
wo
a
wo

OMT Aon cob aceol lathe Gera eae ice leet lee! uae leseral (eens) Ma’ nee oa Waal 2Uibwallenic Bf eerall stra skors\f cre: sil tata otersi[ [scare 5
Korea vi e.g lene 1 2
Japan. colo callecallesltoofleodcaljoodibeallssallSaalleodlibideliseoliseciood! ClisadlGcoleasioooll esac lecalleac lacs 4
Unknown...... Pal bent! etait late [tevate Se ecsh hale Ol, Mee tinea Di fshaveif arava] everaillototei|tayece| orotate oo| LOO) S0)..4 <1 hos

eee eee

specimens from widely different countries. This wide distribution is due to the
systematic circularization of the medical profession. We began by publishing
letters of appeal in scientific journals, such as the American Naturalist; but as
this was rarely seen by physicians it proved a waste of effort. Then, at the sug-
gestion of Professor Minot, a number of articles were published in Wood’s Reference
Handbook in the belief that these would come under the eyes of physicians whom
we hoped to reach; this plan likewise proved of little value. Finally, a circular
was drawn up, widely distributed, and reprinted in most of the medical journals of

18 STUDIES ON PATHOLOGIC OVA.

the country. For a number of years our esteemed colleague, Dr. Howard A. Kelly,
inclosed a copy of this circular with every one of his reprints.

This circularization, we believe, accounts for the responses we first received
from distant and varied points. Furthermore, if the effort is worth while, as a
collection grows a literature develops from it, and papers from studies of our own
collection began to appear in rapid succession. Reprints of these were sent to all
our contributors. This doubtless served to stimulate their interest and encour-
age others to send specimens, for in numerous instances physicians have written to
us, at the suggestion of one of our donors, asking for information and instructions
concerning the preservation and shipment of specimens. Thus, for a number of
years our efforts were directed toward stimulating an increasingly large group of
contributors, and we found that a succession of specimens from a physician gradu-
ally improved in quality as his knowledge and interest increased. In the course of
time certain contributors, who were especially interested in the work, developed
contributing centers, so that in a few instances our collection has been augmented
by a number of specimens received at one time from one or another of these centers.
Aside from those in our own country, such a center was established at Manila,
another at Shanghai, and quite recently one in Korea. The contributors at the
last two points have carried their efforts to the extent of writing letters to the
various Asiatic journals, requesting the preservation of embryos for this collection;
and although unforeseen difficulties are to be overcome in Asia, we hope in the
course of time to acquire at least a representative number of specimens from each
of the important races.

It may prove helpful to others who are making embryological collections to
state that the task will probably be simplified if they will focus most of their
efforts upon the immediate territory. In this way a collector can doubtless secure
all the specimens he can use and, in a way, pay his debt to the local profession by
running a gratuitous pathological laboratory. The collection will thus be made
a central point of interest for the physicians of the community who are scientifically
inclined. Our many accessions from Maryland are due largely to personal
influence through which the codperation of the practising physicians of the Johns
Hopkins Hospital was secured. We have also found that most of the physicians
of Baltimore were not only willing but anxious to send specimens, especially from
cases of repeated abortions. Usually a physician will bring his specimen directly
to the laboratory, thus affording us an opportunity to show him what is done with
it and thereby increase his interest. We do not receive all the embryological
material available in the State of Maryland or in the city of Baltimore, but we
do get a large amount from physicians practising among the poorer classes, as well
asi from gynecologists and obstetricians practising among the wealthier. Most
of the specimens from the poorer people belong in the third to sixth month of
pregnancy and usually appear normal; while those from the upper classes are, as
a rule, younger specimens and most of them are pathological.

After our collection was well established we came somewhat in conflict with
the department of health of the city of Baltimore, owing to the passage of a law

ORIGIN OF THE COLLECTION. 19

requiring physicians to register all miscarriages and still-births. For a time it
seemed as though this would place a ban upon collecting material in the city, but
what appeared at first to be a hindrance later proved to be of great advantage
and help; for the departments of health, both in city and State, have since been
doing everything in their power to facilitate our work. This is well attested by
the following excerpt from the Report of the Commissioner of Health to the mayor
and city council of Baltimore, published in October 1913, and sent to every practis-
ing physician:

“We have through this monthly publication called attention of physicians to the
requirements of the law concerning the proper registration of all abortions or still-births.
We have told you that every abortion or still-birth requires a birth certificate and a
death certificate. As in the application of many new laws, we have found that the
practical working out of this one has produced occasionally some hardships, particularly
on the poorer people, which if they had been anticipated could have been avoided by
application for instructions to this department. So I take advantage of this month’s
publication to inform the physicians that it is not necessary to place their patrons to
the expense of having a fetus, born during the period of gestation of less than five months,
buried by an undertaker. Of course the body must not be disposed of in an irregular
way, such as throwing it down a privy sink or burying it in the yard or cellar, as has
been more or less common in the past, but if the fetal body is properly wrapped up and
placed in a small box and sent to this department, along with the birth certificate and
death certificate, we will see that the body is properly disposed of. I feel quite sure
that this arrangement will meet, or certainly ought to meet, all the reasonable objections
that can be brought against the enforcement of the new law.

“One word concerning the specimens desired by Dr. Mall of the Johns Hopkins
Medical School. We want in every way to assist Dr. Mall in obtaining the specimens
that he so much desires, and this reguletion of the department does not in any way
interfere with it, but probably may be just as easy and certainly safer in supplying the
specimen. Whenever a physician has a specimen to transmit to Dr. Mall, it will not
add much to the physician’s trouble to stop at the Health Department, which is open
at all times, to leave a birth and death certificate and get permission to leave the specimen
with Dr. Mall.”

However, this note delayed unduly the sending of young specimens and doubt-
ful ones from operations, such as uterine scrappings and tubal pregnancies, and
did not, it appears, encourage the reporting of abortions. Later the Department
of Health of the State of Maryland permitted the filing of birth and death certifi-
cates after the specimen had been sent to this laboratory. Many more abortions
are now reported than before, but in order to make the records more complete
the following letter was sent out by the Department of Health in November 1916,
to all practising physicians in Maryland:

“From information this Department has received, we are convinced that we are
not receiving full reports of still-births. It appears that most physicians do not com-
prehend what is embodied in the term ‘still-birth,’ as used in the Registration Law of
this State. For the purpose of learning the extent to which we should expect reports
of still-births under this law, I have requested from the Honorable Edgar Allan Poe,
Attorney General of the State of Maryland (1912-1916), a legal definition of the term,
which I am enclosing herewith. You will note that it is required of you to make a report

20 STUDIES ON PATHOLOGIC OVA.

of all products of conception no matter how early. Every still-birth should, according
to the law, be treated as a birth and a death; that is, there should be filed with the
registrar of vital statistics for each still-birth, no matter how early, a certificate of birth

and a certificate of death. ;
“The Department has learned that Dr. Franklin P. Mall has been endeavoring to

collect embryological material for scientific purposes, and is particularly anxious to receive
fresh specimens. ‘This, or a similar procedure, is a permissible disposition of the materials
in question, and physicians may forward that which comes into their possession to Dr.
Mall, corner Monument and Wolfe Streets, Baltimore, provided that as soon as they
have done so, they file a certificate of birth and death, in Baltimore City with Dr. John
D. Blake, and in the rural districts with the local registrar of the district in which the
birth occurred. The local registrar will issue a burial permit in receipt thereof, which
permit should be forwarded to Dr. Mall immediately. When material is preserved in
formalin or other hardening fluid before forwarding, or in instances when it is disposed
of locally, a certificate of birth and death should be filed and a burial permit received
thereon before it is disposed of. In any instance where a certificate of birth and death
is not filed for a still-birth it will be treated as a violation of the Registration Act.”

These instructions really make it easier for physicians to send specimens to
this laboratory than to dispose of them otherwise, and we have found that the
instructions of the State Board of Health have furthered our work greatly. All
that is necessary is to file the birth and death certificates as usual and send in the
burial permit, either with the specimen or shortly afterwards, and we file it. To
make this clear, Dr. Frederic V. Beitler, chief of bureau of vital statistics, wrote
us as follows:

“‘Tn answer to your communication of December 7th will say that all that is necessary
for you to receive for a still-birth is a burial permit like the inclosed form, which you will
endorse on the back as having received the specimen. At the end of ten days all the
burial permits should be sent to this office.

‘Ordinarily, when a body is disposed of it is necessary to obtain this permit before
removing or disposing of it, but in order to facilitate the rapid transportation of speci-
mens to your office, we allow physicians to register the birth and death without this
permit. They should, however, register the still-birth as a birth and a death as soon as
possible after forwarding the specimen and then send the permit by mail to you.”

A specimen is of very little value, from a medical standpoint, unless accom-
panied by a comprehensive history. Hence, from the very beginning we have been
making every effort to get full data regarding each specimen, with the intention
of determining first its age, later the cause of the abortion. As will be noted in a
subsequent chapter, the former question is approaching solution, but as to the
latter we are still very much in the dark. The various histories given voluntarily
by physicians have served as a basis for a history blank, copies of which have been
sent out quite freely during the past five years. Since this blank has been in use
our histories have improved greatly in value, and as the editions of the blank have
been very small, we have been able to revise it once or twice a year. At the present
writing it comprises the following data:

ORIGIN OF THE COLLECTION. 21

. Patient’s name.
Age.
: father.
. Race ate colored); other.
c -, {father.
‘ Nationality, other.

Date of marriage.
. Number of births at term.
. Total number of abortions, including the present one.
. Order of pregnancies, whether ending at term or in abortion.
Date of beginning of last menstrual period.
. Data bearing upon the cause of the present abortion:

No data.

Associated with disease.

Probably induced.

Probably not induced.
14. Venereal disease{ fatter:

mother.

15. In case of tubal pregnancy an account should be given of the condition of the ovaries, tubes, and uterus.
16. Has the mother, or any of the sisters of the patient, had abortions.
Physician’s name.
Address.
In what fluid was specimen preserved.
How much time elapsed between abortion and preservation of specimen.

WOONAmM BP wO Ne

=

When a specimen reaches the laboratory acknowledgment is promptly made,
accompanied by a history blank and return envelope. Invariably the physician
will fill out and return the blank, and this also is acknowledged immediately. Any
request made by the physician is noted and, in the course of time, whatever infor-
mation we may be able to give is sent to him. In every case a summary of the
description of the specimen is furnished him.

In tendering our thanks to the many friends who have helped in the up-
building of the collection, we wish first to state that it owes its existence primarily
to the encouragement given by the great Swiss anatomist, Wilhelm His, whose
lively interest in it continued until his death in 1904. From 1889 until 1914 the
late Professor Minot also aided us in every way possible, not only in studying our
best specimens, but also in donating many valuable pathological embryos. His
great collection of vertebrate embryos in the Harvard Medical School was likewise
made at the suggestion of Professor His. It will be readily seen by the appended
list of contributors that large numbers of specimens have been donated by certain
individuals during the past 30 years. The names of Ballard, Boldt, Brédel, Cullen,
Hammack, Hunner, Lamb, Terry, Titlow, Trout, West, and Williams appear
repeatedly every year.

One specimen, a negro embryo (No. 460), 21 mm. long, is worthy of special
mention at this time. It was obtained from a hysterectomy performed by Pro-
fessor Thomas §. Cullen, was brought to the laboratory immediately by Dr.
Elizabeth Hurdon, and received alive by Professor Sabin, who injected its blood-
vessels, microscopically, with India ink and preserved it perfectly in a corrosive
acetic solution. During the two years following, numerous surface drawings were
made of this specimen by Professor Evans under the direction of Professor Brédel;
Dr. Essick and Professor Evans cut the embryo into a perfect series; and finally

2 STUDIES ON PATHOLOGIC OVA.

a he

Professor Lewis made an elaborate set of models of the head to illustrate its
anatomy.’

It is impossible to adequately express our obligations to our many contribu-
tors, most of whom are practically unknown to us; but we feel that in many cases
we have made lifelong friends through an extensive correspondence. In general,
the work on the part of these physicians is entirely altruistic, for they hold the firm
belief that the material they gather will be of greater value to science if sent to an
active laboratory than if retained as fine specimens in their own small collections.
We have availed ourselves of every opportunity to accord recognition to the
contributor whenever a publication, dependent upon his specimen, is made.
Adequate return for the trouble he has taken can never be made, unless our work
proves to be of sufficient value to make him feel that he has materially helped the
progress of science.

LIST OF CONTRIBUTORS:

Practically all of the following are physicians. The figures indicate number
of specimens received:

Baltimore City: M. Broedel 54, T. S. Cullen 44, H. B. | Baltimore City—Continued.

Titlow 40, J. L. Truax 37, G. L. Hunner 34,
E. B. Fenby 21, E. C. Lenhert 19, H. M. N.
Wynne 19, V. N. Leonard 17, J. W. Williams
17, H. F. Cassidy 16, F. A. Conradi 16, E. J.
Cook 16, A. F. Ries 16, W. T. Watson 15,
J. G. Murray 14, G. G. Rusk 13, A. H. Schultz
13, J. C. Bloodgood 12, E. K. Ballard 11, G. J.
France 10, A. B. Lennan 10, A. V. Zimmerman
10, C. N. Athey 8, L. E. Beach 8, H. M. Evans
8, Johns Hopkins Hospital 8, J. W. Schlieder
8, C. Vest 8, D. B. Casler 7, J. Girdwood 7,
W. R. Holmes 7, J. M. Hundley 7, H. E. Knipp
7, W. W. Russell 7, H. N. Shaw 7, W. W.
White 7, G. C. Blades 6, G. W. Corner 6,
C. F. Coughlin 6, G. P. Evans 6, A. B. Lyman
6, M. Ostro 6, A. C. Pole 6, J. K. Seegar 6,
W. G. Sexton 6, A. Wegefarth 6, G. Wilkins 6,
W. D. Booker 5, W. 8. Gardner 5, E. C. Gibbs
5, J. A. Luetscher 5, W. E. McClanahan 5,
B. O. McCleary 5, A. W. Meyer 5, E. L.
Mortimer 5, J. C. Neel 5, E. Novak 5, C. S.
Parker 5, M. Rohde 5, J. W. Sanderson 5,
J. B. Schwatka 5, W. Welch 5, J. H. Branham
4, E. H. Cullen 4, I. L. Fetterhoff 4, J. H.
Groshans 4, J. F. Hemple 4, H. A. Kelly 4,
I. Miller 4, J. H. Rehberger 4, A. Shelly 4,
D. Silberman 4, J. Sperry 4, V. Van Williams
4, T. A. Ashby 3, J. Ayd 3, N. B. Bordensky
3, H. Briille 3, W. E. Byers 3, F. A. Carpenter
3, S. A. Dodds 3, W. A. Duvall 3, H. Forsythe
3, H. Fried 3, Gavin 3, F. A. Glantz 3, G. Gold-
man 3, H. G. Jones 3, W. S. Love 3, J. C.
Lyman 3, J. A. Melvin 3, F. K. Nichols 3,
E. H. Richardson 3, H. A. Rutledge 3, W. C.
Sandrock 3, G. B. Scholl 3, G. Stickney 3,
H. H. Arthur 2, R. P. Batchelor 2, C. N.

Branin 2, H. T. Collenberg 2, E. V. Coolahan 2,
G. C. Dohme 2, M. Flexner 2, C. M. Gabriel 2,
H. J. Giering 2, Goldman 2, N. R. Gorter 2,
W. Grant 2, Health Department 2, C. W.
Hoffman 2, A. Horn 2, J. L. Ingle 2, Kemp 2,
G. J. Lochboehler 2, A. M. McGlannan 2, R.
W. B. Mayo 2, W. Neill 2, G. C. Ney 2, E.
J. Russell 2, W. S. Seymour 2, M. E. Shamer
2, T. J. Simms 2, G. W. Simpson 2, A. G.
Singewald 2, W. K. Skilling 2, M. G. Smith
2, G. A. Stewart 2, W. H. Strauss 2, A. Ullman
2, A. S. Warner 2, L. H. Watkins 2, P. Wege-
farth 2, L. H. Wharton 2, K. M. Wilson 2, H. B.
Athey 1, A. S. Atkinson 1, C. Bagley 1, H. H.
Biedler 1, Billingslea 1, C. E. Brack 1, M. L.
Brady 1, W. T. Carr Jr. 1, H. Chabot 1, J.
W. Chambers 1, H. Cushing 1, G. W. Dob-
bin 1, W. M. Dumm 1, R. J. Erickson 1, C. R.
Essick 1, J. M. T. Finney 1, J. Friedenwald
1, A. J. Gillis 1, F. C. Goldsborough 1, G.
Heller 1, K. L. Hichew 1, J. E. Huiskamp 1,
Jose L. Hirch 1, E. Hurdon 1, 8. H. Hurwitz 1,
E. H. Hutchinson 1, M. L. Ingram 1, C. K.
Jump 1, L. Karlinsky 1, T. W. Keown 1, E. Klo-
man 1, H. C. Knapp 1, H. B. Kolb 1, A. J. Laciar
1, Maurice Lazenby 1, Little 1, J. G. Long 1,
J. W. Lord 1, T. B. McCormick 1, D. I. Macht
1, T. H. Magness 1, A. H. A. Mayer 1, J. A.
Miles 1, J. H. Mitnick 1, W. E. Moseley 1,
Moss 1, J. E. Muse 1, L. E. Neale 1, R. B. Nor-
mant 1, E. D. Pleas 1, E. Plummer 1, F. Pol-
lack 1, M. Raskin 1, J. N. Reik 1, F. R. Sabin
1, H. Schmeisser 1, W. J. Schmitz 1, A. W.
Sellards 1, M. Sherwood 1, P. G. Shipley 1,
C. E. Simon 1, F. R. Smith 1, G. A. Stein 1,
A. R. Stevens 1, H. A. Stephenson 1, B. H.

‘A paper dealing with the cartilaginous skull of this embryo has since been published by Dr. Lewis, Carnegie Inst.
Wash. Pub. No. 272.

*This list had been brought up to date by Dr. Mall when this chapter was written. It therefore includes only the
donors of specimens received prior to 1918.

ORIGIN OF THE COLLECTION. 23

Baltimore City—Continued.

Swint 1, G. L. Taneyhill 1, F. N. Tanner 1,
B. E. Tapman 1, G. F. Taylor 1, R. T. Taylor 1,
W. S. Thayer 1, M. H. Todd 1, Eugene Van
Ness 1, A. Wanstall 1, W. T. Willey 1, L. R.
Wilson 1, M. C. Winternitz 1, G. H. Woltereck
1, E. B. Wright 1.

Maryland: G. C. McCormick 81, G. H. Hocking 24,
W. I. Twigg 12, F. Beitler 10, N. H. D. Cox 9,
C. B. Boyle 8, C. M. Hanby 8, A. R. Mackenzie
8, W. J. Todd 7, J. W. Meade 6, W. P. Miller 6,
I. W. Rich 6, C. M. Ellis 5, C. W. R. Crum 4,
W. H. Houston 4, G. Steele 4, S. K. Wilson 4,
J. L. Adams 3, T. H. Henderson 3, R. L. Hoyt 3,
T. W. Linthicum 3, M. G. Porter 3, A. C.
Swink 3, M. A. Birley 2, J. S. Bowen 2, F. C.
Eldred 2, A. T. Gundry 2, W. M. Lewis 2,
W. H. Morris 2, S. M. Wagaman 2, E. C.
Wolff 2, J. H. Bates 1, J. C. Beck 1, C. H.
Beetem 1, T. Brayshaw 1, G. L. Broadrup 1,
W. D. Campbell 1, M. Colton 1, C. F. David-
son 1, H. P. Fahrney 1, F. R. Gough 1, J. O.
Hendrick 1, R. C. Hume 1, T. W. Koon 1,
H. W. Lankford 1, J. R. Laughlin 1, J. R.
Littlefield 1, H. W. McComas 1, I. J. McCurdy
1, H. A. Mitchell 1, M. F. Morrill 1, Nihiser 1,
D. N. Richards 1, J. A. Ross 1, Sampson 1,
H. Schapiro 1, H. H. Simmerman 1, J. D.
Skilling 1, L. G. Smart 1, Wallace 1.

New York: B. F. Terry 20, J. R. Losee 18, O. S. Lowsley
12, H. J. Boldt 9, C. R. Rynd 9, J. B. Harvie 7,
W. G. McCallum 6, A. W. Elting 5, S. H.
Gage 4, N. Jenison 4, H. D. Senior 4, L. J. J.
Commiskey 3, F. R. Ford 3, W. B. Hetfield 3,
PD: Jurist 3; A. T. Kerr 3, A. H. Ritter 3,
M. J. Ross 3, C. K. Winne Jr. 3, F. H. Church 2,
H. I. Davenport 2, Simon Flexner 2, W. F.
Jones 2, B. S. Kline 2, D. H. MecGray 2, N. G.
Orchard 2, R. Sanderson 2, E. Schwarz 2,
E. M. Stanton 2, H. C. Taylor 2, M. Warren 2,
C. A. Bentz 1, H. 8S. Bernstein 1, H. J. Chitten-
den 1, H. C. Coe 1, R. J. Cole 1, E. Comstock 1,
C. W. Dodge 1, Edna D. Fiske 1, H. R. Gay-
lord 1, Burt D. Harrington 1, W. H. Haynes 1,
H. von Hoevenburg 1, J. A. Hymans 1, Johnson
1, F. Kammerer 1, E. Kellert 1, C. Kingsley 1,
W. Kirk 1, L. J. Ladinski 1, J. S. Lewis 1, W.
H. Licht 1, W. C. Lusk 1, McNaughton 1,
Marney 1, Moffatt 1, E. M. Moore Jr. 1, W. L.
Moss 1, C. W. Ottley 1, E. L. Robbins 1, J. A.
Sampson 1, H. 8S. Steensland 1, A. R. Stevens
1, H. F. Swift 1, H. N. Vineberg 1, M. B.
Wesson 1, G. H. Whitcomb 1, S. B. Wolff 1, J.
Woodman 1.

Pennsylvania: P. F. Williams 12, J. M. Jackson 9, R. M.
Pearce 7, A. C. Wentz 7, H. Leaman 6, W. H.
McCurdy 5, H. S. Newcomer 5, John Harvey 4,
H. D. King 4, I. N. Snively 4, E. W. Stick 4,
W. C. Stick 4, J. E. Miesenhelder 3, I. Davis 2,
T. H. Gilland 2, G. M. Gould 2, M. J. Locke 2,
D. F. Unger 2, R. B. Varden 2, D. Dale 1,
J. Y. Dale 1, German Hospital 1, M.S. Hardy 1,
C. C. Hartman 1, Hoge 1, E. B. McGraw 1,
J. H. Sieling 1, F. F. Simpson 1, A. B. Snively 1,
J. S. Swartzwelder 1, T. P. Tredway 1.

Connecticut: T. Wheeler 34, G. B. Cowell 6, E. J.
O'Shaughnessy 5, W. H. Fairfield 4, E. A.
Wells 4, G. W. Cox 3, T. J. Roche 3, D. M.

Connecticut—C ontinued.

Trecartin 3, H. M. Griffin 2, O. Ramsey 2,
J. M. Slemons 2, Anderson 1, J. W. Church-
man 1, F. H. Cooper 1, E. A. Deming 1,
Formichello 1, C. C. Godfrey 1, R. G. Harrison
1, C. N. Haskell 1, E. B. Ives 1, H. B. Lambert
1, R. J. Lynch 1, E. F. Oliver 1, Stevens 1.

Michigan: G. L. Streeter 46, B. N. Epler 9, F. Shilleto 4,
C. Brumme 3, E. H. Cullen 3, L. H. Stewart 3,
L. W. Haynes 2, J. L. Robinson 2, E. J. O’Brien
1, L. S. Crotser 1, L. J. Crum 1, L. H. S.
Dewitt 1, E. G. Knill 1, F. L. Pierce 1, H. N.
Torry 1.

District of Columbia: D. S. Lamb 29, T. C. Smith 14,
Gray 4, E. H. Egbert 3, R. Munson 3, H. L. E.
Johnson 2, E. C. C. Winter 2, O. H. Coumbe 1,
H. T. A. Lemon 1, G. F. Lull 1, W. A. Mon-
crief 1, G. B. Miller 1, M. M. Park 1, M.
Parsons 1, B. F. Poole 1, M. B. Strickler 1.

California: A. Miller 30, R. W. Hammack 19, R. L. Jump
3, E. Rosencranz 2, J. C. Spencer 2, C. M. Faris
1, W. C. McKee 1, A. W. Meyer 1, W. L. Wills 1.

Massachusetts: C. S. Minot 17, D. V. Adriance 2, J. L.
Bremer 2, E. Morse 2, R. S. Perkins 2, R. F.
Rand 2, E. M. Rockwood 2, A. W. Buck 1,
M. S. Haynes 1, J. L. Huntington 1, M. W.
Marvel 1, G. L. Richards 1, M. A. Southard 1,
L. N. Wilson 1.

Philippine Islands: R. W. Hammack 25, C. Fernando 6,
P. K. Gilman 3, B. C. Crowell 1, C. H. Man-
love 1, D. P. Quazon 1, M. Quazon 1.

West Virginia: P. M. Barrett 21, H. G. Steele 3, F. K.
Vass 3, G. Ackermann 2, D. D. Chapman 1,
W. W. Golden 1, P. L. Gray 1, H. O. Henry 1,
D. J. Long 1.

Virginia: J. M. Melton 8, H. B. Disbrow 4, C. O. Miller
4, E. M. Hicks 3, J. S. Speed 3, W. H. Trout 3,
W. E. Nesbit 2, A. G. Hoen 2, R. L. Rhodes
2, S. S. Gale 1, M. D. Hoge Jr. 1, C.S. F.
Lincoln 1, R. H. Wooling 1.

Tezas: W. W. Waite 22, W. L. Hart 3, H. W. Crouse 2,
W. Wilson 2, Brown 1, F. L. Paschal 1.

New Jersey: G. N. J. Sommer 23, T. W. Harvey Jr. 3,
J. L. Fewsmith 3, F. E. Chidester 1, G. K.
Dickinson 1, Orange Memorial Hospital 1.

Tilinois: L. L. Iseman 4, J. H. Bacon 4, R. T. Edwards 2,
M. K. German 2, R. E. Larsen 2, G. W. Bartel-
mez 1, R. Dodds 1, E. C. Dudley 1, E. Dunn 1,
H. F. Dunn 1, M. A. Fitzpatrick 1, S. C.
Glidden 1, L. Hektoen 1, F. Holland 1, W. S.
Lemon 1, Mitchell 1, J. F. Perey 1, W. Ryan 1.

South Carolina: G. T. Tyler 15, D. K. Briggs 4, L.
Peters 2, C. O. Bates 1, W. M. Burnett 1,
D. Furman 1, F. Jordan 1, Powe 1, P. G.
Saussure 1.

Wisconsin: A. F. Fuchs 6, C. R. Bardeen 5, W. G.
Darling 3, A. Egdahl 3, C. H. Bunting 1, G. L.
Kaumheimer 1, A. S. Thompson 1, J. L. Yates 1.

Maine: W. Tobie 14, G. M. Elliott 4, S. P. Warren 4,
A. C. Ferguson 1, L. B. Hatch 1, B. Hunt 1,
E. H. King 1, C. M. Swett 1.

Ohio: H. G. Sloan 4, W. Howard 3, C. A. Bowers 2,
H. McE. Knower 2, C. A. Lamont 2, D. W.
Boone 1, J. M. S. Heath 1, C. C. Jones 1,
H. N. Mateer 1, R. G. Perkins 1, H. Robb 1,
F. Schmitta 1, D. W. Steiner 1.

Minnesota: B. J. Merrill 7, W. S. Miller 4, C. A. Roeder
3, E. H. Loufbourrow 2, F. C. Baier 1.

24 STUDIES ON PATHOLOGIC OVA.

Iowa: J. L. Crawford 6, G. B. Ward 5, J. McMorris 2,
M. Emmert 1, J. T. Miller 1, A. P. Stoner 1.

Kansas: C. E. Caswell 11, M. Hahn 2, M. T. Sudler 1.

North Carolina: R. B. Slocum 5, J. A. Ackerman 1,
A. G. Carr 1, F. W. Griffith 1, F. H. Russell 1.

Canada: J. V. Graham 2, S. H. Quance 2, F. B. Bowman
1, D. A. Campbell 1, R. W. Large 1, R. L.
McCrady 1, J. J. Sheehan 1.

Tennessee: N. I. Ardan 3, W. B. Burns 2, W. T. DeSan-
telle 2, A. E. Douglass 2.

Colorado: C. B. Ingraham 2, H. Sewall 2, W. Boget 1,
F. N. Cochems 1, W. D. Fleming 1, C. Powell 1,
M. R. Stratton 1.

Florida: L. A. Peek 4, E. G. Birge 2, J. C. Dickinson 1.

Indiana: A. G. Pohlman 4, R. E. Troutman 2, N. W.
Cady 1.

Kentucky: J. R. Cottell 2, J. D. Hunt 2, H. A. Cottell 1,
J. F. A. Flexner 1, M. Flexner 1.

Utah: H. Jeidell 7.

Missouri: H. A. L. Rohlfing 3, A. C. Ames 2, A. C’
Eycleshymer 1.

China: O.T. Logan 3, H. S. Houghton 1, C. H. McCloy 1,
Li Yuin Tsao 1.

Georgia: T. E. Oertel 2, J. R. B. Branch 1, C. W. Crane
1, C. A. Rhodes 1.

Oregon: W. J. Weese 3, E. B. Hughes 1.

Idaho: C. L. Dutton 4.

Montana: A. Poska 4.

Korea: R. G. Mills 2, J. W. Hirst 1, T. H. Daniel 1.

Alabama: W. A. Burns 1, H. P. Cole 1, F. A. Lupton 1.

New Hampshire: F. E. Kittridge 3.

Rhode Island: F. A. Coughlin 2, E. A. Stone 1.

Japan: §. Kioshita 3.

Arizona: J. I. Butler 1, C. E. Palmer 1.

Arkansas: M. D. Ogden 1, H. Scott 1.

Louisiana: E. Dreyfus 1, L. J. Genella 1.

North Dakota: W. H. Moore 1.

Nebraska: J. R. Blackman 1.

Washington: H. A. Wright 1.

CHAPTER II.
CARE AND UTILIZATION OF THE COLLECTION.

When a specimen is brought to us in a fresh state, as frequently occurs, we
fortunately are free to use our judgment in methods of fixation and preservation.
If the embryo is perfectly fresh or possibly living, we use, of course, the most
refined fixation, preferably corrosive sublimate with 5 per cent glacial acetic.
When the specimen is not perfectly fresh we generally transfer it to a 10 per cent
solution of formalin. In all of the circulars sent out, physicians are advised to
preserve all abortion material, as soon as possible, in this solution; consequently,
when delivered to us, specimens, if not crushed, are generally found to be so well
preserved that any part is suitable for refined histological technique. In order to
render the physician’s task easier, we always send upon request a number of con-
tainers filled with a 10 per cent solution of formalin in water. Physicians in active
practice frequently allow their abortion material to accumulate, preserving it in
these containers, and when half a dozen or more are filled they send them to the
laboratory or notify us by telephone, and a messenger is sent for them. Specimens
from physicians out of town are, of course, sent by express or parcel post. Although
contributors are instructed to ship by express C.O.D., they apparently often find
it more convenient to send their material by parcel post, for many specimens come
to us in this way.

After a specimen reaches the laboratory it is at once given a serial number.
It is thus identified in our card catalogue, everything relating to it bearing the
same number. The specimen is transferred to another bottle or jar containing
the same kind of fluid in which it arrived—generally 10 per cent formalin. This
jar is not only numbered on the outside, but the serial number of the specimen is
placed within, and if the embryo is large enough, a metal tag, bearing its number,
is attached to one of the extremities. This makes it possible to store several of the
larger specimens in one jar. Likewise, all correspondence concerning the specimen
receives this serial number and all data from the wrappers are transcribed upon
our permanent records. Photographs are made of all suitable specimens and an
objective description recorded on the form shown in figure 2, giving first the
dimensions of the entire mass, then the measurements and a description of the
villi and chorion, after which the ovum is opened and a note made of its contents.
The embryo also is measured, the standard measurement for very young specimens
being the greatest distance in the natural posture from crown to rump. This is
known in our records as the CR measurement. Older embryos are measured
straight and other measurements and weights also are taken. The age of the
embryo is estimated on the basis of weight, crown-rump, and foot length, and the
estimate so obtained is compared with the menstrual age. One or more photo-
graphs are then made and the whole memorandum, together with the clinical
history as supplied by the physician and any other data whatsoever, is placed in

25

26 STUDIES ON PATHOLOGIC OVA.

the permanent files. Special examinations which may be required or suggested
are made subsequently and a summary of our records sent to the donor.

When the collection was taken over by the Carnegie Institution of Washington
it was found necessary to open a book in which are recorded all data relating to
specimens, a page being devoted to each. As these volumes have proved to be of
great value in keeping track of the collection, we have designated them as the Key.
A specimen page of the Key, which records embryo No. 460, is reproduced in

“CARNEGNE INSTITUTION OF WASHINGTON No. 460 Length 2/
~ RECORD KEY OF HUMAN EMBRYOS Diem ie
Ectopic Pathological
Dr Hromas 5. Culler Maternal parts Uterus 1 2) ahauseny:
Street 3 West Prestow Dimensions of Chorion Sox

‘City, Batlmore State Md.
Date received Aprel 20, 19/0

Nationality of Mother Yagro

‘Beginning of last period March 4%, 1910
‘End of last period March 13, 1910
Date of abortion—operation Apr 20, 1910

MEASUREMENT OF EMBRYO

Heap Measurement (Resh, fixative)

Time of fixation April 20, 1910 Length Width Circum. Biaur. age
Fuatve Bechhoride acclic f
‘injection Da clei ke * Histo.ocicaL Recorp

Parts sectioned

EREROR
Recorps on Fite imbedded Dp = =

Notes

10

Letters “} Photos | Drawings | Models Dir

Za age ees
i i,

Publications (Those Illustrated are underscored)

Silo Cochereak

PENS

Cutting

96, 100, 102,105, 112,116, 117, 123, a ieeeinacto sees
sae ee 3 Embryo EE

127, 131, 133, 139, 158 ae Ga

Cumicat History E—Excellent; G—Good; F—Fair; P—Poor.

Ward, 0, Late Path...

No. 14.934 - Bagm. No 16568. Draurings -

Patient, 37, gre mo Laft profle : frout anew (2)
Hick. cessation frm 3 ae hand; tlhood

Fig. 1.—Specimen page from “‘ Key,”’ showing manner in which records of embryos are entered.

figure 1. The data collected are entered in the first column. Only the number of
letters received and the number of photographs made are recorded here, this being
sufficient to show any interested person what may be found in the permanent file.
In the latter, each note is stamped with the catalogue number of the specimen and

CARE AND UTILIZATION OF THE COLLECTION. 27

the date of filing, so that notes entered in successive years can easily be arranged
in sequence. In the upper part of the second column of figure 1 are recorded the
dimensions and general character of the specimen, which, of course, necessitates a
general classification, for at this time it must be determined whether or not the
embryo is normal or pathological. Since the diagnosis is made entirely upon its
general appearance and form, it does not follow, when an embryo is classified as

CARNEGIE INSTITUTION OF WASHINGTON
DAPARTMENT OF EMBRYOLOGY No.
DESCRIPTION OF SPECIMEN

Uterine Size of Abortion Mass Date of Accession
Ectopic Size of Choron Fixation on Arrival
No Pregnancy Size of Chorionic Cavity Preservation

Measurement of Embryo (natural curve, straight)

Foor Lenatn HEAD

(ARLES ce

IG RIOT IN reeecrerensnssensenses soso toseesesteeeasainen toe nscohosonoe ~ oeemsnsnscnnnnreeesaisneiee mem UNDETERMINED

CLASSIFICATION

NORMAL

PATHOLOGICAL ...........
. Vu
& CHORION WITH COELOM
4% CHORION WITH AMNION
@ FODULAR
8 CYLINDRICAL
6 STUNTED
7 MACERATED, MUMMIFIED
CROSS REFERENCE
OVARY
TUBE
UTERUS
SCRAPINGS
IMPLANTATION

PLACENTA OR CHORION

DECIDUA

RACIAL

EXAMINED BY ern ee ce IE ects

LOCALIZED ANOMALY

Fia. 2.—Blank upon which preliminary description of specimen is entered.

normal, that it necessarily is so, but only that it is normal in form. This point
will be discussed later.

In order to facilitate the tabulation of the Key, we have found it necessary to
make all descriptions of a specimen on another form (fig. 2), which is so constructed
that any data entered are easily transferred to the Key. This information is

28 STUDIES ON PATHOLOGIC OVA.

arranged from the card catalogue, a plan we have found essential in order that
any given type of specimen may be located easily. By this time the specimen is
fully recognized as normal or pathological, and it has also been determined whether
new records or drawings should be made for future reference. The photographs,
negatives, letters, notes, and drawings are then filed in numerical order in suitable
metal cabinets in a fire-proof vault.

An effort is made to cut into serial sections, as soon as possible, all small embryos
that are well preserved. Miscellaneous specimens are likewise constantly being
sectioned—for instance, an ovary, villi, portions of a chorion, or parts of larger
embryos. In order that this may be done without confusion to the investigator,
we have found it helpful to record each block under consideration upon a form
somewhat similar in character to figures 1 and 2; this we call the histological
record, which may be compared to a bill of lading. This sheet is dated and the
part of the specimen to be cut is indicated thereon, as are also the directions for
embedding, cutting, staining, ete. After the work has been done, the technician
returns the slides, with the histological record, to the investigator interested in
this particular specimen, who checks up the sections and enters the grade upon
the histological record, which is then placed in the permanent file.

Preparations of many specimens for the microtome are constantly under way.
Since most of the specimens are delicate and can not be touched, we have had very
satisfactory results from passing them through the graded alcohols in shell vials,
closely stoppered with absorbent cotton. Within each vial is a loose tag bearing
the number of the specimen. Experience has taught us that if there is very careful
gradation only five grades of alcohol are necessary, beginning with 60 per cent, then
70 per cent, and so on. With the firm cotton stopper the entrance of the alcohol
is so gradual as to equal an infinite number of gradations. For instance, if the speci-
men is changed from a 60 per cent to a 70 per cent solution, the stopper should be so
tight that the diffusion can not become complete for several hours. When passing
from lower to higher grades it is preferable to invert the vial. If this were not done,
the stronger solution would not enter so quickly, as a 60 per cent fluid has a higher
specific gravity than a 70 per cent, and hence there would be a slower mixture. In
passing from stronger alcohol to water, on the other hand, the vial should be right
end up. The underlying idea of this procedure is based upon the fact that if the
ovum is thrown into strong alcohol, the chorion and outer layers of the embryo
become greatly shrunken, while the deeper tissues are well preserved, as the alcohol
diffuses slowly towards the center of the embryo. After dehydration the specimen
is embedded in either celloidin or paraffin, stained, and cut according to the direc-
tions given on the histological record, and is then ready for permanent filing.

We have found it convenient to segregate the specimens into two groups.
The first includes all embryos which have been cut into serial sections. These
are filed according to length, so that any one wishing to study structures in the
4-mm. stage, for instance, will find all such embryos together in the cabinet.
There is, however, a very large amount of miscellaneous material which we have
been compelled to file merely in numerical sequence, and this constitutes the

CARE AND UTILIZATION OF THE COLLECTION. 29

second group. In order to expedite the work of locating a specimen, each is entered
upon the card catalogue according to its length in millimeters, the groupings
being a millimeter apart. All normal embryos of the same length are entered upon
the same card, with notations as to whether or not they have been cut into serial
sections. The pathological specimens are arranged upon cards according to type,
but the specimens of a given type or group are also arranged in order of size. In
this way it is quite easy to locate a specimen of a given size in any group after it
has been sectioned. It can be seen at a glance, therefore, that we have here a list
corresponding to all the embryos in the collection, both those which have been cut
and those which have not. There are similar cards of all drawings, models, and
photographs, and these, in a general way, are arranged according to their anatomi-
cal topography. For instance, on one card will be found left profiles, on another
right profiles, on another hands, ete.

It is by no means a simple matter to catalogue the miscellaneous material.
We have found it necessary to carry a card for ovaries, another for tubes, and so
forth, as shown in the second column of figure 2. In the course of time we shall
add cards for partial series and for the different tissues and organs of the larger
fetuses.

As will be seen from the appended bibliography, our earliest studies in embry-
ology were made from the viewpoint of gross anatomy. The first paper deals
with the entire anatomy of an embryo 7 mm. long, and therein are recorded several
important discoveries. (As stated before, the model made for this study was by
far the most elaborate piece of modeling that had as yet been undertaken.) Fol-
lowing this were papers written for the Reference Handbook, which are more
general in character. Finally, the names of collaborators began to appear in the
list, the first paper being by J. B. McCallum, on the histogenesis of striated muscle.
As the interest of new investigators was enlisted, the scope of the work gradually
broadened to include almost the entire field of anatomy, and the 159 papers’,
which are dependent largely upon our collection, may be classified as follows:
18 were written for the purpose of propaganda, as efforts have been made from
time to time to gain the interest of physicians who might be in a position to send
specimens. It must be admitted, however, that these individual appeals brought
few results. After such an appeal we would, perhaps, receive two or three speci-
mens. Then there would be a period of quiescence, and we would have to content
ourselves with studying again with greater care the detailed anatomy of small
portions of an embryo, since material for more extensive surveys was lacking.
But as the collection gradually enlarged, papers on embryometrics were published.
These number 14 in all, and include such questions as the age of embryos and
curve of growth. As might be expected, most of the studies have been on anatomy,
although a single specimen calls for a great deal of time in order to work out the
form and relation of the organs. The papers on embryo-anatomy fall naturally
into subdivisions which have been recognized by anatomists for centuries. There
are 9 papers on topographical embryology, 10 on osteology, 9 on myology, 25 on

1 These 159 papers include only such as appeared before 1918. A considerable number have been published since then.

30 STUDIES ON PATHOLOGIC OVA.

angiology, 16 on splanchnology, 15 on the genito-urinary system, and 7 on the
eelom. The study of brain morphology is, to a certain extent, a science in itself,
and there are 24 papers on neurology. Only 9 publications on histogenesis have
appeared, but the histogenetie standpoint is considered in many of the other
papers enumerated above.

As the collection grew we found an increasing number of specimens which,
though peculiar in form, were at first believed to be normal, but which upon closer
study proved to be pathological. Thus we were unwittingly carried into the field of
abnormal development. In fact, the great problem which confronts us always, in
the study of a new specimen, is to determine whether or not it is normal. The
experience of embryologists elsewhere has apparently been identical with our own,
for frequently one observes in the literature an account of a human embryo,
believed at first to be normal, which, upon further consideration, proved to be
pathological. Hochstetter has stated that we have no right to consider an embryo
normal unless it has been removed by a surgeon at hysterectomy, but our studies
along this line have shown that a quite appreciable number of hysterectomies
disclose pathological embryos. The criterion of His, who used the comparative
method of von Baer in determining the normality of human embryos, is probably
more reliable than that of Hochstetter. I believe, therefore, that the best check
in the study of the human is a knowledge of comparative embryology.

There are 14 papers in the list that deal with pathological embryology. The
first (No. 21) included all specimens up to No. 162, which were believed to be
pathological. As we have found the two fields closely related, in these studies
we have naturally drifted from pathology into teratology, there being 10 papers
on this subject.

Of the 500 papers emanating from the Department of Anatomy of the Johns
Hopkins Medical School, there are (in addition to the above-mentioned 159 dealing
with human embryology) 115 on experimental embryology. A study of human
embryology can not be of great scientific significance unless it be extended through
comparative studies and an effort be made to determine, if possible, the causal
relations between the developing parts. From the beginning, therefore, experi-
mental studies have been made upon a great variety of subjects, the most important
being on organ-forming substances and the influence of the eye-vesicle upon the
development of the lens from the ectoderm. We may also at this point call atten-
tion to the brilliant studies of Harrison upon the development of the nerves,
which demonstrate conclusively the validity of the neuron doctrine. In making
these experiments he developed an ingenious method by which the living isolated
cells could be seen under the microscope and their growth followed during a number
of days. Later, this work was extended to the study of growth of all kinds of
isolated tissues in the warm chamber, now well known as tissue culture.

In nearly all studies on embryo-anatomy it is necessary to resort to methods
which will enable one to see the structure and form of organs in their serial sections.
As far as possible this is always done by observing the whole embryo or parts of
one dissected under the dissecting microscope. A valuable specimen, however,

CARE AND UTILIZATION OF THE COLLECTION. 31

can not be treated in this way. Such a specimen is cut into sections and from the
sections an effort is made to reconstruct the anatomy. In the first publication
the anatomy of the embryo was worked out by Born’s (1883) method of recon-
struction, but unfortunately at that time this method gave little more than the
external form, the finer structures being lost in the model. The plan of dissecting
the model was then tried, and it soon became clear that success in reconstruction
depended very largely upon one’s power to visualize the structures from the serial
sections, and to some extent upon inventive ability in eliminating a part of the
model, as deeper structures can not be shown without removing the superficial
ones. Gradually we evolved what we term dissectible wax models, which, however,
are somewhat clumsy and usually warp in warm water. Finally, Dr. Bardeen
(1901), who is skilled in work of this kind, discovered that excellent results could
be obtained by making a foundation model in wax and then projecting and elaborat-
ing it as a drawing by the graphic method of His (1892), thus combining the good
features of two very valuable methods.

At first our record of sections was made by drawing them with the camera
lucida or, better still, in a dark room by the aid of a magic lantern. This, however,
is a very laborious and time-consuming task, and has a tendency to check the
mental activity of the investigator, for unfortunately the work can not be done
successfully by a technical assistant. When the collection was transferred to the
Carnegie Institution we availed ourselves of the opportunity to install an accurate
projection apparatus patterned somewhat after the one used by His (1892). With
this apparatus sections of embryo No. 460, previously referred to, were photo-
graphed on glass negatives with an enlargement of 50 diameters. Thus it was
possible to make several prints. As the photographs were taken with a 50-mm.
planar lens, they show all the details wonderfully well.

As everything which we wished to reconstruct had to be transferred to wax, it
was highly desirable that the final model should be composed of some temperature-
resisting substance. A method has therefore been devised whereby all the struc-
tures desired are eliminated from the wax. Thus, in a block of wax the model is
represented in outline by a hole or a series of holes, according to the number of
structures to be reproduced, and these holes are subsequently filled with plaster
of paris. When this hardens and the wax is removed, the finished plaster model
is liberated.

This process of modeling depends solely upon absolute accuracy in super-
posing the wax plates to correspond to the original sections of the embryo. Hence
a perpendicular line must be established, and this is done as follows: The wax
plates of the sections are placed one upon another until a complete model of the
embryo is built up (fig. 3), the construction being guided by photographs of the
embryo made before it was cut. Thus it is possible to duplicate accurately the
external form of an embryo on an enlarged scale. After this is done it is a simple
matter to mark the wax plates in a perpendicular direction—that is, by right-
angle lines drawn upon every plate through its axis. These constitute what we
call guide-lines, the instrument for marking which was invented by Dr. W. H.

32 STUDIES ON PATHOLOGIC OVA.

SSS

Fic. 3.—Method of piling with cardboard outline as guide: 1, external form piled in wax plates; 2, cardboard outline
guide; 3, posts for attaching same; 4, baseboard.

Lewis (1915) and is known as the Lewis guide liner (fig. 4). After the guide-lines
have been drawn on each wax plate they are transferred to the photographs
or drawings. This is done by superposing each wax plate upon its photo-

graph or drawing and marking
the end of the guide-lines. When
the wax plate is removed, these
points are connected by lines
similar to those on the plates.
After the two principal guide-lines
have been established, it has been
found convenient to use secondary
guide-lines, 5 em. apart, which run
parallel to the primary ones over
the entire surface of the photo-
graph.

#

Fic. 4.—Method of making guide lines: 1, baseboard; 2, perpen-
dicular posts; 3, straight edge; 4, piece at right angles to it.

In order to make a reconstruction of any portion of an embryo it is necessary
first to transfer the outlines of that structure from the photograph to the wax
plates by means of carbon paper and a glass point used as a pencil. These outlines
are then cut and removed from the wax and the plates squared off along the

CARE AND UTILIZATION OF THE COLLECTION. 33

secondary guide-lines sufficiently far outside of the proposed model not to conflict
with its casting.

In order that these finished plates, which we call mold plates, may be kept in
exact apposition, they are piled in a rectangular corner made of plate glass (fig.
5). While this is being done it is necessary to cut certain artificial channels as
vents, so that the air will escape from the openings when the plaster is poured in.

Fic. 5.— Method of piling wax mold: 1, baseboard; 2, perpendicular right angle corner; 3, glass plate; 4, wax mold;
6, vent; 6, galvanized iron wire bridge; 7, gate for plaster between parts of mold.

It is also well to bridge loosely attached parts with copper wire, which is done by
heating the wire and laying upon the wax plates as they are being piled up. The
entire mass forms a mold which, to distinguish it from the others, is called a plate
mold. This is cast with plaster of paris, and after the plaster has set the wax is
removed by heating. Sometimes it is necessary to proceed farther and make a
break mold over the first cast, after which it is possible to make as many duplicate
casts as desired. In the above description the main outlines of this valuable
method of reconstruction, as now practised in this laboratory, have been given.
Numerous general studies have also been made in embryometrics, in which
linear, gravity, and time values are considered. Furthermore, the technique
of gross anatomy has been applied to differentiate, by means of injection, the
arteries, veins, and lymphatics of the whole clarified embryo. Similar specimens
can be prepared to show the entire cartilaginous and bony systems. Thus many
embryos frequently are considered in a single publication, especially those illus-
trating causes of abortion and the production of moles and monsters. Attention
is therefore called to the numbers following the references in the appended list
of publications. These represent the catalogue numbers of the specimens studied.

34 STUDIES ON PATHOLOGIC OVA.

It will be noted that certain specimens are referred to frequently, showing that
these have been of more general use than others. While these numbers may
seem somewhat confusing as they here appear, references to a given embryo are
found together in the Key, and this makes it quite easy to find the published
description of that embryo. Where the description is accompanied by illus-
trations, the specimen number is printed in bold type. A comprehensive view of
the entire bibliography shows that the papers are sometimes general but often
special in character. Whenever the line of thought is general, it is necessary to
consider the topic in many different embryos, and one topic is frequently repre-
sented by several collaborators. In other words, our department is a large
codperative effort on the part of many contributors and collaborators.

Our first papers were published in the Journal of Morphology and the Johns
Hopkins Hospital Bulletin and Reports, as well as in the foreign journals. We
had hoped at that time that the excellent Journal of Morphology would continue,
and that it would publish all of our best papers; but unfortunately it could not be
financed, and thus for a time we had no adequate outlet for our work. At the
Christmas (1900) meeting of the American Association of Anatomists, held in
Baltimore, a committee was named to consider the advisability of founding a new
journal for the publication of serious anatomical studies. In May following,
three trustees (Huntington, Mall, and Minot) were appointed to launch this
enterprise. In November of that year the first number of the American Journal
of Anatomy appeared, and at the next meeting of the Anatomists, held in Chicago,
it was voted to substitute the new journal for the Proceedings of the Association,
without additional expense to the members. In this way national support was at
once assured. A glance over the first ten volumes of the Journal discloses the
fact that about 30 per cent of the papers emanated from the Anatomical Labora-
tory of the Johns Hopkins Medical School. In other words, our collection was one
of the chief incentives for its publication. In rapid succession other journals were
established and published in Baltimore; first, the Journal of Experimental Zoédlogy
in 1904, then the Anatomical Record in 1906. The stimulus given by these national
efforts brought about the revival of the Journal of Morphology by the Wistar
Institute in 1908, the opening volume consisting of a monograph entitled “A
study of the causes underlying the origin of human monsters” (Mall). These
serial publications mark the conversion of our studies of embryology from a local
to a national enterprise.

About this time codperative effort was regenerated by Professor Keibel of
Freiburg, and during one of his visits to Baltimore it was agreed that the leading
embryologists compile all known facts regarding human development. This com-
pilation was undertaken by 15 embryologists (1 Canadian, 1 Swiss, 2 German,
3 Austrian, and 8 American) and resulted in the production of a two-volume
work published in both German and English. One-half of this was produced by
the American contributors, and 6 of these 8 used our collection of embryos almost
exclusively. The work as a whole certainly does represent progress, and it has
also brought our collection into scientific position; but the editors were not satisfied

CARE AND UTILIZATION OF THE COLLECTION. 35

with their effort, believing it was possible to produce a better work. Before this
could be done, however, it was deemed necessary to organize our forces more
thoroughly, and to bring this about a plan for the study of human embryology
was drawn up by one of the editors', which embraced the following features: (1)
Much larger collections must be made; (2) much better histories of the various
specimens must be obtained; (3) the necessary material must be placed at the
disposal of the most competent investigators.

This plan received the full indorsement of leading embryologists, including
Keibel and Waldeyer, and was presented to the officers of the Carnegie Institution
of Washington, who responded generously with an initial grant of $20,000 to carry
on the work for one year as an experiment. At the end of that time a department
of embryology of that Institution was established. The Department of Publica-
tions of the Carnegie Institution has been of the greatest value to us in our work,
for it publishes adequately certain studies which, on account of their expense,
could not appear in the journals. These publications, known as the ‘“‘Contribu-
tions to Embryology,” are brought out in series at irregular intervals. The first,
“On the fate of the human embryo in tubal pregnancy,” fills an entire volume.
The individual papers appearing therein since then will be found in the appended
bibliography.

1 Mall.
PUBLICATIONS BASED ON STUDIES OF THE CARNEGIE COLLECTION.

aC

(The numbers following each publication represent the catalogue numbers of the specimens described therein. Where
the description is accompanied by illustrations the catalogue number is indicated in bold type.)

Matt, F. P., 1891.

A human embryo twenty-six days
old. Jour. Morph., vol. 5, p. 459-480.

12.

Matt, F. P., 1898. Development of the ventral ab-
dominal walls in man. Jour. Morph., vol. 14,

2 p. 347-366.
2, _____, 1891. Development of the lesser peritoneal 2, 12, 22, 43, 74, 76
cavity in birds and mammals. Ibid., p. 165- 13. , 1898. The value of embryological specimens.
179. Maryland Med. Jour.
2 1, 2, 5, 6, 11, 12, 16, 17, 18, 19, 22, 23, 26,
3. —_, 1893. A human embryo of the second week. 27, 28, 30, 31, 34, 35, 42, 45, 46, 49, 52, 57,
Anat. Anz., vol. 8, p. 630-633. 72, 76, 79, 80, 81, 87, 88, 92, 94, 95, 96,
11 98, 99, 105, 106, 109, 116, 117, 118, 121
4. ____,, 1893. Early human embryos and the mode of 14. , 1898. Development of the internal mammary
their preservation. Johns Hopkins Hospital and deep epigastric arteries in man. Johns
oe vans p. 115-121. Hopkins Hospital Bulletin, p. 232-235.
NG) leet) , 2, 43, 76
5. —__, 1893. Colom. Ref. Handb. Med. Sci. 15. ..___, 1898. Development of the human intestine
an vol. 9, p. 184-189. and its position in the adult. Ibid., p. 197—
208.
G2 aa The heart. Ibid., p. 391-395. 2, 6, 9, 10, 11, 12, 34, 45, 48
. 16. MacCauium, J. B., 1898. On the histogenesis of the
7. ____, 1898. Development of the thymus. Ibid., striated muscle fiber, and the growth of the
Ds Se: sartorius muscle. Ibid., p. 205-215.
“ : 64, 65, 98
8. ——_, ss Pune of ‘the thyroid. Ibid., 17. Henpricxson, W. F., 1898. The development of the
Pp. sa 1. bile capillaries as revealed by Golgi’s method.
. 3 Ibid., p. 220-221.
ee aes ee 20S 20 18. Matt, F. P., 1899. Supplementary note on the
10 1893. Development of the human cclom. development of the human intestine. Anat.
Jour. Morph., vol. 12, p. 395-453. meee eee
, 6, 8, 9, 10, 11, 12, 13, 14, 16, eas
p a ap Be 21. 22. 24. 98 29, 32, 34, 19. Barker, L. F., 1899. The nervous system. D.
37, 42, 43, 45, 48, 53, 55, 57 Appleton & Co., New York.
11. _____, 1897. Ueber die Entwickelung des mensch- 2, 6, 9, 12, 18, 19, 43

lichen Darmes und seiner Lage beim Erwach-

. CuarK, J. G., 1900. The origin, development and

degeneration of the blood vessels of the human

senen. Arch. f. Anat. u. Physiol., Anat. / s
Abth., Supplementband, p. 403-432. ovary. Johns Hopkins Hospital Reports, vol.
2, 6, 9, 10, 12, 34, 45, 48 9, p. 593-676.

36

21.

24.

26. Harrison, Ross G., 1901.

to
~I

29.

30.

31.

32.

33.

. Lewis, W. H., 1901.

. Mat, F. P., 1901.

. Barppen, C. R., and W. H. Lewis, 1901.

- MacCaurtum, J. B., 1902.

STUDIES ON PATHOLOGIC OVA.

A contribution to the study of the
Ibid.,

Ma tt, F. P., 1900.
pathology of early human embryos.
p. 1-68.
1, 2, 5, 6, 10, 11, 12, 13, 14, 16, 17, 18,
19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29,
30, 31, 32, 33, 34, 35, 37, 42, 45, 46, 49, 52,
54, 55, 57, 58, 60, 69, 70, 71, 72, 76, 77,
78, 79, 80, 81, 82, 87, 88, 93, 94, 95, 96,
97, 98, 99, 104, 105, 106, 109, 110, 115, 116,
117, 118, 121, 122, 123, 124, 127, 128,
129, 130, 132, 133, 134, 135, 136, 137,
138, 141, 142, 143, 144, 145, 146, 147,
148, 150, 152, 153, 159, 161
Berry, J. M., 1900. On the development of the villi
of the human intestine. Anat. Anz., vol. 17,
p. 242-249.
6, 9, 34, 45, 48

. MacCaitum, J. B., 1900. On the muscular architec-

ture and growth of the ventricles of the heart.
Johns Hopkins Hospital Reports, vol. 9, p.
307-335.
Matt, F. P., 1901. On the development of the human
diaphragm. Johns Hopkins Hospital Bulletin,
p. 158-171.
2, 12, 43, 74, 76, 80, 109, 113, 114, 116,
136, 144, 148, 163, 164
Observations on the pectoralis
major muscle in man. Ibid., p. 172-177.
22, 43, 90a, 109, 129, 163
On the occurrence of tails
in man with a description of the case reported
by Dr. Watson. Ibid., p. 96-101.
43, 144, 370
Age of human embryos. Ref.
Handb. Med. Sci., 2d ed., vol. 3, p. 794-797,
1, 2, 5, 6, 11, 12, 16, 17, 18, 19, 22, 23,
26, 27, 28, 30, 31, 34, 42, 45, 46, 49, 52.
57, 72, 76, 79, 80, 81, 87, 88, 92, 94, 96,
99, 105, 106, 109, 116, 117, 118, 121, 138,
144, 145, 146, 148, 149
Develop-
ment of the limbs, body-wall, and back in
man. Amer. Jour. Anat., vol. 1, p. 1-35.
2, 12, 22, 43, 76, 106, 109, 144, 148, 163,
167, 175
Matt, F. P., 1901. Comparative development of the
celom. Ref. Handb. Med. Sci., 2d ed., vol.
3, p. 166-171.
2
—_____, 1901. Development of the human cclom.
Ibid., p. 171-189.
2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,
17, 18, 19, 21, 22, 23, 24, 28, 34, 42, 43,
45, 48, 57, 58, 123, 130, 134, 137, 143, 147
Lona, Mancaret, 1901. On the development of the
nuclei pontis during the second and third
months of embryonic life. Johns Hopkins
Hosp. Bull., p. 123-126.
45, 75, 86, 95
Lewis, W. H., 1902. The development of the arm in
man. Amer. Jour. Anat., vol. 1, p. 145-183.
2, 12, 22, 43, 76, 80, 109, 163, 164
Matt, F. P., 1901. Pathological human embryos.
Ref. Handb. Med. Sci., 2d ed., vol. 3, p. 797-
S09.
11, 13, 14, 21, 24, 25, 29, 32, 37, 54, 55,
58, 60, 69, 70, 72, 77, 78, 79, 81, 82, 87,
93, 94, 97, 104, 110, 115, 122, 123, 124,
128, 130, 132, 133, 134, 135, 136, 137, 141,
142, 143, 147, 149, 150, 152, 153, 161
Notes on the Wolffian body
of higher mammals. Amer. Jour. Anat., vol.
1, p. 245-259.
2, 75, 76, 109, 128, 144, 163, 164

35.

36.

37.

38.

39.

40.

42.

. —___—, 1904. Development of the thyroid.

. Meyer, A. W., 1904.

Matt, F. P., 1902. Development of the heart. Ref.
Handb. Med. Sci., 2d. ed., vol. 4, p. 573-579.

2 :
Supter, M. T., 1902. The development of the nose
and of the pharynx and its derivatives in man.
Amer. Jour. Anat., vol. 1, p. 391-416.
2, 12, 22, 43, 106, 109, 144, 163, 175
Matt, F. P., 1903. Second contribution to the study
of the pathology of early human embryos.
Contr. to Med. Research. Dedicated to
Victor C. Vaughan, Ann Arbor, Mich., p.
12-28.
13, 20, 25, 29, 32, 54, 55, 69, 70, 71, 77,
82, 93, 110, 115, 123, 124, 130, 132, 134,
135, 136, 141, 142, 143, 147, 153, 158,
159, 162, 166, 174, 177, 180, 181, 182,
185, 188, 189, 190, 191, 195, 196, 198,
200, 201, 204, 205, 207
WituraMs, J. W., 1903. Obstetrics.

19, 82
Lewis, W. H., 1903. Human embryology. New
Internat. Encycl. New York.
2, 12, 22, 109, 163
Matt, F. P., 1903. Notes on the collection of human

embryos in the Anatomical Laboratory of the
Johns Hopkins University. Johns Hopkins
Hosp. Bull.
1 to 85 inc., 37, 42, 43, 45,46,48,49, 52 to 55
inc., 57, 58, 60, 64, 65, 69 to 72 inc., 74 to
82 inc., 86, 87, 88, 90a, 92 to 99 ine., 104,
105, 106, 109, 110, 113 to 118 ine., 121 to
124 ine., 127-130 inc., 132 to 138 ine.,
141 to 150 inc., 152, 153, 158, 159, 161 to
164 inc., 166, 167, 174, 175, 177, 180, 181,
182, 185, 188, 189, 190, 191, 195, 198,
200, 201, 204, 205, 207
, 1903. On the transitory or artificial fissures
of the human cerebrum. Amer. Jour. Anat.,
vol. 2, p. 333-339.
1, 2, 4, 5, 9, 12, 18, 19, 22, 43, 45, 48, 57,
74, 76, 80, 86, 88, 95, 96, 100, 105, 106,
109, 113, 114, 116, 118, 138, 139, 144,
146, 148, 149, 151, 163, 164, 169, 170,
175, 179, 196, 206, 218
Prance, R. M., 1903. The development of the islands
of Langerhans in the human embryo. Amer.
Jour. Anat., vol. 2., p. 445-455.
22, 23, 34, 42, 45, 48

. Gace, 8S. P., 1903. Serial order of segments in the

fore-brain of three and four weeks human
embryos. Science, n. s., vol. 17, p. 486.
148
, 1904. The mesonephros of a three weeks
human embryo. Amer. Jour. Anat., vol. 3,
p. VI.
148

. Matt, F. P., 1904. Development of the thymus gland.

Ref. Handb. Med. Sci., 2d ed., vol. 6, p. 568-
570.

2, 12, 109, 163
Ibid.,
p. 570-574.

2, 109, 163, 175

. Lewis, W. H., 1904. Development of the foetus.

Ibid., p. 450-457.
2, 12, 22, 109, 163
On the structure of the human
umbilical vesicle. Amer. Jour. Anat., vol. 3,
p. 155-156.
2, 11, 12, 18, 22, 76, 80, 113, 145, 163,
167, 175, 176, 184, 187

. Srreeter, G. L., 1904. Peripheral development of

the cranial and spinal nerves in the occipital
region of the human embryo. Amer. Jour.
Anat., vol. 4, p. 84-116.

2, 144, 148

50.

61.

64.

56.

57.

58.

59.

61.

62.

. Bropet, Max, 1905.

CARE AND UTILIZATION OF THE COLLECTION.

Matt, F. P., 1904. On the development of the blood-
vessels of the brain in the human.embryo.
Ibid., p. 1-18.
2, 74, 109, 144, 145, 163, 225, 234, 234b,
235, 237, 238
Pouiman, A. G., 1904. Concerning the embryology
of kidney anomalies. Amer. Med., vol. 7,
p. 987-990.
175
, 1905. Abnormalities in the form of the kidney
and ureter dependent on the development of
the renal bud. Johns Hopkins Hosp. Bull.,
p. 51-60.
2, 22, 43, 76, 114, 144, 163, 164, 175, 221
, 1904. Has a persistence of the Mullerian duct
any relation to the condition of the eryptor-
chidism? Amer. Med., vol. 8, p. 1003-1006.
22, 88
, 1905. A note on the developmental relations
of the kidney and ureter in human embryos.
Johns Hopkins Hosp. Bull., p. 49-51.
2, 22, 43, 45, 48, 74, 75, 80, 84, 88, 113,
114, 144, 163, 172, 211, 224

. Gaas, S. P., 1905. The total folds of the fore-brain,

their origin and development to the third week
in the human embryo. Amer. Jour. Anat.,
vol. 4, p. IX.
12, 148, 209
BarveEren, C. R., 1905. Studies of the development of
the human skeleton. Ibid., p. 265-302.
2, 10, 17, 22, 45, 57, 74, 75, 76, 79, 84, 85,
86, 97, 109, 144, 145, 163, 175, 188, 216,
226, 229
, 1904. Numerical vertebral variation in the
human adult and embryo. Anat. Anz., vol. 25,
p. 497-519.
6, 7, 9, 10, 17, 22, 43, 45, 57, 74, 75, 79,
80, 86, 94, 96, 100, 106, 108, 144, 145, 175,
178, 184, 188, 207, 211, 216, 224, 226, 229

, 1905. Development of the thoracic vertebre
in man. Amer. Jour. Anat., vol. 4, p. 163-
174.

2, 17, 22, 23, 44, 45, 76, 79, 80, 84, 96,
106, 108, 109, 144, 145, 163, 175, 184,
186, 216, 221, 241
Gage, S. P., 1905. A three weeks human embryo with
especial reference to the brain and the nephric
system. Ibid., p. 409-443.
12, 80, 148, 164, 209
The embryology of the vermi-
form appendix. In Kelly and MHurdon:
Vermiform Appendix and its Diseases. Saun-
ders, Philadelphia, p. 55-58.
9, 10, 28, 52, 89, 202
Jackson, C. M., 1905. On the topography of the pan-
creas in the human fetus. Anat. Anz., vol.
27, p. 488-510.
43, 114
Streeter, G. L., 1905-06. Concerning the develop-
ment of the acoustic ganglion in the human
embryo. Verhandl. d. Anatom. Gesell. Anat.
Anz., vol. 4, and Amer. Jour. Anat., vol. 5, p. I.
2, 22, 86, 109, 144, 148, 163

63. Maru, F. P., 1904. Catalogue of the collection of

human embryos in the Anatomical Laboratory
of the Johns Hopkins University, Baltimore.
(Printed privately.)

1 to 253 inc.

64. Hitt, Espen C., 1906. On the Schultze clearing method

as used in the Anatomical Laboratory of the
Johns Hopkins University. Johns Hopkins
Hosp. Bull., p. 111-115.
, 1906. On the embryonic development of a
case of fused kidneys. Ibid., p. 115-117.
43, 144

66.

67.

68.

69.

70.

71.

72.

73.

74.

75.

37

Streeter, G. L., 1906. Development of membraneous
labyrinth and acoustic ganglion in the human
embryo. Amer. Jour. Anat., vol. 5, p. VII.

Gage, S. P., 1906. Total folds of the brain tube in the
embryo and their relation to definite structures.
Tbid., p. IX.

Matt, F. P., 1906. A study of the structural unit of
the liver. Ibid., p. 227-308.

2, 6, 9, 10, 12, 22, 76, 80, 109, 117, 148,
163, 186

——_,, 1906. On ossification centers in human em-
bryos less than one hundred days old. Ibid.,
p. 433-458.

22, 42, 53, 59, 156, 167, 168, 202, 214,
240, 263b, 263b!, 263b%, 263c, 266, 271,
272, 274, 282, 284, 288b, 300, 306a, 306b,
306c, 326, 329, 333

Gace, 8S. P., 1906. The notochord of the head in
human embryos of the third to the twelfth
week, and comparisons with other vertebrates.
Science, vol. 24, p. 295.

SrrEETER, G. L., 1907. On the development of the
membraneous labyrinth and the acoustic and
facial nerves in the human embryo. Amer.
Jour. Anat., vol. 6, p. 139-165.

2, 22, 75, 86, 109, 144, 148, 163, 175, 229,
371

Matt, F. P., 1907. The collection of human embryos at
the Johns Hopkins University. Anat. Rec.,
vol. 1, p. 14-15.

BarvDEEN, C. R., 1907. Development and variation of
the nerves and the musculature of the inferior
extremity and of the neighboring regions of the
trunk in man. Amer. Jour. Anat., vol. 6, p.
259-386.

2, 22, 109, 144, 145, 163

Streeter, G. L., 1907. Development of the inter-
forebrain commissures in the human embryo.
Anat. Rec., vol. 1, p. 55

3

Matt, F. P., 1907. A study of the causes underlying
the origin of human monsters. (Third con-
tribution to the study of the pathology of
human embryos.) Jour. Morph., vol. 19, p.
3-368. Also monograph published by the
Wistar Institute of Anatomy, Philadelphia,
1908.

1, 2, 5, 6, 10, 11, 12, 13, 14, 16, 17, 18, 19,
20, 21, 22, 24, 25, 26, 27, 28, 29, 30, 31, 32,
35,37, 42, 45,53, 54,55, 57,58, 60, 69, 70, 71,
72, 76, 77, 78, 79, 80, 81, 82, 87, 88, 93, 94,
95, 96, 97, 99, 104, 106, 109, 110, 115, 116,
118, 122, 123, 124, 127, 128, 129, 130, 132,
133, 134, 135, 136, 137, 140, 141, 142, 143,
144, 145, 147, 148, 150, 152, 153, 154, 155,
156, 158, 159, 160, 161, 163, 164, 166, 168,
169, 173, 174, 175, 176, 177, 178, 180, 181,
182, 185, 186, 187, 188, 189, 190, 192, 194,
195, 196, 198, 199, 200, 201, 202, 203, 204,
205, 206, 207, 208, 209, 211, 212, 213, 214,
215, 216, 217, 221, 223, 224, 226, 227, 228,
229, 230, 232, 233, 239, 240, 241, 242, 243,
244, 245, 246, 247, 248, 250, 251, 252, 253,
255, 256, 257, 258, 259, 261, 262, 263d,
264, 268, 269, 270, 274, 275, 276, 278, 279,
280, 282, 285, 286, 288a, 289, 290, 291,
292a, 293, 295, 297, 298, 299, 301, 302,
304, 307, 308, 309, 310, 311, 312, 316, 317,
318, 320, 321, 323, 324, 325, 328, 329,
330a, 330b, 334, 336, 338a, 339, 340, 341,
342, 343, 344, 345, 346, 347, 348, 353, 357,
358, 360, 361, 362, 363, 364, 365, 366, 367,
369, 373, 375, 3774, 378, 379, 384, 388, 389,
391, 395, 396, 398, 399, 400, 402, 403

79.

80.

81.

83.

84.

85

56

. Banpesn, C. R., 1908.

. Srneeter, G. L., 1908.

STUDIES ON PATHOLOGIC OVA.

Vertebral regional determina-
tion in young human embryos. Anat. Rec.,
vol. 2, p. 99-105.

2, 109
The nuclei of origin of the
cranial nerves in the 10 mm. human embryo.
Anat. Rec., vol. 2, p. 111-115.

148

. Barpggen, C. R., 1908. Early development of the

cervical vertebrw and the base of the occipital
bone in man. Amer. Jour. Anat., vol. 8, p.
181-186.

22, 144

Rerzer, Roserrt, 1908.
gations on the mammalian heart.
vol. 2, p. 149-155.

Evans, H. M., 1908. On an instance of two subclavian
arteries of the early arm bud in man and its
fundamental significance. Ibid., vol. 2, p.
411-424.

148

Essicx, E. R., 1909. On the embryology of the corpus
pontobulbare and its relation to the develop-
ment of the pons. Ibid., vol. 3, p. 254-257.

22, 45, 81, 382

Some results of recent investi-
Anat. Rec.,

2. Sabin, F, R., 1909. The lymphatic system in human

embryos with a consideration of the mor-
phology of the system asa whole. Amer. Jour.
Anat., vol. 9, p. 43-91.
6, 22, 74, 82, 84, 95, 96, 106, 109, 128,
144, 172, 224, 296, 350, 353, 382, 397,
413, 423, 424
F. P., 1910. Die Alterbestimmung von
menschlichen Embryonen und Feten. Keibel-
Mall Handbuch der Entwicklungsgeschichte
des Menschen, Leipzig, vol. I. Eng. ed.
Philadelphia, p. 185-207.
1, 5, 6, 8, 9, 10, 11, 12 ine., 15, 16, 17, 18,
19, 22, 23, 26, 27, 28, 30, 31,.33, 34, 35,
38, 39, 40 to 54 inc., 56, 57, 59, 61, 62,
64 to 68 inc., 71, 72, 74, 75, 77, 79, 80,
84 to 90d inc., 92, 93, 94, 96, 97, 98, 99,
100, 105, 106, 108, 109, 113, 114, 116,
117, 118, 120, 121, 125 to 131 inc., 136,
138 to 141 inc., 144, 145, 146, 148, 149,
151, 152, 153, 155, 156, 163,
167, 168, 169, 170, 171, 173,
176, 178, 183, 184, 186, 188,
193, 194, 199, 200, 202, 206,
210, 211, 213, 214, 216, 217, 219,
224, 227, 229, 231, 239 to 242, 245, 248,
249, 256, 259, 260, 263a, 263b, 263b!,
263b?, 263c, 266, 267, 269, 272, 273, 274,
278, 282, 283a, 283b, 283c, 284, 288b, 288c,
296, 300, 301, 305, 306a, 306b, 306c, 306d,
306f, 306g, 306h, 308, 313, 314, 315, 317,
318, 319, 322, 326, 327, 329, 331, 337,
349, 350, 351, 352, 353, 354, 355, 356,
360, 361, 362, 363, 368, 371, 372, 373,
374, 375, 376, 377b, 377c, 377d, 380, 382,
383, 384, 387, 388, 389, 390, 391, 392,
393, 394, 397, 403, 405, 406, 409, 410,
411, 412
, 1910. Die Pathologie des menschlichs Eies.
Ibid., p. 208-248.
12, 21, 32, 77, 78, 79, 80, 115, 122, 124,
128, 133, 135, 162, 201, 243, 250, 256,
257, 258, 278, 285, 286, 292a, 293, 297,
304, 310, 323, 328, 340, 343, 360, 364,
367, 379
- Barveen, C. R., 1910. Die Entwickelung des skeletts
und des Bindesgewebes. Ibid., p. 296-456.
2, 12, 22, 76, 79, 80, 84, 108, 109, 144,
145, 163, 175, 184, 186, 241
. Lewis, W. H., 1910.
systems. Ibid., p. 457-526,
2, 22, 109, 144, 163

MALL,

Die Entwickelung des Muskel-

87. Mau, F. P., 1910. Die Entwicklung des Céloms und
des Zwerchfells. Ibid., p. 527-552.
2, 12, 43, 74, 76, 80, 109, 113, 116, 136,
144, 148, 163, 164, 239, 391
88. Danpy, W. E., 1910. A human embryo with seven
pairs of somites measuring about 2 mm. in
length. Amer. Jour. Anat., vol. 10, p. 85-98.
391
89. Minot, C. 8., 1910. Laboratory Textbook of Embry-
ology. Philadelphia.
391
90. Streeter, G. L., 1911. Die Histogenese des Nerven-
gewebes. Keibel-Mall Handbuch, Bd. 2,
Leipzig and Philadelphia, p. 1-156.
2, 22, 109, 144, 163, 220, 234
91. Maui, F. P., 1910. A list of human embryos which
have been cut into serial sections. Anat. Rec.,
vol. 4, p. 355-367.
1 to 10 inc., 12, 13, 17, 18, 19, 22, 23, 34,
43, 44, 45, 48, 57, 74, 75, 76, 80, 84, 86,
87, 88, 95, 96, 100, 106, 108, 109, 112,
113, 114, 116, 120, 128, 134, 136, 144,
145, 146, 148, 163, 164, 170, 172, 175,
179, 184, 186, 187, 199, 208, 209, 211,
216, 219, 220, 221, 224, 227, 229, 231,
234, 239, 240, 241, 242, 245, 248, 249,
250, 253, 256, 267, 268, 278, 289, 293,
296, 306a, 314, 317, 318, 338a, 349, 350,
351, 352, 353, 368, 371, 372, 380, 382,
383, 384, 387, 388, 389, 390, 391, 397, ©
404, 405, 406, 409, 422, 423, 424, 431,
432, 447, 449, 452
Witson, L. B., and B. C. Wr1u1s, 1911. A comparative
study of the histology of the so-called hyper-
nephromata and the embryology of the ne-
phridial and adrenal tissues. Jour. Med.
Research, vol. 24, p. 73-90.
144, 353, 371, 406
Lisser, H., 1911. Studies on the development of the
human larynx. Amer. Jour. Anat., vol. 12,
p. 27-66.
22, 43, 109, 128, 144, 317
Lewis, F. T., 1911. Die Entwicklung des Darmes
und der Atmungsorgane. Keibel-Mall Hand-
buch, vol. 2, Leipzig and Philadelphia, p.
282-482.
391
Minor, C. S., 1911. Die Entwicklung des Blutes
Ibid., p. 483-517.
350, 353
Evans, H. M., 1911. Die Entwicklung des Blutgefass-
systems. Ibid., p. 551-688.
2, 6, 43, 57, 80, 108, 109, 144, 145, 148,
163, 229, 349, 353, 368, 382, 390, 391,
448, 449, 453, 460
97. Sasrn, F. R., 1911. Die Entwicklung des Lymphge-
fass-systems. Ibid., p. 688-724.
6, 22, 57, 74, 86, 96, 106, 109, 128, 144,
163, 172, 224, 296, 317, 350, 353, 382,
397, 409, 423, 424, 448
Pouutman, A. G., 1911. The development of the
cloaca in human embryos. Amer. Jour. Anat.,
vol. 12, p. 1-23. 3
2, 12, 22, 43, 76, 80, 87, 109, 113, 114,
116, 128, 148, 164, 175, 186, 209, 221,
240, 241, 256, 296, 317, 350, 353, 371,
383, 391, 397, 409
Waiteneap, R. H., and J. A. Wapprir, 1911. The
early development of the mammalian sternum.
Ibid., p. 89-106.
109, 144, 175, 296, 423, 424
- Matz, F. P., 1911. Report upon the collection of
human embryos at the Johns Hopkins Univer-
sity. Anat. Rec., vol. 5, p. 343-357.
1 to 500 ine. (No illustrations.)

92.

93.

94.

95.

96.

98.

99.

101.

102.

103.

104.

105.

106.

107.

108.

109.

110.

113.

114.

115.

116.

117.

. Mat, F. P., 1913.

. Sapin, F. R., 1916.

CARE AND UTILIZATION OF THE COLLECTION.

Essicx, C. R., 1912. The development of the nuclei
pontis and the nucleus arcuatus in man.
Amer. Jour. Anat., vol. 13, p. 25-54.
22, 75, 84, 86, 95, 96, 128, 145, 172, 184,
199, 211, 219, 227, 368, 382, 405, 484,
490, 491, 508, 509
Matt, F. P., 1912. On the development of the human
heart. Ibid., p. 249-298.
2, 3, 33, 43, 46, 80, 86, 90a, 90b, 90c, 90d,
109, 113, 116, 136, 144, 163, 175, 239
241, 249, 283b, 296, 317, 318, 353, 356,
360, 368, 380, 384, 386, 390, 397, 406,
409, 422, 423, 424, 426, 431, 432, 434,
460, 463, 470
Lowstey, O.S., 1912. The development of the human
prostate gland with reference to the develop-
ment of other structures at the neck of the
urinary bladder. Ibid., p. 299-346.
34, 54
Matt, F. P., 1912. Bifid apex of the human heart.
Anat. Rec., vol. 6, p. 167-172.
90b, 118, 283b, 353, 360, 434, 455
Sasrn, F. R., 1912. On the origin of the abdominal
lynphatics in mammals from the vena cava
and the renal veins. Ibid., p. 335-342.
460
Matu, F. P., 1912. Aneurysm of the membranous
septum projecting into the right atrium. Ibid.,
p. 291-298.
113, 164, 353, 391, 463
Huser, G. Cart, 1912. On the relation of the chorda
dorsalis to the anlage of the pharyngeal bursa
or median pharyngeal recess. Ibid., p. 373—
404.
221, 371, 389, 406
Metis, ©. L., 1912. The development of the
cerebral cortex. Amer. Jour. Anat., vol. 14,
p. 107-117.
491
Wiuiams, J. W., 1912. Obstetrics.
19, 82, 164, 278, 550
Lows tey, O. 8., 1913. The human prostate gland at
birth with a brief reference to its fetal develop-
ment. Jour. Amer. Med. Assn., vol. 60, p. 110.
34

3d ed., N. Y.

A plea for an institute of human

Ibid., p. 1599-1601.

The origin and development of
the lymphatic system. Johns Hopkins Hosp.
Reports, n. s., vol. 17, p. 347-440.

86, 153, 353, 397, 460

Matt, F. P., and E. K. Cutten, 1913. An ovarian
pregnancy located in the Graafian follicle.
Surg., Gyn. and Obst., vol. 17, p. 698-703.

550

Matt, F. P., 1913. Report on Embryological Re-
search. Carnegie Inst. Wash. Year Book No.
12.

Evans, H. M., 1914. An appeal to surgeons for em-
bryological material. (Printed privately.)
391, 626, 763
Sasrn, F. R., 1913. Der Ursprung und die Entwicke-
lung des Lymphgefass-systems. (Ergebnisse
der Anatomie und Entwickelungs-geschichte.)
Anat. Hefte, Abth. II, p 1-97.
86, 163, 353, 460
Matt, F. P., 1914. On stages in the development of
human embryos from 2-25 mm. long. Anat.
Anz., vol. 46, p. 78-84.
2, 5, 9, 19, 22, 43, 74, 80, 106, 109, 127,
128, 144, 156, 163, 167, 175, 208, 221, 229,
240, 241, 245, 248, 256, 296, 317, 349, 353,
350, 368, 371, 372, 387, 388, 389, 390, 397,
405, 406, 409, 422, 423, 424, 431, 447, 453,
460, 463, 485, 492, 500, 511, 536, 544, 547,
552, 558, 562, 566, 576, 584a, 590, 617,
623, 626, 630, 632

embryology.

118.

119.

120.

128.

129.

130.

131.

. Evans, H. M., 1914.

- BEItLer,

5. Meyer, A. W., 1914.

. Matt, F. P., 1915.

- Cuark, E. R., 1915.

39

Barpeen, C. R., 1914. The critical period in the
development of the intestine. Amer. Jour.
Anat., vol. 16, p. 427-436.
2, 6, 9, 10, 34, 43, 45, 79
Bremer, L., 1914. The earliest blood-vessels in man.
Ibid. p. 447.
391
Bicztow, P., 1914. Colom. Ref. Handbook Med.
Sci., 3d ed., vol. 3, p. 138-148.
2,6, 9, 12, 18, 19, 22, 34, 43, 45, 391
An appeal to physicians for em-
bryological material. (Printed privately.)
391, 626, 763
F. V., 1914. Still-born children. State
Dept. Health of Maryland, Bureau of Vital
Statistics.

- Matt, F. P., 1914. Annual report of the Director of

the Department of Embryology. Carnegie
Inst. Wash. Year Book No. 13, p. 107-115.
1 to 811 ine.

, 1915. Department of Embryology. Re-
printed from ‘‘Scope and Organization” of the
Carnegie Institution of Washington.

Curves of prenatal growth and

autocatalysis. Arch. f. Entwicklungsmech. d.

Organ., Bd. 40, p. 497-525.

On the fate of the human embryo

in tubal pregnancy. Contributions to Em-

bryology, No. 13, Carnegie Inst. Wash. Pub.

No. 221, p. 5-103.

109, 154, 175, 179, 183, 196, 197, 256, 294,
298, 307, 314, 324, 338c, 342, 350, 352,
361, 367, 369, 378, 387, 389, 390, 396, 402,
415, 418, 422, 426, 430, 431, 432, 448, 449,
456, 458, 472, 473, 477, 478, 479, 481, 484,
487, 488, 495, 496, 497, 503, 507, 513, 514,
515, 517, 519, 520, 524, 535, 539, 540, 553,
554, 561, 567, 570, 575, 576, 597, 602,
612, 634, 640, 657, 659, 667, 670, 678, 676,
685, 686, 694, 697, 706, 720, 726, 728, 729,
734, 741, 742, 754, 762, 763, 765a, 766,
772, 773c, 775, 777, 782, 784, 787, 790,
794, 804, 808, 809, 809b, 809c, 815, 825,
835, 836, 838, 846, 851, 867, 874, 881, 882,
889, 891, 892, 898, 899, 900b, 900c, 900d,
900e, 900f, 900g, 900j, 904, 908, 910, 911,
919, 927, 928, 932, 934, 938, 939, 945, 953,
967a, 967b, 967c, 974, 977, 990, 992, 995,
998

An anomaly of the thoracic duct
with a bearing on the embryology of the
lymphatic system. Contributions to Embry-
ology, No. 3, Carnegie Inst. Wash. Pub. No.
222, p. 45-54.

460

Essicx, C. R., 1915. Transitory cavities in the corpus
striatum of the human embryo. Contribu-
tions to Embryology, No. 6., Carnegie Inst.
Wash. Pub. No. 222, p. 95-108.

144, 350, 409, 431

Watt, Ivan E., 1913. A human embryo of thirteen
somites. Amer. Jour. Anat., vol. 15, p.
319-331.

1201la 5

Meyer, A. W., 1915. Fields, graphs, and other data
on fetal growth. Contributions to Embry-
ology, No. 4, Carnegie Inst. Wash. Pub. No.
222, p 55-68. (Many of our embryos con-
sidered.)

Streeter, G. L., 1915. Thedevelopment of the venous
sinuses of the dura mater in the human
embryo. Amer. Jour. Anat., vol. 18, p.
145, 178.

84, 95, 96, 128, 144, 145, 199, 224, 234a,
296, 349, 350, 382, 448. 449, 458, 460, 544,
588, 613, 632, 886, 940, 966

40

132

133.

134.

135.

136.

137.

138.

139.

140.

144.

145.

146.

147.

STUDIES ON PATHOLOGIC OVA.

_ Lewis, W. H., 1914. Development of the fetus. Ref.
Handbook Med. Sci., 3d ed., p. 373-384.
2, 12, 22, 91, 109, 163
, 1915. The use of guide planes and plaster of
paris for reconstruction from serial sections:
some points on reconstruction. Anat. Rec.,
vol. 9, p. 719-729.
460
Mat, F. P., 1915. The cause of tubal pregnancy and
the fate of the inclosed ovum. Sur., Gyn. and
Obst., vol. 22, p. 289-298.
154, 196, 298, 307, 314, 324, 361, 367, 378,
396, 415, 418, 430, 472, 477, 478, 479, 488,
495, 507, 513, 514, 515, 517, 519, 520, 524,
539, 540, 553, 554, 561, 567, 570, 575, 602,
659, 673, 685, 686, 694, 720, 726, 729, 734,
741, 754, 762, 765a, 766, 772, 773, 775, 777,
784, 787, 794, 804, 808, 809b, 809c, 815,
825, 835, 838, 846, 874, 881, 882, 891, 892

Kinassury, B. F., 1915. The development of the
human pharynx. Amer. Jour. Anat., vol. 18,
p. 329-386.
105, 213, 301

Matt, F. P., 1915. Development of the heart. Ref.

Handbook Med. Sci., 3d ed., vol. 5.
2

Lowstey, O. S., 1915. The prostate gland in old age.
Annals of Surgery, vol. 62, p. 716-737.
Jenxins, Georce B., 1916. A study of the mor-

phology of the inferior olive. Anat. Rec., vol.
10, p. 317-334.
491, 619, 625
Srreeter, G. L., 1916. The vascular drainage of the
endolymphatic sac and its topographical rela-
tion to the transverse sinus in the human
embryo. Amer. Jour. Anat., vol. 19, p.
67-89.
96, 448, 449, 458, 460, 632, 1018, 1131
Miter, W. S., 1914. Digestive tract. Ref. Hand-
book Med. Sci., 3d ed., vol. 3.
6, 9, 10, 45

. Cutten, Toomas §S., 1916. Embryology, anatomy and

diseases of the umbilicus. W. B. Saunders
Company, Philadelphia and London.
2, 86, 317, 391

. Matt, F. P., 1917. Annual report of the Director of the

Department of Embryology, Carnegie Inst.
Wash. Year Book, No. 14, p. 111-125.

, 1916. The human magma réticulé in normal
and in pathological development. Contribu-
tions to Embryology, No. 10, Carnegie Inst.
Wash. Pub. No. 224, p. 5-26.

12, 21, 78, 79, 94, 104, 122, 135, 136, 148,
164, 211, 230, 244, 250, 261, 270, 278,
318, 391, 402, 463, 470, 486, 512, 531,
533, 543, 545, 560, 576, 584a, 588, 604,
605, 636, 651g, 660, 763, 779, 813, 836,
991, 1117, 1189

, 1916. The embryological collection of the
Carnegie Institution. Circular No. 18.
(Printed privately.)

Evans, H. M., and G. W. Bartetmez, 1917. A human

embryo of seven to eight somites. Anat. Rec.,
vol. 12, p. 355.
1201
Srreeter, G. L., 1917. Histogenesis of the otic cap-
sule. Anat. Rec., vol. 12, p. 417.
22, 84, 86, 95, 172, 353, 588, 1018, 1373,
1400-30
Wueeter, T., 1917. Study of a human spina bifida
monster with encephaloceles and other ab-
normalities. Anat. Rec., vol. 12, p. 431.
862a

148.

149.

150.

151.

152.

153.

154.

155.

156.

157. STREETER, GeorcE L., 1917.

158.

159.

Matt, FRANKLIN P., 1917. Organization and Scope
of the Department of Embryology, Circular
No. 19. (Printed privately.)

, 1917. Note on abortions with letters from
the Health Commissioner of Baltimore and
from the Chief of the Bureau of Vital Statistics
of Maryland regarding registration and ship-
ment of embryos to the Carnegie Laboratory
of Embryology at the Johns Hopkins Medical
School. Baltimore. Circular No. 20. (Printed
privately.)

, 1917. Annual report of the Director of the
Department of Embryology, Carnegie Inst.
Wash. Year Book No. 15, p. 103-120.

1 to 1458 considered.

Sapin, F. R., 1915-16. The method of growth of the
lymphatic system. The Harvey Lectures,
Series XI, p. 124-145.

Srreeter, G. L., 1917. The development of the scala
tympani, scala vestibuli and perioticular cis-
tern in the human embryo. Amer. Jour.
Anat., vol. 21, p. 299-320.

84, 199, 886, 1018, 1400-30

Maun, FRANKLIN P., 1917. Cyclopia in the human
embryo. Contributions to Embryology, No.
15, vol. 6, Carnegie Inst. Wash. Publication
226, p. 5-33.

12, 148, 163, 201, 391, 470, 559, 836,
1165, 1178a, 1178b, 1201.

Youna, H. H., and E. G. Davis, 1917. Double ureter
and kidney with calculous pyronephrosis of
one half; cure by resection. The embryology
and surgery of double ureter and kidney.
Jour. Urol., vol. 1, p. 17-32.

371, 453, 800, 873, 988, 1075, 1197, 1354

Gaag, S. H., 1917. Glycogen in the nervous system
of vertebrates. Jour. Compar. Neurol, vol.
27, p. 451-464.

Mati, FRANKLIN P., 1917. On the frequency of
localized anomalies in human embryos and
infants at birth. Amer. Jour. Anat., vol. 22,
p. 49-72.

6, 10, 12, 31, 80, 81, 94, 112, 124, 128, 164,
182, 186, 189, 201, 212, 226, 228, 230,
242a, 242b, 249a, 249b, 250, 276, 293,
295, 302, 306a, 314, 316, 328, 335, 338a,
338c, 344, 364, 365, 370, 371, 413, 433a,
466, 499, 510, 511, 552, 558, 559, 584a,
622, 627, 646, 649, 65la, 651f, 653, 676,
710, 732, 740, 749, 768b, 768c, 779, 785,
789, 796, 797, 802, 808, 813, 839, 842,
862, 862a, 862b, 868, 874b, 982, 996,
1140b, 1289, 1295g, 1315, 1330, 1477,
1523, 1690, 1749

(1000 specimens—from 1 to 900g—
treated statistically.)

The factors involved in
the excavation of the cavities in the cartilag-
inous capsule of the ear in the human embryo.
Amer. Jour. Anat., vol. 22, p. 1-25.

86, 95, 96, 296, 409, 453, 455, 575, 695,
719, 721, 886, 1373

Weep, Lewis H., 1917. The development of the
cerebro-spinal spaces in pig and in man. Con-
tributions to Embryology, vol. 5, No. 14,
Carnegie Inst. Wash. Pub. No. 225, p. 7-16.

75, 144, 199, 390, 405, 406, 409, 431, 448,
453, 460, 544, 576, 617, 632, 695, 721,
745, 782, 836, 849, 870, 900h, 9286,
1008, 1131, 1134

Witurams, J. Waitripnae, 1917. Obstetrics. 4th ed.
D. Appleton & Co., New York and London.

19, 88, 164, 278, 550, 782

CHAPTER III
CLASSIFICATION.!

In the now historically very interesting “Prolegomena of the development and
metamorphosis of the human ovum” contained in the excellent “Graphic Illustra-
tions of Abortion” published by Granville in 1834, some attempt was made to
group the abortuses there reported. The first 6 specimens are spoken of as
“lanuginose”’ ova of several types; the next 3 are designated as denuded or diaph-
anous; a few are spoken of as opaque; one as “uviform,” that is, hydatiform; and
several as moles of various kinds. Most of the rest of the 38 specimens were given
long individual descriptive names, although several were spoken of as ‘“‘coriaceous”’
and others as “avellanated.” A case of tubal and the well-known case of ovarian
pregnancy are among these specimens.

In speaking of the uviform ovum, Granville emphasized that hydatiform
degeneration is a very rare occurrence and gave a very good short characterization
of it, saying that although, in this instance, three months had @lapsed since
pregnancy supervened, nature evidently had spent most of this time “playfully
modelling, forming, and cutting out what would appear an artificial plaything,
so fantastical it looks.”

Panum (1860), from a study of collections of monsters found in various Euro-
pean laboratories, and also from extended experimental work with eggs, formulated
a more elaborate classification of deformities, but did not concern himself particu-
larly with the routine material from abortions. It may be recalled, however,
that he also spoke of amorphous and cylindrical chick embryos, and that
these groups of Panum’s practically were equivalent to the nodular and cylindrical
embryos of His, Giacomini, and Mall. Panum’s group of monstruositates totales
cylindrice among abnormal chick embryos were described as young specimens with
formless heads and somewhat deformed, rather rod-like bodies, which he ascribed
to lowering of the incubator temperature.

His (1882), while considering only younger abortuses, did not recognize the
occurrence of empty chorionic and amnionic vesicles, saying that, aside from the
two or three specimens in which these cavities were filled with solid blood-clots
which made the finding of an embryo impossible, he never saw vesicles devoid of
anembryo. This observation is particularly interesting, because empty chorionic
vesicles, after all, are not very uncommon and one can hardly escape the conclusion
that his failure to see them was due to the fact that physicians sent only the
specimens containing embryos. This is not at all unlikely, for they knew, of course,
that His’s interest centered so very largely upon the form of early human embryos.

All younger embryos abnormal in form, below 15 mm. in length, were classified
by His as nodular, atrophic, and cylindrical. Sometimes he also spoke of some
of the atrophic forms as flexed or kinked because of the marked drooping of the
- *Uneredited quotations are from notes or circulars written by Mall.

41

42 STUDIES ON PATHOLOGIC OVA.

head upon the chest noticed in some of them. Since these three types of early
embryos seem to recur, His emphasized that it was very probable that normal
development can be disarranged easily at certain definite stages in prenatal life,
a surmise confirmed by contemporary experimental embryology. In the opinion
of His, this faulty development almost invariably led to abortion at the end of
the second or the beginning of the third month, which period had been noted by
A. Hegar (1863) as the time of most frequent abortion of early specimens. It is
striking, indeed, that not a single abortus from the later months of pregnancy,
which His regarded as capable of continued growth, ever came to his attention.

Giacomini (1888, 1893) also described several nodular atrophic embryos and
very significantly stated that he never met with nodular or atrophic forms in
rabbits. In these animals he found only advanced deformities, and these he re-
garded as often merely being the result of death of the fetus with subsequent
retention. Hence he did not consider them at all comparable to those found in
man. Giacomini also stated that he could experimentally produce all forms of
nodular and cylindrical embryos in rabbits, and believed that the atrophic forms
were due to changes after death, although he preferred not to emphasize this
opinion.

Later, when Giacomini studied these anomalous forms microscopically, he
concluded that a classification based on gross appearance only really tells nothing
about the nature of the process which has inhibited development, of the time when
the changes began, or of their localization and distribution. Hence he emphasized
the necessity of a microscopic examination for purposes of scientific classification.
He further stated that both the flexed (or kinked) and the cylindrical forms of
His could be classed under the atrophic and declared that abortuses can be placed
into two main groups, those with and those without an embryo. In 1895 Gia-
comini further suggested two subdivisions under each of these groups. He divided
those without an embryo into (1) specimens with only the embryo missing, and
(2) those with little else than the chorion present. Since Giacomini believed that
the embryo and even the amnion can migrate from the chorionic vesicle and the
hole through which they pass close again by healing, he further differentiated
specimens in which the embryo had migrated out entirely, those in which it had
reached the coelom externum, those in which the embryo and amnion had mi-
grated from the chorion, and finally, those in which the active migration of the
embryo and amnion had everted the chorion. Since the idea of an active migra-
tion of the embryo, not to mention that of some of the adnexa, from out the
chorion, does not hold, these four types of empty chorionic vesicles require no
further consideration. Specimens in which embryos were present Giacomini
classed as nodular and atrophic, after His, the latter class including both the
cylindrical and the flexed forms of His. Giacomini’s great merit lay in recog-
nizing a group of specimens without an embryo, in making a careful microscopic
study, and especially in undertaking experimental work in order to elucidate some
of the problems which presented themselves to him in a study of abortuses. These
aspects of his work will be referred to again in later chapters.

CLASSIFICATION. 43

Although other anatomists, and also some clinicians like Giacomini, took up
the problem suggested particularly by the work of His, no one followed it with
more devotion that Mall. In saying this I am not ignoring the able and extensive
treatises on teratology, such as those of Ahlfeld, Ballantyne, Dareste, Saint Hilaire,
Schwalbe, and Taruffi. These treatises are more specifically concerned with
the problems presented by malformations, while His, Giacomini, and Mall gave
especial attention to questions presented by all abortuses, and Giacomini and Mall
especially to such as Mall later grouped as pathologic. I realize that I thus raise
the question of the relation of uterine pathology to teratology, but that is
unavoidable. Moreover, as everyone knows, it is still decidedly unsettled. This
attitude was taken also by Mall (1908) when he wrote:

“Whether the early pathological embryos are young monsters of so extreme a
degree that they will not continue to grow, is now the most important question of the
capital problem in teratology.”

In this monograph Mall did not attempt to classify the 163 pathologic embryos
collected during a period of 15 years. Nevertheless, as his collection grew, some
classification became highly advisable. In referring to this matter later, he wrote:

“In considering a large number of specimens from a scientific standpoint, their
classification’ is one of the most important things. All of our specimens are placed in
one of two great divisions—normal or pathological. As stated before, the normal ones
usually are easily segregated because, for the sake of expediency, we have decided to
regard as normal all embryos and fetuses which are normal in form, although they may
be inclosed in diseased chorions. These normal specimens are first arranged according
to size and subsequently also according to age.”

All normal embryos and fetuses further are placed in one of three grades,

according to the preservation of their body form. The basis of this gradation is
‘wholly gross morphologic. Moreover, it would perhaps be more correct to say that

the deciding factor is not the degree of normality of form which may once have
existed, but the extent to which it is preserved. If the form is preserved perfectly,
the embryo or fetus is placed in the first of these grades unless it has a localized
anomaly. However, abnormal specimens also are found among the group of
normals, and, as already indicated, some of the normal specimens no doubt have
developed upon a somewhat diseased endometrium, but so far we have been unable
to recognize these in the early stages of development.

All specimens the form of which is excellently preserved are put into grade 1
of the normal, but if the external form is changed slightly, either by external forces,
by maceration, or by developmental abnormalities, they are put into grade 2.
All other specimens regarded as normal in form, with or without anomalies, fall into
grade 3. Abnormalities are noted especially by cross-references, but no separate
category of abnormal embryos is maintained. Hence, under this plan, a double
monster, such as No. 2107, with six extremities, some of which also are monstrous,
with one set of deformed genitalia, and with totally fused trunks, becomes classified

1 For the earlier classification of the specimens in the Mall Collection see Mall (1900, 1903, and 1904).

44 STUDIES ON PATHOLOGIC OVA.

as a normal fetus with localized anomalies. Nor is provision made for such
specimens in the pathologic group. Since an embryo or fetus may be entirely, or
at least approximately, normal in form, even if somewhat macerated, it follows
that macerated specimens also are found in these grades of the normal. But, as
will appear later, maceration soon changes the form of the embryo. Hence it
follows that none except perhaps extremely small specimens can be markedly
macerated and still apparently retain their normal form. In these the maceration
which is present may become evident upon microscopic examination only.

None of the specimens in grades 2 and 3 is perfect in form, and these grades
contain relatively more macerated specimens than grade 1. A splendid example
of anormal, slightly macerated fetus is No. 782; although obtained at hysterectomy,
it undoubtedly is macerated, yet in spite of this fact it is found in grade 1. This
fetus probably died some time before operation, perhaps in consequence of en-
dometritis. The embryonic tissues are markedly macerated in spite of the fact
that the entire uterus was placed in formalin immediately. Since the chorionic
cavity was not infected, this maceration must have taken place under absolutely
aseptic conditions, yet it nevertheless is quite evident.

A series of embryos that really does not belong within these two grades of
normal specimens are those with localized anomalies. These, of course, really
are abnormal, though not necessarily pathologic in the sense of being themselves
diseased. They may, however, be the products of disease elsewhere or have arisen
from defective ova or spermatozoa. ‘The division of normals also contains speci-
mens not perfect in form merely because they have sustained fractures or have
been mutilated, and since no separate group is maintained for those possessing
hereditary abnormalities, some of these too are included among the normal.

Specimens which are not included in any of the above three grades of normal
embryos or fetuses are classed as pathologic. This does not imply, however, that
they themselves necessarily are diseased. In fact many (most?) of these specimens
probably were the victims of accident, interference, or untoward conditions, and
hence may have been entirely normal at the time of death. In this division also
are found empty normal chorionic vesicles from which the embryo was expelled
after the membranes had ruptured, or in which the embryo had become disinte-
grated in consequence of maceration changes due to interference or to other causes.
It also contains specimens of fetuses which, for one reason or another, died after
the escape of the amniotic fluid, and which then were retained for some time in utero
after being expelled from the chorion. The same thing is true of some normal
specimens which died in consequence of degenerative changes in the chorion or the
placenta. All these specimens, although possibly wholly normal in development,
might, if retained long enough, even under aseptic conditions, fall into the
pathologic division. This division, as well as that for the normal embryos, no
doubt also contains embryos and fetuses which have been affected by maternal
uterine or constitutional diseases, especially by endometritis or lues. Since, as
already stated, abnormal embryos or monsters are not grouped by themselves,

CLASSIFICATION. 45

some of these also are included in the pathologic division, though most of them
are classed as normal with localized anomalies. Moreover, it has been found that—

“A certain number of specimens can not be classified satisfactorily in any of the
groups, either normal or pathologic. For example, we have in our collection 4 specimens
of cyclopia. One is in an embryo which is perfectly normal, except that it contains a
single eye; the second is a stunted embryo which is more or less macerated; the third is
a fetus compressus, and the fourth is a double monster. These have been entered in our
catalogue as follows: Normal with cyclopia; stunted with cyclopia; fetus compressus
with cyclopia; double monster with cyclopia. These varieties naturally include all
specimens usually designated as monsters. The double monster mentioned above,
curiously enough, becomes recorded as a normal twin embryo with cyclopia, but it is
difficult to avoid this contradiction with the method of classification we have adopted.”

The pathologic division, which does not comprise the greater number of
specimens, is subdivided into seven classes, largely on the basis of the degree of
destruction of the ovum or embryo. This holds unless we are to assume that the
chorionic and amniotic vesicles can develop regardless of the presence of a cyemic
primordium. Particularly in the first three groups, the degree of destruction of
the cyema is the determining factor, for in all of the specimens in these groups it
ismissing. (1) The first group among the pathologic is composed of small remnants
of specimens which usually are found to consist of villi only; most of these are
derived from tubal pregnancies. (2) The second group is composed of small
specimens which are represented by chorionic vesicles wholly devoid of contents
save blood and the disintegration products of the embryo and amnion, blood,
coagulum, or magma. (3) In the third group are placed specimens in which, in
addition to the chorion, the amnion, in part or in its entirety, is present. These
specimens usually are somewhat larger.

Although the absence of the cyema is the determining factor for the inclusion
of a specimen in the first three groups in the pathologic division, its presence, no
matter in how modified a form, is the criterion which places the specimen in one
of the last four groups of this division. In general, it may be stated that the speci-
mens in the last four groups are classified according to the degree of the change
which they have undergone. ‘If the embryo is affected so as to appear as an
amorphous nodule, it is placed in group 4; but if a cephalic or caudal extremity
still can be recognized, it is placed in group 5.”” The word affected, as used here
by Mall, does not, however, carry with it the idea of dismemberment by force,
for a macerated fragment of a normal embryo manifestly should not be classed
here. However greatly the form of an embryo may have been modified, this
modification must not have resulted from the mechanical removal of a portion of
its substance. It is true that it is often impossible to determine whether a given
modification in form has thus arisen. Sometimes, indeed, it is impossible to dis-
tinguish, by external examination alone, the stump of a cord or the yolk-sac from
a nodular embryo, for in the main the classification of a specimen is determined by
inspection alone with or without the aid of low magnification. Some of the speci-

46 STUDIES ON PATHOLOGIC OVA.

mens in the nodular group also contain rudiments of the extremities, for even with
these present it has not always been possible to recognize the cephalic or caudal
extremity by inspection alone. Since the position of the extremities ordinarily
would suffice to make such recognition possible, it is necessary to recall in this
connection how pronouncedly the body-form of the nodular embryos often is
changed. In addition to such specimens, the nodular group contains three other
kinds, such as stumps of the umbilical cord, isolated yolk-sacs, and sessile nodular
embryos, many of which have nothing that could properly be regarded as a cord.

In specimens classed in the fifth group of the pathologie division the embryo
is destroyed almost entirely, but its head end can still be recognized. Hence it
is designated as cylindrical, but the use of this term does not imply that these
specimens are hollow, or wholly without limb-buds even.

“Tn this group are often included specimens of embryonic remnants which, upon close
examination, prove to be the naked umbilical cord. As soon as such specimens are
detected they are distinguished by a second entry—cord. Unfortunately, these two
types of specimens, although out of relation, fall together in our catalogue, but this
discrepancy can not be avoided without giving up our plan of retaining the first entry of
a specimen.”

Indeed, specimens in which the body of the embryo has been so modified as
to represent a rod are often indistinguishable upon inspection alone, not only from
remnants of the cord, but also from rolled-up decidual or from cyemic remnants
or polyps.

In the next or sixth group of the pathologic division, “the embryo can easily
be recognized, but it is unusual in appearance, the head, extremities, or some
other part of the body being atrophic, and for this reason this type is termed
stunted. Usually all the parts are more or less degenerated. Most of these em-
bryos are small, but they also can be classified according to their length. The
histories show that these embryos are much older than normal ones of the same
size, indicating that an arrest of development must have taken place.’ In these
specimens the normal proportions also have changed. Moreover, since the adjec-
tive stunted implies a physiologic cause, it is necessary to add that in some of them
the stunting, no doubt, is apparent only and is the result of distortion incident to,
if not consequent upon, maceration. In such cases, then, the stunting is in no
sense the consequence of an interference with the nutritive supply of the embryo.

Specimens of pathologic embryos and fetuses, mainly the latter, not included
in the above six groups, are classed in group 7. ‘This last group is composed
mainly of large specimens which are atrophied, dried up, or macerated. If the
tissues are soft and edematous we call the specimen macerated; if it is dried up
and atrophic we call it fetus compressus. In the course of time we may find that
these two forms should be classed separately, but for the present it appears as if
one is the forerunner of the other.”

Anyone who reflects upon this classification will easily recognize its short-
comings. These were not overlooked by Mall. In the handling of a large series

CLASSIFICATION. 47

of specimens, a simple, serviceable, even if rough classification.is extremely useful.
Moreover, under present circumstances, the first examination must be a gross and
also a rather superficial one, unless technical assistance adequate to make a final
diagnosis within a few days of the receipt of the specimen is available. This not
having been the case, it has been found that a certain amount of shifting becomes
inevitable unless the groups are to become mixed. The shifting necessitated by
further examination is indicated in table 4. However, as the histories become

TaBLE 4.—Showing the shifting within the groups necessitated by microscopic examination.

No. Specimens transferred to— j Final
No. of origi- number
group. | nally in in each
group. |Group 1./Group 2. Group 3. Group 4. Group 5. Group 6. Group 7.| group.
70
1 17 0 {ous } LY Mises ceo ita cde HEA HOGS OOe AO Seo Oe tame 16
2 42 O44 es debe MCLEE 1 | eceyperetois premiered hyete aval sie Secin | erates Grehiaa ciate pat alt siesta 48
3 MER ete Be cement ae 2 ens vial ores ave4s elf iovasese,o, chaip i iesanaif(S: ays: 6:ajave araiere sf nai avatals, ele ow care vpieic|leele, cory ea 45
i 130 469
123 143 531 325
i es gage Mae Fecal) adacsbwer: 839 { oe } See 63
770 257 +803
791
25 433
279 960a 32 446
483 976 37 441
518 985 166 528 104
y 556 189 610 232
5 73 0 93 584b LOSP G74 lh Selecta nesses SEDs 2 eined| Paiccieieee 48
689 692 653
701 244 795 771b
723b 253 807
814 275 830
| 291a 943
161 115 413
264 142 414 124
6 AM pstaac so SxcPel ace anata erate vob: Sieheicvayecee: 309 DAG STO hikers apatetarcrerars srerace te 649 80
433a 347 797
573 399
150 188 60lce 739
205 334 635e 802
7 OM SNe kaaeececrslllew seecaree COG Btliisetos test 289 348 65la 962) |) 22.00. 53
400 375 681 983a
655 521f 732 993

more complete, and the data which they contain also more reliable, and especially
as our knowledge of chorionic and placental pathology becomes fuller, an entire
reclassification may become advisable, if not inevitable. This, however, should
not be cause for regret, for it is in the line of progress. Indeed, it was not un-
anticipated, and the revision indicated in table 4 was made at the request of Mall.
It would seem, moreover, that a modification in classification is indicated also by
the main thesis of Mall, that faulty implantation is the cause of abnormalities.
Yet under the present classification, as Mall himself explained, cyemata with
marked abnormalities frequently are classed as normal. Moreover, normal speci-
mens are included among the pathologic division, which, strangely enough, con-
tains no group of abnormals. This difficulty can be remedied easily, but how soon
other difficulties indicated above can be overcome or be eliminated will depend

48 STUDIES ON PATHOLOGIC OVA.

very largely upon the further development and utilization of this already unique
collection and upon the degree of codperation which can be secured from clinicians
and administrators.

After considerable reflection upon this classification, and some experience
in its daily application to material as received from physicians, I shall permit my-
self certain suggestions, especially since they were invited by Mall himself. It
would seem that a division of all conceptuses into the long-established classes of
normal and abnormal has certain advantages. This would be true even if it were
as: difficult to discriminate between the normal and the abnormal or atypical as
between the normal and the pathologic. A careful structural examination can
always decide the former, at least after the establishment of an arbitrary limit for
the range of normal variation. But until we can recognize the earliest morphologic
and cytologic changes resulting from pathologic conditions, it often must remain
impossible to decide between the normal and the pathologic. That day seems to
lie far in the future—much farther, indeed, than the possibility of a final determina-
tion regarding the normality or abnormality in form of early eyemeta or chorions.

A division into normal and abnormal also would avoid the awkward necessity
of classifying monsters as normal and of putting all specimens composed of normal
villi, of normal empty, damaged, chorionic vesicles, and of normal ruptured cho-
rionic and amnionic vesicles into the pathologic division. A grouping into the
normal and abnormal also would enable us to frankly recognize the fact that
normal specimens may become decidedly macerated, but should therefore not be
grouped among the pathologic. Furthermore, it would enable us to recognize the
possibility, first emphasized by Giacomini, that normal cyemeta possibly may be
changed so as to perfectly simulate the atrophic and stunted forms.

The division of abnormals also could be understood as including not only
specimens resulting from anomalous development, 7. e., true malformations, but
also those which have been affected by disease. Some of the latter, if not anoma-
lous also, would fall in the group of normals, as they rightly should. Moreover,
unless it can be confidently assumed that abnormal ova and spermatozoa have no
existence, some of the cyemata now classed as pathologic evidently are not the
direct products of disease. A specimen certainly may be abnormal without
being pathologic and pathologic without being abnormal in form.

Phisalix (1890) also called attention to the fact that an embryo which is
pathologic is not necessarily abnormal. A fetus that dies in utero while the mother
is suffering from an infectious disease may well be, and often is, pathologic, but
it is not necessarily abnormal. Neither is a specimen necessarily pathologie which
dies under fortuitous circumstances and is retained sufficiently long so that macera-
tion changes very materially alter its form. Likewise, fetuses which die as a
result of extreme twisting or strangulation of the cord, or from premature sep-
aration of the placenta, or from some other accident of pregnancy, are not neces-
sarily pathologic. Yet all these, if retained sufficiently long, might, under the
present classification, fall into this division.

CLASSIFICATION, 49

Although we know very little about the existence of abnormal ova, the relative
frequency with which anomalous forms of spermatozoa occur would alone seem
to make decidedly venturesome the assumption that there is no such thing as
germinal anomalies. In view of the fact that we frankly recognize the occur-
rence of hereditary anomalies, germinal causes certainly can not be excluded.
Yet I presume it would be difficult to refer to such specimens as pathologic unless
we extended the customary meaning of this term very materially.

After grouping all specimens among the abnormal and the normal, each of
these classes could then be subdivided very much as the group of pathologie speci-
mens under the Mall classification—~. e., fragments of villi or vesicles may be either
normal or abnormal; and I think it will be possible to show that the same may be
true, certainly of the macerated, and probably also of most of the stunted cyemeta,
for death in these may have been due purely to mechanical or other causes, which
have not resulted in any abnormality of development, the changes in external form
being the result of postmortem antepartum changes, as suggested by Giacomini.

By the addition of three groups before that composed of villi only, all abor-
tuses would seem to be provided for. These groups would be composed of those
containing syncytial remnants only, those containing trophoblast only, and those
containing both syncytium and trophoblast. However, since as Miiller (1847)
emphasized, normal embryos may be found in diseased vesicles and abnormal
embryos in normal vesicles, it also will be necessary to classify vesicles and cyemata
separately whenever both do not fall into the same group.

3%

ee Vere oe Ser

CHAPTER IV.
ANALYSIS OF ABORTUSES CLASSED AS PATHOLOGIC.

GROUP 1. SPECIMENS COMPOSED OF VILLI ONLY.

A. UTERINE.

Among the series of over 2,000 abortuses in the Carnegie Collection I have so
far been able to find only a few specimens which undoubtedly fall into the category
of intrauterine absorption. Among these are Nos. 698, 970, 1640, and 1926.
Nevertheless, not even in these cases had total absorption occurred, and from
evidence to be considered I have really come to doubt whether absolutely complete
absorption occurs in man in any but the earliest stages of development or under
the rarest conditions.

As stated by Mall, specimens of the first class of the pathologie division,
7.e., those composed of villi only, are obtained very largely from tubal pregnancies.
Nevertheless, Mall emphasized that ‘“‘a very large number belonging to this group
would be found in uterine pregnancies also if our methods of collection and study
were as reliable as they are for tubal pregnancy.” Of the 353 uterine specimens
classed as pathologic among the first 1,000 accessions, only 17, or 4.8 per cent,
are composed of villi only, as compared to 35, or 32.4 per cent, of 108 tubal speci-
mens. That is, specimens composed of villi only are nearly seven times more
common among tubal than among uterine gestations. However, this is due almost
wholly to the fact that the uterine specimens are fairly representative of the whole
period of gestation, while the tubal specimens are derived almost wholly from the
first two months of pregnancy. Specimens composed of villi only would form
about the same proportion among uterine abortuses contained in the first two
groups of the pathologic, as among the tubal, but they form only 12.9 per cent of
all uterine specimens contained in the first four groups of this division. Hence
the inference that the great majority of tubal conceptuses come to an early death
seems indicated by these facts alone.

That villi only are so frequently found in tubal pregnancies is probably due
also to the occurrence of tubal abortion, in consequence of which the conceptus
may be ejected from the tube but some of the villi left attached, and more especially
to the effect of repeated hemorrhage. The conceptuses often are strangulated as
a result of hemorrhage which detaches them completely and then leads to their
disintegration. Although the villi may be, but probably are not, inherently more
resistant than the rest of the chorionic vesicle, some of them usually survive, be-
cause in the absence of a decidua which becomes detached, they remain attached
to the implantation site, thus retaining their connection with the source of nourish-
ment. In uterine specimens this is impossible, for the entire decidua is cast off.
For these, and probably also for other reasons, Mall found that villi almost always
can be detected by microscopic examination of serial sections of the implantation

51

52 STUDIES ON PATHOLOGIC OVA.

eavity in cases which clinically are tubal pregnancies, even if they can not be
detected by the most careful inspection of the gross specimen or by microscopic
examination of frozen sections of portions of the implantation site.

Whether or not the surviving elements of a conceptus are villi only depends
very largely upon the age of the conceptus and upon the sequence of events respon-
sible for its death. Indeed, if the entire conceptus is erupted from its implantation

cavity by a sudden severe hemorrhage, it is very unlikely that the villi will be
the surviving elements, unless the conceptus is extremely young. The same thing
would be true of a conceptus which a severe general inflammatory process had
suddenly detached. For in both of the assumed cases the villi would undoubtedly
succumb to the destructive processes earlier than the chorionic membrane, the
syncytium, or the trophoblast. If, on the other hand, the infectious process gains
entrance into the cavity of the chorionic vesicle itself, the latter and the embryo
rapidly disintegrate and are destroyed, while some of the villi may long remain
in a state of relatively good preservation.

From these considerations it is evident that it would be possible to form three
other groups of specimens in addition to those composed of villi only—those
composed of remnants of both trophoblast and syncytium, or of one or the other
alone. That such specimens actually occur will become evident in the course of
this discussion. At present they are included in group 1. However, it is not for
this reason alone that the designation “‘villz only” does not fully describe the first
group in the pathologic division. Three specimens in this group, for example, are
hydatiform moles, one of which, No. 323, forms a large, compact mass, a portion
of which is shown in section in figure 6. Another is composed largely of blood-
clot surrounded by decidua, and still another consists largely of a decidual cast
with mere traces of syncytium, trophoblast, and perhaps of portions of one or two
villi. Furthermore, since it is practically impossible to examine all specimens in
their entirety in a complete microscopic series, there is some possibility that the
portions examined may not form an adequate basis for the correct classification
of the specimen. Hence, for this reason also some specimens are bound to get into
incorrect categories. Nor is it without significance that no provision is made
among the normal specimens for a group of villi only. Under the present classifica-
tion all of these are placed in the pathologic division. This would seem to imply
that normal villi are never aborted alone in uterine pregnancy or found alone in
tubal pregnancies or in tubal abortions. Yet material from curettage, or from
abortions the result of interference by the patient herself, no doubt may contain
none but normal villi. I have seen the question raised nowhere, but it seems
doubtful whether, except perhaps in the earliest stages, villi can ever develop
wholly normally ina tube. Hence the above objection to the present classification
might be waived for tubal but not for uterine specimens.

Among the possible causes of the destruction of conceptuses, inflammatory
conditions, as indicated by infiltration, as a rule seem largely predominant. They
existed in the great majority of the uterine specimens, protocols of which are

SPECIMENS COMPOSED OF VILLI ONLY. 53

attached, and sooner or later seem to lead to fetal death. It is interesting that
fetal death in these cases is not the result of invasion of the conceptus, or even of
its villi, by the inflammatory process itself. It is possible that the production
of toxins may be a factor, but the morphologic evidence seems to point to inter-
ference with the nutritive supply through decidual and chorionic changes. It is
not difficult to see that the accumulation of pus in the region of attachment of the
villi, or even the accumulation of large masses of leucocytes, must seriously inter-
fere with the free intervillous circulation. Obstruction to the blood-current, if
sufficiently severe, would also lead to the death of the cyema, and finally to that
of the chorionic vesicle itself in consequence of interference with the indispensable
gaseous interchanges.

No matter how severe the infection of the uterus was found to be, or how large
the accumulations of pus at the region of implantation, well-preserved villi never
were found infiltrated with cells of maternal origin. When infiltration was present
within the stroma the latter, and especially the epithelium of the villi, could be
shown to be degenerate. If, on the other hand, the infectious process was intro-
duced directly into the chorionic vesicle, the latter soon disintegrated and the
infection extended into the stroma of the villi also. An insuperable difficulty
encountered in connection with the question of infection in many cases is the
inability to determine positively whether the infection existed within the uterus
before implantation occurred, or whether it was incidental to mechanical inter-
ference. An examination of the material seems to show that the final effect upon
the villi, and of course also upon the membranes of the embryo, rarely may be the
same in both cases. This probably is due to the fact that a young conceptus
may be loosened partially only, at the time of interference or of infection, thus
establishing conditions which lead to its death. As a rule, however, in these cases
maceration changes are likely to be much more rapid than under conditions of a
chronic endometritis pre-existent to the conception. Nevertheless, mild general
or a severe local preimplantation endometritis no doubt could produce results
wholly comparable to those resulting from a mild general uterine infection incident
to mechanical interference, especially in the case of young conceptuses. It is
conceivable that in the case of a low-grade endometritis, the fertilized ovum may
undergo a perfectly normal development for a restricted period, and then suffer
from more or less sudden interference with its development through exacerbation
or extension of the infectious process, just as might be the case under other condi-
tions. Ordinarily, however, it would seem that the changes within the conceptus
should be more gradual, and also much more general under conditions of a chronic
endometritis than under those of accidental or incidental infection. Nevertheless,
the changes in the villi sometimes appear wholly comparable in both cases. The
stroma in many of them finally undergoes what Mall has called mucoid degenera-
tion, with complete disappearance of the mesenchyme and final disintegration
of the epithelium. The blood-vessels generally become effaced at a very early
day before the stroma has undergone any important changes. Rarely, as the en-

54 STUDIES ON PATHOLOGIC OVA.

dothelium degenerates, it leaves a faint, more or less incomplete outline marked
by the degenerating nuclei. Consequently it happens that the surviving remnants
of a vessel may be represented merely by a small number of poorly preserved nuclei.

The epithelium of the villi usually is preserved longer, but finally the syncy-
tium may fuse with the Langhans layer, forming a dense coagulum. Or the pye-
notice nuclei of both layers may retain their relative positions, ultimately becoming
resolved into fine granules which Mall, in several of his publications and also
repeatedly in the protocols, has spoken of as nuclear dust. This fine granulation
seems to herald beginning calcification. Later the granules may fuse with each
other and with the necrotic cytoplasm, forming a hyalin band at the periphery of
the villus, which stains heavily with eosin and also with iron hematoxylin. It
alone may make the outline of the pre-existent villus evident. Fibrosis of the
villi is seen but rarely in these early specimens, and when it occurs, hyalin degenera-
tion is not infrequently present in the form of trabecule or a framework in the mid-
portion of the villus. Remnants of the syncytial masses or of trophoblast usually
survive everything else.

Since no decidua and very little trophoblast were found upon the villi of several
young conceptuses, it seems doubtful in some cases whether good implantation
occurred at all, as suggested by No. 1848, shown in figure 7. In these specimens the
villi nevertheless seem to undergo considerable development, but the embryo,
after it becomes dependent upon the circulation, finally dies, probably by asphyxia-
tion, and then the processes of maceration, digestion, and absorption begin. In
other cases it also seems likely that the young ovum becomes embedded quite
normally, but that strangulation results from severe hemorrhage which loosens
the attaching villi, thus interrupting the intervillous circulation. Since the result-
ing stagnation of the blood must make impossible the indispensable chemical inter-
changes upon which the life of the cyema depends, the latter probably dies first.

It is decidedly interesting that considerable hemorrhage, sufficient to result
in the death of both eyema and chorionic vesicle, can occur while the whole con-
ceptus is still surrounded by the early decidua capsularis without rupture of the
latter. Such a specimen was discovered in No. 698, which is in the final stages of
absorption. In this unique specimen (received from Dr. N. E. B. Igelhart), which
has a menstrual age of 56 days, there remains only the merest trace of a chorionic
vesicle in the form of a striated coagulum, a few questionable “shadows” of villi,
several small fragments of syncytium, and a few detached accumulations of tropho-
blast. The place of the conceptus is occupied by blood-clot formed into an elon-
gated body 50 by 20 by 13 mm. This body is completely surrounded by an intact
decidua capsularis.. The latter is easily recognized, both in the gross and in the
microscopic specimen, and the decidua vera, which also is intact, can be seen
clearly with the unaided eye in every detail of its relations, as shown in figure 8.
This indeed is a unique specimen and especially significant in connection with
No. 970, to be discussed in the next group, and with certain better-preserved
specimens recorded in the literature. The failure of complete absorption of the
last few small remnants of this conceptus is probably due to the fact that the small

SPECIMENS COMPOSED OF VILLI ONLY. 55

remnants of degenerated trophoblast and syncytium which remained were no
longer able to inhibit menstruation. Hence the decidua of pregnancy, together
with these few small remnants of the conceptus, was expelled in toto at the time of
onset of the next period, and it may be extremely significant that this occurred
exactly two menstrual months after the beginning of the last period. Since 3
other specimens of a series of 16, composed of villi only, were aborted at the time
of recurrence of the regular period, the idea that abortion occurs oftener at that
than at any other time would seem to receive some confirmation. Moreover, it
would appear quite natural that a decidua which has subserved its functions
would be more likely to be shed at this time and that an unabsorbed conceptus
which had been converted essentially into a foreign body should then be expelled.

It is impossible to decide how far the development of this conceptus had
progressed before its death, but the extent of absorption shows beyond any doubt
that the latter would have been absolutely complete before the advent of the next
or third period had the second period also been inhibited. Since in the assumed
case the decidual cast then would have been expelled after the ovum had been
completely absorbed, this decidual cast might have directed attention to the possi-
bility of the existence of a tubal rather than a uterine pregnancy. In view of the
facts here revealed, such a sequence of events might well give the impression of
the existence of an early tubal pregnancy which had undergone spontaneous retro-
gression without ever having given rise to the characteristic symptoms. In this
connection I am reminded of the fact that gynecologists have been of the opinion
that some tubal pregnancies undergo spontaneous cure. In many of these cases
the healing probably follows tubal abortion, but specimens in this collection also
indicate the possibility of another sequence of events. In some instances, for
example, the small intratubal blood-clot in which a small conceptus becomes
enclosed at the time of hemorrhage seems to undergo reduction within the tube.
Under these circumstances the conceptus, which was separated from its implan-
tation site, may then undergo retrogression, maceration, disintegration, and finally
may be completely absorbed, and the tube heal. Nor does it seem impossible
that the chorionic vesicle may remain and undergo a similar fate within the tube
in cases in which the cyema alone is aborted.

Of the 16 specimens finally classed in group 1, all of which were examined
both macroscopically and microscopically, 7, or 43.7 per cent, show hydatiform
degeneration. In each of these specimens the abortion very probably was not
induced. In 5 of these specimens in which some or all of the decidua accompanied
the specimen, it showed changes indicative of endometritis. In 4 of these the
infiltration was marked and in one it was slight. One specimen counted as showing
hydatiform changes was extremely degenerate, however, and unaccompanied by
decidua, and may therefore perhaps be rejected, thus leaving 6 specimens, or 37.5
per cent, definitely showing hydatiform degeneration.

The decidua was included in 13 of the 16 specimens in this group, but the
material was very necrotic in one case and too little of it accompanied another.
The infiltration was slight in one of the remaining 11, and very marked in the other

56 STUDIES ON PATHOLOGIC OVA.

10 cases. Hence, although infiltration of the decidua was present in only 10, or
62.5 per cent, of the 16 specimens of this group, the decidua showed definite signs
of inflammation in every one of the 10 in which it was present and sufficiently
well preserved. Some decidua, in fact, contained considerable masses of purulent
material. The infiltration was often very marked locally, small accumulations
of leucocytes being scattered about more or less at random; but this form of infil-
tration frequently was accompanied also by an infiltration more or less general
and uniform in character, and by other changes. Whether or not these infil-
trations were confined to the decidua I am not able to say, for uterine muscu-
lature was not included. In most eases, however, the process had the appearance
of a low-grade chronic inflammation. In only a few was a severe infection very
evidently present.

Of the abortuses composed of villi only included in the first 1,000, all but 3
had a maximum length of less than 50 mm. One measured 68 mm., another 100
mm., and a third 120 mm. However, since considerable allowance must be made
for distortion, for variations in the length of villi, and for maceration, as well as
for increase in size due to the surrounding decidua and blood-clot, it is evident that
the measurements of the abortuses are often too large to represent, even approxi-
mately, the true age, not only of the accompanying cyema, but of the chorionic
vesicle or placenta as well. It is evident also that, in case of abortuses composed
of villi only, the measurements, even if not affected by the presence of blood-clot
and decidua, could in no sense be more than roughly indicative of the age of the
specimen unless the chorionic membrane were preserved sufficiently to retain its
form and size. Furthermore, since the specimens in this group include material
from curettage also, a discussion of their size as related to their anatomical or
menstrual age can have no value.

The largest specimen in this group is a hydatiform degeneration, containing
no trace of the cyema. Such a specimen can not with propriety be designated as
villi only; nevertheless, the exigencies of the situation make its inclusion here of
-some practical value. In other instances one could speak of the size of the mole,
perhaps, but unless composed of solid masses of villi, moles really belong in the
second group. In still other instances, such as No. 698, the main mass of the
abortus was composed of decidua, so that although only what was originally taken
for the chorionic vesicle was measured, this measurement nevertheless is wholly
erroneous, for it is impossible to exclude the blood-clot, which, in this case, very
greatly affects the size of the specimen.

Unfortunately, menstrual age is not a reliable criterion of the true age of the
specimens in this group, the state of preservation of which alone indicated that
many of them were retained a considerable length of time after their death. The
latter is indicated, not only by the disproportion between the size of the abortus
and the menstrual age, but also by the degenerative changes present in the speci-
mens themselves. The longest menstrual age (218 days) is found in specimen No.
70, in which the size of the conceptus or cyema indicates an anatomical age of
only 50 days.

SPECIMENS COMPOSED OF VILLI ONLY. 57

Upon attempting to correlate the clinical data with the objective examination,
it was found that in one case in which abortifacients were held responsible for the
termination of pregnancy, an intense infection was present. This was true also
in four other cases, in which it was specifically stated that infection was absent, a
conjunction of things to be referred to again.

B. TuBAL.

In contrasting the tubal specimens composed of villi only with similar speci-
mens from the uterus, the lesser number of villi contained in the tubal cases is very
striking. It may be recalled that the number of villi found in uterine specimens
varies from none to large hydatiform masses weighing several pounds. But even
aside from the latter, which properly do not belong in this group, villi found in
uterine specimens are far more numerous, as a rule, than in the tubal cases. One
of the main reasons for this difference lies in the fact that the tubal specimens as
a whole undoubtedly are much younger and hence less resistant. Their youth may
be explained very largely by the anatomical conditions under which development
proceeds in the tube and in part probably also by the efforts at abortion which
probably are inaugurated very early through the occurrence of tubal peristalsis.
It is not unlikely that this peristalsis may expel most of the villi, with the surround-
ing blood-clot, into the peritoneal cavity, leaving behind only a few stragglers.
In the absence of anything truly comparable to decidual development within the
tube, the villi at best must be embedded less securely and also may degenerate
faster when once detached. Moreover, in the absence of such a nidus as the hyper-
trophied endometrium, the whole development of the conceptus necessarily must
be retarded.

Most of the villi in tubal specimens lie isolated in the contained blood-clot;
hence matting of the villi was practically absent and calcification and coagulation
necroses were not seen, facts which suggest the occurrence of early interference
with development. Sometimes a few villi which lay near each other were decidedly
necrotic, but they were not fused into a large, solid mass by degeneration or by
inflammatory products in any of the cases in this group. This fact and the ap-
pearance of the clots would seem to suggest that there often is a constant trickling
of blood from the distal extremity of the tube, so that old clots form slowly, new
blood being added more or less constantly, thus prolonging the life of some villi,
or at least of the chorionic epithelium. In several cases the villi were quite well
preserved, though fibrous, but by far the greater number were decidedly degen-
erate. Except in instances in which the whole villus was necrotic, the epithelium
was preserved better than the stroma, a fact which probably may be explained by
the presence of fresh blood. In all except the necrotic specimens, the epithelium
not only was well preserved, but also was not infrequently very active, as noted in
several instances by Mall (1915). Considerable masses of trophoblast were present
in a number of instances, and smaller syncytial masses (or more frequently syncytial
buds) also were seen. Usually some portions of both were extremely well pre-
served, and in one instance large masses of degenerate trophoblast completely filled

58 STUDIES ON PATHOLOGIC OVA.

the interplical spaces and the mucosal diverticule along a considerable sector of
the tube. In two other instances the degenerate trophoblast which bordered,
and to some extent invaded, the musculature reminded Mall of Hofbauer cells.

The stroma of the villi was non-vascular in practically all instances, and only
a few small remnants of the degenerating vessels remained in some. To some
extent absence of vessels may be due to the youth of the specimens, but in the
main it is probably due to other factors. Even the villi that were capped by
considerable trophoblast and syncytium and which still were implanted in the
musculature were often non-vascular, and their stroma, as noted by Mall, was
usually mucoid. In contrasting the changes in the stroma of the villi found in
tubal with that of the same group of uterine specimens, the more degenerate
character of the stroma in the former is very evident. Moreover, not a single villus
with a fine, clear, glassy, translucent stroma was seen in this group, nor were any
present which had a well-preserved young cellular stroma, or others in which the
formation of more than a few Hofbauer cells was in progress. The whole appear-
ance was rather that of a rapid destruction, although most of the clots in which the
villi were embedded were relatively fresh. Considerable portions of the clots
often contained a fibrin network, but all were unorganized, and no instances of an
ingrowth of connective tissue from the tubal wall were seen, in spite of the fact
that a few of the clots were relatively old and necrotic.

In two instances in which no portion of the tube had been cut, the presence
of infection in it was made probable by the appearance of the contained clots.
In most of the latter the leucocytes were congregated more or less, or were formed
into small clumps even. Phagocytosis of the fetal membranes by the leucocytes
or by other cells was not noticed, although leucocytes had accumulated at the
periphery or even had entered into the interior of the stroma of degenerate villi.
No embryonic remnants whatever were found in the sections of a portion of one
tube, and degenerate trophoblast and syncytium only were present in two. This
fact, however, does not imply that phagocytosis was responsible for the absence
of villi.

Out of the 33 specimens originally in this group, 2 were found to contain
remnants of the chorionic membrane and of the amnion, and hence were trans-
ferred to groups 2 and 3 respectively, and 10 were added. In 3, or 9 per cent, of
the 42 cases remaining, no infiltration, either of the clot or the wall of the tube, was
noticed. In 12, or 28.6 per cent, the infiltration was marked, and in 17, or 40.4
per cent, it was slight.

Changes simulating those of lues were noticed in no tubal conceptuses in this
group, but several excellent examples of hydatiform degeneration were found in
Nos. 415, 602, 686, 772, and 889. According to Seitz (1904°), the occurrence of
hydatiform moles was observed in connection with tubal pregnancies by Freund,
Matwejew and Sykow, Otto, and Wenzel. Others no doubt have observed it
since then, but as only a few villi are contained in a single cross-section of the tube,
and but few cross-sections of each specimen were examined in our series, one can

SPECIMENS COMPOSED OF VILLI ONLY. 59

not be certain of one’s diagnosis in every instance. If more villi were present this
difficulty would be obviated, although it must be remembered that a large series
of specimens necessarily supplement each other. Furthermore, the changes in
many villi are so typical, both as to outward form and structure, as to be undoubted.
Since many of the villi were decidedly degenerate, one could hardly expect to find
much proliferation of the endothelium, but remarkable specimens, such as that in
figure 9, were occasionally found. In some cases the presence of hydatiform
degeneration became probable only through comparison of the villi in question
with those found in many undoubted cases of hydatiform degeneration examined
previously.

Two unusually fine specimens of hydatiform degeneration were transferred
to this from group 2. No. 367 was a fine, clear, partly cystic specimen in which
syncytial buds were invading the stroma of some of the villi. Although only
vestiges of the vessels remain, the trophoblast is well preserved and syncytial
buds are found on some of the trophoblastic nodules. The outlines of many villi
are very sinuous and the epithelium is well preserved. In some respects this is
one of the most unusual specimens I have found in the entire series, both of ectopic
and uterine specimens. In the other specimen, No. 720, some of the implanted
villi which remain show hydatiform degeneration, and many of them have fine,
long syncytial buds. Although no vessels were seen in this specimen, the tropho-
blast nevertheless is abundant.

In the 5 cases above mentioned the presence of hydatiform degeneration was
undoubted, and in 6 others its presence was highly probable, making 11 cases, or
26.2 per cent of the entire group. This is a somewhat lower incidence than in the
uterine cases in this group, which was 37.5 per cent. Either the tube-wall or the
contained clot gave evidence of the presence of infection in 8 of these 11 cases. If
we exclude one case in which the tube was not included in the section, we get a
percentage of infiltration of 80. Moreover, since only a few sections of each
specimen were examined, and since the evidences of an old infection are not always
easily detected in a markedly dilated and altered tube, it is not improbable that
infiltration was present in more of these cases of hydatiform degeneration, as was
the case in the uterine specimens. The existing infiltration was intense in one
and slight in the other half, and since only one case not included among those
showing hydatiform degeneration had an apparently normal tube, infiltration
hence was almost constantly present also in the entire series of cases included in
the group of the tubal specimens.

Although the alleged menstrual age ranged from 6 to 113 days, only a rough
correspondence between it and the structure of the specimens was found to exist.
The specimen with the longest duration contained only a few questionable degen-
erate syncytial remnants, and in No. 900g, which had a menstrual age of 69 days,
no embryonic remnants whatever were found. No. 967c, which had a menstrual
age of 70 to 100 days, contained only a few degenerate villi, although the same
thing was true also in other instances with a much shorter duration.

60 STUDIES ON PATHOLOGIC OVA.

Group 2. CHORION WITHOUT AMNION OR CYEMA.

A. UTERINE.

The absence of the amnion in these specimens seems to be the result of destruc-
tion by lysis. However, absence of it in young specimens also might be due to
failure of formation. The latter was the opinion of Giacomini (1888), who never-
theless believed that deformities of the amnion are rare. The only specimens in
which the absence of the amnion could be ascribed to failure of development is
No. 1843, donated to Stanford University by Dr. Falk, of Modesto, California.
This is a very young specimen, however, and it is not impossible that a small
cavity found in it represents the early amniotic cavity, as suggested by Meyer
(1919e). Moreover, it may be doubted whether the human embryonic disk
could develop far if formation of the amnion were inhibited. It is true that Panum
(1860) and Dareste (1883) both reported cases of absence of the amnion in the
chick and that Dareste emphasized that all the cephalic or the caudal portions
may be absent. But since it is possible that the process of formation of the amnion
is a totally different one in man, the direct application of these observations upon
the chick to man is open to question. Panum and Dareste both believed that the
anomalies of the amnion, observed by them in the chick, were secondary and the
opinion of Giacomini was based largely upon the failure to secure absorption of
the amnion experimentally in rabbits.

Specimens of human abortuses in which the amnion has undergone partial
destruction are very common. Moreover, all degrees of destruction are represented
in these cases, and since the cyema, too, is usually lacking, the assumption that
absence of the amnion is due to failure of formation naturally would neeessitate a
similar conclusion regarding the embryo. This would leave one in the position
of assuming that a chorionic vesicle which never had contained an embryo or
amnion nevertheless might develop independently and attain some size.

Since the absence of the cyema in some of these vesicles is undoubtedly due
to the mechanical injury incident to interference with a purely normal gestation,
it follows that some of them were unquestionably normally developed chorionic
vesicles and hence do not belong in the pathologie division. The difficulty lies in
identifying them. Nevertheless, the structural characteristics of some are sug-
gestive, even if not wholly unequivocal. In one instance, for example, in which a
small nodule was seen upon opening an apparently intact ovum, this nodule was
found to be composed of fragments of villi which could have been introduced into
the chorionic vesicle only at the time of interference, or accidentally when it was
opened in the laboratory. In another instance the chorionic vesicle contained
foreign material when opened. Besides, the splendid preservation of the tissues
of some specimens also shows that they were obtained in a practically normal,
fresh, and unmacerated condition, which rarely is the case in any but instances of
induced abortions, whether they be therapeutic, accidental, or criminal.

As already indicated, there is no hard and fast line of demarcation between
the first three and later groups of the pathologic division. Indeed, it is not always

CHORION WITHOUT AMNION OR CYEMA. 61

easy to determine, even histologically, whether or not cyemic remnants are present,
for it is sometimes impossible to decide whether a small hyalin or webbed mass
contained within the chorionic vesicle is or is not a remnant of the cyema itself.
Then, too, some of the specimens included in this group contain clumps or small
accumulations of erythroblasts, which probably had their source in the blood-
vessels of the body of the embryo, although they may also have come from the
vessels of the cord or of the chorionic membrane itself. In most instances these
cells really are cyemic remnants, yet their presence has not excluded the specimens
from this group of empty vesicles. Moreover, in another instance (No. 663),
considerable remnants of the yolk-sac were found, although nothing could be
positively identified as a remnant of either embryo or amnion. In other eases
either of the last two structures or both may be represented by a very degenerate
fragment, which is merely a so-called shadow or (better) gossamer form. Indeed,
the entire chorionic vesicle is sometimes reduced to a mere gossamer form, as
illustrated by No. 606 shown in figure 11.

From these things it is evident that group 2 nevertheless includes chorionic
vesicles which contain free erythroblasts within their cavities or remnants of the
yolk-sae and even of the amnion itself. However, since all specimens in the first
three groups differ from each other only in the degree of destruction of the embryo
and fetal membranes, this overlapping is a matter of no serious consequence for
any except statistical deductions. Moreover, since the whole of a specimen is
examined only seldom in a complete series, it follows that some of them will be
classified incorrectly for this reason alone. No. 771a, for example, contains an
undoubted remnant of the amnion, and hence belongs in the next group. No. 644
is composed of villi only, and therefore falls into group 1. Since No. 663 was
found to contain numerous undoubted remnants of the yolk-sac, it is not at all
unlikely that some embryonic masses which could not be identified certainly as
such were nevertheless contained in this specimen, which would then be classified
in group 4. This particular specimen is contained in a very degenerate hyalin
abortus measuring 35 by 15 by 10mm. The conceptus is composed of an extremely
folded and almost structureless chorionic vesicle and of included and isolated
cyemic remnants. As so often is the case, this abortus was much larger than the
contained chorionic vesicle, which measured only about 5 by 3 mm. in section.

Hence, if Nos. 29, 664, and 771a are excluded from this group, only 40 uterine
specimens remain, to which must be added three transferred from other groups.
It is stated that in one case (No. 970) the specimen was obtained at autopsy,
and in another (No. 865) at hysterectomy, and that in a third the abortion was
induced.

In three instances (Nos. 71, 278, and 771a) it was stated that the patients had
a chronic endometritis, and in one case (No. 865) the patient was said to suffer
from “‘an old pelvic inflammation,” but showed “‘no evidence of venereal disease.”
In two cases reported as having a chronic endometritis (Nos. 71 and 278) the clini-
cal diagnosis was confirmed by microscopic examination. In the case in which an
old pelvic inflammation but no venereal-disease was said to have been present,

62 STUDIES ON PATHOLOGIC OVA.

it was found that a severe endometritis with abscess formation was nevertheless
indicated histologically. Only five cases (Nos. 661, 663, 753, 876, and 986) were
reported as having no infection, but four of these contained evidence of the
existence of an intense endometritis, accompanied in two instances (Nos. 876 and
986) by abscess formation. The specimen from the fifth case (No. 663) was so very
necrotic that a positive diagnosis could not be made, but it is unlikely that a severe
infection was present. Infiltration of the endometrium was present in 30 of the
48 cases, including 2 doubtful ones. This makes a percentage of 62.5, but since
the decidua was not included in 20 cases, was too degenerate for study in 3
of the rest, and especially since only a relatively small portion of each abortus was
examined microscopically, it is very probable that this percentage of evidence of
infection, high as it is, nevertheless is entirely too low. Omitting the doubtful
cases, the decidua was found infiltrated in 28 of 29 cases, or in 99.6 per cent. In
82.8 per cent of these the infiltration was marked. In 5 cases the infiltration of the
endometrium was comparatively slight, but in 24 it was severe. In one case
infection was found to be present within the chorionic vesicle, and although no
decidua accompanied this specimen, it is unlikely that the infection was confined
entirely to the vesicle. In 4 cases both the interior of the vesicle and the decidua
undoubtedly were infected, and in 2 (Nos. 435a and 750) no decision could be
reached.

Twenty specimens, or 41.6 per cent, were identified as showing hydatiform
degeneration, 3 cases being doubtful and 2 others probable. In 15 of these cases
in which the decidua was included it showed inflammatory changes. These changes
were marked in 12 and slight in 3 cases.

Among the alleged causes of the termination of pregnancy in the cases not
accounted for otherwise, we find that a fall was mentioned in case No. 71, in which
evidences of chronic endometritis were present; anxiety is given as the proximate
cause in No. 664, and fright in No. 883, both of which cases show the presence of
an intense infection, which in one was so severe that the chorionic vesicle was
destroyed almost completely. Two of the 3 abortions reported as having been
spontaneous (Nos. 750 and 829) show the presence of a severe infection. In 4
instances in which the uterus was considered to be normal, evidence of infection
was found in 2. In No. 883 it was found to be severe and in No. 978 it was mild.
Although only one of these 39 specimens was said to have been induced, it is more
than likely that this is true of more of them, although it seems exceedingly unlikely
that an ovum could become implanted, and decidual formation actually progress in
a normal way in so infiltrated and abnormal an endometrium as is present in many
of these specimens. The anatomical condition of some of the chorionic vesicles
among the non-infected group suggests that some of these abortions also were
induced.

The histological changes found in this group differ in no essential respect
from those present in group 1. Mall also found that the changes in the villi of the
chorionic vesicle from an ovarian pregnancy (see No. 550 in the next group) showed

CHORION WITHOUT AMNION OR CYEMA. 63

essentially the same changes as uterine specimens developing “under faulty
implantation or infection.”” Maceration changes are present in all specimens,
but vary extremely in degree. Coagulation necroses are absent, except in small
areas, and beginning “‘infarct”’ formation was present only in portions showing
especially severe infection. In the latter the destruction apparently had been very
rapid and hence the degenerative changes differ somewhat from those produced
by a low-grade chronic endometritis pre-existent to the implantation.

In most of the specimens, as noted by Mall, two forms of degeneration of the
villi exist side by side, a fibrous and a ‘“‘mucoid”’ transformation of the stroma.
The former usually affects but few villi, the latter affects many. Sometimes the
degenerate stroma, instead of being “‘mucoid,” was finely granular. In some cases
many villi show intense so-called granular hyperplasia. Blood-vessels were absent
in both the chorionic membrane and the villi of many of the specimens, a fact
which is especially significant in connection with the duration of the changes under
consideration. In one instance (No. 596) many of the vessels were in the last
stages of degeneration; another specimen showed the presence of numerous small
abscesses between the epithelium and the stroma of the chorionic membrane.
In those specimens in which the cavity of the chorionic vesicles had been infected,
the chorionic membrane was not only decidedly thickened as a result of the loosen-
ing up of the fibrous tissue, but also was undergoing a very rapid destruction. In
these instances it is not uncommon to find the infectious process invading the
stroma of the villi from that of the chorionic membrane, but as long as the chorionic
epithelium was found intact an extramural infection, no matter how severe, was
never noticed to have caused an inflammatory reaction in the villi or in the chori-
onic membrane, not even in cases in which the latter was surrounded by a wall of
polymorphonuclear leucocytes.

The content of these amnionless chorionic vesicles was usually a coagulum,
which was generally amorphous or finely granular, but rarely also finely webbed
or reticulated, reminding one of the “corps réticulé” of Velpeau (1855). The
only histological elements which this magma contained were small fragments of
or cells from the chorionic membrane and clumps of erythroblasts, composed
either of individual or of coalescing cells,-or the degeneration forms of these or of
other embryonic cells. Some foreign materials and remnants of the yolk-sac rarely
also were present, and fibrosis of the decidua, which is to be discussed separately,
was quite common.

It was especially interesting that this group also contained specimens illus-
trating the process of intrauterine destruction and absorption of early conceptuses.
In one specimen (No. 606) measuring 18 by 13 by 6 mm., all the tissues, even
including the last or smallest remnant of the nuclei, had been destroyed completely.
Not a single cell contour was preserved; not even by coagulum, as is frequently
the case in non-degenerate deciduz. Yet in spite of these things, the form and
relative proportions of the entire vesicle, with its surrounding villi, were preserved
so well that in describing the gross specimen, Mall noted: “In appearance the

64 STUDIES ON PATHOLOGIC OVA.

specimen is normal,” although under later microscopical examination he found it
“difficult to make out any structure whatsoever. In fact, even the nuclei of the
chorionic membrane have disappeared entirely, leaving only a fine reticular struc-
ture.’ One might say of this specimen, a photograph of some of the villi of which
is shown in figure 11, that only an extremely finely textured, disordered web of
hyalin material composes the apparently intact chorionic vesicle and the envelop-
ing villi. What we really have here is a cast of the entire chorionic vesicle, includ-
ing villi, which is formed by hyalin degeneration products that have preserved
the form of the vesicle in every detail. From these things it is evident that only a
little longer retention of this vesicle in utero would have sufficed to effect its com-
plete disappearance. It does not therefore follow, however, that the disintegra-
tion products necessarily would have been completely absorbed. They might, to
be sure, have been expelled, at least in part, with the decidua.

The finding of this specimen recalled a personal communication made to me
by Professor Mall which suggests that a small cyema received some years ago
probably was in a similar structural condition. This specimen was found appar-
ently well-preserved and normal in form when the intact chorionic vesicle was
opened in the laboratory, but had completely disintegrated a few moments later.

An exceedingly interesting specimen bearing upon this question of intrauterine
destruction and absorption of conceptuses is one received from Dr. R. W. Ham-
mack, of Manila. This specimen, No. 970, which was referred to in the preceding
chapter, was found in the uterus at autopsy. The uterus contained some blood-
clot, and the decidua was described by Mall as being “covered with hemorrhagic
nodules measuring in general about 10 mm. in diameter. One of these, located
medially, is larger than the rest, and a narrow block of tissue cut out of it and
sectioned was found to contain part of anovum. The ovum with its villi measures
3by5mm. The ccelom is filled with a homogeneous substance, through which are
scattered individual cells and also some strands of tissue from the chorionic mem-
brane. The villi are about 0.5 mm. in length and covered with an active tropho-
blast. This layer of trophoblast ramifies into the adjacent tissue, is intermingled
with a great deal of fibrinoid substance and cells, and penetrates the blood-sinuses.
There are many buds of syncytium and considerable inflammatory reaction in the
surrounding tissues. Towards the lumen, the ovum is covered with decidua
reflexa, marked off with a layer of fibrinoid substance. The sections examined show
no trace of an embryo.” On account of the swollen condition of the chorionic mem-
brane and the lack of sharpness of the mesenchyme, it is evident that pronounced
degeneration of this conceptus has occurred. However, the internal limits of the
chorionic membrane are well defined and the mesenchyme has become decidedly
loosened, disordered, and degenerated. Groups of mesenchyme cells have wandered
out into the magma, which contains cellular detritus also. The stroma of most of
the villi is decidedly degenerate and in some cases is represented by a coagulum
containing cellular remnants surrounded by necrotic epithelium. The syncytial
islands are ill preserved and the trophoblast also is degenerate. The entire ovum

CHORION WITHOUT AMNION OR CYEMA. 65

is surrounded by a decidedly hemorrhagic, degenerate, and inflammatory decidua
and mucosa. Although some evidences of maceration seem to be present in the
latter, they are relatively slight and can in no way account for the condition of the
chorionic vesicle, the whole appearance of which suggests rapid degeneration.
The extent of this degeneration is indicated by the entire absence of the cyema
itself, by the appearance of the remaining tissues, and by the absence of remnants
of the amnion and yolk-sac. All these things make it impossible that the embryo
was well preserved up to the time of the death of the patient and the subsequent
autopsy.

The presence of a severe infection in the endometrium naturally directs atten-
tion to the possibility of the destruction of the amnion and cyema of this specimen
directly from this cause. However, since there is no infection of the cavity of
the chorionic vesicle, such an assumption becomes untenable. Besides, the char-
acter of the changes in the chorionic vesicle itself makes it quite evident that this
degeneration was produced by other conditions than a severe sudden infection.
A low-grade endometritis may have been not only a contributory but the prime
factor, but, in view of the severe hemorrhage which surrounds the vesicle and which
must have produced rapid stasis and hence asphyxiation of the conceptus, it is
unnecessary to assume any other contributory cause whatsoever; for, as No.
698 so well illustrates, hemorrhage alone, no matter what its cause, is entirely
sufficient to effect the complete destruction of either embryo or vesicle, or of both.
Nor is it necessary to assume that such a severe outpouring of blood from the
tapped vessels in the uterine mucosa is necessarily or even probably pathologic.
Indeed, it may be purely accidental and the result of a number of physical factors,
none of which necessarily is related to diseases of either the ovum or the endome-
trium, or of the maternal organism as a whole.

A very interesting specimen belonging to this group is No. 1224, a portion of
which is represented in figure 10. This specimen was received in an unopened
uterus removed by hysterectomy for cervical myoma. The conceptus, which
measures 36 by 25 by 13 mm., was collapsed, free in the uterus, and embedded in
mucus. The only content of the chorionic vesicle was a dark-grayish coagulum
which contained no remnant of the embryo or of the amnion. This amorphous
magma included only a few isolated cells, yet in spite of this fact the trophoblast,
which had markedly proliferated, was well preserved over large areas and many
of the vessels in the chorionic membrane were filled completely with erythroblasts.
A few degenerate masses of trophoblast and fused degenerate villi also were present.
Some of the villi show evidences of maceration, others of mucoid hydatiform
degeneration, as shown in figure 12, although they still may contain vessels. Some,
however, are represented by a hyalin outline only. Both the stroma and the
epithelium of many of the villi are well preserved, however, and the same thing
holds for the chorionic membrane.

The decidua shows slight general and very marked local infiltration. Some
remarkably dense periglandular and perivascular zones of infiltration are present.

66 STUDIES ON PATHOLOGIC OVA.

The regenerated mucosa, too, is infiltrated and contains islands composed exclu-
sively of round cells. In view of the condition of the decidua, the clinical observa-
tion of the presence of a weakly positive Wasserman reaction may have special
significance. Besides maceration effects evident in the chorionic vesicle, many
of the villi show changes undoubtedly hydatiform in character. It is decidedly
unlikely that the cause of this intrauterine destruction, and probably also of the
absorption of the embryo, is to be sought in the presence of the cervical myoma.
Indeed, it is unlikely that the latter played any réle other than that of obstruction
of the cervical canal, and so furthered absorption of the conceptus. We have here,
then, perhaps an evidence of the effect of endometritis upon the implanted ovum.
Since the latter contained no evidence of violence, and since it was wholly unopened
and noninfected, and above all, since the infikration within the decidua suggested
a chronic rather than an acute condition, such a conclusion would seem to be
justified, although interference with the gestation can not be excluded absolutely.

The dimensions of the abortuses in this group (in many instances, at least)
convey a very incorrect idea of the actual size of the conceptuses. This is due
to the fact that the main bulk of the specimen often is blood-clot and decidua.
Besides, chorionic vesicles which originally were recorded as having a certain
diameter, later were recorded in three dimensions, because they appeared ap-
proximately spherical. In still other cases, such as No. 71, the chorionic vesicle
is folded so extensively that accurate measurements are impossible. Then, too,
the increase in size of the vesicles, in consequence of maceration and infection, also
must be borne in mind in considering the true size of the normal specimen from
which they may have arisen. Although the large dimensions of some of the abor-
tuses suggest that their menstrual age is considerable, most of them really are rela-
tively young. The longest menstrual age recorded for any of those among the first
1,000 specimens is 280 days. However, an inspection of the specimen with this
age, as well as a microscopic examination of it, suggests that the menstrual his-
tory is not a reliable criterion, even if we assume, as suggested by Mall, that in
this instance the chorionic vesicle grew somewhat after the death of the embryo.
A comparison of the histologic picture in this specimen with that found in placente
retained only approximately as long, shows a very marked contrast indeed, largely
because of the absence of the inevitable age changes present in the latter.

B. TUBAL.

Any lingering doubts as to the correctness of the conclusion that a very large
percentage of the tubal specimens composed of villi only when received really
belong in the class of hydatiform degenerations were dispelled quickly by the
examination of this group. This is due largely to the fact that instead of isolated
or detached villi in more or less advanced stages of degeneration and embedded
completely in blood-clot, the preparations contain sections of whole chorionic
vesicles, sometimes entirely free from blood. Some of them were implanted almost
perfectly in the wall of the tube, and although many of them were folded
extremely and collapsed more or less, small areas of several were nevertheless

CHORION WITHOUT AMNION OR CYEMA. 67

implanted undisturbed. The villi in some of these implanted specimens were so
characteristic, and the whole picture so exquisite, that these specimens rightly
belong among the very finest instances of hydatiform degeneration found among
all specimens, both tubal and uterine.

Many of the tubal specimens are remarkable indeed, and this is true in particu-
lar of a case of double-ovum twin pregnancy received from Dr. Cecil Vest. In
this specimen the two chorionic vesicles, the intervillous spaces of which were
devoid of blood, lay in almost the same transverse diameter of the tube, and hence
had distended the latter considerably. Both were implanted quite well over the
entire area of contact, which included the whole perimeter of the tube. The
chorionic vesicles were flattened at the region of mutual contact, which divided
the tube somewhat unequally, as shown in figure 13, one of the original drawings.
Although the cyema and the amnion had long disintegrated completely, and
although the chorionic membrane itself is thin, covered by degenerate epithelium
and also disintegrating, the epithelium of the villi not only is well preserved, but
is accompanied by large masses of trophoblast and considerable syncytium.
Syncytial buds are found on the chorionic membrane also. The tubal mucosa is
largely, and the tubal wall partly, destroyed by the invading trophoblast. Only a
few small vestiges of the walls of the villous vessels remain, and the stroma of all
of the villi has undergone changes characteristic of hydatiform degeneration.
One villus also contains an epithelial cyst resulting from epithelial invagination
with subsequent isolation of the distal extremity, a process to be referred to again in
connection with the uterine specimens. Since most of these villi still are implanted
in the tube, there no longer can be any question as to the conditions under which
hydatiform changes in the stroma of the villi are inaugurated. As illustrated in
previous instances in which isolated and small groups of villi were still implanted,
the advent of degeneration of the stroma usually, if not always, occurs, in part at
least, before the villus is detached. Hence it is not merely a maceration change.

As shown in section in figure 14, some exceedingly fine hydatiform villous
trees were found among the specimens in this group. Scaffoldings or frameworks,
formed by the proliferating sycytium arising from the epithelium of the chorionic
membrane, were also seen. Since syncytial buds were found far out on prolifera-
tions of trophoblast which capped the villi, and also in the center of trophoblastic
nodules, the origin of the syncytium from the Langhans layer would seem to be
exceptionally well illustrated. In some cases a detached hydatiform villus was
fastened to two portions of the tube-wall. It is well to remember, however, that
these attachments may have been gained, and indeed probably were gained,
before the separation of the particular villus from the chorionic vesicle.

In most of the cases of tubal specimens belonging to this group and not show-
ing hydatiform change, the few isolated villi were so degenerate, or necrotic even,
that no diagnosis of any kind would seem to be justified. In these instances the
partly or wholly collapsed chorionic vesicle also was very degenerate and usually
folded extremely, the folds radiating more or less from the unfolded portion of the

68 STUDIES ON PATHOLOGIC OVA.

vesicle. Not rarely the apposed fibrous surfaces of these folds had been fused so
intimately that they simulated villi very closely indeed and could easily be mis-
taken for them. Both isolated villi and chorionic vesicles were almost invariably
embedded in blood-clot, and in some instances hyaline outlines only remained of
the villi. Viuilli with a dense, fibrous, non-vascular stroma were seen in a few
instances only, and they usually were found in the presence of severe infections.

Infiltrations of the tube-wall or of the clot were found in 20 (or 57.1 per
cent) of the specimens in which it was cut, as compared with 93.3 per cent of infil-
tration of the deciduz in the uterine series. Of the former, 65 per cent showed
slight and 35 per cent marked infiltration. In by far the majority of cases the
picture was that of a low-grade chronic, rather than of a severe acute infection.
Moreover, in several instances the infiltration was so slight that one possibly
might attribute it to the effect of the pregnancy itself. Chronic changes, especially
in the mucosa of the tube, were quite common, however.

Of the 37 cases in this group, 17, or 46 per cent, showed the presence of un-
doubted hydatiform degeneration. In one additional case its existence was doubt-
ful. Of these 17 cases of hydatiform degeneration, 12, or 70.6 per cent, came from
tubes which were infiltrated. In 4, or 23.5 per cent, of these cases, the infiltration
was marked, and in the rest it was slight. Although the incidence of infiltration
is high, it is decidedly lower than in the corresponding uterine group, in which
it was 100 per cent. The incidence of infiltration of the tube-wall or of the clot,
usually sufficiently pronounced to be indicative of infection, was 70.6 per cent,
as compared with 93.3 per cent in the corresponding uterine group. Nevertheless,
the incidence of hydatiform degeneration was somewhat higher in the tubal cases,
in which it was 46 per cent, as compared with the uterine, in which it was 40
per cent. Furthermore, the fact that many of these tubes showed the effects of
chronic rather than of acute changes seems to suggest that the mere presence
of an infection is not enough to cause the advent of hydatiform degeneration.
These changes would seem to result rather from the modifications produced in
the decidua and in the tube by the infectious process, and it is not unlikely that
the greater incidence of hydatiform degeneration in the tube may, as already sug-
gested, be due in part to the absence of a nidus comparable to the endometrium,
for it is not unlikely that even a somewhat fibrous decidua may offer better con-
ditions for implantation than a perfectly normal tube.

Some fibrous villi were found, and matting and gluing of the villi occasionally
were present. Degenerative changes in the nuclei of the syncytium, up to and
beyond the stage designated by Mall as ‘‘nuclear dust,” were noticed in several
specimens, which probably had been retained longer after isolation within the
blood-clot so as to inaugurate calcification. Contrary to what one might assume,
the length of the period of recurring hemorrhages is not a reliable guide to the
condition of the villi. Indeed, one can not say even that the longer the duration
the greater the degeneration and necrosis, for repeated hemorrhage apparently
may and does occur as a result of only partial detachment of the chorionic vesicle.

CHORION WITH AMNION. 69

However, if the latter is detached completely by the first hemorrhage, and if the
salpingectomy is not performed until weeks later, the detached villi necessarily will
be found necrotic, especially if they are embedded in a clot rather than bathed in
fresh blood. In one case, with a history of recurrent hemorrhages during a period
of 44 days, only a few necrotic, detached villi were found in the sections examined;
and in a second case in which the period of hemorrhages had lasted 18 days, none
but incipent changes were present in the vessels of the villi. The chorionic vesicle
was ruptured in this, as in a number of other cases, a fact which probably may
be attributable, in part, at least, to tubal peristalsis.

Group 3. CHORION WITH AMNION.

A. UTERINE.

As stated in Chapter III, fetal vesicles without an embryo, except a few
specimens filled completely with coagulum which might make the finding of an
embryonic remnant difficult or impossible, never came to the attention of His
(1882). Yet Miiller (1847) had spoken of moles with a cord only or with a cord
with a fringed or free end, and even of cords without a trace of an embryo. Such
abortuses, according to Miiller, usually are from the second and third months.
The singularity of his experience was regarded by His as noteworthy, and he
added that ‘‘one would a priorz expect that an embryo which has died in utero
would be dissolved completely at body temperature in the fluid in which it is
contained, as certainly would seem to be the case extra uterum.”’

Rokitansky (1842-1846) also believed that the embryo might disappear, for
he wrote:

“The entire fetus may be atrophic, the consequence of the cachectic state of the
mother; but those cases are of greater importance which result from disease of the
membranes, the placenta, and the cord; and, if occurring in the earliest period of embry-
onic life, may cause the embryo to disappear entirely, or so far as to leave but few traces.”

Seiler (1832) also reported finding an empty ovum, and Robin (1854) called
attention to a “rapport sur un cas de mort et de dissolution de l’embryon, par
suite a’hemorrhagie des membranes de |’ceuf,’’ observed by M. Boussi and pub-
lished by Robin in 1846. Hence it would seem that the experience of His was
exceptional, although the report of Robin would indicate that specimens devoid
of an embryo were regarded as rather rare.

It was emphasized by Miiller (1847) that the amnion often is preserved in
macerated ova. Not infrequently it is covered or even completely embedded in
coagulum, as stated by Rokitansky (1861). Since, as Miiller rightly emphasized,
the amnion may be firmly adherent to the chorion, it is not always possible to
tell by inspection of the gross specimen alone whether or not it is present. This
difficulty is due also to the fact that the internal surface of the chorion is often
exceedingly smooth and the chorion itself very thin. As stated further by Miiller,
the amnion may be torn, fused with the embryo or with the chorion, or be destroyed
completely. As illustrated by several specimens in the next group, it may also

70 STUDIES ON PATHOLOGIC OVA.

be detached completely from the chorion and bear only a small sessile embryo.
Whether or not the amnion can be recognized in the gross specimen depends not
alone upon age or upon whether it has fused with the chorion, but also upon the
condition of the other content of the chorionic vesicle. If the contained fluid
is a clear liquid of the character of the normal amniotic fluid, it is usually very
easy to detect the amnion, but if the fluid is exceedingly turbid from degeneration
products of the embryo and blood, the recognition of the amnion becomes much
more difficult, especially if the latter is partly disintegrated. This difficulty is
increased still further if the chorionic vesicle and the amnion are filled with a
flocculent magma or with a dense, blood-tinged coagulum. The ease of recognition
of the amnion depends also upon the degree of distension of the amnion itself.
Nevertheless, even if it be distended and splendidly preserved, but fused together
with the chorion, detection becomes possible only upon microscopic examination.
Since fusion of the fibrous layers of both chorion and amnion in these abortuses
is often so intimate that no line of demarcation can be detected between the two
membranes even by means of the microscope, the presence of the amniotic epithe-
lium remains the only criterion.

Very often, too, the amnion is not preserved in its entirety, but is represented
by tags of membrane only. Whenever it is practically coextensive with, but not
adherent to, the chorion it is easily recognized, because it is distended and also
because of the presence of a narrow extra-amniotic or peri-amniotic space con-
taining a clear fluid and some strands of “magma.’’ Rarely, the amnion has
collapsed completely and lies in folds forming small masses which it is not always
possible to distinguish from small cyemic or cordal remnants by inspection alone.

Since, as His (1882) stated, the amnion is folded closely around embryos
1 cm. in length, remains only a few millimeters distant when an embryonic length
of 15 mm. is reached, and is coextensive with the chorionic cavity at a length of
about 25 mm., the ease of its recognition depends also upon the age of the particular
specimen, although its relative size is subject to considerable variation. More-
over, in the case of very young conceptuses, a further difficulty in identification
by the unaided eye is introduced through the presence of a thin, distended yolk-sac.

Although the amnion is an exceedingly delicate membrane, it is undoubtedly
true, as stated by Miiller, that it may be preserved, for a considerable period after
the death of the embryo, in conceptuses of not altogether too early an age. Never-
theless, its destruction no doubt is much more rapid before it is fused with the
chorion. This is true particularly in case of intrachorionic infections which
quickly lead to disintegration of the amnion if they occur in the period before
fusion with the chorion has occurred; after this period, on the contrary, the amniotic
epithelium, unless degenerate, seems to act as a formidable barrier to the passage
of the infection into the chorionic membrane, in the same manner as does the
chorionic epithelium in cases of extramural infection. If the chorionic vesicle is
infected previous to the fusion of the fetal membranes, the infection can easily
enter the stroma of both the amniotic and chorionic membranes and destroy them,
especially the amnion, in a relatively short time, thus leaving villi only.

CHORION WITH AMNION. 7G

That a severe endometritis might not result in thickening by fibrous prolif-
eration of the fetal membranes is well illustrated by No. 922, in which both mem-
branes were extremely thin, especially as compared to their size, although the
infection of the endometrium was severe.

The resistance to infection, especially, perhaps, of young conceptuses, seems
very striking and recalls the experimental work of Maffuci (1894), but the ap-
parent failure of the tissues of young conceptuses to react toward infection as do
the tissues of the maternal organism is still more striking. However, this apparent
absence of defensive proliferative reactions on the part of embryonic tissues may
be due partly to the immaturity and the inadequately differentiated nature of
some of the tissues.

In two specimens included in this group (Nos. 65le and 682), Mall found
remnants of the yolk-sac and the cord respectively; and in No. 645 also an epithelium-
lined cavity in the chorionic membrane, probably allantoic in origin. The presence
of these structures did not, however, affect the classification of the respective
chorionic vesicles. Nevertheless, these observations are interesting because, like
other similar observations previously mentioned, they indicate that the yolk-sac and
a portion of the cord or the allantoic stalk may persist even after the destruction
of the amnion and embryo has become complete. That the embryo and amnion
disintegrate relatively easily was emphasized also by Mall (1908).

The amniotic conditions in some of the specimens of this group seem to imply
a growth of the chorionic vesicle after the death of both embryo and amnion.
Since the early amnion is related very intimately to the embryo, and since its
growth probably is very largely dependent upon the maintenance of the normal
composition of the amniotic fluid, a slightly continued growth of the chorion would
seem to be not improbable. But since the composition of the amniotic fluid must
change soon after the death of the embryo, it is probable that such an exceedingly
delicate and non-vascular structure as the amnion can not long survive. None
of these things is true, however, of the chorion, which often retains its connection
with its nutritive supply through the fastening villi, and hence is not seriously
affected at once by the degenerative changes within the contained vessels. In-
stances in which the amniotic vesicle is only a fraction—say one-fifth or even one-
eighth—as large as the chorionic vesicle, are not very rare, and others in which, at
the time of abortion, the relative proportions of these membranes are wholly unlike
the normal, are not uncommon. In one instance, for example (No. 1962), which
came under my direct observation, the dimensions of the chorionic vesicle were
61 by 44 by 34 mm., but the largest diameter of the slightly collapsed amnion was
only 19mm. In this case the peri-amniotic and intra-amniotic fluids were entirely
normal in gross appearance and contained no suspended matter whatever. The
embryo was detached but intact and was represented by a small irregular nodule
3.5 mm. long. From this it will be seen that although the amnion was relatively
too large for the embryo, it nevertheless was too small for the chorion. That the
small size of the amnion was not due to retraction seems to be indicated by the
absence of any thickening in its walls. Indeed, the latter were entirely transparent,

72 STUDIES ON PATHOLOGIC OVA.

so that the whole amniotic cavity could be carefully inspected without opening the
vesicle. In view of these facts, no other explanation for the abnormal proportions
between the two vesicles seems possible than the assumption of the growth of the
chorionic vesicle after the death of the embryo and amnion. It also is possible
that both embryo and amnion may have been retarded and the chorion accelerated
in its growth, but the great disproportion between the embryo and amnion makes
even this assumption, as sole cause of the disproportion, rather improbable.

It is not at all surprising that the idea that the fetal membranes can continue
to grow independently after the death of the embryo was once quite generally
held, for the disproportion between the size of the membranes and that of the
contained embryo is often very striking. Seiler (1832) also stated that the embryos
in aborted ova usually are too small. In most of the cases the disproportions may
be due largely or wholly to the existence of a genuine or of a pseudohydramnios,
but in others this apparently is not the case. The fact that the yolk-sac, too,
may be entirely too large in comparison with the embryonic disk also seems to
suggest that it, too, is somewhat independent in its development, and since the
amnion usually is non-vascular, it is not at all unlikely that its growth is not
inhibited immediately after the death of the embryo. Yet such growth probably
could not be long continued before the amnion is fused with the chorion, for with
death of the embryo and consequent change in composition of the amniotic fluid
further growth probably would become difficult. But after fusion of the amnion
with the chorion, the former obtains a more or less independent source of nutrition
and consequently is affected less by a change in composition of the amniotic fluid.
That the chorion may remain well implanted some time after the death of the
embryo can not be doubted, and although cessation of the fetal circulation probably
would seriously interfere with its proper nutrition, this interference would not neces-
sarily prevent some growth on its part. This would be true especially of early con-
ceptuses in which the circulation had not as yet been long established. However,
that the chorion can undergo considerable independent development is open to
grave doubts, and it may be recalled that it used to be held quite generally that the
placenta also grew after the death of the fetus. Schickele (1907) also doubted
the occurrence of growth of the chorion after the death of the embryo.

Most of the specimens in this, as those in the two previous groups, are small.
This becomes evident especially if it is recalled that, as stated in the previous
chapter, the main bulk of these abortuses often is due to blood-clot, decidua, and
even to the products of inflammation. This is splendidly illustrated by No. 77,
which measured 70 by 40 by 30 mm., although the contained chorionic vesicle
was only about 22 mm. large. Similar instances are Nos. 408 and 564.

The same pathologic conditions which were present in group 2 recur here
with somewhat the same frequency. In the case of No. 813 the chorionic cavity,
which measured 70 by 25 mm., had an extremely thickened wall, which, in con-
nection with other changes present, suggested changes produced by lues, although
the history carried the comment ‘No venereal disease.’’ This specimen contains

CHORION WITH AMNION. 73

evidences of the presence of an old inflammatory condition also, and in spite of
the small size of the conceptus has a menstrual age of 200 days. Since the coalesced
fetal membranes are extremely thick—indeed, the thickest of any specimens of
this size that came to my attention—one might assume that the chorionic vesicle
probably grew after the death of the embryo. That some growth occurred is not
at all impossible, but it does not seem likely that this growth was considerable.
The decidua is very necrotic and a considerable number of inflammatory areas are
present. Consequently, it seems more likely that the fibrosis of the membranes
and of some of the villi is the result of other things than retention only. As is
well known, extremely long retention of the dead conceptus has long been regarded
as very common inlues. This specimen is interesting also because if the fetus had
been present, no matter in how macerated or mummified a condition, the con-
ceptus, instead of falling into this group, would have been classified in group 7.
The same thing is true no doubt of other specimens also, and seems to suggest that
an attempted classification on an etiological basis may throw more light on the
genesis of the various morphological types here described, even if it would be
largely tentative.

Of the 44 specimens out of the first 1,200 accessions which fall into this group,
24, or 54.5 per cent, showed evidences of infiltration. But, since the decidua often
was not included in the sections, and generally also not in the respective gross
specimen, these percentages can not represent the true state of affairs. It is true
that the same thing may be said if the incidence of infection, as indicated by
infiltration, is determined upon the basis of those cases only in which the decidua
is present, for all cases in which the chorionic vesicle, unaccompanied by decidua,
contains evidences of infection are then excluded. Nevertheless, that the decidua
in all such specimens, if present, would be found infiltrated can scarcely be doubted,
for all these chorionic vesicles are small. If we take the 54.5 per cent of the
cases in which the decidua was present and not too degenerate, we find that 100
per cent of them showed infiltration. In 16 of these specimens, or 66.6 per cent,
the infiltration was marked, and in 8, or 33.3 per cent, it was slight. The sections
of one specimen showed no evidences of infiltration, and in a second specimen the
decidua was too degenerate. In 7 instances, Nos. 408, 468, 922, 77la, 814, 960a,
and 985, of those suggesting infection, its presence was noted in the history. One
of these was a case of peritonitis; another, that of an old gonorrhea with salpingitis;
two of leucorrhea, one since girlhood; two of endometritis; and one of gonorrhea
and syphilis. In three cases, Nos. 159, 813, and 976, the infiltration was severe
locally and may have been both luetic and pyogenic in character. In one of the
cases of probable lues the presence of this disease was suspected by the physician,
and although a Wasserman test was found negative, changes suggestive of lues
were present in the chorionic vesicle.

Fifteen of the cases, or 34 per cent, showed the presence of undoubted
hydatiform degeneration. In some of these cases the change apparently was
incipient, and in 3 cases not included in the 14 no definite conclusion could be

74 STUDIES ON PATHOLOGIC OVA.

reached; 2 of them, Nos. 651d and 652e, were received at the same time from
the same physician, Dr. G. C. MeCormick, Sparrows Point, Maryland. Other
similar specimens were also received from Dr. McCormick. In one of these
specimens, No. 65le, a remnant of the yolk-sac still was present. Since all these
specimens of hydatiform degeneration will be discussed separately, no further com-
ment is necessary here, except to add that in every case the microscopic findings
were confirmed by an examination, by means of the binocular microscope, of
portions or the entire gross specimen itself. The changes in the decidua will be
discussed in greater detail separately, and aside from what has already been stated,
it suffices here to say that, in addition to the other changes, fibrosis of the decidua
was noticed in a large percentage of the specimens.
B. TuBAL.

Of the 3 tubal specimens remaining in this group little can or need be said.
The walls of the tubes were infiltrated, the mucosa showed inflammatory changes,
and the clots were infected in two specimens. Nothing was left but a few non-
vascular, fibrous, and necrotic villi. In one specimen the chorionic membrane
was thickened somewhat and densely fibrous. The epithelium, syncytium, and
trophoblast of some villi also were degenerate, and the villi themselves somewhat
matted. Until the larger series of cases contained in the rest of the collection
and falling into this group can be studied, a comparison of these few with the
corresponding uterine group can be of no value.

Group 4. CHORIONIC VESICLES WITH NODULAR CYEMATA.

A. UTERINE.

Panum believed that certain small nodules, which he called monstruositates
amorphoides, resulted from pathologic changes in the original form of the embryos,
which changes converted them into more or less compact, rounded masses. He
further believed that even older chick embryos could become transformed into
amorphous masses and represented some of these; also, that these changes in form
arose during the life of the embryos and were to be explained by regression of the
organs and fusion with neighboring ones, as a result of disturbances in nutrition.

Giacomini (1889) stated that, although he could produce atrophic embryo
forms in the rabbit by the use of experimental methods similar to those described
by him in man, he did not regard these forms in man and in the rabbit as wholly
comparable.

His (1891) stated that he found 5 nodular embryos in 45 cases. This is an
incidence of 11.1 per cent, but Mall (1917°) found 51 nodular specimens among
396 pathologic, or a percentage of 12.9 per cent. In view of His’s small series, it
is striking that these percentages are so nearly alike, and it might seem that nodular
forms occur with considerable constancy.

Giacomini (1894) claimed to have studied the first nodular specimens micro-
scopically in 1893, and stated that the nodular forms have not been studied much
because they are more difficult to understand. Giacomini, who stated that atrophic
forms occur chiefly in the tubes and in peritoneal implantations, apparently used

aed

NODULAR CYEMATA. (o

the term nodular as synonymous with amorphous, for he characterized nodular
embryos as ‘‘specimens in which no organs are visible.’’ Furthermore, he believed
that nodular specimens are without a cord.

With the exception of a portion of a full-term specimen which we owe to the
generosity of Dr. Morris Slemons (No. 1682, fig. 15) and which was described
by him in 1917, none of those in this group measures over 5 mm. in length. Indeed
it is unlikely that any other specimen strictly belonging here exceeds a length of
4mm. Consequently, all embryos from among the first 1,000 accessions which
unquestionably are nodular in character have a maximum length of less than 4
mm. But this group is distinguished not only by the small size of the embryos,
for that might imply that they merely are very young. The latter is the case,
but their menstrual ages nevertheless are much greater than their size would
indicate; nor are they all in any sense immature, normally developed embryos
which merely have been universally and equally retarded in their growth. They
undoubtedly have been retarded, but this retardation has been decidedly unequal.
Moreover, they not only have been stopped in a very early stage of development,
but they had not reached that stage in a wholly normal way.

Although one would not suspect it from external appearances alone, this
group of the pathologic is by far the most interesting. Some of these specimens
show an astonishing simplicity in form and structure. Perhaps it was this fact
which caused His (1891) to doubt whether they really were remnants of the whole
embryo. His query is justified by the form and microscopic structure of many
of them, as is so well illustrated by Nos. 2288, 1369, and 651g, shown in figures
16, 17, 18.

Next to the small size of the cyemata in these abortuses, the disproportion
between their size and that of the chorionic vesicles in which they are contained
is what attracts one’s attention. This lack of correspondence is so great that the
chorionic vesicle may be not only 10 or 20, but even 50, 60, or 70 times as large
as the cyema; nor should the occurrence of such disproportions be surprising, for
if the eyema can wholly vanish it stands to reason that infinite disproportions
must occur as it becomes smaller and smaller in size, to finally disappear altogether.
For, even if the body of the cyema eventually were to disappear by solution, it
would still be true that its development could be checked at any time between
the appearance of the first rudiment and the completion of growth at the time
of birth. A similar disproportion in size not infrequently exists between the
amnion and cyema. The amnion not infrequently is entirely too large for the
embryo, but nevertheless much smaller than the chorion. Hence it seems that
the amnion, too, must have considerable power of independent growth in spite
of the absence of vessels in its walls. In some instances it was found to contain
blood-vessels, however, and in several cases large cyst-like dilatations were present,
some of which may have been the result of fusion of portions of the adjacent walls.

The body is by no means the most resistant of the strictly cyemic structures,
however. The umbilical vesicle or the cord, or indeed the allantoic stalk of the
amnion, may survive it. Such cases do not belong in this group, but since it is

76 STUDIES ON PATHOLOGIC OVA.

impossible to recognize the true nature of a small nodule upon gross inspection
alone, it is often impossible to make a correct classification except by careful
microscopic examination of the stained sections. Consequently, some of these
doubtful specimens are bound to get into the wrong category, for they must be
classified when received, and largely upon the basis of inspection by the unaided
eye and slight magnification with the hand-lens or the binocular microscope.
Hence, it was later found that 13 of the specimens placed in this group do not
belong here. None of these 13 specimens contained a cyema, and in the case of
2 others a decision was impossible, even upon microscopic examination of stained
sections of the specimens.

Although some of these small nodular cyemata measure but a few millimeters
in length, they nevertheless should show considerable differentiation had they
undergone normal development. This, however, is not the case, for some of them
are composed simply of undifferentiated mesenchyme, with or without a cavity,
and a slightly differentiated outer layer. None of them have even approximated
the differentiation of a normal specimen of the same size, wholly regardless of
age. In certain cases the rudiments of some of the organs can be recognized, but
others have undergone partial or complete dissociation, making recognition of
individual organs impossible. Usually a somewhat undifferentiated portion can
be recognized as belonging to the central nervous sustem; the ccelom is frequently
indicated, and some myotomes; liver and heart tissue can be detected. Neverthe-
less, most of them are small sessile nodules showing little differentiation. In some
instances these nodules are composed of one kind of tissue only, usually mesen-
chyme, wholly uncovered by what could be spoken of as either ectoderm or epider-
mis. In others, however, epidermis is present, and the specimens containing heart
and liver tissues are those which border upon the next group.

Although 4 or 5 mm. long, these nodules generally show less differentiation
than a normal specimen of the length of 2 or 2.5 mm. As is well known since the
description of a 4.5 mm. embryo by His, specimens of this length should show
considerable development of the central nervous system with differentiation into
its various main divisions. The eye and ear should have begun to form, and the
maxillary and mandibular processes should be present. The dorsal segmentation
also should be very evident, and the differentiation of the circulatory, urogenital,
and digestive systems should be considerable. That the cyemata in the nodular
group fall behind the stage of development reached by normal specimens of corre-
sponding length quickly becomes evident, even upon cursory examination. Not
rarely the amnion upon which these small nodules are sessile has become de-
tached from the chorion. In two eases the latter was absent altogether, but its
absence must undoubtedly be attributed to mechanical causes.

The histologic condition of some of these small specimens is well characterized
by the term “dissociation,” introduced by Mall. Phisalix (1890) also spoke of
the tissues of some of the embryos being “desagregre.”” As I understand this
term, it refers to the disorderly mingling of the tissues which belong to different
organs, so that the outlines of these organs no longer can be distinguished. This

NODULAR CYEMATA. 740 f

implies that such cyemata had once reached a higher stage of development, and
that they then underwent retrogressive changes. However, this does not neces-
sarily imply that the tissues composing the different organs have migrated out
actively, mingling with each other after the manner of cells in tissue cultures.
In the case of dissociation, as implied above, the disorganization of the cyema has
been a passive rather than an active process, occurring during and being incidental
to the process of maceration and disintegration. When the dissociation is at all
marked, sections of specimens, when examined microscopically, are rather uniform
cytologically.

The decidua was included in only 23, or 37.1 per cent, of the specimens belong-
ing in this group, and infiltrated in all of these; 69.5 per cent were listed as marked
infiltrations and 31.5 per cent as mild. Although these percentages are practically
the same as in the preceding group, the infiltration is milder. In the former group
severe infections predominated and abscess formation was relatively common.
In this group, on the contrary, the infection, as judged by the character of the
infiltration present in the decidua, was milder in all save a few cases which plainly
suggest mechanical interference with the gestation. This may be one reason why
the cyemata, though rudimentary, nevertheless are present. All of the cases of
infection, except these, could, I believe, be designated quite correctly by the term
chronic endometritis. I came to this conclusion largely from a study and com-
parison of those specimens in which the presence of a chronic endometritis had
been diagnosed clinically. Indeed, it is quite inconceivable that such an inhibition
of normal growth as existed in the nodular embryos could possibly occur in the
presence of a sudden severe infection. The latter could destroy only portions of a
normally developed cyema, for it would quickly die.

The homocytic nature of some of these specimens also impressed Giacomini
(1888), who spoke of a lymphoid transformation of the embryo. In 1894 Gia-
comini also spoke of a “uniformity of the elements which are like lymphoid cells
so that one might think at sight that one dealt with a lymph follicle.”’ Giacomini
found this lymphoid transformation both local and general and stated that the
elements which composed the organs in a case observed by him were transformed
into round cells. However, he did not regard this transformation as wholly
passive, for he, like His, believed in post-mortem cell proliferation. While empha-
sizing that a microscopic examination is indispensable for an understanding
of abortive forms of embryos, His (1891) added that we are not far wrong if we
speak of certain small accumulations of pycnotic cells found in abortive forms as
a “Brut von Wanderzellen.”’ Although His described dissociated specimens and
regarded an invasion of abortive forms by round cells as undoubted, he neverthe-
less stated that, although not all cells may be dead, one can not regard abortive
forms of embryos as living.

In later years Mall used the term dissociation in another sense, and appar-
ently also felt that more or less independent and continued development might
take place after the death of the embryo, much after the fashion of a tissue cul-
ture in vitro.

STUDIES ON PATHOLOGIC OVA.

~J
io a)

One of the most interesting of these nodular embryos is No. 788b, received
from Dr. Anfin Egdahl, shown in figure 19. This is one of double-ovum twins in
which the chorionic vesicles were wholly distinct. The smaller of the twins is
but 2 mm. long, with a greatest diameter of about the same dimension. The mate,
on the contrary, is relatively a normally formed, somewhat stunted fetus, with a
crown-rump length of 17 mm. The abortus containing the chorionic vesicle with
the little nodule was somewhat larger than the one containing the fetus, although
both chorionic vesicles were covered by approximately the same quantity of
decidua. The dimensions of the chorionic vesicle belonging to the stunted embryo
were 60 by 45 by 40 mm., and those of the one containing the nodular embryo
65 by 55 by 40 mm. The greater size of the latter was due probably to the greater
distension of the chorionic membranes, which are thinner and possess only poorly
developed villi. The other vesicle, on the contrary, shows very definite placental
development, although one of its dimensions actually was smaller than the cor-
responding dimension of the chorionic vesicle belonging to the small nodule.
Both specimens evidently were very decidedly macerated when aborted.

As shown in figure 20, this small nodule contains a large cavity lined by
epithelium, within which there is a large mass of cells, probably erythroblasts.
The exterior is covered by ectoderm, and the wall, which varies greatly in thick-
ness, is composed largely of mesenchyme containing blood-cells, particularly
erythroblasts, some of which lie in exceedingly thin-walled vessels. In the thickest
region a degenerate rudiment of the central nervous system and a mass of some-
what differentiated cells, which may be rudimentary myotomes, are indicated.
At one point on the periphery there is also a small, round knob, which looks like
the remnant of the cord, and at another point a small, denser, and more differen-
tiated protuberance which may be an early limb-bud. The caudal and cephalic
extremities can not be differentiated even with the microscope.

The other fetus, shown in figure 21, which is to be described in group 6, is a
relatively well-formed specimen of 27 somites. It is somewhat atrophic and the
head adheres to the chest, but in development it is far in advance of its nodular
mate. Since the latter measures only 2 mm., it is evident that the respective
chorionic vesicle is much too large, and since it is wholly inconceivable that this
small nodule could ever have reached, even approximately, the stage of develop-
ment represented by its mate, it would seem that the accompanying chorionic
vesicle must have continued to grow some time after the death of the small embryo
which never reached any special differentiation. Furthermore, since there is no
very evident difference in the degree of the degeneration of the chorionic vesicles,
it is not unlikely that the one containing the minute nodule survived almost as
long as the other. The villi and membranes of both are non-vascular and the
stroma clear, suggesting hydatiform degeneration.

The decidua is well preserved but infiltrated. However, a severe infection
could not cause a gradual inhibition of growth. A mild process, on the other
hand, can conceivably exert a general inhibition over a considerable period of
time, and thus possibly lead to all the changes, remarkable though they be, which

NODULAR CYEMATA. 79

are found in these specimens. However, it is necessary to bear in mind that such
errors in development as are here described need not necessarily be the product
of the environment in which the conceptus finds itself, but may in fact be changes
or abnormalities which resulted from defects inherent in the spermatozoa, in the
unfertilized ovum, or in the fertilized ovum even. However, in order not to
interrupt the description of this group, a consideration of this question is post-
poned until all the groups have been considered.

Although the nodular embryos themselves are so very abnormal in form and
structure, there was very little indeed in the outward form and gross appearance
of the corresponding chorionic vesicles to prompt special comment at the time
of the first description. Sometimes it was noted that the villi were unusually
long and thread-like, or that they were absent over considerable areas; but nothing
else attracted attention as a rule. Some of the chorionic vesicles are translucent,
but this is true also of many in other groups. Upon closer examination, however,
the presence of numerous ‘‘appendici durate’’ can be determined in many specimens,
and upon magnification of about 11 diameters with the binocular it was found that
a very surprising number of chorionic vesicles included in this group showed the
presence of a very marked and wholly typical hydatiform degeneration of the
vili. In many instances the appearance of these villi is an exceptionally artistic
one. The characteristic vesicles can be seen in all degrees of development, even
when they were too small to have attracted attention upon inspection of the
gross specimen with the unaided eye. Indeed, it was not until my attention was
directed especially to the possible meaning of certain forms of degeneration so
frequently seen and usually referred to as ‘‘hyaline”’ or “‘mucoid”’ in the protocols,
that the relationship between the two was established. These degenerations, and
especially the absence of vessels in most of the specimens examined, had also
attracted my attention earlier in the year, while engaged with a study of Hofbauer
cells in abortuses.

Under microscopic examination it was found that the most constant and
interesting change in'the stroma of the villi in this group of nodular cyemata is
the occurrence of hydatiform degeneration which is present in 29 per cent, includ-
ing two doubtful cases. In order not to confuse matters, it is necessary to add
that the term is being used in its literal meaning, entirely aside from any clini-
cal implications. As a rule, the stroma of these villi tends to become clear or is
clear, or is even replaced completely by a clear fluid. This change is usuaily
designated as a hyaline or mucoid degeneration in the protocols, and sometimes
also as fibrous degeneration. As emphasized by Mall, the use of the word ‘“‘mu-
coid’’ does not imply that the material is mucous, although Mall noticed that it
frequently stains blue with hematoxylin. As is well known, however, true mucin
nevertheless has been found in small amounts in the fluid contained in the vesicles
of hydatiform moles.

In the early stages of hydatiform degeneration the stroma of the villi may
still contain remnants of blood-vessels, but usually these are completely absent.
In these or somewhat later stages the nuclei are pycnotic and may be quite well

80 STUDIES ON PATHOLOGIC OVA.

preserved long after cell outlines can no longer be recognized. Later they become
very irregular and finally disappear completely, leaving only a glassy substance
which fills the otherwise well-preserved epithelial shell. The latter usually stands
out in marked contrast to the degenerated stroma. The epithelium not only is
well preserved, but the syncytium is often absent and the trophoblast shows
signs of marked activity. Usually it is increased in amount and ‘appendici
durate”’ are relatively common.

During the process of this degeneration even the very young villi become
swollen, so that their unusual caliber, and also the great variation in size of dif-
ferent portions of the same villus and of different villi at once attract attention.
The walls are often smooth, buds are absent, and the villi are sparse though long.

Since none of the specimens of this group had been designated specifically as
hydatiform moles, and especially since an inspection of the gross specimens did
not confirm the existence of what currently passes for hydatiform or cystic de-
generation of the chorion, the contrast between the microscopic and gross pictures
was at first puzzling. However, under low magnification with the binoculars
(about 4 to 20 times), every one of the specimens which was found to show the
characteristic changes in the villi under higher magnification was also found to
contain villi or groups of villi, the form of which was typical of hydatiform moles.
In some instances it was necessary to remove a small group of villi and carefully
separate them by teasing before the typical gross changes could be observed. In
other instances in which a severe infection apparently had supervened upon the
hydatiform degeneration, or in which the villi were glued for other reasons, no
good preparations could be made by this means. However, it was found that an
examination of the cut surfaces of the chorionic vesicles, especially when embedded
in celloidin, under similar magnification would always easily reveal the presence
of this degeneration. In one specimen, for example, which was obtained by hys-
terectomy, the chorionic vesicle was still embedded within the uterus and the
implantation cavity extended around the greater portion of its periphery. The
microscopic examination of a section from this uterus showed the presence of the
characteristic degenerations, and upon examination numerous groups of typical
vesicles could be seen lying in the cut surface of the densely matted villi. In
view of these facts, I can no longer entertain any serious doubt as to the nature
of these changes. It stands to reason, however, that the very incipient histologic
changes undoubtedly could not be verified by gross examination, for neither the
structure, the optical properties, nor the form of the villi in such specimens would
have changed sufficiently from the normal to become evident under low magni-
fication.

B. TuBAL.

Since two of the four specimens originally placed in this group belong in groups
1 and 2 respectively, only two remain here. The tube of one was not included in
the sections, but the walls of the other tube were infiltrated and the villi exemplified
a fine case of hydatiform degeneration in its early stages. Some of them which
were still implanted evidently were being detached by the hemorrhage, and both

CYLINDRICAL CYEMATA. 81

the fragment of the embryo and the torn chorionic vesicle were being extruded
from the tube, for they lay some distance distal to the site of implantation. No
remnant of a cyema, definitely recognizable as such, remained in No. 342, but a
small conical mound of cells, located at the distal extremity of the cord, neverthe-
less may have been a remnant of it. The few sections of a portion of the cyema
found in No. 874 suggest that the development of this specimen apparently had
not been changed greatly.

Group 5. CYLINDRICAL CYEMATA.

A. UTERINE.

The cylindrical specimens forming this group comprised 7.5 per cent of the
first 1,200 accessions or 18.9 per cent of the pathologic. Hence the frequency of
the cylindrical cyemata is far greater than that of the nodular, although it must
be remembered that the group of cylindrical contains some specimens which are
not embryos at all, but merely remnants of the cord.

As already stated, this group is not separated from the preceding or succeeding
group by any definite division. Transition forms could easily be found. However,
since the limb-buds begin to appear at a length from 4 to 5 mm., it is evident that
the specimens in this group also must be small, for as soon as limb-buds have
fairly developed an age is reached in which stunting becomes evident and the
specimen then falls into the next group. The inference is not that stunting becomes
evident in the extremities only, but that it is quite easy to recognize it here with
the unaided eye. Not all the specimens of this group are less than 4 or 5 mm.
in length, however; for even when they are exceedingly atrophic or when miniature
limb-buds are present, it is sometimes impossible to distinguish the cephalic from
the caudal extremity in the presence of an atrophic cephalic region. Consequently,
some specimens rightfully belonging in the next group remain among the cylin-
drical; and since the classification is determined very largely by gross appearances,
portions of the umbilical cord also are frequently classed in this group. On many
of these not a remnant of the cyema can be found, even upon microscopic examina-
tion. But since the absence of remnants of the body of the cyema may be due
solely to mechanical interference, it follows that some specimens of wholly normal
conceptuses become included in this group.

The largest cyema is No. 710, which has a length of 13 mm. The next is
No. 288a, which is 11 mm. long. Both of these fetuses are macerated and the
organs are greatly dissociated. Had they been better preserved, stunting could
have been recognized and they would undoubtedly have been classed in the next
group. These considerations, and the further fact that extremities were present,
seem to suggest that the causes which contribute to the death of these cyemata
apparently do not wholly prevent the development of the extremities or retard
their growth appreciably beyond the retardation felt in other parts of the body.
This conclusion does not imply, however, that the changes produced in the ex-
ternal form and structure of cylindrical cyemata may not have been pronounced.
A reference to figures 22 to 28 will show that this is the case. To what extent

82 STUDIES ON PATHOLOGIC OVA.

such changes in form as there represented may be the result of maceration alone
will be considered in a later chapter.

That lysis of the entire conceptus, even including cyemata belonging in this
group, may become complete is indicated by such a specimen as No. 2197, shown
in figure 29. The cyema of this specimen not only has become markedly modified
in external form, but upon microscopic examination is composed of nothing but a
web containing remnants of nuclei, the whole forming a perfectly homogeneous
mass. In view of this fact, the external form of this specimen really was remark-
ably preserved.

An interesting specimen belonging in this group is No. 587, represented in
figures 30 and 31. While studying this specimen attention was attracted by the
small cavity in the wall of the main chorionic vesicle, which contained the cylindri-
cal eyema. Upon further examination it became evident that this smaller cavity
was surrounded by a degenerate chorionic membrane which was not a diverticulum
of the main vesicle, and that in fact we were dealing with a twin pregnancy similar
to No. 1840, to be referred to later. The larger of these two chorionic vesicles,
in the villi of which the smaller is contained, measures 58 by 38 by 29 mm., but
the smaller measured only 9 by 6.5 mm. in the fixed condition. The latter con-
tained no trace of the cyema at the time of examination, and the very degenerate
condition of the chorionic wall, and especially of the amnion, makes it decidedly
unlikely that the small though not necessarily rudimentary cyema which it may
have contained earlier in its history was lost before it came to my attention. The
photograph of the portion of this abortus shown in figure 31 suggests, and an
examination of the gross specimen confirms, the surmise that the smaller vesicle
was located at the point indicated by the leader in figure 30, the photograph origi-
nally taken of the specimen, which shows the presence of the cylindrical cyema.
Since a degenerate decidua still separates the villi of the respective vesicles in the
area of most intimate contact, it is evident that the larger vesicle must have cap-
tured the smaller, as it were, by surrounding it. It thus probably hastened its
strangulation and death, which may, however, have been fully assured by the
existence of an inflammatory decidua. The only content of the smaller chorionic
vesicle is coagulum (magma) with some faint traces of the amnion in the form of
coagulum. The villi of the smaller specimen are almost completely degenerate,
and the stroma of the villi of the larger, which is non-vascular, has undergone
mucoid degeneration.

From what has been said, it is evident that we have here not an evidence of
superfetation but double-ovum twins, one of which survived for a considerable
period beyond the time of death of the other. Moreover, although both ova may
have begun their uterine development equally well, the smaller must soon have
been throttled or surrounded by the larger. Or the smaller, perchance, may have
become implanted in a more unfavorable portion of the decidua and therefore
have succumbed earlier. Since it is wholly unlikely that any portion of the eyema
was preserved in the smaller vesicle, this specimen becomes classified in group 3
or 2, accordingly as we do or do not recognize a trace of the amnion in the fine line
of coagulum which extends along the interior of the chorionic membrane. The

CYLINDRICAL CYEMATA. 83

larger, on the other hand, falls into this group. It may be recalled that a similar
instance of twins falling into different groups was mentioned in the discussion of
group 4, and two more instances will be mentioned in the succeeding group.

The disproportion between the size of the cyemata and that of the chorionic
vesicle, though pronounced, is not so great in this as in the preceding group. What
was said there regarding the relation of the dimensions of the abortus to those of
the chorionic vesicle applies here also. As all the specimens of this group contain
eyemata varying from 2.5 to 13 mm., it is evident that the amnion must have
developed considerably in some of them. Subsequent retrogression of the cyema
or hydramnios, then, left the amnion proportionately too large as compared with
the cyema, for (so far as I am able to see) there is little retrogression in the
size of the amnion, even when that of the cyema is considerable or total. The
amnion generally was relatively too large, although rarely it was folded about the
eyema very intimately. When large it frequently was greatly folded, with adjacent
folds adherent to each other, and in one instance a small vesicle so constituted
could easily have been mistaken for a yolk-sac. The amnion in this case had under-
gone decided structural changes.

The number of chorionic vesicles wholly encased in blood or in blood and
decidua was relatively small. The layer of blood which was interposed between
the decidua and chorion varied from 1 to 10 or more millimeters in thickness.
Whether the condition of this blood is of any value in determining the time that has
elapsed since the detachment of the conceptus and its expulsion from the uterus,
I am at present not able to say. The contrast between the states of preservation
of the blood and the contained conceptus naturally was sharp in many cases.
Often the blood was preserved well, even in instances in which the stroma of the
chorionic vesicle was very degenerate. The conceptuses in this group have pro-
gressed somewhat in development beyond those in the preceding group, both as to
external form and the internal organs, but in general the changes noted in the
cyema and its appendages, or in the chorion or amnion, or even in the decidua,
did not differ in kind from the changes noted in the previous groups. However,
since the specimens in this group are somewhat older, it would seem to follow that
the duration of these changes must have been somewhat longer. Nevertheless,
the rate of change must have been much slower. Hence a longer duration does not
necessarily imply the production of a more pronounced change. It is also not
impossible that, with increasing maturity, the tissues may become more capable
of resistance and thus affect the rate of change produced by a given cause of
constant intensity.

As was true of some of the nodular cyemata, so also several of the cylindrical
were sessile, being attached directly to the amnion, sometimes by their caudal
extremities, apparently without the instrumentality of an umbilical cord. But, asa
rule, a short umbilical cord is present, even if not wholly normal in form, structure,
or relations. Indeed, the cord quite frequently is distended greatly, and micro-
scopic examination usually shows that the condition of the umbilical vessels, even
when present, is not normal. In many instances they are absent altogether and

84 STUDIES ON PATHOLOGIC OVA.

the tissues of the cord, like those of the eyema itself, have undergone great changes.
Rarefaction of the mesenchyme and cavity formations are very common. Portions
of the allantoic stalk were frequently preserved, although sometimes in a form so
greatly modified as to make their recognition doubtful.

The yolk-sac also frequently was present, though changed so very much that
recognition of it could not always be certain. It frequently had a greatly thick-
ened, fibrous wall which was fused completely with the chorion.

The decidua was present in only 31.2 per cent of the 48 specimens in this
group and was infiltrated in 80 per cent of these, excluding 2 doubtful cases. This
infiltration was marked in 58.3 per cent and slight in 41.7 per cent of the speci-
mens. Abscess formation was relatively rare. The infiltration also was less
marked than in the preceding groups, especially in the first three, and cases sug-
gesting interference were rare, although several were noted.

Hydatiform degeneration was present in 38.5 per cent, with a probable addi-
tional 6.3 per cent. Infiltration of the decidua was present in only 3 or 4 of
these specimens, but not much reliance can be placed upon this small number.

Since the decidua was absent in 6 of the 10 cases in which it was definitely
stated in the history that there was no venereal disease or evidence of it, it is
impossible to throw any further light on these specimens; for, as already stated,
infiltration does not occur in the chorionic vesicle until the latter is extremely
degenerate. Hence, in the absence of the decidua, one can only draw inferences
as to its condition from changes in structure of the chorionic vesicle. Since hydati-
form degeneration was present in 4 of these 6 cases, the inference that the decidua
of these, if present, would also have shown infiltration is justified. In 4 of the 9
cases in which the absence of venereal disease was reported, and in which the
decidua was present, the latter undoubtedly was infiltrated. This infiltration was
mild in 2 cases and severe in 2. In one of these instances in which it was especially
emphasized that the patient stated that she had never had leucorrhea, and in
another in which it was stated that leucorrhea was present but that the patient
had never had venereal disease, the infiltration was very marked. Further con-
firmation of the clinical diagnosis was found in three cases of lues and in one of
endometritis.

In two cases of this group in which the alleged cause of the abortion was
respectively a blow in the abdomen and a fall, severe infection and even abscess
formation were present; and in a third, in which an accident was blamed, hydati-
form degeneration was recognized, and hence endometritis probably existed. In
a fourth case in which abortifacients were supposed to be responsible for the
termination of pregnancy, a mild endometritis and changes suggestive of lues were
present; and in a fifth instance, in which the abortion was attributed to quinine,
the specimen plainly suggested that it came from an induced abortion. The sixth
case, which was said to be spontaneous, had the microscopic appearance of an
old retained specimen.

The structural changes noticed in the decidua, in the chorionic vesicle, and
in the amnion, did not differ in kind from those seen in previous groups. Calcifica-

STUNTED CYEMATA. 85

tion was present in small areas in only a few specimens, which had the characteris-
tics of old retentions. Coagulation necrosis, or so-called “infarct” formation, so
common in the next group, was rare here; but fibrosis and cytolysis of the decidua
were aS common in this as in the other groups. Rarely, the decidua was so
fibrous as to simulate the degenerate chorionic membrane very closely.

B. TuBAL.

Since 2 of the 5 specimens originally placed in this group were found to contain
no embryo, only 3 remain. Of these, No. 697 contains a very small nodule of
embryonic tissue, the appearance and structure of which suggest that it very
probably belongs in the preceding group of nodular cyemata. However, since the
sections of this nodule do not form a complete series, one can not be absolutely
certain of this. Another specimen, No. 346, also belongs to the group of nodular
cyemata, for neither the caudal nor the cephalic end can be distinguished with the
naked eye. This leaves only one specimen, No. 729, in the group of cylindrical
tubal eyemata. Since the only remnant of the cyema itself found in this specimen
is a small group of cells on the end of the umbilical cord, the existence of a cylindri-
cal eyema in this case can be a matter of surmise only, for the condition of the cord
has not been found to be a reliable criterion for distinguishing between the previous
existence of a nodular or a cylindrical eyema. Moreover, since Mall thought it
probable that the cyema was normal, this specimen can be retained in this group
only if we desire to classify portions of the cords as cylindrical cyemata. From
these considerations it follows that the group of cylindrical cyemata is left without
a true representative from among the tubal pregnancies found in the first 1,200
accessions. This does not mean, however, that cylindrical forms can not or do
not occur among tubal pregnancies.

Infiltration of the tube was present in 3 of the 5 specimens originally placed
in this group in which it was included in the sections. Hydatiform degeneration
was found in 3 specimens, but the tubes of 2 of these have not been examined
microscopically. One of these 3 cases was a very fine example of hydatiform degen-
eration. A second was very clearly an early case, but too few villi were included in
the third to make a definite decision possible.

Group 6. STUNTED CYEMATA.
A. UTERINE.

It was emphasized in Chapter III that stunting, in a physiological sense, can
not be limited to cyemata in any particular group; but since the difficulty of
recognition increases with the decrease in the size of the specimen, it is only rarely
that stunting can be detected by inspection alone in cyemata below the stage of
limb formation. Furthermore, if the limbs themselves are to be used as a criterion,
limb formation must not merely have begun, but must have proceeded far enough,
and normal growth must have been inhibited sufficiently to effect a change in
form clearly recognizable with the unaided eye. This, however, does not imply
that the effect or the recognition of stunting is confined to the imb-buds. Rarely,
it is noticeable quite early in the entire caudal or cephalic extremities, or even in

86 STUDIES ON PATHOLOGIC OVA.

the head itself. This is illustrated by Nos. 2173 and 2233, shown in figures 32. 33,
and 34. As is evident from these illustrations, the last cyema borders very closely
upon the cylindrical in form.

The word ‘‘stunting,” as here used, also implies a disproportion in normal
form, not merely a reduction in size of the entire specimen. Hence none of the
stunted specimens are merely undersized, normally proportioned fetuses; for
although an equal, universal retardation in growth is conceivable, it is unlikely
that such a thing really occurs. Such an assumption would imply that all organs
and tissues are equally resistant to interference with the blood or nutritive supply,
or to toxins or other influences. It may seem strange, indeed, that no fetuses
beyond the length of 20 mm. are included in this group. This fact would seem to
imply either that the causes productive of stunting which may be operative up to
this time cease to be effective later, or that portions of the cyema have become so
resistant that they can no longer become affected in such a way as to produce
stunting. It has long been recognized, however, that stunting of an organism can
occur as the result of various influences at any time throughout its period of
growth in post-natal life. Hence an assumed increase in resistance of the tissues
sufficient to withstand all influences affecting such young fetuses as those here
concerned can hardly be offered in explanation for the absence of stunted fetuses
among those more than 20 mm. long. Nor can one assume that the causes opera-
tive until this stage is reached, or at some particular time before this stage of
development has been reached, always come into abeyance when a fetal length of
20 mm. has been attained.

If, on the other hand, we assume that the various tissues or organs are affected
only during a transitional sensitive period, perhaps in certain formative stages,
we are in conflict with the facts; for upon this assumption we should be able to
group the stunted fetuses by the effects produced upon their tissues, organs, or
systems of organs even, but this does not seem possible. Nor are the organs
affected serially in the order of their development; for, entirely aside from certain
things to be discussed in a subsequent chapter, some changes present within these
stunted cyemata are quite universal and comparable, no matter at what stage com-
plete inhibition of further development has occurred. Moreover, what impresses
one most is not the striking modifications of external form, pronounced as these
at times are, but the marked structural changes within the organs themselves.
To what extent these changes may be attributed to maceration with consequent
disintegration, or to dissociated or uncorrelated growth, and whether or not true
stunting can be simulated by the effects of maceration alone, will be considered
more fully in a succeeding chapter. The explanation for the absence of stunted
fetuses beyond a length of 20 mm. is not only the failure to recognize stunting
in them, but that maceration changes often become so pronounced that they
mask the changes which have been characterized as stunting. When such is the
case the specimen is placed in the next group.

Although gradual death of cyemata or of entire conceptuses in consequence
of interference with the source of nutrition has not as yet been established, such a
phenomenon is not only possible but highly probable. Death of the cyema or of the

STUNTED CYEMATA. 87

entire conceptus in consequence of chronic endometritis, or in consequence of
other chronic changes, or even perhaps in consequence of toxins, seems likely,
however. Hence, although the cyemic circulation be maintained in the main,
lack of nutrition nevertheless might occur locally and show itself first in outlying
eyemic parts, as in the tips of the extremities or in the facial relief, in which places
slight changes in form easily become evident. However, the fact that the present
group of stunted cyemata is limited to a comparatively early age very seriously
contradicts such an assumption, and the well-known fact that ill-nourished,
stunted, viable infants are born with certain constitutional diseases would seem
to imply the occurrence of stunted forms in all groups of pathologie eyemata and
perbaps also the occurrence of stunted chorionic vesicles as well.

Excellent examples of stunting are No. 2473, a 13 mm. fetus, and No. 675,
a 10 mm. fetus, represented in gross and in median section in figures 35 and 36.
The head of No. 675 has been so deformed as to look like that of a frog, and the
whole outward form has become rounded. Since this specimen was retained long
after death, marked maceration changes had occurred, and it is a question to
what extent the changes in form here shown can be attributed to maceration
alone. The limb-buds in these stunted embryos soon become more rounded,
smoother, and shorter, or even somewhat clubbed, losing all details of form as
illustrated by No. 2233, represented in figure 34. The head loses its natural curves
and becomes atrophic or reduced; the maxilla is often beaked and the mandible
depressed greatly, thus producing gaping. In some cases the mandibular region
may fuse with the chest, as represented in figure 37 (No. 788a), and with increase
in flexure the eyes may come to lie practically opposite the liver. The caudal
region looks stubbed or flattened, the caudal process being less evident. Both
local and diffuse epidermal thickenings are not uncommon, and sloughing of the
epidermis is frequently preceded by bleb formation. The umbilical cord is often
distended, especially near its attachment to the abdominal wall, and at this point
decided bleb formation is common.

Miiller (1847) also noticed instances of bleb formation on the umbilical cord
and stated that Albinus and Sandifort called them “processus infundibuliformis’’
when they occurred at the point of attachment of the cord to the abdomen.
Miiller further stated that Ruysch described a cord so full of ‘‘hydatids” that
he spoke of it as being a ‘‘concatenatio vesiculorum.”’

The internal organs of the specimens become distended, lose their clear out-
lines (as illustrated by No. 983a, shown in figure 38), blood-cells seem to pass out
from the vessels in all directions, the normal cell relations are disturbed, cytolysis
occurs, nuclei of various cell types become pyenotic and circular in outline, until
all areas of the specimen seem to be composed of one type of cell only. This is
due to the fact that all nuclei have assumed a similar form and appearance, but
in more advanced stages these nuclei, too, disappear and only a homogeneous
necrotic mass remains to represent the fetal tissues.

The length of the fetuses in this group varies from 4.5 to 20 mm., and the
menstrual age from 30 to 127 days. But neither the former nor the latter can be
regarded as more than roughly indicative of their true age; for, although 30 days is

88 STUDIES ON PATHOLOGIC OVA.

approximately the correct age for an embryo of 4.5 mm. long, 127 days is entirely too
old for one with a length of 20mm. Specimens of approximately the same alleged
menstrual age are found to differ widely in length, and fetuses of approximately
the same length may differ greatly in menstrual age. Nor can these discrepancies
be attributed to the unreliable character of the menstrual histories, for specimens
with identical menstrual ages often vary considerably in size. This is illustrated
splendidly in cases of double-ovum twins. In one of these instances (No. 1840)
the fetuses have a length of 15.9 and 38.5 mm. The larger of these twins is
normal in every respect and macerated but slightly, but the smaller is greatly
macerated and stunted. Since both these specimens are of identical age, they
illustrate how misleading even a reliable menstrual history may be.

In a second case, that of No. 788 a, 6, one is a nodular cyema described under
group 4 and the other a stunted specimen included in this group. The organs of
the latter or larger fetus, though dissociated, are all well outlined, and the vertebral
disks especially well defined, in spite of the fact that it must have been dead a
considerable period of time. The umbilical vessels are degenerate and the limbs
atrophic. The menstrual history unfortunately is not known, or it would be pos-
sible to make some conjecture at least as to the probable length of retention in
utero after fetal death. However, if we assume that the large fetus is smaller than
it should be, as undoubtedly is the case, and take its anatomical age to be that of
a length of 20 mm., it would have a normal menstrual age of about 7 weeks. The
small nodule (788b), which was only 2 mm. long, does not show a development
corresponding to that of a normal specimen of this length, and on the basis of
size would have an age of less than one month. This, however, does not necessarily
imply that it died at that time. Indeed, the relative preservation of the tissues
of the two fetuses makes this very unlikely, although we must remember that such
a small nodule as 788b could probably be preserved for a long time in such a large
quantity of sterile amniotic fluid as that in which it was contained.

Another instance which shows the misleading character of the menstrual
histories, even when known, is that of No. 1914, a case in which a large mass of
hydatiform cysts accompanied a normal, living fetus of 7 months. A still better
illustration is the case of Slemons (1917*), in which a nodular mass, apparently a
twin, accompanied a normal viable fetus. Since it is not improbable that such
specimens as some of these have been taken to establish the occurrence of super-
fetation, they will be mentioned in a later chapter.

In the other three cases of twins included in this group the cyemata fall into
the same instead of into different groups. In two instances (Nos. 207 a, 6, and
341 a, b) this may be due to the fact that they are single-ovum twins, even if they
are not of the same size. In the third case (No. 330 a, b), although from double
ova, both fetuses were of the same length. The appearance of these conceptuses
indicates that they were retained for a considerable period after fetal death, and
the history confirms this. Syphilis was suspected in this case and bleeding began
six weeks before the abortion occurred. Furthermore, the sizes of these fetuses, as
well as the condition of the tissues themselves, clearly indicate that both had
probably been dead some time before hemorrhage began.

STUNTED CYEMATA. 89

Whether or not twin cyemata fall into the same group of the pathologie
very evidently depends upon whether they have been subjected to identical
influences. That the exact conditions under which they develop may easily vary is
evident, and that they may be variously affected previous to implantation is also
possible. Nor does the occurrence of twins which fall into different groups neces-
sarily imply that the processes responsible for the physical differences were neces-
sarily or essentially different from those which are responsible for the disproportion
in size of normal, full-term twins. It may be simply a matter of degree. In the
case of 788 a,b, for example, the decidue were infiltrated, but not to the same degree.

A few of the specimens in this group are of particular interest because of the
great disproportion that exists between the size of the fetus and that of the chori-
onic vesicle. In No. 135, for example, in which the fetus was 9 mm. long, the
dimensions of the chorionic vesicle were 105 by 65 by 65mm. Since the villi practi-
cally were absent and the surrounding layer of decidua was very thin, the above
dimensions practically are those of the amnion also, for it had fused with the
chorion. Although the wall of this abortus is composed of these three layers, it
nevertheless is almost papyraceous. Microscopic examination shows it to be
decidedly degenerate and to contain many leucocytes. The amnion, too, is very
degenerate, although its epithelium is still present. Even if mechanical distension
were the chief factor in the enlargement of this vesicle, it is unlikely that it was
solely responsible for the disproportion between the chorionic vesicle and the size
of the fetus. Part of this disproportion is attributable to some recession in the
size of the embryo, and more to the failure of the latter to develop normally. To
what extent the chorionic vesicle grew after the death of the fetus must remain
a matter of conjecture; but in view of its very degenerate character, it seems
unlikely that it could have grown much. The absence of the menstrual history
unfortunately leaves us without data that might be of some assistance in arriv-
ing at a conclusion regarding this matter. Although the organs of this fetus have
lost their clear definition, and although dissociation and maceration are marked,
yet on the whole it is preserved better than one would expect from an examination
of the chorionic vesicle. Though epidermal blebs are present, not all the epidermis
has sloughed. Indeed, in some places the superficial layer has formed marked
local thickenings which now and then are so definitely circumscribed that they
could probably be designated as warts or papille. Similar, although more diffuse,
epidermal thickenings are found also in No. 201, a fetus of 20mm. The same phe-
nomenon apparently was observed by Rokitansky (1861), who spoke of papilla-
like growths of the epidermis in a fetus.

The most interesting thing seen in the stroma of the villi of this group was the
presence of epithelial vesicles at various depths from the surface in No. 276.
Although many of these vesicles which are not well preserved could easily be con-
fused with degenerating vessels, in the case of others this is impossible, because
their relations to the epithelium can be established easily. The epithelial lining
of many of them is fairly well preserved, and in some instances the vesicles can

90 STUDIES ON PATHOLOGIC OVA.

be shown to communicate with the surface by means of an epithelial invagination.
Most of them, however, lie isolated in the stroma.

In looking about for a possible explanation for the presence of these vesicles,
it became evident that they had their origin in epithelial invaginations. The
opposite walls of these invaginations apparently become fused proximally and
their strands of epithelium then connect the vesicles with the surface. Further
examination of the sections of the villi in this specimen shows that instead of
having a fairly regular border, the epithelium is decidedly crenated or folded, quite
in contrast with the usual condition of things. Hence it would seem that prolifera-
tion of the epithelium has resulted in foldings into the stroma of the villus, instead
of accumulations on the surface. The presence of proliferation of the epithelium
in this case seems to lend further confirmation to the presence of hydatiform
degeneration.

Out of 73 specimens originally placed in this group, 16 were found to belong
elsewhere, and 23 were added, making 80, from which 1 must be subtracted be-
cause of twins in one chorionic vesicle. The decidua was present in 45.5 per cent
and infiltrated in 88.9 per cent of these, excluding 2 in which infiltration was
doubtful. This infiltration was marked, even up to abscess formation, in 56.2 per
cent of the specimens and slight in the rest. Hydatiform degeneration was present
in 24 per eent, excluding 5 in which its occurrence was probable. Infiltration
was present in 90 per cent of the specimens in which the decidua was included
and not too necrotic for examination.

In attempting to correlate the clinical histories with the objective examina-
tion, it was found that the clinical diagnosis of infection is confirmed in 4 out of 5
cases. In the fifth case the decidua was not included, but since hydatiform de-
generation was present, infiltration can be assumed and the clinical diagnosis of
infection be regarded as confirmed in this case also. Of the 6 cases which were
reported as showing no evidence of venereal disease, the decidua was not included
in one and was too degenerate to assist in the diagnosis in a second case. Of the
remaining 4 cases, 3 show the presence of a severe and 1 of a mild infiltration.

Although mechanical interference with the course of the gestation seldom was
reported in this series, several specimens were noted in which abortion probably
was induced. In one case in which the termination of pregnancy was attributed
to fright, the decidua, unfortunately, was not included; but since the chorionic
vesicle showed hydatiform degeneration, the decidua undoubtedly was infiltrated.
In a second case in which fright was given as the alleged cause, Mall noted that
the decidua was “markedly inflamed.” In a third case, in which the termination
of pregnancy was attributed to work, death of the conceptus must have occurred
long before. As stated in the introduction, I fully realize that this contradiction
between the alleged cause and the findings may be apparent only, for it is entirely
possible that exertion, psychical disturbances, or an accident may precipitate an
abortion which is more or less imminent at the time.

The structural changes encountered in this group do not differ in kind from
those present in previous groups. However, the incidence of infiltration of the

STUNTED CYEMATA. 91

decidua was more than twice as high as in group 5, and was divided equally between
the severe and the slight cases. The presence of hydatiform degeneration was
somewhat more common, although the percentage of these cases in which the
decidua was included was somewhat lower. In 90 per cent of the latter the
decidua was infiltrated.

Although they frequently were not especially noted, ‘‘appendici durate”’
seemed somewhat commoner in specimens of this than in those of the previous
groups.

B. TuBAL.

The small number of stunted tubal cyemata among the first 1,200 accessions
is especially interesting, because the average length of these specimens is only
half as great as the average length of those in the corresponding uterine group.
After certain specimens had been excluded only 6 stunted tubal specimens re-
mained. The corresponding uterine group, on the other hand, contained 61
specimens. But in spite of the small number of stunted embryos in the tubal
group, the significance of the fact, nevertheless, is clear. It is only very rarely
that a tubal pregnancy lives beyond the earliest stages of development, while
in the uterus, on the contrary, this is relatively very common. This conclusion is
not based upon a comparison of the relative number of specimens found in these
two groups of uterine and tubal pregnancies alone, nor upon the comparative
size of the specimens, but upon the respective percentages that the total number
of specimens in the uterine and tubal groups of the stunted form among the entire
series of specimens in the pathologie division which were examined. Although
the stunted embryos form 19 per cent of the total number of uterine specimens,
stunted embryos form only 5.7 per cent of the total number of the tubal speci-
mens. This marked difference scarcely can be explained in any other way than
as suggested above.

Although 11 specimens originally were placed in this group of stunted tubal
eyemata, 5 were found to fall elsewhere. One (No. 338c) was a uterine specimen,
being accompanied by considerable decidua. Two others (Nos. 196 and 934)
belong in group 4. The former has a length of only 3 mm., and the latter, although
6 mm. long, was recorded as having no extremities, and described as looking
like a grain of wheat. Moreover, the anatomy, especially of No. 934, is that of a
nodular rather than of a stunted cyema. One specimen (No. 992) belongs in
group 3, and another (No. 881) can not properly be classed as stunted, in view of
the fact that it was only 3 mm. long.

Of the 6 remaining specimens, 5 lay in tubes the walls of which were infil-
trated intensely in the case of 2, and but slightly in 3 specimens. In the sixth case
too little of the tube was included to serve as an adequate basis for examination.

Hydatiform degeneration undoubtedly is present in 4 of these 6 cases, or in
66.6 per cent. In another specimen (No. 477) some villi seem to show incipient
changes indicative of hydatiform degeneration, but since marked maceration
changes also are present, one can not be certain of this case. Too few villi were

92 STUDIES ON PATHOLOGIC OVA.

included with the remaining specimen to make a positive diagnosis justifiable,
but the structure of those present did not suggest a hydatiform change.

The cyemata were all macerated and some were fragmented. In two speci-
mens (Nos. 838 and 882), Mall stated that limb-buds were not present. Since
the respective specimens were 6 and 8 mm. in length, it is evident that they should
have been present, and their absence must be attributed either to inhibition of
growth or to disintegration. In the absence of a complete series of sections, this
point unfortunately can not be decided. It was possible to recognize outlines of
various organs in one specimen only, and since most of the specimens were very
young, they had a structure comparable to that of the nodular and cylindrical,
rather than of the stunted uterine group. Maceration and dissociation were
very marked, as a rule.

Group 7. FETUS COMPRESSUS.

A. UTERINE.

The term fetus compressus was used by Mall in a much more general sense
than usual. It has been customary to restrict this term almost wholly to one
twin which died early and became softened and compressed by the living, well-
developed companion. Instances of a single fetus similar to a true fetus com-
pressus are recorded in the literature, however. Strahl and Henneberg (1902),
for example, stated that they found such a specimen, although the presence of
abnormal pressure exerted directly upon it by the uterus could not be established.
Hohlweg (1903) also implied that Kiistner thought that cases of fetus compressi
could occur in single pregnancies, and I am quite certain that I am representing
Mall correctly when I say that his observations were to the effect that quite typi-
cal fetus compressi occur not rarely in single pregnancies in the presence of abun-
dant amniotic fluid. Although Schickele (1907) regarded macerated forms from
the second months as rare, His (1891) emphasized that the softness of aborted
forms easily results in abnormal folds and flexures, and Waldstein (1913) stated
that von Winckel found deformities of the extremities extremely common in tubal
embryos.

As previously intimated, this group is a very inclusive one. In some respects
it really is a group of left-overs not characterized by maceration alone. Specimens
in any of the preceding four groups may be, and indeed they nearly all are macer-
ated. However, since many of those in the normal division also are macerated,
the presence of maceration can not be regarded as distinguishing any group.
Differences in the degree of maceration may and do exist; but since maceration
becomes evident externally much more quickly in older fetuses, gross appearances
often are a very unreliable guide for the determination of the degree of maceration.
One thing, however, is true of all specimens in this group, except such as are com-
posed of material from curettage, and that is that maceration often is present
even in specimens composed solely of fragments of wholly normal embryos or
fetuses.

Some of the specimens are macerated and swollen and others are shriveled
and mummified. The latter Mall distinguished as fetus compressi. The use of
this term does not imply, however, that they have necessarily been subjected to

FETUS COMPRESSUS. 93

pressure, although such usage is at variance with the historical meaning and the
usual application of the term. Moreover, very macerated fetuses, the forms of
which have not been very materially changed, are not included. These things
must be borne in mind in order to avoid misunderstanding. It is true that some
of the so-called fetus compressi look as though they had been subjected to pres-
sure, and in some instances, even of single pregnancy, there is no doubt whatever
about this. Other fetuses look compressed, although a quantity of liquor
amnii seemingly sufficient to prevent direct uterine pressure still surrounds
them. The head is collapsed from side to side, the hands and feet are flattened,
and the trunk also is collapsed. In most of these cases the appearance of com-
pression is apparent only, and probably resulted from the softening and collapse
of the tissues consequent upon maceration and dehydration under aseptic condi-
tions. The skull sometimes is practically devoid of brain tissue and decidedly
flattened, all the tissues have become degenerate and necrotic, and those of adjoin-
ing parts have often fused more or less, so as to obliterate the natural boundaries.

If, as stated, mummification sometimes may occur while the fetus is contained
in a large amount of fluid, it would seem to have to result from chemical changes
in the amniotic fluid. Indeed, it not only is conceivable but inevitable that the
composition of the amniotic fluid is changed soon after the death of the fetus.
As is well known, death of the membranes makes them more permeable, and
hence offers greater facility for the absorption of fluid, thus leading to the greater
concentration of the liquor amnii, with consequent dehydration of the fetus. It
is evident, however, that absorption must be slow, for otherwise the amniotic
fluid, although rarely large in quantity, would soon be absorbed and the fetus would
subsequently be subjected to direct pressure from the uterine wall. Sometimes,
indeed, such is the case, and then the macerated or mummified fetus may be rolled
up firmly into a ball, as illustrated by Nos. 921 and 1041, shown in figures 39
and 40. In the last case the decidua, placenta, and membranes were wrapped
tightly around the fetus, the whole constituting a firm, rounded mass.

It is difficult to characterize this group as a whole, because it contains such
diverse things as portions of a cord, material from curettage, embryonic fragments
of mutilated normal specimens, as well as macerated fetuses falling among the
groups of the nodular, cylindrical, stunted, or normal. Figures 41 to 50 inclusive
afford some idea of the diversity existing among the specimens of this group.
This diversity is extreme, not only in form, size, and age, but also in the matter
of preservation. No. 1245 (fig. 41) is a good illustration of fragments. Whether
they came from specimens which developed under normal or pathologic conditions
it was not always possible to state, even upon microscopic examination, for the
decidua was not always included. No. 1806 (fig. 43), though classed in this
group, was originally described as normal in form and could be placed among
grade 3 of the normal division, for some specimens in this grade show even
greater maceration.

Specimen No. 65la (fig. 58) and to a lesser degree No. 1301 (fig. 44) illustrate
beginning changes in form which, though slight, are quite characteristic of many
of the specimens of this group, and when present always exclude them from the

94 STUDIES ON PATHOLOGIC OVA.

division of normals which it should be recalled contains specimens with develop-
mental anomalies. Besides being macerated, both these specimens are charac-
terized by a peculiar sag or droop of the extremities present on the left side only
in No. 1301. This is noticeable first in the arms. These distortions, though
slight in these fetuses, are shown in a much more advanced stage in No. 1931
(fig. 51), a considerably older fetus which had been retained longer after death.
Although this specimen is only 35 mm. long, it unquestionably is anatomically
older than No. 1301, which measured 50 mm., a difference largely attributable to
the presence of marked maceration. Nos. 1925, 1239, and 1515, shown in figures
48, 49, and 50, are merely older and still more macerated and deformed specimens,
No. 1515 being in the early stages of dismemberment.

In order to illustrate the fact that many specimens in this group of the patho-
logic division are quite comparable to some of those in grade 3 of the normal
division, I have selected a number of roughly corresponding stages and placed
the photographs parallel, for the sake of comparison, in figures 53 to 63 inclusive.
Anyone familiar with the material here concerned will know that photographs are
not adequate evidence for illustrating the classification of a specimen; but even an
inspection suggests, and the microscopic examination supports, the statement
that there is no sharp dividing-line between some of the specimens in the third
grade of the normal division and others in this group of the pathologic division.
Specimens found in the pathologie division often are better preserved in every
way and wholly without developmental anomalies, while some specimens in the
normal division are macerated and have pronounced anomalies. Indeed, this
is what one should expect, for whatever the cause or causes of the changes repre-
sented by specimens which have been classified in group 7, these changes must
have a beginning. However, these beginnings undoubtedly would not be clearly
recognizable by the unaided eye or perhaps not even with the aid of the micro-
scope. Consequently, the same person may classify one specimen differently from
succeeding similar ones, merely because various aspects or characteristics of it
impress themselves more upon him at different times. These cases apparently
would constitute a border-line group as far as the morphological changes are
concerned.

The lengths of the specimens in this group included among the first 1200
accessions range from 1 to 210 mm., and those of all those in the entire collection
from 1 to 286 mm. This range is due partly to the fact that the idea of the group
developed as the material accumulated. Moreover, a number of different indi-
viduals were engaged at widely different times in the classification of the material.
For these and for other reasons this group also has been reviewed in accordance
with the wishes of Mall. It is interesting that the reclassification has affected
almost solely the swollen, macerated specimens and only a few so-called fetus
compressi. Hence it is evident that there is practical unanimity of opinion
among those concerned as to the gross characteristics of a fetus compressus, even
if some of these were placed in the normal division. This unanimity of opinion
is explained largely by the fact that the term is applied almost wholly to larger

FETUS COMPRESSUS. 95

fetuses. The smaller specimens disintegrate completely before the stage of mummi-
fication is reached, while in older fetuses the skin, the cartilages, even when still
wholly unossified, and the ligaments, as well as the fibrous tissue as a whole, resist
disintegration more. The smaller specimens soon become so soft that they liter-
ally fall to pieces before they can become dehydrated and mummified. This is
illustrated splendidly by Nos. 379 and 717. It is recorded by Mall that the former
fell to pieces upon being handled, and of No. 717 it was stated that a slight amount
of shaking would cause the entire specimen to disintegrate.

All the small specimens found in this group undoubtedly could be classed
among the other groups of the pathologic or normal divisions, for they have been
placed in this group merely because they are macerated more completely than the
specimens usually classed in the normal divisions. The exclusion of these would
limit this group to fetuses beyond the length of 25 to 30mm. At this time a stage
of development much more resistant to disintegration is reached, and the changes
in form regarded as peculiar to this group can then arise. As recorded by Mall,
small specimens macerated so thoroughly that they almost fall apart, even when
handled in fluid, sometimes have undergone very slight changes in form and could
be placed in the other groups.

It is an old story that the outward appearances of the specimens in this group
often are grotesque. This is true particularly of the so-called fetus compressi.
These strange appearances are very largely attributable to the distorted extremi-
ties, the gaping mouth, and the pointed features. There is no limit to this dis-
tortion, as No. 1925, shown in figure 48, illustrates. Sometimes the greatly and
abnormally bent extremities become adherent, as in case of the legs of No. 1859,
shown in figure 64, and in other instances, as in Nos. 1860 and 627, bleb forma-
tion of considerable size occurs and later the skin may slough or become rolled
up and fused so as to form marked welts. Sometimes it may hang in shreds from
the fingers and toes or from other parts of the body. These strands of sloughed
epidermis may then simulate amniotic bands, and when accumulated about the
fingers and toes may hide them completely, giving the appearance of a mittened
hand. However, epidermal thickenings, local or diffuse in character, are sometimes
present, as shown in figure 65. These give one the impression that they result
from epithelial proliferation rather than merely from fusion of accidentally apposed
cells. Fusion of adjacent surfaces of the digits is also common, and occasionally
the upper or lower extremities may be united quite firmly in places through fused
areas of epidermis, as is illustrated by No. 1859.

The contortions of the extremities are due not merely to the relaxation of the
joints and consequent abnormal mobility, but result also from a bending of the
cartilaginous shafts of the bones, even up to or beyond an angle of 90°. The smaller
cartilages of the hands and feet may lose their distinct outlines, and under con-
ditions of advanced maceration may fuse somewhat with one another. Rarely,
areas of coagulation necrosis are also seen at the distal extremities of the terminal
phalanges. Degeneration of the precartilage and cartilage opposite the ossified
areas may also be complete, thus presenting the appearances of bones with

96 STUDIES ON PATHOLOGIC OVA.

extremely enlarged cartilaginous extremities. Although no measurements were
taken and no exact comparisons made with normal specimens, it is not unlikely
that the extremities of some of these developing cartilages are somewhat enlarged,
although not necessarily as the result of growth.

A survey of a considerable number of these fetuses shows that the distortion
of the extremities, and indeed also those of the trunk, are purely haphazard.
They seem to follow no law, except perhaps that of gravity, but often are in diverse
directions in the different extremities of the same fetus. Whether or not the initial
sag is in the same general direction in all the extremities depends considerably
upon the age of the fetus. Below a length of 25 to 30 mm. the limbs still extend
stiffly from the body, and in these specimens both pairs of the extremities usually
droop, as represented by Nos. 65la and 1710, shown in figures 58 and 66. After
the extremities assume their normally flexed posture the abnormal positions
which they then take become far more diverse. This is well illustrated by Nos.
1751 and 1931, shown in figures 67 to 68. Similar distortions are present also in the
digits, as shown in figure 69. Nor do fetuses of corresponding ages necessarily
show the same degree of distortion, or possess distortions in the same general
direction, even if they show approximately the same degree of maceration. How-
ever, the degree of distortion nevertheless is roughly correlated to the degree of
maceration and the duration of the post-mortem intrauterine retention. Fresh
and unmacerated specimens never show the characteristic distortion.

The haphazard character of these distortions seems to indicate quite con-
clusively that they did not result from contractures arising during the gradual
death of the fetus. To be sure, the loss of tone accompanying gradual death or
following it must finally become extreme, but since the specific gravity of the
amniotic fluid, even when altered, is so little if any less than that of the fetus itself,
it is difficult indeed to see just why marked changes in the position, even if not
in the form, especially of the extremities, can occur without the instrumentality
of external pressures.

The umbilical cord of many of these specimens, especially of the fetus com-
pressi, is abnormally and often extremely twisted and thin. As is well known,
this twisting is unlike that normally present, though it seems always an accentua-
tion of it. I have never seen it occur in a direction opposite to that normally
present in a given cord. That most of the extreme torsion of the cord is purely
a post-mortem and not an intra-vitam phenomenon is indicated by the fact that
these extremely tortuous cords always can be untwisted easily up to the point of
the customary twisting. The excessive tortuosity also varies more in degree, and a
single turn does not always involve the same length of cord in fetuses of approxi-
mately the same age, even when about the same amount of twisting is present in the
entire cord. Indeed, a single turn may occupy different lengths of the cord of the
same fetus, and it is not uncommon to find only a portion of the cord twisted and
the rest of it wholly untwisted, a fact which probably can be attributed in part to
the varying degree of maceration.

While observing the nature of this twisting more closely, it became evident
to me that it probably was not produced intra-vitam, but rather resulted from post-

FETUS COMPRESSUS. 97

mortem passive fetal movements. Had this twisting occurred during the life of
the fetus and been the cause of its death, one would expect to find some adjustment
to it on the part of the growing tissues. Such an adjustment, however, does not
exist. The tissues are necessarily displaced mechanically, but no adhesions be-
tween adjacent turns were observed save such as easily could be attributed to
maceration changes. Since no external forces save those of the uterine contrac-
tions can reach a dead fetus, it seems that this twisting, even if not always present,
must result from uterine contractions. Since these contractions in many instances
may have been more pronounced and prolonged than usual until abortion finally
occurred, the greater twisting present in these cords could easily be explained in
this way. If we assume that ina given uterus this peristalsis occurs in a uniform
direction, and that in a small percentage of uteri it may occur in an opposite
direction, torsion in different directions could be accounted for. I realize fully that
direct observations upon the living uterus are necessary to make this supposition
valid, but in any case it is difficult to conceive of any other agent than uterine
contractions that possibly could rotate a dead fetus. It also is evident that this
rotation probably would have to occur very largely before marked absorption of
the amniotic fluid had occurred and entirely before the fetus became embedded
in a mass of coagulum, such as is illustrated by No. 261, a specimen with a very
tortuous cord.

Although it is conceivable that coils of the cord could cause the amputation
of an extremity, this probably could occur only in comparatively early stages of
development and hardly so late in fetal life as implied in figure 187 of Broman
(1911). It is also noteworthy that, although coils of the cord about the extremi-
ties were frequently found, not a single instance of partial amputation or of macer-
ated amputated extremities is contained among over 2,000 specimens in the
Carnegie Collection.

It does not seem unlikely that the location of the placenta in utero may be
instrumental in determining both the amount and the extent of torsion, but until
more is known regarding uterine peristalsis all this remains merely a matter of
surmise. The tubal and ovarian specimens unfortunately do not throw much
light on this question, for they usually are very young and too macerated or dam-
aged. Only one of all the tubal specimens, among both normal and pathologic,
contained in the Carnegie Collection, had a cord sufficiently long to be of any
value in this matter, and in this specimen definite torsion was present. This
fact does not prove, however, that peristalsis is not a factor in torsion, for tubal
peristalsis could produce similar results.

Not infrequently the cords show marked bleb formation, as illustrated in
Nos. 1475 and 1523 (figs. 54 and 70), but bleb formation, which is present else-
where in many of these specimens, is not peculiar to the group, for it is common
also in younger cords and fetuses, and may also be localized elsewhere on the
body, as in Nos. 1523 and 2261 (figs. 71 and 72). In other instances, as in No.
590, the entire cord is decidedly swollen, or alternately swollen and constricted,
and in still others it is practically without a turn and wholly without knots,
although long and filamentous. Coils of the cord about various portions of the

98 STUDIES ON PATHOLOGIC OVA.

fetus seem to be very common in this group of macerated fetuses, and probably
can be attributed to the same factors which produce the twisting. This, how-
ever, does not imply that the structural changes in these cords are different from
those present in other groups or that torsion was the cause of fetal death. It is
largely, if not wholly, a matter of degree of difference, and this degree is deter-
mined very largely by the age of the fetus, the length of retention, and perhaps
by the irritability of the uterus. The greater tortuosity of these, as compared
with normal cords, as stated above, can be explained in the same way.

The decidua was present in 45.3 per cent of the 53 specimens remaining in
this group. It was infiltrated in 17, or 70.8 per cent. The infiltration was marked
in 29.1 and slight in 70.9 per cent. Although decidual infiltration was present in
88.9 per cent of all cases in group 6 in which the decidua was included, this was
the case in only 70.8 per cent of the cases in group 7. The percentage in this
group is lower than in any other save group 5, suggesting that the infiltration is
not entirely dependent upon the length of retention in utero after fetal death.

Hydatiform degeneration could be recognized in only 10.9 per cent of the
eases. The decidua was infiltrated in the 2 cases in which it was present, but
since the number of cases concerned is so small, no special importance can be
attached to this fact did it not accord with the findings in the other groups. All
chorionic vesicles in which this change was noted were in relatively early stages of
development.

In trying to correlate the clinical histories of the uterine specimens with the
objective examination, nothing especially interesting was revealed. The corre-
spondence between the two is no better in this than in the other groups. In
general it may be said, however, that the specimens of this group have been
retained longer after death, and that this fact is supported by the great frequency of
the presence of calcification and coagulation necroses, or so-called ‘“infarct” for-
mation, which was relatively common in the placenta. The greater maceration
of the specimens clearly is evident from inspection alone. Subchorial hemato-
mata were present in several specimens, and chorionic cysts were noticed in one.
Changes reported by Welch (1888) as hyaline metamorphosis of the placenta were
present in a fair percentage, especially in the older and longer retained placente,
and will be considered further in a subsequent chapter.

The frequency of divergence from the normal form on the part of the fetuses
in abortuses also impressed Granville (1834), and Panum (1860) stated that he found
the frequency of double malformations among museum collections to be twice that
in actual life. Panum found cyclopia in 16 of 618 human deformities, 25 among 143
simple deformities in sheep, and 37 in 91 deformed fetuses. He also believed that
various deformities of the jaws in certain quadrupeds probably are due to intra-
uterine pressure. He came to this conclusion, it seems, because of his experience
while incubating eggs. However, according to Panum, spina bifida occurs much
more commonly in man than in animals, and he expressed the opinion that the
study of comparative teratology may contain the open sesame for a comprehen-
sion of many, even if not of all, abnormalities.

FETUS COMPRESSUS. 99

His (1882, 1891) found 22 per cent of 62 aborted specimens pathologic, and
J. Kollman (1889) stated that it is generally known that one-half of all abortuses
are pathologic. Giacomini (1894) claimed that as many as 80 per cent of all abortuses
are abnormal, and Phisalix (1890) declared that normal specimens are rare among
abortuses; but Mall (1917°) found only 39.6 per cent pathologic conceptuses among
the first 1,000 accessions in the Carnegie Embryological Collection. However,
cyemata classed as pathologic formed only 26.8 per cent among these accessions,
the rest being composed merely of vesicles classed as pathologic.

Because of the presence of certain changes in the chorionic vesicle, Crosti
(1896) concluded that the cause of abortion is primary in the vesicles. Giacomini
(1894) declared, however, that it was impossible to decide whether the change
noticed by him was primary or secondary, and emphasized particularly that
the decidua should be studied because of its great influence on early develop-
ment. His (1882) concluded that all abortive forms are primary, but later (1891)
decided in favor of a secondary origin, a view held also by Mall (1917°). One
would hardly seem justified in assuming, however, that all eyemic abnormalities
or malformations are secondary in origin, for such an assumption would completely
ignore or deny the existence of true hereditary anomalies such as polydactyly,
hyperphalangism, ete. However, the mere possibility of the occurrence of anoma-
lies of secondary origin makes the identification of these extremely desirable and
important, although some of the achievements of experimental teratology seem to
suggest that it may remain impossible to distinguish between anomalies which are
primary and those which are secondary in origin.

Since the extension of our knowledge of the subject of human embryology
necessarily has been from the older to the younger, it was inevitable that atten-
tion should be first directed especially to placental changes. Hence the literature
upon the subject of placental pathology is extensive, while that upon the pathology
of the cyema and chorion and also upon the decidua is small or even fragmentary.
_ However, now that our knowledge of extremely early conceptuses is being extended
much more rapidly, we soon shall be able to recognize the normal with more
certainty, which alone will be a great step in advance.

Giacomini (1894) stated that many observers have noticed that abnormal
changes arise in the membranes as soon as the development of the embryo is
interfered with. He described these changes as the formation of vesicle-like
structures in relation to both amnion and chorion.

A very interesting question is that of the invasion of the conceptus by cells
of maternal origin. As long as the chorionic epithelium remains intact I never
have seen any evidence of it, not even in the stroma of villi which were directly
in contact with an abscess. These observations also are in accord with those of
Nattan-Larrier and Brindeau (1905). Nor have I ever seen anything suggesting
direct invasion of the fetal circulation by cells from the maternal circulation.
When one recalls the intimate relationship of the two circulations, it is surprising
that such an invasion does not occur, for it would seem to be especially easy, but
it is only after the chorionic epithelium is destroyed that maternal leucocytes seem

100 STUDIES ON PATHOLOGIC OVA.

to gain access to the stroma of the villi. Indeed, the only invasion of the stroma
which I have ever seen in preserved villi is due to invaginations of and extensions
from the Langhans layer, for the presence of large numbers of Hofbauer cells hardly
can be regarded as an invasion, even if these cells themselves are not fixed in
position.

Besides lytie and degenerate changes due to retention or putrefaction, the
occurrence of Hofbauer cells and other appearances suggesting tissue-cultures,
thickening of the amnion and chorion was also frequently present. Amniotic
villi and fusion of adjacent amniotic folds were seen quite frequently, but the
rarest of all changes encountered were such strange appearances on the surface
of the amnion as represented in figures 73 and 74. As indicated by the accom-
panying scales, both of these chorionic vesicles were small. Upon microscopic
examination of these amnions it was seen that the hummocky appearance was
due to local thickenings formed by increase in the connective tissue of the amnion.
The amniotic epithelium was never found to be involved in these thickenings, and
since only two specimens were observed I am at a loss for an explanation of this
peculiar condition.

If the condition of the uterine mucosa at the time of implantation of the
impregnated ovum may show variations in structure at all comparable to those
frequently seen in the decidue# accompanying abortuses, then it is easily conceiva-
ble that the fate of the conceptus may be determined by the structure of the
implantation site. Not infrequently a small area of the decidua surrounding an
abortus shows all the transitions represented in figures 75 to 77. Figure 75 shows
the fine, large, clear, polygonal decidual cells slightly infiltrated and hence rather
homogeneous in appearance. Figure 76 shows considerable infiltration and autol-
ysis, but there are marked changes in the cell-form which remind one of the con-
dition of the post-menstrual endometrium, as described by Hitschmann and Adler
(1908). The decidual cells in these areas seem to take on the character of fibro-
blasts, and this characteristic is brought out still more in figure 77. In some
specimens the decidua is composed of a decidedly fibrous mass, which reminds one
at once of connective tissue. I do not know how far these changes of fibrosis may
be present before implantation occurs or before placental differentiation has
taken place; but if at all pronounced they can scarcely fail to affect profoundly
the nutrition and growth of the conceptus.

It also may be urged that fibrosis of the decidua is but an effect of the death
and retention of the conceptus rather than of pathologic conditions pre-existent
to the advent of pregnancy, but the many instances in which the decidua is very
degenerate and also infiltrated would seem to argue against such an assumption.
Besides, many deciduee surrounding specimens retained for a considerable period
of time do not show comparable changes, and (as Orloff, Iwanoff, and L. Fraenkel
have shown) restoration of the mucosa actually may begin before the conceptus is
expelled from the uterus. In the few cases I have seen of partial regeneration of
the mucosa, the decidua was not markedly fibrous. Infiltration of the decidua
may possibly arise after the death of a conceptus, but that it is frequently present

FETUS COMPRESSUS. 101

long before this time would seem to be indicated by the fact that it does not appar-
ently bear any definite relation to the duration of the retention. Moreover, the
existence of endometritis is in itself evidence of the latter fact.

B. TuBAt.

Although one of the six tubal specimens among the first 1,200 accessions
was 80 mm. long, the others were relatively small. One (No. 535) was com-
posed of a fragment including only the upper two-thirds of the trunk. The
length of No. 685 apparently was estimated from the development shown in the
few cross-sections, which showed it to have been macerated and disintegrated.
Two specimens were 20 and 22.5 mm. long, respectively, and the other measured
8mm. Hence it is evident that the average length of the uterine specimens fall-
ing in group 7 was very much greater, for their length was almost always above
25 mm., instead of below, as is the case with tubal specimens. This difference
between the two groups is attributable, no doubt, verly largely to the different
conditions under which development proceeds. As already indicated, mummi-
fication probably is impossible below a length of 3 mm. Consequently, such
specimens in tubal cases could occur only if the surgeon failed to intervene and if
both the patient and the fetus survived the rupture of the tube and its sequele.
Moreover, in the case from which the 80 mm. tubal fetus was obtained, the speci-
men would never have lived to reach such a length had the patient come into
experienced hands earlier, as is evident from the history. Furthermore, since
Mall recorded that all the changes in this fetus ‘‘can be accounted for by the
death of the fetus, which must have occurred at the time of rupture of the tube,”
it is clear that he regarded this specimen simply as a macerated normal fetus.
The placenta which accompanied this fetus is of particular interest, because it
illustrates an atypical form of hydatiform degeneration not previously seen.
Although cross-sections of many of the villi are enlarged and have the clear stro-
mata characteristic of certain stages of hydatiform degeneration, many of them
contain vessels which, though relatively small in caliber, also contain blood-cells.
Giant cells are quite common, and epithelial vesicles also are present in the stroma
of the villi.

Upon examining the placenta with the unaided eye, and also under low magni-
fication with the binocular, the villi again appear quite atypical and different
from any examined so far. Some of them are very fine, long, and filamentous,
but others, which are far more numerous, lack the typical hydatids, though
bulbous. Many of them look blunt and swollen and possess enlargements lacking
the tapering ends so well shown in cases typical of hydatiform degeneration. This
modification in form of the villi may have resulted from the crowding to which they
were subjected by the surrounding tube.

Regarding No. 478, which is 22.5.mm. long, Mall wrote: “It looks normal
but unnatural.’’ This fetus is very dark and hemorrhagic, and evidently is de-
formed by pressure, either within or without the tube, or probably even after its
removal from the amniotic cavity, which the protocol states was contained in the

102 STUDIES ON PATHOLOGIC OVA.

blood-clot. Of another specimen (No. 535) it is stated that it also was apparently
normal, and consequently these 3 may be regarded as macerated normal fetuses,
which leaves only 3 others. Of these, No. 307 had no head in any true sense, for
the place of the head was taken by an empty fold which overhung the chest, and
gave to cross-sections of the cephalic extremity of the embryo a form resembling
the head of a grasshopper. Marked maceration and dissociation were present
throughout the entire body of the specimen. The other two specimens (No. 685
and No. 846) were small, macerated, and dissociated fetuses, No. 685 being also
disintegrated. Although No. 846 had not been cut serially, it was very similar in
structure to No. 685, and it is not unlikely that both of these specimens also could
be regarded as macerated normal cyemata; or, if we emphasize the hydatiform
degeneration, we may prefer to group them as macerated, stunted, or cylindrical.

Hydatiform degeneration was present undoubtedly in two specimens, and
probably in four. In a fifth (No. 846) the appearance was that of a very degen-
erate and macerated hydatiform change. This does not necessarily imply,
however, that the cyemata contained in all these chorionic vesicles were abnormal,
for I have found hydatiform degeneration in a number of chorionic vesicles, the
cyemata in which appeared perfectly normal and which had been regarded and
classified as such. Moreover, since relatively few villi were contained in any of
these specimens, it is possible that the hydatiform degeneration, especially in
these, although also in some of the specimens in other groups, may have been
purely local instead of general in character. Furthermore, the villi contained in
the clots which surrounded the specimens in this group usually were very macerated
and necrotic even, so that the true picture was often decidedly masked. Marked
infiltration of the wall of the tube was present in 2, or 40 per cent, of the 5 specimens
in which it was included in the section. In the other 3, or 60 per cent, the infil-
tration was slight.

SUMMARY.

Uterine—As shown in table 4 (Chapter III), the number of specimens in the
different groups varied from 17 in the first to 74 in the sixth. The other groups con-
tained almost an equal number of specimens. The percentage of instances in which
the decidua was included in the specimens varied from approximately 44 to 76.8 per
cent, the first and last groups being comparable in this respect. The high per-
centage of presence of the decidua in the first group is due to the fact that implanted
villi remain attached to the decidua until the latter is expelled, but this explana-
tion manifestly can not hold for the high percentage of its presence in the specimens
in group 7. Here it probably is due to the fact that a sluggish but contracting
uterus often molds into a ball the secundines, the chorionic vesicle, and the contained
fetus, together with the decidua and blood-clot, the ball being finally expelled as
a unit. In the younger specimens, and especially in undelayed abortion, this is
less frequently the case, and decidua and conceptus are more frequently expelled
separately. In some instances, too, the decidua is purposely removed by the
practitioner in order to expose the contained conceptus and free it from the sur-
rounding clot.

SUMMARY. 103

The variation in the percentages showing infiltration of the decidua is consid-
erable, ranging from 45.5 to 100 per cent. In the first three and in the sixth
group the percentage ranges from 90 to 96. It is 100 per cent in the fourth
group and 46 and 50 per cent in the fifth and seventh groups, respectively. There
is also considerable variation in the incidence of slight as compared with intense
infiltration. The former ranges from 11 to 86 per cent, and its incidence is approxi-
mately comparable in the first, second, and third groups, in which it ranges
from 11 to 19 per cent. Slight infiltration was most frequent in group 5, that of
cylindrical embryos, where it was present in 86 per cent. Its incidence was quite
comparable in the stunted fetuses (group 6), but very low in group 7. The rela-
tively high incidence of intense infiltration in this group, unless largely secondary,
is surprising, in view of the fact that many of these specimens have been retained
so long and are so degenerate. That intense infiltration is so frequent in group
1 is not surprising, and its presence likely leads to an early termination of the ges-
tation, no matter whether the endometritis existed previously to the gestation or
was incidental to or consequent upon interference.

The occurrence of such a decided variation in the presence of infiltration of
the decidua would seem to be the best possible evidence that this infiltration has a
pathologic significance. Were the leucocytes, upon the presence of which the
opinion regarding infiltration was mainly based, a constant constituent of the
normal decidua, they should have been present in all specimens. This could fail
to be true only if this infiltration occurred in the earlier months of pregnancy
alone.

A slight increase in the frequency of the occurrence of hydatiform degenera-
tion is seen in the first three groups, in which it rises from 69 to 85 per cent, being
lowest in group 5 and next lowest in the last group. The gradual increase
in its presence in the first three groups is easily explained by the fact that some
time is necessary for its development, and that it is difficult to recognize it in its
early stages or in macerated fragmented villi. The decline in its occurrence in the
last groups may be due to abortion of the conceptus soon after the development
of the degeneration. Its relatively extreme rarity in full-term births can be
explained similarly. The most interesting thing in this connection is the fact
that the decidua was infiltrated in every instance in which it was included in
the cases of hydatiform degeneration occurring in the first four groups. Since the
last three groups contained so few specimens, the percentages for each group are
of very little value, but the presence of infiltration seems to be far less common
in the specimens in these groups. This may be due to the fact that some low-grade
infections spontaneously disappear, but not before they have seriously damaged
the conceptus, which may then be retained for some time.

The occurrence of changes suggestive of lues rises gradually from zero in
the first group to 10 per cent in groups 3 and 7, the incidence being roughly com-
parable in groups 4, 6, and 7, although group 5 contains only about half as many
as these three groups.

Tubal.—Approximately 73 per cent of all the tubal specimens classed as
pathologic in the first 1,200 accessions fall into the first two groups, which

104 STUDIES ON PATHOLOGIC OVA.

are composed of villi only and of empty whole or of fragmented chorionic vesi-
cles. This leaves only 27 per cent to be distributed among the other five groups
of the pathologie division. Furthermore, the preponderance of the specimens fall-
ing into the first two groups actually is even more pronounced than this, for not
a single tubal specimen formed of villi only is included among the accessions below
No. 415. This is due mainly to the fact that Fallopian tubes containing what
appeared to be blood-clot only were not retained in the earlier days of the col-
lection.

If we assume that the incidence of specimens containing villi only was the
same among the first 400 as in the last 800 of the first 1,200 accessions, then the
total number of specimens composed of villi only rises from 39 to 78, and the per-
centage of those in the first two groups from 73 to 78. These percentages stand
in very marked contrast to those in uterine abortuses, in which specimens
composing the corresponding groups form only 18.4 per cent of all the path-
ologic. Since all the specimens contained in these two groups necessarily are
young, and hence also relatively small, it is evident that it probably would be
incorrect to attribute to the unusual conditions within the tube this difference
between the relative number of the uterine and tubal specimens contained in the
first two groups. It would seem that the tube, although small, is sufficiently
large and sufficiently distensible to permit growth to proceed sufficiently actively
to assure development beyond the stage represented by the specimens composing
these two groups. Consequently, it seems that the death of the embryo, with
subsequent disintegration of it and of the surrounding amnion, and in almost half
of the cases also of the chorionic vesicle itself, must be due to other things than a
mere lack of space within the tube. Nor can the large percentage of young tubal
specimens be attributed solely to the diagnostic skill of the surgeon, for in this
case the chorionic vesicles falling into group 2 not only should contain an amnion
and an embryo, but the whole conceptus should still be in a splendid state of pres-
ervation. This, however, is not true of any of these specimens, not even in the
instance of twin tubal pregnancy already referred to, although in this case both
chorionic vesicles are still implanted within the tube-wall throughout the whole
area of contact.

The high incidence of hydatiform degeneration, especially in these groups, as
well as the presence of infiltration of the wall of the tube, probably points directly
to the real cause for this difference, which very likely is to be found in the absence
of a nidus sufficiently favorable for implantation and growth. Nevertheless,
development within the tube must proceed under more unfavorable mechanical
conditions than within the uterus, for the latter probably undergoes expansion
more spontaneously, pari passu with the growth of the conceptus. The tube, on
the other hand, undoubtedly does not do so to the same degree, but becomes
distended while its walls are being eroded by the trophoblast. Consequently (as
so well illustrated in the case of No. 825, a twin tubal pregnancy), the tube, by
virtue of its elasticity alone, must subject the contained, growing conceptus to
considerable pressure. Nor is it only the elastic recoil of the tube-wall that the

SUMMARY. 105

growing conceptus must overcome, for the latter is periodically, or at least inter-
mittently, subjected to the force exerted by tubal peristalsis whenever the tube
attempts to rid itself of its unusual guest.

It is interesting that there does not seem to be the least evidence that the
tubal musculature regularly undergoes a marked hypertrophy in these cases.
Although I have examined carefully a series of specimens with regard to this
point, I have never been able to find any indication of a protective reaction on the
part of the tubal musculature or of the other tissues which were being invaded and
destroyed by the proliferating trophoblast. Aside from a certain amount of hyper-
emia and of infiltration, which may be provoked by the presence of the conceptus
within the tube, the latter seems to be largely passive, except for the intermittent
attempts at tubal abortion. These may be provoked very largely by the destruc-
tive and irritative effects of the trophoblast, and only to a minor degree through
mechanical distention incident to the increase in size of the conceptus, for this
distention necessarily is an extremely gradual one. This, however, does not affect
the fact that if more or less sudden hemorrhage rapidly distends the tube, the latter
probably may be thrown into violent peristalsis through this agency alone and also
undergo marked hypertrophy, under conditions of gradual distention by clot alone.

The tissue changes observed in the tubes were far less varied than those
seen in the uterus. This was due partly to the absence of anything comparable to
the decidua, and also to the absence of specimens that had been retained an
unusually long time. Densely fibrous villi were not common; hyalin degeneration
was rare, and calcification, except perhaps in its incipient stages, was not observed.
Since the villi were scattered about in the blood-clot, coagulation necroses, or mat-
ting, were practically absent. Marked maceration changes were exceedingly
common, however, and most evident where the surrounding blood was least
well preserved. Almost all save a few specimens were contained in much clot,
but since nothing comparable to a detachable decidua intervened between the
implanted villi and the tube-wall, such villi frequently had beer left in loco, even
when they had undergone marked degeneration. In several specimens the degen-
erate muscle-cells, together with the degenerate trophoblast overlying them, from
which they could not be distinguished, formed a considerable layer between the
tips of the villi and the tube-wall. In others this layer appeared roughly like a
decidua, although a layer of fibrinoid was never seen.

Aside from the many instances of splendid hydatiform degenerations, no other
change than a fibrosis of the stroma of the villi was encountered. This fibrosis
seemed to be more common in cases of severe infection, especially if evident also
in the contained clot. Hofbauer cells, when present at all, were few, and instances
of villi which were filled with them were not found. Aside from maceration, the
changes in the stroma and in the vessels of the villi were limited to hydatiform
degeneration and fibrosis. The syncytium and trophoblast often gave evidence
of having been very active, however, a fact which may be due largely to the
recurring accessions of fresh blood which bathed the chorionic vesicle, and which
not only nourished but probably also stimulated both villi and syncytium to

106 STUDIES ON PATHOLOGIC OVA.

proliferation. The tendency to decidual separation, with the onset of hemorrhage,
would seem to make the conditions of the uterus much less favorable in this
regard. Since most of the tubal specimens were very young, changes suggestive
of lues were seen but once.

A comparison of the summaries of the findings in uterine and tubal abortions
shows that a marked parallelism exists between them. ‘The incidence of infiltra-
tion, of hydatiform degeneration, and of the presence of infiltration in cases of the
latter, is remarkably similar. In 315 uterine specimens the incidence of infiltra-
tion of the decidua was 79.9 per cent, while infiltration of the tube wall was
present in 78.8 per cent of the tubal specimens. In spite of the remarkable
agreement between them, these percentages tell only a part of the truth, for they
do not express the differences in intensity of infiltration or the presence of abscess
formation. My impression is very definitely to the effect that, as a whole, the
uterine infiltrations were far more severe than those of the tube. Many of the
latter were so slight that one possibly might regard them as due to the pregnancy
itself; not that normal pregnancy is necessarily accompanied by infiltration, but
this might especially be the case if pregnancy occurred in abnormal surroundings,
as it does in the tube.

Hydatiform degeneration was present in 31.2 per cent of the uterine and in
51.6 per cent of the tubal specimens. The higher incidence of hydatiform degen-
eration in the tubes may be due to the fact that three-fourths of all the tubal speci-
mens fall into the first two groups, while only 57.1 per cent of the uterine do so.
It is, of course, in the early stages of development that hydatiform degeneration is
particularly frequent. Moreover, in comparing the incidence of hydatiform de-
generation in the first four groups of the tubal and uterine specimens, we find
that they are practically identical. That for the tubal is 41.4 per cent and that
for the uterine specimens actually somewhat higher, or 42.1 per cent. Further-
more, the incidence of infiltration in all cases of hydatiform degeneration in the
tubal specimens is 78.8 per cent and in the uterine 79.9 per cent. This shows not
only that a parallelism between the two groups exists in regard to these changes, but
that there is also a parallelism between the incidence of hydatiform degeneration
and infiltration in the specimens in each group. It will be seen that in the first
four groups the incidence of infiltration of the decidua in the uterine specimens is
just about as much higher than infiltration of the tube in the tubal specimens as
the incidence of hydatiform degeneration in the uterine specimens is higher than
that in the tubal. This is not what one would expect a priori, but it is interest-
ing that the greater incidence of hydatiform degeneration in the first four groups
of the uterine specimens also is in harmony with the slightly greater incidence of
the presence of infiltration in these specimens.

A similar parallelism is found to exist also between the incidence of infiltration
in all the tubes, portions of which were examined, and its incidence in the decidua.
It was 88.5 per cent in the former and 81.5 per cent in the latter. Hence, infiltra-
tion was found somewhat more commonly present in the tubes than in the decidua.
This fact might seem to stand in contradiction to the relationship between infiltra-

SUMMARY. 107

tion and hydatiform degeneration just referred to, but such is not necessarily the
case. It is accounted for, in a large measure, by the greater frequency of very
poorly preserved decidue, which often make the determination of infiltration ex-
ceedingly difficult. The tubes, on the other hand, always are sufficiently well
preserved, even if not perfectly so, to make a decision in this matter comparatively
easy.

Although the series of cases showing hydatiform degeneration is unprece-
dentedly large, only 315 uterine and 104 tubal specimens were included in this
study. This, of course, is too small a series for statistical purposes, but the rela-
tively small size of these groups is compensated for to a remarkable degree by the
very striking parallelism existing between them. This parallelism was found to
exist not only between the incidence of hydatiform degeneration and of infiltration
in the first few groups of the tubal and uterine specimens, but also between these
two, and seems to indicate an extremely close relationship between infiltration and
hydatiform degeneration. It is not unlikely, however, that it is not so much the
presence of an infection itself as the changes induced by it, especially in the decidua,
which may be the real cause for the advent of hydatiform degeneration.

DESCRIPTION OF SPECIMENS.

Readers will notice direct contradictions between the first and last portions of
some of the following descriptions. This is due to the fact that the first portion
of the description is based upon the gross appearance alone and the second upon
histologic examination in addition. Things taken for embryonic rudiments were
not always found to be such. Moreover, since Mall wrote the original protocols
at widely different periods, some of the descriptive terms, among which are fibrous,
hyaline, and mucoid, are not always used in exactly the same sense. With chang-
ing conceptions old terms also took on a new meaning. In the earlier protocols
the term dissociation is used largely, if not wholly, in the sense of disintegration,
but later it takes on the further idea of an uncorrelated or helter-skelter growth.
Hence, in the earlier protocols a nodular embryo is said to be completely disso-
ciated when it shows practically no differentiation whatever, having a homo-
geneous structure. The boundaries of any organs which may have been there
have become effaced so completely that the individual organs can no longer be
recognized.

The chief items in each protocol have been numbered for the sake of con-
venience. The figures mark (1) the name and address of the physician who was
the donor, (2A) the dimensions of the abortus or chorionic vesicle, (2B) the length
of the embryo or fetus, (3) the relevant clinical data, (4) notes on the gross speci-
men, (5) notes from the microscopical examination of a portion of the specimen,
and (6) comments or some significant facts bearing upon the abortus. In some
instances the dimensions of the abortus also represent those of the chorionic vesi-
cle, both with free and matted villi. It was not the purpose to make a final diag-
nosis, but merely to call attention to facts which might throw an interesting
sidelight upon the condition of the conceptus.

108

STUDIES ON PATHOLOGIC OVA.

These protocols are not presumed to be complete descriptions of the specimens.
To have made them such would have required considerably more revision and would

often have been superfluous for the present purpose.

In many cases the decidua

and the chorionic vesicles really require further description, but since my attention
was directed especially to them, and since their condition was particularly noted in
the discussion, this deficiency in the protocols in no way prejudices the discussion.

The clinical histories we owe to the donors of the specimens; the original de-
scriptions of the first 827 specimens were made by Dr. Mall himself, and the later
gross descriptions are based on original notes by various associates of Dr. Mall,

expecially Drs. Evans and Streeter.
Dr. Wheeler at Dr. Mall’s request.

GROUP 1.

No. 223.

(1) Max Brédel, Baltimore, Maryland.

(2) A40X18X15 mm. \

(4) At the point of attachment to the uterus the “fibroid
mass” is very rich in villi. At its rounded end it is com-
posed wholly of blood.

(5) The entire mass is surrounded by a layer of pus and
necrotic decidua. In certain portions the intervillous
spaces are filled with degenerating trophoblast. Where
the trophoblast cells are far removed from the blood they
are often necrotic. Some villi contain numerous Hofbauer
cells and the stroma of many suggests a rapid degeneration
of a rather fibrous non-vascular stroma.

(6) Marked infiltration of the decidua.

No. 290.

(1) S. P. Warren, Portland, Maine.

(2) A 50X15X10 mm.

(3) The specimen is said to be from a six weeks’ gesta-
tion and the abortion is believed to have been induced by
some emmenagogue.

(5) Sections were cut from different portions of this
irregular mass and the remnants of a few villi, more or less
infiltrated with leucocytes, were found. The bulk of the
specimen is composed of decidua, mucous membrane,
blood, fibrin, pus, and a few degenerate, necrotic villi.

(6) Marked infiltration of the decidua.

No. 323.

(1) V. Van Williams, Baltimore, Maryland.

(2) A 1209065 mm.

(4) The specimen was brought fresh to the laboratory
and was found to be composed of enlarged villi and vesicles,
most of which measure 5 mm. and a few fully 20 mm. in
diameter. On one end the specimen is fibrous, and from
there the villi extend into a bloody mass.

(5) The latter villi are very irregular in form, the meso-
derm being hyaline, with numerous spindle-shaped nuclei.
Between the villi there are great masses of necrotic tropho-
blast, some blood, and occasionally small masses of leuco-
oe. A few of them contain irregular clefts with cells, a
clear fluid, and some coagulum.

_ (6) Slight infiltration and decided hydatiform degenera-
tion.
No. 395.

(1) R. M. Pearce, Albany, New York.

(2) A 17X10X7 mm.

(3) Dr. Pearce writes: “I am sending you today a
small encapsulated mass, found among curettage material,
which appears to be a young ovum. I have refrained
from attempting to determine definitely whether or not it
contains an embryo, for fear of injuring a specimen which
might be of value to you. The specimen was removed

A few protocols were entirely rewritten by

six weeks after the last menstruation. The uterus was
emptied because the patient had eclampsia three years
ago, and since then has had premature delivery of two
dead children. The specimen is preserved in 10 per cent
formalin.”

(4) The whole mass was cut into serial sections, but no
embryo was found.

(5) The sections show it to be composed of a few very
degenerate villi and inflammatory decidua. Most of the
villi are also fibrous and degenerate. A few, however,
contain blood-vessels filled with blood; others contain
obliterating vessels. The fragmentary wall of the chorion
is very fibrous and the growth of the syncytium is very
irregular. Undoubtedly the ovum “collapsed”’ some days
before the uterus was scraped. The whole specimen is
buried more or less in a slimy mass rich in leucocytes,
which indicates that the uterime mucosa was markedly
inflamed.

(6) Marked infiltration.

No. 565.

(1) Dr. W. A. Duvall, Baltimore, Maryland.

(2) A 502020 mm.

(4) The solid mole appeared to be composed of mucous
membrane of the uterus, fibrin, and blood. Its macro-
scopic appearance was much like that of the decidua.

(5) Sections show that it is composed almost entirely
of decidua containing spaces lined with fibrinoid substance.
These seem to be degenerating uterine glands. There are
isolated villi which have undergone marked degeneration,
and also a few buds of syncytium. Portions of the mass
are very markedly degenerated, there being large groups of
pycnotic nuclei in certain necrotic areas.

No. 644.

(1) Edwin B. Fenby, Baltimore, Maryland.

(2) A 45X29X35 mm.

(3) Patient a rather frail, nervous woman, 35 years old,
who, since January, had been nursing a sick child. Last
regular period December 15. February 15 she felt badly;
menses appeared and continued with intermissions until
March 9, when her physician curetted.

(4) The specimen consists of a pear-shaped mass, the
small end of which includes long, delicate, bulbous villi,
some of which had the appearance of blood-clot.

(5) Transverse section of the block shows that its
interior is filled entirely with blood. Around the periphery
are villi and remnants of a degenerate decidua showing
very extensive inflammatory reaction. Most of the villi
are necrotic, but a few of them still seem to be preserved.
These have undergone fibrous and mucoid degeneration,
and occasionally are capped by trophoblast which has
undergone almost complete fibrinoid changes. Extremely
degenerate portions of the chorionic wall are present
throughout the clot.

(6) Marked infiltration and hydatiform degeneration.

SPECIMENS COMPOSED OF VILLI ONLY.

No. 698.

(1) N. E. B. Iglebart, Baltimore, Maryland.

(2) A 50*20X13 mm. Decidual cast with some
syncytium and trophoblast.

(3) Patient 38 years of age, mother of three children,
this being her first abortion. Last period April 11 to 14;
abortion June 6. No history of infection.

(4) The specimen looks like a solid irregular mole and
measures 50X20X13 mm. On sectioning, it is found
filled with blood, with a space between the inner wall and
the decidua.

(5) Transverse sections of the same suggest that it is
composed entirely of decidua and clot. What appears to
be the chorionic wall is the decidua capsularis, the
interior of which is filled entirely with blood. Between
the slight traces of the chorionic wall and the blood-clot
containing them a few small masses of syncytium and
trophoblast are found. The ovum apparently has been
destroyed almost entirely, so that the sections remind one
very much of the type of pregnancy found in the uterine

tube.
(6) Marked infiltration.

No. 749.

(1) Dr. G. C. McCormick, Sparrows Point, Maryland.

(2) A 100100100 mm.

(3) Patient aged 19 years, married five months and
thought she was pregnant four months. Symptoms re-
semble placenta previa. Irregular. Hemorrhage for two
months.

(4) The specimen is a hydatiform mole in several pieces,
which, when placed together, form a large mass 100 mm. in
diameter. The exterior is covered with numerous wart-
like prominences from 1 to 3 mm. in diameter, and with
hypertrophic villi, some of which are 40 mm. in length and
over 10 mm. in diameter. Most of these are attached to
the main wall of the chorion by thread-like processes. No
embryo was found.

(5) The villi are very large and most of them have
undergone mucoid degeneration, the interior not staining
well by any of the methods used. The trophoblast is
mostly necrotic, but at points it seems to be active. The
mesenchyme of some of the villi appears to be more or
less fibrous and contains large nests or groups of cells
appearing to come from degenerating blood-vessels. There
are also masses of Hofbauer cells in these villi, which are
covered by a fairly active trophoblast.

(6) Hydatiform degeneration; decidua absent.

No. 861.

(1) C. W. R. Crum, Brunswick, Maryland.

(2) A 35X25X15 mm.

(3) Woman, aged 40, married 16 years. Eleven preg-
nancies: eight full-term children; abortion between first
and second child; two abortions since last child, now 244
years old. Last menstrual period February 14 to 18 and
abortion March 29 following. No infection apparent in
pezaition of uterus. No venereal diseases. Family fer-
tile.

(4) The specimen consists of two irregular masses which
measure 11X10X5 mm. and 35X17X11 mm., respec-
tively. The large mass is firm and at several points villi,
which attain a length of 7 mm., protrude from it.

(5) These have undergone fibrous as well as mucoid
degeneration and are matted together by an inflammatory
exudate which contains great masses of leucocytes. The
trophoblast is scanty.

(6) Severe infection; some hydatiform degeneration.

No. 866.

(1) Thomas S. Cullen, Baltimore, Maryland.

(2) A 26209 mm.

(3) Patient aged 36, married 17 years. Seven preg-
nancies: children 16, 14, 10, and 7 years; miscarriages
1910, 1913, and this one, March 16, 1914. Patient missed

109

no menstrual period. In July 1913 there was flooding and
afterwards a little continuous bleeding until the abortion.
Last periods March 6 and one month before abortion.
Uterus slightly enlarged. No venereal diseases.

(4) The specimen measures 26X20X9 mm. and is
covered with villi, which are so flattened over the greater
part of the surface as to form an almost smooth exterior,
but a portion of the circumference of the specimen supports
thin, shaggy villi from 5 to 7 mm. in length. The ovum is
solid, and on being cut open no chorionic cavity is apparent.

(5) The completely degenerated villi which are outlined
by fibrinoid only are matted together with fibrin. The
extensive trophoblast is necrotic. It appears as though
the specimen had been completely detached for some time
before the abortion, and that it must be far older than
the history suggests.

(6) Necrotic early confluent hydatiform degeneration.

No. 914.

(1) Benjamin O. McCleary, Baltimore, Maryland.

(2) A 401010.

(3) First pregnancy of a woman aged 24 years, married
in 1910. Last menstrual period May 12 to 16, 1914, and
abortion June 17 following. Condition of uterus negative.
Venereal diseases negative. Fertility of family good.

(4) The specimen is a firm elongated abortus 40 X10 X10
mm.

(5) It is composed of a large piece of hemorrhagic and
inflamed decidua, scattered through which are large
strands of fibrinoid substance and a few villi which have
Badergone mucoid degeneration. There is some tropho-

ast.

(6) Marked infiltration.

No. 920.

(1) Hiram Fried, Baltimore, Maryland.

(2) A 505050 mm.

(4) The specimen consists of large hemorrhagic frag-
ments which together constitute a mass about 100 mm. in
diameter. One of these fragments forms a shell 50 mm.
in diameter, which contains a cavity about 30 mm. in
diameter.

(5) Sections through its wall show it to be composed of
blood-clot, throughout which are scattered occasional villi
more or less completely dissociated. In some of them the
mesenchyme is fibrous. Some of the remnants of the villi
are surrounded by two zones of nuclei—the remnants of
the two epithelial layers—and lie in masses of leucocytes,
thus giving an appearance such as is frequently seen in
tubal pregnancy.

(6) Severe infection.

No. 929.

(1) R. A. Hammack, Manila, Philippine Islands.

(3) Patient aged 22 years. ‘Two pregnancies, both end-
ing in abortion, this being the second. Normal period was
delayed about one month before abortion. No history of
infectious diseases.

(4) The specimen consists of numerous small fragmeats
of blood, measuring together about 30 mm. in diameter,

(5) Sections through a piece of what appears to be
chorionic tissue proved it to be a scrap of uterine mucous
membrane and a large clot of blood, a portion of which is
fairly rich in leucocytes. A few very small fibrous villi
are found, and attached to them are very small, irregular
clumps of trophoblast.

No. 941.

(1) John Wade, Baltimore, Maryland.

(2) A 30X20X10 mm.

(4) The embryonic mass measures 60X40X20 mm.,
and sections, as well as careful inspection, show it to be
composed mostly of decidua. On one side of it an ovum,
measuring 30X20X10 mm., was found, completely
filled with dense reticular magna, and a small vesicle 3

110 STUDIES ON PATHOLOGIC OVA.

mm. in diameter was closely adherent to the chorion. On
opening, it appears to contain granular débris. In general
its walls are tough, and at its attachment to the chorion
there is a small nodule, probably the umbilical vesicle.
The villi of the ovum are well formed, but long and slender.

(5) Sections show that they have undergone mucoid
degeneration and are matted together with a great mass
of inflamed decidua.

(6) Marked infiltration.

No. 994.

(1) A. F. Ries, Baltimore, Maryland.

(2) A 68X26 X24 mm.

(3) Patient aged 25 years, married about 7 years. Four
pregnancies: normal birth five years ago, another three
years ago, an abortion in May 1913, at four months, and
this abortion. Beginning of last period, September 5,
1914. Abortus protruding from mouth of cervix Novem-
ber 25; curetted November 28. Fertility of family good.

(4) The abortus measures 682624 mm. and con-
sists of villi and a pointed hemorrhagic mass. Probably
this lay within the cervix. The villi are of very irregular
shape, some of them long and shaggy, and have attached
to them numerous opaque nodules which, in some cases,
are more than a millimeter in diameter—the trophoblastic
nodules or appendici durate.

(5) Sections of the mole show the villi to be matted
together with a large mass of fibrinoid substance, to con-
tain considerable numbers of leucocytes, and to have
undergone mucoid degeneration in many cases. Between
the villi there is more or less fresh blood, within which are
buds of syncytium showing a quite active growth.

(6) Marked infiltration and early confluent hydatiform
degeneration.

No. 1015.

(1) A. F. Ries, Baltimore, Maryland.

(2) A 41X37X31 mm. :

(3) The patient had a miscarriage 10 years ago, this
being the third one. Menses appeared “‘on and off” from
July to November 26, with alternate weekly flowing. On
the latter date the bleeding was profuse and abortion oc-
curred on December 7.

(4) Specimen consists of ‘a hard, firm mass, which on
section gives no evidence of pregnancy. Apparently a
tumor.”

(5) Microscopic examination reveals a mass of necrotic
dicidua and villi.

GROUP 2.

No. 20.

(1) J. W. Williams, Baltimore, Maryland.

(2) A 2014.6 mm.

(4) From the exterior the ovum appears to be quite
normal, with well-developed villi, which are represented
better near one end and look somewhat swollen and matted.
Within the ccelom, however, there is a great quantity of
magma, within which were buried several nodules. ‘These
were removed and sectioned.

(5) Sections revealed no amnion lining the chorion, and
the small nodules are only masses of magma which contain
no cells. The villi, the stroma of which is clear, are
covered by the usual quantity of trophoblast. They are
non-vascular and slightly macerated. At isolated points
between the villi are small masses of a granular substance
which present the Bp eesti of coagulated albumin.

(6) Probably early hydatiform degeneration. Decidua
not included.

No. 21.
(1) T. 8S. Cullen, London, Canada.
(2) Chorion 1295 mm.; vesicle within, 5.53.5 mm.
(4) From external appearances, the ovum is apparently
normal, with well-developed villi branching a number of
times. Upon opening the chorion it was found that the

ccelom was filled with a quantity of magma réticulé, within
which was embedded a very large transparent vesicle.

(5) The main vesicle is brought into contact with the
chorion by means of a small secondary vesicle; both are
inclosed by a layer of mesoderm within which are numerous
blood-islands. The smaller vesicle is lined with a layer of
large, spindle-shaped cells. The cavities of both vesicles
contain cells which are scattered throughout the magma.
There are no blood-vessels in the chorion. The syncytial
layer is diminished but well formed upon the tips of the
villi. Here in many places it accumulates in layers, form-
ing masses. Both chorion and yolk-sac are very degen-
erate. The amnion is absent. The yolk-sac has finger-
like extensions, some of which may represent cyemic
remnants, but this is unlikely.

(6) Decidua not included.

No. 29.

(1) W. D. Booker, Baltimore, Maryland.

(2) A 30X30X30 mm.

(4) The ovum was covered by a few atrophic villi, and
within no trace of an embryo could be found. The celom
was filled with a cheesy mass of granular magma as usual.
After the magma had been searched through most com-
pletely, the portions of the chorion which might have a
remnant of the embryo attached were stained and cut into
serial sections, but nothing whatever could be found.

(5) Sections of the chorion show that its walls and villi
are fibrous and thickened. The amnion is absent. A few
villi show mucoid degeneration, but the stroma of most of
them is fibrous and macerated. Some few show very
intense so-called granular hypertrophy or, better, hyper-
plasia. Many are non-vascular. Appendici durate are
numerous, and groups of degenerate villi are contained
within degenerate masses of trophoblast. The latter and
fusion of the villi are most numerous opposite areas of
greatly thickened chorion. Leucocytic infiltration is
wholly absent.

(6) Decidua absent.

No. 55.

(1) W. T. Watson, Baltimore, Maryland.

(2) A 35x20X14 mm.

(3) Last period, January 18 to 22; abortion March 13.

(4) The specimen is a very fleshy mass containing a
sharply defined, spherical cavity, 15 mm. in diameter, with
smooth walls, but no trace of an embryo.

(5) Sections showed that the sharply defined cavity was
the ccelom, as its walls were formed by the chorion. The
thick, fleshy mass is composed of villi, syneytium, blood,
fibrin, and pus. The fibrous walls of the chorion, which
contain remnants of blood-vessels and decidua, are in-
vaded by leucocytes and partly disintegrated. The main
bulk of the villi and syncytium stains poorly and appears
necrotic. The stroma is fibrous, more or less degenerate,
invaded by leucocytes, and covered in part by very active
syncytium. The cavity of the ccelom is partly filled with
a granular magma, in which are embedded some cells.
The whole picture is that of severe infection. Very little
decidua is present, and this is fibrous, infiltrated, and necro-

tic.
(6) Marked infiltration of the decidua; severe infection.

No. 70.

(1) C. M. Ellis, Elkton, Maryland..

(2) A 45X30X28 mm.

(3) Patient had regular periods until July 28, 1896,
when she missed one. On October 20 she had a profuse
hemorrhage; after this there was no flow until February 4,
when this specimen passed.

(4) The gross specimen is very solid because of the large
amount of clot at one end, at which groups of character-
istie hydatids are found.

(5) Sections show it to be composed of a mass of dis-
tended and cystic chorionic villi undergoing mucoid de-

ee ee eee EE EEE SE EE

CHORION WITHOUT AMNION

generation characteristic of hydatiform mole. Between
the villi there is a large quantity of blood, with an excessive
amount of trophoblast, which on one side forms a large
mass. Within the center of the specimen there is a small
collapsed chorion with poorly defined walls. The speci-
men was not cut into serial sections, so it is impossible to
state whether or not the embryo has been entirely de-
stroyed, but in all probability this was the case.
(6) Marked infiltration; hydatiform degeneration.

No. 71.

(1) G. H. Whitcomb, Greenwich, New York.

(2) A 10X95 mm.

(3) Dr. Whitcomb writes: ‘‘The specimen is from a
woman 23 years old, who had been married three months
before the abortion occurred. She had been troubled with
chronic cystitis and endometritis, but menstruated regu-
larly. After marriage she had two menstrual periods, but
the third failing to appear, she concluded she was pregnant.
Seven days after the lapsed period she slipped while
descending the stairs, and this was followed by some
tenesmus. Four days later I examined her and found a
free flow of unstained mucus from the uterus, with tender-
ness, hyperemia of the pelvic organs, and irregular pains.
An examination of the urine on the following day showed
it to be loaded with pus and blood, and it contained also
the ovum. Two days later the decidua was discharged.
The specimen was preserved in 50 per cent alcohol.
Shortly after this the woman became pregnant again and
went to full term.” From the above data the abortion
occurred 40 days after the beginning of the last menstrual

eriod.
3 (4) When the ovum came to the laboratory three years
later it was well preserved and had not been opened. The
villi were even but slightly deficient on one side. Within
there was a small amount of magma réticulé, and at the
bottom of one of the halves of the chorionic vesicle there
was found a very small nodule.

(5) The nodule, which was embedded and cut into
sections 20 microns thick, appears to be of foreign material.
The syncytium of the chorion is normal, except for macera-
tion changes. There are no blood-vessels.

(6) Decidua absent.

No. 82.

(1) H. F. Cassidy, Baltimore, Maryland.

(2) A 75X60 X40 mm.

(3) “Last period began June 3, 1896, and the tumor
was passed March 8, 1897, 40 weeks later.”

(4) The specimen was brought to the laboratory fresh.
It was pear-shaped, purulent on the pointed end, and the
interior appeared to be composed of fresh blood-clots.

(5) Sections of the large, solid mass, mainly composed
of clot, show that it contains a collapsed ovum with folds
of the fibrous chorion extending throughout the specimen.
On one side of the specimen there are a few slender villi.
Most of the folds of the chorion are composed of double
walls, usually in apposition and occasionally completely
blended. All of the chorionic membrane and some of the
few remaining villi are composed of relatively well pre-
served, dense, fibrous connective tissue. There is no
amnion. Along the main central body of the chorion
large quantities of fresh blood are found. The rest of the
tumor is composed of blood-clots and nests of leucocytes
and of syncytium. The syncytial nests, located in great
part along the chorion, are preserved better where they
come in contact with fresh blood, but are necrotic else-
where. At no point does the syncytium invade the cho-
rionic membrane. It is impossible to interpret this speci-
men without assuming that the chorion continued to grow
long after the death of the embryo.

(6) Infection. Decidua absent.

No. 93.

(1) H. F. Cassidy, Baltimore, Maryland.
(2) A 40X20 mm.

OR CYEMA. 111

(4) The specimen contained a cavity into which pro-
jected a large tongue of fleshy tissue. Within the latter
there is a blood-clot, as well as a sharply defined cavity.

(5) Sections through different portions of the specimen
show the outer sac to be the decidua and the tongue of
tissue, the chorion. Within the central cavity of the
tongue (ccelom) lies the greatly macerated amnion. It can
not be stated definitely whether or not remnants of the
embryo are present, as the specimen was not cut into
serial sections. The walls of the chorion are thickened
and irregular, and around it are packed hypertrophied
villi, with great quantities of blood between them. Cover-
ing the villi is a laver of blood and fibrin separating them
all from the decidua. The latter is fibrous and shows
decided general infiltration.

(6) Marked infiltration.

No. 123.

(1) H. J. Boldt, New York.

(2) Ovum 17X14 mm., with vesicle 1.81.51 mm.

(3) “The last menstrual period prior to the abortion
occurred August 14 or 15. Abortion September 10. The
whole ovum was placed in 95 per cent alcohol within 10
minutes after abortion.”

(4) The entire ovum was covered with villi, apparentl
normal, but surrounded by a layer of pus and plodd
After opening it, the ecelom was found filled with a mass
of coagulated fibrinous albumin, the magma réticulé,
within which no embryo could be seen. The two halves
of the ovum were then stained, which brought out promi-
nently a small vesicle embedded in the magma. This
vesicle had a rounded opening upon one side, with a long
pedicle upon the other, which extended towards, but was
not attached to, a small mound on the inside of the chorion.
Vesicle and chorion were both cut into serial sections.

(5) The sections of the vesicle appear to be those of the
normal umbilical vesicle. The opening on the side is
undoubtedly due to a tear, judging by its broken edges.

(6) Marked infiltration of the decidua.

No. 147.

(1) A. C. Pole, Baltimore, Maryland.

(2) Ovum 30X27 X20 mm.

(3) “Last period began January 1, and the specimen
was discharged March 23.”

(4) The ovum is only in part covered with villi, the
remaining portion of the chorion being clear and trans-
parent. The ccelom is completely filled with magma, which
has turned very white in the alcohol in which the speci-
men was preserved. On one side of the chorion and closely
attached to it, there is a small vesicle and an irregular mass
which may represent the remnants of the embryo. The
magma contains some degenerating erythroblasts.

(5) Sections of the chorion show that the mesoderm is
very fibrous and rich in cells. The vesicle within is about
a millimeter in diameter, and is located 2 mm. from the
chorion, but not attached to it. Its walls are composed
of only one layer of cells on one side of the vesicle, while
on the opposite side there is a second layer of mesoderm
0.5 mm. thick, in which are embedded numerous blood-
vessels filled with blood. There are also a few blood-
vessels in the chorion in the immediate neighborhood of the
vesicle, which are likewise filled with blood.

(6) Decidua not included.

No. 153.

(1) E. W. Stick, Glenville, Pennsylvania.

(2) A 502020 mm.

(3) Last period began April 30; abortion July 15.

(4) The mass is pear-shaped and proves to be a ruptured
chorion partly inverted and embedded in an organized clot
of blood and fibrin. The chorion is, of course, ruptured,
and at the point of rupture there is a mass of blood which
forms the large end of the pear-shaped mass. There is no
amnion within the degenerate chorion, nor could the

112

embryo be found. A portion of mucous membrane of the
uterus is attached to the chorion. This shows marked
inflammatory infiltrations and fibrosis.

(5) The villi of the chorion are swollen, show marked
mucoid degeneration, and the stroma of many of them has
undergone a kind of coagulation necrosis. The stroma is
non-vascular and Hofbauer cells are common. The
trophoblast cells are generally normal in appearance.
There are many leucocytes, especially within the decidua,
considerable areas of which are purulent. Except for
relatively small regions, the chorionic membrane, although
devoid of endothelium and disintegrated in places, is but
slightly invaded, in spite of the fact that it is surrounded
in part by a narrow zone of leucocytes.

(6) Marked infiltration and hydatiform degeneration.

No. 173.

(1) L. R. Jump, Tesla, California.

(2) A 25X15X10 mm.

(3) Marriage December 15, 1899; last menstrual period
December 20; abortion February 12. Several other masses
about the same size, which appeared to be composed of
blood-clots, were passed at this time.

(5) Upon section the specimen was found to be com-
posed of a collapsed ovum well covered with villi. The
chorionic membrane is almost wholly destroyed. Within
the cavity of the ccelom there is an irregular, ill-defined
mass of blood-clot. The small sclerotic fragments of
accompanying decidua are markedly infiltrated.

(6) Severe infiltration; early hydatiform degeneration.

No. 181.

(1) D. 8. Lamb, Washington, District of Columbia.

(2) A 18X18X10 mm.

(4) The ovum is filled with reticular and granular
magma, and no remnants of an embryo could be found,
although every particle which might contain it, with the
adjoining chorion, was cut into serial sections.

(5) The mesoderm of the chorion and villi is edematous
and shows mucoid degeneration. The epithelial covering
. beer developed, often being composed of but one layer
of cells.

(6) Decidua absent.

No. 185.

(1) F. R. Sabin, Baltimore, Maryland.

(2) A 402515 mm.

(3) The abortion occurred seven weeks after the begin-
ning of the last menstrual period.

(4) The specimen was brought to the laboratory in
formalin. Upon opening, it was found that the ecelom
was filled with reticular and granular magma. No trace
of an embryo could be found, although the entire ovum
was cut into serial sections.

(5) The main wall of the chorion is decidedly thickened
and completely filled with leucocytes with nuclei in all
stages of fragmentation. They form a fairly sharp border
on the ccelom side, making the chorion appear as the wall
of an abscess. The leucocytic invasion must have been
merely from the ccelom side, for the villi are not affected
to any extent. Some of them are edematous; others show
marked mucoid degeneration.

(6) Severe infiltration of the decidua and infection of the
chorionic vesicle.

No. 190.

(1) C. M. Ellis, Elkton, Maryland.

(2) A 25X22 12 mm.

(4) The ovum is filled with magma, within which no
trace of an embryo can be found, although the entire
specimen was stained and cut into serial sections.

(5) The chorion and villi are apparently normal, except
for slight maceration and hydropic degeneration. Some
villi contain blood-vessels.

(6) Decidua absent.

STUDIES ON PATHOLOGIC OVA.

No. 191.

(1) C. M. Ellis, Elkton, Maryland.

(2) A 161111 mm.

(3) The specimen is from a supposedly induced abortion,
and had been in Dr. Ellis’s collection for 10 years before it
was sent to us.

(4) The cavity of the spceimen is filled with a small
amount of granular magma, and the villi are matted. No.
embryo was found.

(5) The chorionic wall is somewhat fibrous, as are also
the cores of the villi. The trophoblast may be normal, and
there is no indication of surrounding inflammation.

(6) Probably macerated, induced. Decidua absent.

No. 195.

(1) D. S. Lamb, Washington, District of Columbia.

(2) A 30X30X30 mm.

(4) The specimen was well covered with villi and con-
tained some reticular magma. No embryo could be
found, although the entire ovum was cut into sections.
The mesoderm of the chorion appears normal and is rich
in blood-vessels filled with blood, but that of the villi is
non-vascular and rather clear.

(6) Dedicua not included.

No. 204.

(1) D. 8S. Lamb, Washington, District of Columbia.

(2) A 14X12X8 mm.

(4) The specimen, said to be three weeks old, was found
filled with a mass of granular magma.

(5) The whole ovum was stained and cut, but no trace
of an embryo could be found. The chorion and villi
appear normal.

(6) Decidua not included.

No. 233.

(1) W. P. Miller, Hagerstown, Maryland.

(2) A 704540 mm.

(4) The irregular mass appears to be an ovum filled
with blood.

(5) Sections, however, show that there is a mixture of
distorted villi, blood, syneytium, decidua, and pus. Most
of the villi are completely degenerate, their place being
occupied by detritus mixed with leucocytes. The decidua
shows marked infiltration and fibrosis.

(6) Severe infiltration.

No. 243.

(1) Max Brédel, Baltimore, Maryland.

(2) A 302010 mm.

(4) The specimen is pear-shaped, with smooth, thin
walls, over which are scattered a few thin villi.

(5) The latter and the chorionic membranes show
maceration changes.

(6) Normal macerated. Decidua absent.

No. 255.

(1) Max Brédel, Baltimore, Maryland.

(2) A 202010 mm.

(5) The villi are matted; some are fibrous, but others
mucoid. At points the syncytial layer is well mixed with
leucocytes, which also have invaded some of the villi as
well as the mesoderm of the non-vascular chorion. The
whole chorion was cut into serial sections, but no trace of
an embryo or remnants of amnion were found.

(6) Infected. Decidua not included.

No. 278.

(1) E. M. Stanton, Albany, New York.

(2) A 6X4 mm.

(3) This specimen was found accidentally in curettings
from a woman supposed to have chronic endometritis
following pregnancy. ‘There is nothing in the history by
which the age of the specimen could be estimated. Before

CHORION WITHOUT

the specimen was sent, part of it had been cut into sections
and the accompanying record stated that no embryo had
been found.

(4) The part received at the laboratory contained a
chorionic vesicle 32.5 mm., filled with magma, in which
was a cavity about 1.51 mm.

(5) Sections showed that the cavity was natural, but
not sharply defined, with nothing to indicate that an
embryo had been in it. On the contrary, it was found
that the magma réticulé was filled with a loose network
of mesoderm cells, which unite one side of the chorion
with the other. These cells are directly continuous with
those of the mesoderm and resemble them in every particu-
lar. At one point there is a small group of epithelial cells,
which may represent what was originally the embryo.
Otherwise the chorion and villi are normal in appearance,
being encapsulated in decidua which has in it some uterine
glands. All in all, this specimen reminds one very much
of Peters’s ovum. There is some general infiltration in
the decidua, and also a few accumulations of leucocytes
are present in the mucosa. The specimen shows some
maceration. We consider this specimen one in which the
embryo has been destroyed, leaving a normal chorion.

(6) Slight infiltration.

No. 280.

(1) Thomas H. Magness, Baltimore, Maryland.

(2) A 402525 mm.

(4) Within the mole, which is said to be five or six weeks
old, there is an irregular cavity with smooth walls measur-
ing 10X5X5 mm.

(5) Sections were cut of the thick hemorrhagic walls.
These showed the walls of the chorion to be thin, with
considerable reticular magma attached to them on the
inside. No amnion was found. The villi, though not
very large, are well developed, contain remnants of blood-
vessels, and are covered with a mass of necrotic syncytium.
The blood and mucus over the syncytium is filled with
leucocytes which invade the mesoderm of many of the
villi. The latter are very degenerate and are surrounded
by severe leucocytic accumulations. The exterior of the
clot which surrounds the villi is formed by a thick wall
of densely packed leucocytes, which replaces the decidua
almost completely. It is probable that the whole ovum
had been dead for several weeks, the embryo and amnion
having been destroyed entirely.

(6) Severe infection and rapid degeneration.

No. 299.

(1) W. B. Burns, Memphis, Tennessee.

(2) A 16X12X10 mm.

(4) The specimen, which apparently is normal, is filled
with a mass of dense magma réticulé.

(5) Serial sections failed to show even a remnant of an
embryo. The structure of the chorion and villi is normal,
possibly a little edematous from maceration. No blood-
vessels are present.

(6) Possibly a very early hydatiform degeneration.
decidua.

No

No. 310.

(1) W. T. Watson, Baltimore, Maryland.

(2) A 18X14X14 mm. :

(4) The specimen is covered with villi, which on section
proved to be markedly changed.

(5) The mesoderm has undergone mucoid degeneration
and contains vacuoles in which there are free nuclei. The
epithelial layer is irregular. The villi are vacuolated,
contain some blood-vessels, and are covered with a fairly
active and preserved trophoblast. The interior of the
ovum is filled with magma réticulé, at the periphery of
which degenerated erythroblasts—Hofbauer cells of Minot
—are found. Many of the villi also contain numerous
Hofbauer cells. There is no trace of embryo or of the
amnion. The degenerate decidua is decidedly infiltrated.

(6) Marked infiltration; hydatiform degeneration.

AMNION OR CYEMA. 113

No. 358.

(1) C. M. Swett, Bangor, Maine.

(2) A 301610 mm.

(3) Pregnancy of six weeks’ duration.

(4) The outer surface of the ovum is smooth, and the
specimen runs out into a pedicle which undoubtedly was
attached to the uterus. z

(5) Sections show that the villi are matted together,
and that much blood and syncytium is between them.
Around this there is a fibrous decidua containing many
leucocytes and necrotic areas. The mesoderm of the
chorion is swollen from maceration, and some of the villi
are rather fibrous. No blood-vessels are present in the
latter. The ccelom measures 8X66 mm. and is lined
by a layer of reticular magma, but contains no trace of
amnion or embryo.

(6) Marked infiltration.

No. 435a.

(1) F. A. Conradi, Baltimore, Maryland.

(2) A 30X20X15 mm.

(4) The ovum is filled with a dense reticulated magma
and contains a cavity measuring 201510 mm.

(5) The ovum, which was cut into serial sections, con-
tains no embryo or amnion. The villi are non-vascular
and atrophic, having undergone degeneration, partly mu-
coid and partly fibrous. They are covered with very
little trophoblast. The chorionic wall is fibrous, and
numerous cells are scattered throughout the dense magma.
The degenerate remnant of decidua which is present
suggests the presence of an infection.

5 6) Suggestive of hydatiform degeneration; too little
ecidua.

No. 593.

(1) Abraham Poska, Hobson, Montana.

(2) Ovum 30X25 X20 mm.

(3) Patient said she did not know she was pregnant
having had her last menstrual period four weeks before
the abortion.

(4) The ovum, which is covered with large villi, has
a pedicle. The entire specimen measures 45X25 X20
mm. ‘The interior apparently is solid, and upon cutting it
open no cavity is found, nor can a remnant of the embryo
be seen.

(5) Sections of the pedicle show it to be markedly in-
filtrated, much blood and pus being scattered through the
tissue. Several villi present here are degenerate, but
those on the main body of the specimen are large and
beautifully branching. Sections through these include
their points of attachment, which consist of chorionic
membrane practically destroyed by an invasion of leuco-
cytes. Apparently an abscess destroyed the main body
of the ovum almost entirely. The villi are disintegrating,
for the mesenchyme is breaking down. The spaces are
becoming larger and the nuclei fewer. The stems of the
villi are being invaded by leucocytes, but there are small
remnants of embryonic blood-vessels. The trophoblast
is scanty.

(6) Marked infiltration and early hydatiform degen-
eration.

No. 594.

(1) Abraham Poska, Hobson, Montana.

(2) A 47X40X30 mm.

(3) There were several severe hemorrhages previous to
the abortion, which were interpreted by the patient as
met menstrual periods. She passed much clotted

ood.

(4) The specimen, which is solid, is composed mostly
of blood containing a solid ovum with a long, narrow, slit-
like eelom. No remnant of the embryo could be found.

(5) The folds of the swollen, hemorrhagic chorion have
coalesced in certain areas, and at points numerous large
ridges of mesenchyme have grown into the celom. These
folds contain a great many Hofbauer cells. The chorionic

114

wall is thickened, edematous, and also contains some
Hofbauer cells and blood-vessels filled with blood. A
very few villi are present, and these are undergoing mu-
coid degeneration, but most of them are fibrous. The
degenerate, transformed remnants of the decidua show
extensive leucocytic infiltration, but in general the leuco-
cytes do not reach to the chorionic wall. There is some
coagulation necrosis.
(6) Marked infiltration.

No. 596.

(1) T. C. Smith, Washington, District of Columbia.

(2) A 25X20X15 mm.

(3) Last menstruation February 21, this being her first
pregnancy. Patient claimed at the time of her abortion
that this was her regular menstrual period.

(4) The ovum is covered almost entirely with villi
which branch three or four times, and which on one side
are much less numerous and atrophic. Upon opening the
ovum it was found to be lined with a smooth surface,
but although examined under the most favorable condi-
tions in direct sunlight, no trace of an embryo could be
found. On one side there appeared to be a small mass of
reticular magma, and it was thought possible that the
embryo might be within it. Since the specimen was
perfectly white and transparent, however, it would have
oa almost impossible to miss the embryo had it been
there.

(5) Upon section, the wall of the chorion appears to be
normal in structure, but the villi have undergone partial
mucoid degeneration. The trophoblast is not plentiful,
but there are numerous nodules of it and tufts of syn-
cytium. Within the nodules of trophoblast there is some
fibrinoid and, often, scattered groups of vacuolated syn-
cytium. Although the entire ovum was embedded in
paraffin and cut into serial sections, no embryo was found.
Fine examples of vessels in the last stages of degeneration
are found in some of the villi. No decidua is included
in the sections.

(6) Early hydatiform degeneration.

No. 606.

(1) C. 8S. Parker, Baltimore, Maryland.

(2) A18X13X8 mm.

(4) Part of the ovum is covered with branching villi,
quite uniform in size and 2.5 mm. long. The entire speci-
men projected would measure about 18138 mm.
Viewed in direct sunlight, no trace of an embryo could
be seen, but it may have been lost with the missing por-
tion of the specimen.

(5) The entire specimen was cut into serial sections,
which do not show any trace of an embryo. However, the
chorion and villi are so badly macerated that it is difficult
to make out any structure whatever. In fact, even the
nuclei of the chorionic membrane have disappeared en-
tirely, leaving only a fine reticulated structure.

(6) Almost complete lysis. Decidua not included.

Decidua absent.

No. 661.

(1) G. L. Wilkins, Baltimore, Maryland.

(2) A 452525 mm.

(3) Patient is a recently married woman who had
missed one period. No history of uterine or venereal
disease. Patient decidedly anemic.

(4) The specimen is a smooth, pear-shaped mass, with
a stem 25 mm. long. The walls are thick and spongy,
and within there is an irregular cavity about 8 mm. in
diameter, which is lined with a smooth membrane and
filled with delicate reticular magma. It was thought
that the embryo might be present.

(5) Sections show that the very thickened fibrous
chorion is encircled by a large hemorrhagic mass contain-
ing many villi and buds of syncytium, surrounded by a
thin layer of markedly inflamed decidua. The chorionic
wall, which is markedly fibrous, contains numerous blood

STUDIES ON PATHOLOGIC OVA.

directly in contact with the chorionic wall. In the center
of the ccelom the magma is partly granular and contains
a few Hofbauer cells. No trace of an amnion could be
found. Most of the villi are decidedly fibrous, but a
few show mucoid degeneration, with fenestration of the
stroma. The former retain some vessels.

(6) Marked infiltration.

No. 663.

(1) Lindsey Peters, Columbia, South Carolina.

(2) A 30X15X10 mm.

(3) Patient 30 years of age. Five pregnancies: first
term, child still living; second, twins at term, one child
living; third, stillbirth at term; fourth, term, child livin B
fifth resulted in this abortion. Last menstrual pai |
January 18 to 22; abortion, March 15. No infection of
uterus; position normal.

(4) The specimen is a smooth, almond-shaped body
containing a small cavity filled with reticular magma.
No remnants of an embryo could be seen. The specimen
had been opened when received.

(5) The chorion and some of the villi are fibrous; others
are mucoid and are attached to the inflamed decidua by
means of an extensive blood-clot. There is very little
fibrinoid substance or trophoblast, but numerous buds of
syncytium intermingled with fibrin and many leucocytes.
No amnion could be found.

(6) Marked infiltration and some hydatiform degener-
ation.

No. 702.

(1) George H. Hocking, Govans, Maryland.

(2) A 502020 mm.

(3) Patient is 42 years old and has two children, the
younger aged 6 years. Last menstrual period April 16,
but on May 20 there was a slight flow of a dark color.
On June 3 the mass was expelled without pain or special
discomfort.

(4) The specimen apparently is solid, measuring 50
20X20 mm. It appeared to be composed of numerous
clots and had a smooth external surface. Within it was
composed mostly of blood and contained a cavity a centi-
meter in diameter, filled with reticular magma. In the
center of the magma there was an opaque body, 5 mm. in
diameter.

(5) Sections of the specimen do not show any remnants
of an embryo or amnion. The chorionic wall is loosened
up and destroyed almost completely for a considerable
extent. Large quantities of blood are present between the
villi. The entire mass is encircled by an intensely in-
flammatory necrotic decidua. The non-vascular villi
mostly have undergone mucoid degeneration. The inter-
villous spaces are filled with blood and the trophoblast
is necrotic.

(6) Intense infiltration.

No. 723b%.

(1) L. L. Iseman, Chicago, Illinois.

(2) A 452525 mm.

(4) Chorionic wall smooth and thin.

(5) Sections show it to be composed of necrotic mem-
brane and a few necrotic villi. The intervillous spaces
are engorged with fresh blood. A necrotic, somewhat in-
filtrated decidua encircles the chorion, marked off on the
mur side by a layer of fibrinoid substance. No tropho-

ast.
(6) Marked lysis of the decidua and slight infiltration.

No. 736.

(1) R. B. Varden, Mercersburg, Pennsylvania.

(2) A 385X16X16 mm.

(4) Almond-shaped hard mass measuring 35X16X16
mm., and entirely filled with hard, coagulated blood.
Towards one end there is a cavity 7X4 mm., lined with
smooth membrane. : ;

(5) This cavity is in a collapsed ovum filled with reticu-

vessels filled with bood. The magma is very dense and | lar magma and some blood-vessels in the chorion which

CHORION WITHOUT AMNION OR CYEMA.

do not stain with the Heidenhain method. The chorionic
wall and most of the villi are fibrous and locally thickened.
The latter are degenerate, surrounded by necrotic zones,
and anastomose freely. A strand of reflected mesen-
chyme bridges one end of the celom. A few buds of
syncytium protrude into the extensive mass of surrounding
blood. The entire specimen is encircled by considerable
fibrous substance, as well as by an outer, markedly in-
flammatory, and in part necrotic decidual zone.
(6) Marked infiltration.

No. 750.

(1) J. M. Jackson, Pittsburgh, Pennsylvania.

(2) A 201515 mm.

(3) Patient aged 23 years; married March 25, 1913;
no previous pregnancies; last menstrual period June 6
to 10, 1913, and abortion August 19 following. First
intercourse two weeks after June 10 (Jewish law). Con-
Bitions of uterus normal; no veneral diseases. Family
ertile.

(4) The entire mass consists of a blood-clot, decidua,
and a large piece of an ovum, which together measure
453025 mm. The ovum alone measures 201515
mm., and is covered with numerous knob-like villi.
The main wall of chorion is very thin and transparent,
and when opened was found to be lined with a delicate
membrane. One half of the specimen is filled with an
extremely delicate reticular magma, and although the
inspection was made under favorable conditions, no trace
of an embryo was found. After the specimen was thor-
oughly examined, it became more and more doubtful
whether an amnion was present.

(5) Sections later showed that it was absent. Small
fragments of decidua which were in the specimen were
decidedly fibrous. The chorionic membrane and _ villi
have undergone fibrous and mucoid degeneration. The
tropkoblast is scanty, and there are a few buds of syncy-
tium, surrounded by a small amount of mucoid substance,
between the largely non-vascular villi.

(6) Some hydatiform degeneration and probably chronic
endometritis. Decidua fibrous.

No. 753.

(1) L. A. Peek, West Palm Beach, Florida.

(2) A 453025 mm.

(3) Patient 23 years old; married about a year; first
pregnancy. Usually about 32 days between menses.
First day of last period, May 19; abortion August 1 fol-
lowing. No infection of the uterus; no venereal diseases.

(4) The specimen was found to consist of blood-clot
containing a cavity about 12 mm. in diameter, lined
with smooth membrane. No trace of embryo or amnion
could be found.

(5) The sharply defined cavity of the ecelom is sur-
rounded by a thin, somewhat macerated chorionic mem-
brane. The magma is granular and contains disinte-
grating cells. In the fresh blood a few fibrous and mucoid
villi are contained. Outside there is a decidedly hemor-
rhagic and inflamed, partly necrotic decidua. In many
respects the chorionic wall resembles that of No. 752,

‘oup 6.
a6) Marked endometritis; lysis in decidua.

No. 765b.

(1) J. B. Harvie, Troy, New York.

(2) A 55X35X20 mm.

(3) Patient unmarried; one miscarriage 18 months be-
fore the present one.

(4) The specimen, which was expelled spontaneously
while the patient was being etherized in the hospita
measures 553020 mm. and appears to be composed
of a collapsed, very hemorrhagic chorion. No trace of an
embryo could be found.

(5) The cavity of the ovum, which is small (about 10
mm. in diameter), is infected, and the chorionic membrane

115

is prec peelly destroyed by a severe inflammation. The
villi, which are packed together, show mainly fibrous and
some mucoid degeneration. A great quantity of mucoid
substance is found between them. In this numerous buds
of syncytium and some small abscesses are contained.
The surrounding trophoblast and decidua are markedly
inflamed and the latter necrotic in several portions.
(6) Marked infiltration; hydatiform degeneration.

No. 770.

(1) C. S. Parker, Baltimore, Maryland.

(2) A 12X96 mm.

_(3) Negro patient, aged 30 years, married 12 years.
Six births at terms and three or four abortions. Copula-
tion September 22. Menstrual period due September 28,
appeared September 30, lasting 9 days. Abortion Octo-
ber 5, probably induced. Vaginal discharges not foul-
smelling. No venereal diseases. Husband’s family fertile.

(4) Ebecimen consists of chorion with a few blood clots
attached. It is covered uniformly with villi, all of which
are equally developed. The ovum measures 12%9X6
mm. It was opened with great care and found to be well
filled with granular and reticular magma. The magma
was removed in a single mass, and on one side of the cho-
rion an irregular body about 2 mm. long wasfound. This
was at first thought to represent the embryo, but when
cut into serial sections was found not to be such.

(5) The chorionic wall and villi are quite normal in
form and the trophoblast is plentiful. The specimen is
somewhat macerated, but it appears as though there is
some mucoid substance, in addition to the trophoblast,
between the villi. The nodular mass looks much like
an extension of mesenchyme into the ccelom, with
strands of empty blood-vessels on either side of it.
There is an epithelial tube-like structure, which might
pass for the allantois or for the central nervous system.
Adjacent to this structure is an umbilical vesicle, the
blood-vessels of which communicate freely with those of
the chorion.

(6) A normal, slightly macerated specimen.
not included.

Decidua

No. 791.

(1) Ira L. Fetterhof, Baltimore, Maryland.

(2) A 302020 mm.

(3) The specimen is said to be two months old.

(4) The ovum, which measures 302020 mm., is
entirely covered with villi about 4 mm. long, and from
one end arises a pedicle about 15 mm. long. The interior
is filled with a delicate reticular magma, and on one side
is an irregular body, 3 mm. long, which is adherent to
the chorion.

(5) This small nodular mass is not well formed, and
appears to be largely disintegrated. Apparently it is
composed of two bodies, between which there is a clear
body, no doubt representing the yolk-sac. Sections of
the chorion show that the wall is somewhat thickened.
The villi are mostly mucoid and filled with a clear
mesenchyme without any blood-vessels. The tropho-
blast is composed mostly of small patches arising directly
from the surface of the villi, and at points it forms
rounded nodules, the centers of which are sometimes ne-
crotic. There is asmall mass of mucoid substance between
the villi.

(6) Hydatiform degeneration.

No. 829.

(1) Austin Miller, Portersville, California.

(2) A 38X38 X30 mm. t

(3) Woman about 30 years of age, married 5 years.
Two previous pregnancies at term. Last menstruation
about November; abortion January 20. Uterus normal.
No venereal diseases. Family fertile. _

(4) This specimen consists of a white, shaggy ovum,
measuring 38X38X30 mm. About one-half of it is
devoid of villi, and in the denuded area a perfectly trans-

Decidua absent.

116 STUDIES ON

parent chorion can be seen. On the opposite side the
shaggy villi reach probably 10 mm. in length. They are
extremely complex, branching many times, and almost
all of the stems have a clear, bulbous appearance. The
ovum, which was opened through a careful slit in the
denuded area, contamed a voluminous cavity filled with
a fluid, and was crossed by extremely delicate strands of
reticular magma. An embryonic remnant was not found.
In the part of the wall where the most luxuriant villi
occur, many circular, opaque white nodules, about 1 mm.
in diameter, could be seen.

(5) The villi seem to have undergone mucoid degenera-
tion. The trophoblast is scanty and mostly takes the
form of buds of syncytium and nodules which have under-
gone partial fibrinoid degeneration. These nodules of
trophoblast are frequently vacuolated.

(6) Hydatiform degeneration. Decidua absent.

No. 865.

(1) Walter Tobie, Portland, Maine.

(2) A 50X20 mm.

(3) Woman aged 35 years, married 10 years. Six preg-
nancies: five abortions and one birth at 7 months, dead.
Beginning of last menstrual period uncertain; said to have
been about 114 to 2 months pregnant. At operation
amputation of uterus at cervix; double salpingo-oopher-
ectomy and appendectomy. No definite history of vene-
real disease. Dilatation and curettage, with ventral sus-
pension, 4 years before. Said to have had tubal preg-
nancy one year ago. Family fertile on both sides and
easily pregnant.

(4) The specimen consists of the uterus with both
tubes and ovaries. The uterus measures 65X58 X58
mm. It was cut six times in the antero-posterior plane,
disclosing an implanted ovum 55X20 mm., apparently
beginning to dislodge, the portion pointing toward the
cervix being free. The small slit in the chorion measures
about 26X3 mm.

(5) The right ovary measures 32X18 mm. and con-
tains six old copora and a small carcinoma measuring
1012 mm. in cross-section. This shows to the right
in figure 78, and upon higher magnification is seen to be
studded with numerous small cell-nests which are barely
visible in the mounted section with the unaided eye.
Practically all of these nodules are discrete, as shown in
figure 79, and all look decidedly quiescent, for very few
nuclear figures suggesting mitosis were seen. All these
cell-nests are well defined and none are edematous in
character. Some of them contain a few small areas of
calcification, and some of the latter are contained also
in the ovarian stroma of the carcinomatous nodule.

The left ovary, shown in section in figure 80, which
contains several old corpora and a recent one, measures
35X19 mm. and is cystic. The largest of these cysts,
which by reference to the original specimen is found to
be approximately spherical, measures 11.5X9 mm. on
section. It is devoid of contents and immediately outside
of the lining epithelium a small teratoma is found. Ex-
amination of the original specimen shows that this tera-
toma extended somewhat farther into the lateral half,
and that the greater part of it still is contained in the
more medial portion of the ovary (which is embedded in
celloidin) and lies in the dorso-medial area of this portion.
As shown in figure 81, it is represented by a grayish-white
cartilaginous plaque, 8 mm. fag by 1.5 mm. thick, with
a markedly triangular process extending outward from
its medial side. An examination of the stained sections
shows this teratomatous mass to be composed of cartilage,
at one extremity of which small plaques of bone are found.
Surrounding this there is some adipose tissue which con-
tains a number of tubules cut mainly in cross-section
which from their appearance suggest those of suderiparous
glands, but which probably are sebaceous. At the oppo-
site extremity a considerably larger lobulated mass of
glandular tissue is found, which seems to be sebaceous in
nature. A few small tubules also are found near these

PATHOLOGIC OVA.

lobules, which are partly separated from each other by
trabecule of fibrous tissue. No remnants of epidermis,
but some of a few hairs were found. A few degenerate
hair-follicles also are present, and considerable accumu-
lations of round cells are found near some portions of
the teratoma.

After cutting the uterus into blocks, it was found that
part of the ovum is detached and protrudes from the
cervix. A portion of the chorion is well implanted and
to the naked eye shows mottling. These spots, when
cut into sections, are shown to be composed partly of
hypertrophic degenerated villi, mostly with a mucoid
stroma, some of which are very rich in Hofbauer cells.
The villi, which are of all shapes and sizes, are matted
together with fibrinoid substance and a great quantity of
leucocytes and pus. At points the leucocytes burrow into
the trophoblast and also enter the mesenchyme of the
villi. Most of the trophoblast is necrotic and contains a
great many plaques of nuclear dust. The leucocytes have
entered the cavity of the ovum and line the inside of the
chorion, which is undergoing fibrous degeneration. Nei-
ther amnion nor embryo was found.

(6) Severe infiltration; hydatiform degeneration.

No. 876.

(1) C. W. R. Crum, Brunswick, Maryland.

(2) A 46X30X23 mm.

(3) Patient aged 25, married in 1909. Five pregnan-
cies: two children at term, followed by three abortions;
August 1913, January 1914, and this one, April 19, 1914.
Last menstrual period February 3 to 8. On February 15
patient was nauseated as in early pregnancy. No infec-
tion of uterus. Temperature normal. Retroversio uteri.
No venereal diseases. Family fertile.

(4) The specimen consists of an irregularly shaped,
abortion mass which measures 463023 mm.
protrude at one end, but most of the surface seems to be
firm decidual tissue. The specimen contains a perfectly
smooth-walled cavity measuring about 32X22 mm. in
diameter, with no trace of an embryonic rudiment.

(5) Sections of the wall show that the chorionic mem-
brane is of normal texture, but thickened. Some of the
villi are somewhat fibrous, but most of them show marked
mucoid degeneration. Some are intermingled with active
trophoblast, which in some instances contains fibrinoid
substance and coagulated blood. The surrounding de-
cidua is markedly inflamed and contains abscesses.

(6) Marked infiltration; hydatiform degeneration.

No. 883.

(1) G. H. Hocking, Govans, Maryland.

(2) A 37X26X20 mm. ;

(3) Patient aged 34 years, married May 4, 1905. Two
pregnancies; birth at term February 2, 1906, and abortion
April 21, 1914. Slight flow which continued until abor-
tion on April 21. Condition of uterus negative. No
venereal diseases. Family small.

(4) The specimen consists of a small, pear-shaped, mass
measuring 372620 mm. It is friable, and on being
opened, a smooth-walled, oval chorionic cavity 209mm.
is disclosed. This is filled with a coagulated albuminous
material containing cellular elements. The remains of
the embryo could be seen. } i

(5) Sections show that the cavity of the ecelom is
almost obliterated. On one side there are curious
globules of degenerated pus which stain with eosin. The
chorionic membrane and villi have undergone mucoid
degeneration, and the latter are embedded in a clot of
blood. There is a great deal of leucocytic infiltration,
especially in the degenerated inflamed decidua. Leuco-
cytes have invaded the mesenchyme of the chorionic
membrane as well as that of the villi, and numerous small
pus cavities are found between the chorionic epithelium
and the stroma of this membrane. ee: :

(6) Severe endometritis and intra-chorionic infection;
some hydatiform degeneration.

firm
Villi

CHORION WITHOUT

No. 9684.

(1) D. P. Quezon, Manila, Philippine Islands.

(2) A 604525 mm.

(3) Specimen from young Filipino woman.

(4) The chorionic sac, which measures 604025
mm., had been cut into irregular pieces, and was found
intermingled with blood clot. In addition, about 50 c.c. of
free masses of blood were separated from the chorion.

(5) The chorionic membrane appears normal, but the
villi are almost wholly non-vascular and many show
mucoid degeneration. The trophoblast is active and the
tips of the villi are well implanted in the large piece of
decidua. Where the two come into contact the fib-
rinoid substance is very evident. The chorionic vesicle
contains no blood-vessels, but a great many Hofbauer
cells. In the decidual fragments which have undergone
fibrinoid changes there is considerable infiltration.

(6) Slight infiltration; hydatiform degeneration.

No. 970.

(1) R. W. Hammack, Manila, Philippine Islands.

(2) Chorion 3X5 mm. with celom. Jn situ.

(3) The specimen came from a Filipino girl, aged 16
years, who had taken hydrochloric acid with suicidal
intent four days before her death. At the autopsy acute
broncho-pneumonia, congestion of the kidneys, and hyper-
plasia of the endometrium were diagnosed, which led the
physicians to suspect early pregnancy.

(4) The description of the uterus at the time of autopsy
is as follows: ‘‘Uterus large and soft and the serosa red.
The folds of the vaginal mucosa are present. The entire
vagina is purplish red; cervix slightly enlarged and soft.
In the fundus the mucosa is red, greatly thickened, soft
and irregular. On the posterior wall beneath the mucosa
is a firm, slightly movable nodule, a little less than 10
mm. in diameter. This was not opened. The cavity of
the uterus is enlarged; the musculature is very slightly
thickened and pink. The Fallopian tubes are of normal
size, moderately hyperemic. The right ovary contains a
large corpus luteum. The left ovary contains a small
cyst, 20 mm. in diameter, containing reddish fluid.”

The specimen received at the laboratory consists of
vagina and uterus, with both tubes and ovaries, all in
one mass. The uterus had been opened, and adherent
to the mucosa were masses of blood. The entire uterine
mucosa is covered with hemorrhagic nodules measuring
in general about 10 mm. in diameter. One of these,
located medianly, is larger than the rest, and a narrow
block of tissue cut out of this and sectioned was found to
contain part of the ovum. All of these sections were
saved, and an adjoining block was taken and cut into
serial sections in celloidin. Even this did not contain
the entire ovum, but careful examination of the next
block revealed the remainder.

(5) The ovum with its villi measures 3X5 mm. The
ccelom is filled with a homogeneous substance, through
which are scattered individual cells and also some strands
of tissue from the chorionic membrane. The villi are
about 0.5 mm. in length and covered with an active
trophoblast. This layer of trophoblast, which ramifies into
the adjacent tissue, is intermingled with a great deal of
fibrinoid substance and cells, and penetrates the blood-
sinuses. There are many buds of syneytium and con-
siderable inflammatory reaction in the surrounding tis-
sues. Towards the lumen the ovum is covered with de-
cidua reflexa, marked off with a layer of fibrinoid substance.
The sections examined show no trace of an embryo. On
account of the swollen condition of the chorionic mem-
brane and the lack of sharpness of the mesenchyme, the
specimen does not appear normal.

Sections through the corpus luteum show it to be lined
by a layer of lutein cells about 2 mm. in thickness. There
is no central cavity, although the surrounding ovarian
tissue is very hyperemic. There is no blood within the
central cavity, but regarding this point it is impossible

AMNION OR CYEMA. 117

to make a definite statement, as both ovaries had been
cut into before the specimen reached the laboratory.
(6) Slight infiltration; intra-uterine absorption.

No. 978.

(1) G. C. McCormick, Sparrows Point, Maryland.

(2) A 311615 mm.

(3) Patient aged 39 years; married Otcober 8, 1902. Six
pregnancies: five at full term and this abortion, Novem-
ber 13, 1914. Last menstrual period September 19 to 23.
Condition of uterus good. No venereal diseases. Fam-
ily fertile.

(4) The specimen consists of a shrunken chorionic sac,
partly embedded in blood-clot. The whole mass measures
31X16X15 mm. On opening the sac the interior was
found to be filled with caseous magma. No embryo could
be seen.

(5) The chorion is composed partly of well-formed villi
and partly of a hemorrhagic mass. Sections through the
latter show that the blood is penetrated by villi which
have undergone fibrous and mucoid degeneration. There
are also numerous buds of syncytium in addition to masses
of syncytium which have undergone necrosis. The de-
cidua is thin, necrotic, and somewhat inflamed. Clumps
of erythroblasts lie along the inner surface of the chorionic
membrane. Neither the latter nor the villi contain pre-
served blood-vessels.

(6) Marked infiltration; some hydatiform degeneration.

No. 986.

(1) W. C. Stick, Hanover, Pennsylvania.

(2) 45X28X17 mm. .

(3) Patient aged 24 years; married in 1912. Two preg-
nancies, both ending in abortion, May 27, 1914 (specimen
No. 905), and this one, November 19, 1914. Last men-
strual period began about September and lasted for six
weeks. No infection of uterus. Venereal diseases nega-
tive. Family fertile.

(4) The specimen consists of an irregularly flattened
sac 45X28 X17 mm., to which is attached a blood-clot.
On one end there is an oval area measuring 27 X27 X22
mm., which is covered with chorionic villi. On openin
the chorion it was found to be filled with a pronounce
layer of thick, creamy material which could be pulled
off only with difficulty. The particles thus detached
proved to be very tough.

(5) Sections of the chorion show that it is covered with
villi which have largely undergone mucoid degeneration.
They are largely non-vascular and some of them are
fibrous. Between the villi are numerous islands of tro-
phoblast and also considerable stringy matter in which
masses of syncytium are buried. The overlying decidua
is marked by a zone of fibrinoid substance and contains
numerous small abscesses.

(6) Severe endometritis with abscess formation; prob-
ably very early hydatiform degeneration.

GROUP 3.

No. 77.

(1) A. Horn, Baltimore, Maryland.

(2) A 70X50X30 mm.

(4) When the specimen was cut in half there was found
within it a spherical cavity 20 mm. in diameter, lined with
a smooth, fibrous membrane and filled with a clear fluid
which permitted a careful inspection of its interior. On
one side of the cavity was a small elevation 1 mm. in
diameter and 0.25 mm. high.

(5) Sections are made of the walls of the specimen
through the elevation, which proved to be a fibrous thick-
ening of the amnion at its junction with the chorion.
There are no blood-vessels in any portion of the chorion
which have not undergone mucoid and fibroid degeneration
and contain some Hofbauer cells. Except for a new
nuclear remnants, the stroma of some villi is completely

118

degenerated. Between the villi there is a great quantity
of trophoblast, fresh blood, and fragmented leucocytes.
When fresh blood and syncytium come in contact there
are many fragmented leucocytes. Slight infiltration of
the decidua is present. The latter is also fibrous.

(6) Mild infiltration; hydatiform degeneration.

No. 130.

(1) P. G. de Saussure, Charleston, South Carolina.

(2) Ovum 15X10X6 mm., with vesicle 4X3 1.5 mm.

(3) “The specimen was passed by the patient while
urinating, 14 days after the beginning of the last menstrual
period. She had no idea that she was pregnant, and
thought that the specimen was a piece of mucous mem-
brane from the bladder. It was hardened entirely in 50
per cent alcohol.”

(4) When received the specimen was only half covered
with villi, the other half having apparently been stripped
off. There was also a tear in the chorion through which
a vesicle was protruding. Upon lifting the ovum this
vesicle fell out. The ovum was then carefully cut open
and was found to contain a considerable quantity of
magma réticulé. Within this there was a long pedicle,
measuring 7X2 mm. There was also a space in the
magma large enough to hold the vesicle which had escaped.
Both ovum and vesicle were cut into serial sections.

(5) The serial sections of the ovum show that the am-
nion is still unbroken. Its greatest measurements are
10X4 mm., into which extends the umbilical cord. At
the end of the cord there is a mass of tissue, mostly broken
down, the remains of the embryo. This mass is ragged,
without any form corresponding to an embryo, and had
the amnion been torn no doubt it would have fallen out.
The blood-vessels of the cord are gorged with nucleated
blood-cells, but they do not extend into the embryo.
The chorion is normal in appearance. The umbilical
vesicle is pear-shaped and completely closed. At no place
is there a break to show its attachment to the cord. Al-
though considerably macerated, the sections show the
characteristic structure of an umbilical vesicle.

No. 143.

(1) W. C. Stick, Glenville, Pennsylvania.

(2) Large double sac, 15X10 mm., attached to the
wall of the chorion.

(4) The chorion appears normal. The double, cyst-
like body has thin walls and is filled with a clear fluid.
The specimen has been in strong alcohol for nearly 20
years.

(5) Serial sections show a very degenerate chorion to
which the double vesicle is attached. The structure of
the walls of the two sacs is identical with that of the meso-
derm of the chorion with all of the epithelial cells fallen
off. The two sacs do not communicate; the larger has
smooth walls; the smaller has numerous small vesicles,
about 1 mm. in diameter, opening into it, and the cluster
of vesicles are directly blended with the mesoderm of the
chorion. The specimen undoubtedly belongs to the ve-
sicular forms, peculiar only on account of its size.

No. 159.

(1) W. W. Golden, Elkins, West Virginia.

(2) Fragments of chorion with amnion.

(3) ‘From a woman in good health who had aborted
about a year before during the third month. During the
second month of the sed from which the present
specimen was obtained there was a slight flow of blood
without any pain. It continued for 2 days; 10 days later
it recurred and continued for 24 hours. Three days later
it recurred again, became profuse, and the abortion fol-
lowed. The supposed duration of pregnancy is 10 weeks.
No indication whatever of endometritis. Both father and
aed are perfectly healthy and are very anxious to have
children.”

STUDIES ON PATHOLOGIC OVA.

(4) The specimen consists of portions of the mucous
membrane of the uterus, large portions of the chorion,
the amnion, but no embryo.

(5) The decidua is markedly infiltrated, and leucocytes
have invaded portions of the chorion. The syncytium
is very active, and at numerous points the syncytium and
leucocytes have invaded the mesoderm of the chorion.
Some villi show a good deal of ‘granular hyperplasia”
and are being fused into a solid mass. The membranes
are greatly thickened and composed of a dense connective
tissue. The vessels are largely obliterated. The amnion
is curled up and thickened, and its walls have undergone
hyaline degeneration. The amniotic epithelium has pro-
liferated, forming islands at many points.

(6) Mild infiltration.

No. 180.

(1) C. W. Dodge, Rochester, New York.

(2) Ovum 201510 mm.; vesicle 2 mm.

(3) The woman was a patient of Dr. Edward Mott
Moore, of Rochester. On March 28 her right ovary was
removed. She left the hospital on April 15 and coitus
occurred on May 13. On June 19 menstruation appeared
and this ovum was expelled.

(5) Sections of the chorion show that its mesoderm is
of normal thickness, but that it is fibrous and rich in
nuclei. Throughout the main wall of the chorion, but
not in the villi, there are numerous blood-vessels filled
with blood, showing that at one time an embryo may have
existed. The villi are normal in form, with a very exten-
sive syncytial layer of cells over them. At points this
forms large islands which can easily be seen with the
naked eye. Within, immediately over the vesicle, an
island of this kind, a millimeter in diameter, arises from
the main wall of the chorion and sends processes up
between the villi. The mesoderm just below this island
is thinner than the rest, making it appear as if the violent
growth of the syncytium took everything before it, but
that in the attempt to produce new villi the fibrous meso-
derm of the chorion would not follow. At many points
between the villi there is a slimy mass of albumen, well
infiltrated with leucocytes and numerous small islands of
syncytium, some of which can be followed back to their
origin from the villi. The vesicle is composed of but one
layer of cells, that of the mesoderm with blood-islands
embedded within it. No trace of an entoderm can be
made out, although the lumen of the vesicle extends into
a pedicle which, as a single strand of cells, attaches itself
to the chorion.

No. 257.

(1) A. W. Lankford, Baltimore, Maryland.

(2) Ovum 55X40X40 mm., containing a pedicle 142
mm., to which is attached a nodule 40.5 mm.

(4) A large portion of the chorion is covered with well-
formed and apparently normal villi. One portion is
hemorrhagic and another fibrous, appearing as though it
had protruded through the os.

(5) Sections through this portion show that the villi are
atrophic and have undergone fibrous degeneration. The
chorion is thickened and the decidua infiltrated with
leucocytes. The inside of the thickened chorion is lined
with epithelial cells which are continuous with those over
the cord; it en as if the amnion had become com-
pletely blended with the chorion. The cord is also fibrous
with some spots which have undergone mucoid degener-
ation. It contains three large blood-vessels—a vein and
two arteries—which show perivascular infiltration and
fibrosis. The body at the end of the cord is simply its
continuation, with the umbilical vein running through its
entire length.

(6) Marked endometritis.

No. 279.

(1) Dr. Kemp, Baltimore, Maryland.
(2) A 1006060 mm.

CHORION

(4) Part of the chorion is hemorrhagic; the rest appears
normal. Sections show that some of the villi are nearly
normal, but with a deficient amount of syncytium, even
where they are well-embedded in blood. The amnion
and a worm-like process (30 X 5 mm.), which proves to
be the umbilical cord with its three blood-vessels, are
present. The latter are well-developed and fully 1 mm.
in diameter. There are also numerous vessels in the villi
of the chorion. The tissue of the chorion is hyaline and
contains a diminished number of nuclei.

(6) Marked infiltration and early hydatiform degen-
eration.

No. 408.

(1) J. Park West, Bellaire, Ohio.

(2) A 50X30 mm.

(3) The specimen came from a delicate, anemic woman
who had been sick for a week with peritonitis. She
menstruated normally June 10 to 14, then slightly for a
day and a half, and considerably for three days before
the specimen was expelled August 13.

(4) The solid specimen was cut through lengthwise and
found to be composed mostly of a hemorrhagic mass con-
taining a collapsed cavity lined with an amnion and
measuring 12X4 mm. The chorionic membrane is
greatly thickened and very necrotic.

(5) The solid mass is filled with necrotic and fibrous
villi matted together in an irregular manner, and of many
nests of trophoblast which in places are reduced to masses
of nuclear dust. Beginning calcification is present. At
numerous points the villi are invaded by trophoblast,
showing that the latter continued to grow long after the
death of the villi (?). At the periphery of the mole there
is an extensive infiltration with leucocytes, indicating an
inflammatory process of the uterus.

(6) Marked infiltration.

No. 429.

(1) Elizabeth Dunn, Chicago, Illinois.

(2) A 452510 mm.

(4) The cavity of the vesicle is filled with a smooth
membrane—the amnion. The chorion measures 45 x 25 X10
mm. and the amniotic cavity 35X15 mm. Sections of
the chorion, as well as two small nodules which accom-
panied it, were cut, but no remnants of the embryo
could be found.

(5) The villi are matted together and degenerate, and
many are irregular and atrophic. The amnion is in appo-
sition with the chorionic membrane. Apparently we have
here a specimen from which the embryo fia escaped after
it had been well developed, and which, on account of the
detachment of the chorion, became necrotic. There is
but little decidua, and this shows inflammatory reaction.

(6) Decidua infiltrated.

No. 468.

(1) J. M. Jackson, Pittsburgh, Pennsylvania.

(2) A 14115 mm.

(3) The specimen was discharged spontaneously a week
after the cessation of one menstrual period. The mother
has the following history: At about the age of 18 she ac-
quired a gonorrheal infection which was not treated, and
about a year later she was treated for an infection of one
tube and ovary, at which time the vaginal and cervical
discharges were examined, but no gonococci were found.
After a later exacerbation of the tubal trouble, one ovary
and tube were removed by the abdominal route. ‘Three
years later she married, and after two years of sterility
became pregnant. Pregnancy normal, and fetal life was
determined up to within three days of delivery. No
fetal heart-beat could be heard thereafter, and after an
easy labor a slightly macerated dead child was born. ‘The
placenta was adherent and the microscopic appearance
peented a gritty, granular area at the adherent portion.

pecimen No. 468 was discharged one year later. She
is now pregnant for the third time at six months.

WITH AMNION.

119

(4) The specimen is evidently a collapsed ovum, meas-
uring 14X11X5 mm. Its external surface is smooth
and on it blood-vessels are coursing. Along the edge of
one surface club-shaped villi (?) are seen. The specimen
is very hard from the alcohol. On opening, a fine mold-
like magma fills the cavity, from which it can be extracted,
hanging together so as to form a cast of the cavity. The
cavity is smoothly lined. No embryo could be seen.
The fragments were then stained in cochineal, and the
specimen afterwards cut in serial sections, but still no
trace of an embryo was found.

(5) Sections of the chorion show that the ovum is lined
by an amnion which is more or less adherent to the cho-
rionic wall. The latter and the villi are very fibrous and
matted together with blood and pus, indicating that there
had been a very extensive inflammatory reaction within
the uterus. The decidua is decidedly fibrous in places.
Practically no trophoblast is gHached. to the decidua.

(6) Severe infiltration.

No. 469.

(1) Joseph M. Jackson, Pittsburgh, Pennsylvania.

(2) A 273010 mm.

(3) Father had several attacks of gonorrhea before
marriage, at which time he was supposed to be well.
Never had syphilis. Mother is a sound, healthy, robust
woman, age 26 years, married 6 years. Her family his-
tory is bad; many cases of tuberculosis on both sides of
her line. She has one healthy child 4 years old. One
miscarriage almost 3 years ago at 2 months; no ascertain-
able cause. The present specimen was discharged spon-
taneously 3 weeks after skipping one regular period. She
is now pregnant for the fourth time and has gone 2 weeks
over one period. She has no symptoms of adnexal and
no evidence of tubercular trouble. Menstruation nor-
mal, but of unusually foul odor.

(4) Collapsed ovum 273010 mm., covered com-
pletely on one side and partially on the other by branch-
ing villi about 3.5 mm. long, although some along one
lateral margin are fully 6 mm. long. A large, relatively
bare area, 2015 mm., exists on one side, where the
small scattered villi are seldom branched and not over 1.5
mm. long. On opening the ovum, no distinct cavity is
met, as many white “cheesy” trabecule obscure it. No
evidence of an embryo is found. The magma is very
extensive, completely filling the exocclom, and may be
described as reticular with much white granular or cheesy
substance in its meshes.

(5) On one side of the chorion a shaggy body, about 3
mm. long, was found embedded in the magma. This,
with the adjacent chorion, was cut into serial sections.
These show that the body seen before cutting was the
umbilical vesicle, all of which is filled with round cells.
No embryo could be found. The chorionic wall and villi
are somewhat fibrous, and the trophoblast is scanty. At
points it seems to be invading the mesoderm of the cho-
rion. Some of the villi contain blood-vessels. No am-
nion, or only a remnant of it, is present. The magma,
which forms a thick layer within the chorion, is composed
of fine granules, through which are scattered numerous
small round cells.

No. 483.

(1) Charles A. Lamont, Canton, Ohio.

(2) A 20X12X6 mm.; B 3 mm. :

(3) The patient is a primipara, age 33 years. Last
menstruation October 23; previously had been invariably
regular. On January 3 she noticed a slight flow which
increased at times, but had little pain until the night of
January 5. The following morning the ovum was expelled.

(4) The specimen consists of a smooth sac which proved
to be the amnion, and upon which the embryo is sessile.
This sac contained a granular deposit and a cylindrical
embryo 3 mm. long, the external form of which is irregular.

(5) Sections show extensive changes within. The cen-
tral nervous system is irregular and the otic vesicles are

120

lacking. The eye-vesicle can still be made out and the
heart can be outlined. Within the body the spinal cord
is irregular and contains a lumen which at points appears
to communicate with the pharynx. In other portions of
the body the cord is absent. The amnion is attached
along the entire length of the body.

No. 498.

(1) Guy L. Hunner, Baltimore, Maryland.

(2) A 404040 mm.

(3) “Patient aged 30 years, with one child 6 years old
and no miscarriages. Physician first saw patient June 10,
1909, because of backache, Gragg fees g, and slight
piles. Menstruates every 5 or 6 weeks, stops 1 day, then
a scant flow for 3 or 4 days. I found uterus far back in
pelvis and containing a small round fibroid fundus. Cor-
rection of position and introduction of pessary. January
28 period began with terrible bearing down in lower abdo-
men. No flow until February 1. A large clot and free
flow on February 2; no more until Monday, February 6.
Another terrible cramp and some blood. This period was
3 weeks late; is often 1 week over time. Pessary removed
about 1 week before. Examination: Uterus far back in
pelvis, easily brought forward. Size of 2 months’ preg-
nancy, but rather too firm feeling. Cervix soft, enlarged.
Breasts enlarged, firm colostrum. Diagnosis: Probable
pregnancy; fibroid. Patient was advised to keep quiet
and report in 1 month. On March 1, after pains during
the night, passed the specimen.”

(4) The chorion is partly covered with villi and entirely
encircled by the decidua. In the portion of the chorion
which is devoid of villi there is a large space between the
chorionic membrane and decidua. The interior of the
ovum is lined by a smooth membrane—the amnion—and
between it and the chorion there is a gelatinous mass of
reticular magma about 1 mm. in thickness and distributed
equally around the whole circumference of the ovum. No
remnant of the embryo could be found.

(5) Sections through the wall include the amnion, the
chorion, a thick layer of fibrinoid substance with cells, and
a layer of decidua. The latter is infiltrated with leuco-
cytes. The chorion is thin and the villi are atrophic and
well separated, having undergone fibrous and hyaline
degeneration. There is considerable trophoblast, some
large masses of which are degenerate. There are also
small nodules of necrotic trophoblast scattered between
the villi and fusing with the chorionic epithelium. There
is a great deal of blood in the magma which lies between
the amnion and chorion, into which numerous strands
of mesoderm cells from the chorion radiate. Between the
blood and the chorionic membrane there are some Hof-
bauer cells, which also are found within the mesenchyme
of the chorion and its villi, which also contain some blood-
vessels.

(6) Mild infiltration; early hydatiform degeneration.

No. 505

(1) Thomas S. Cullen, Baltimore, Maryland.

(2) A 70X35 X25 mm.

(4) The mole has a thick wall and contains a smooth
cavity measuring 502010 mm. A small nodule
was found attached to the lining membrane, but serial
sections show that it contains no embryonic remnant.

(5) Sections of the chorion and amnion show that both
are fibrous. The wall is degenerate, many of the villi hav-
ing undergone fibrous degeneration, while a few are mucoid.
Others show “granular hyperplasia.’’ Some of the villi
contain large central cavities. There is considerable fresh
blood between the villi which seems to nourish them. The
main wall of the chorion is necrotic in places and has been
invaded by leucocytes. There are many islands composed
- Resenete trophoblast and areas of villi are matted and

used.

(6) Severe endometritis.

STUDIES ON PATHOLOGIC OVA.

No. 518.

(1) Thomas C. Smith, Washington, District of Columbia.

(2) A 504540 mm.

(3) The specimen came from a patient whose period was
two weeks overdue.

(4) The ovum is covered with well-formed villi which
appear to be normal in shape as well as in their mode of
branching.

(5) Sections show masses of trophoblast between the
villi, many of which have undergone necrosis. The villi
and chorionic wall contain numerous large blood-vessels,
showing that at one time a normal embryo must have been

resent. The cord-like structure seen within is 10 mm.
ong and 1.5 mm. in diameter. This proves to be the
umbilical cord and contains a very large cavity, the tissue
of which is more or less dissociated. Scattered through
this tissue are a few very pronounced groupings of ce
which appear much like syncytium or trophoblast. It is
remarkable that this large, cord-like structure contains no
blood-vessels.

(6) Hydatiform degeneration.

No. 531.

(1) C. A. Rhodes, Atlanta, Georgia.

(2) A 19X19X19 mm.

(3) The specimen is from a multipara. This was her
sixth pregnancy, menses having been 17 days overdue.

(4) One side of the spherical specimen is covered with a
crescent-shaped group of villi, and the rest of it is nearly
naked, only a few very small villi being present. Within
the chorionic vesicle there is a delicate reticular magma
and a detached umbilical vesicle suspended in the center
of the cclom. There are also very opaque particles
present.

(5) The sections stained by the Mallory method show
beautifully the continuity of reticular magma with the
mesenchyme. The chorionic villi are covered with a
relatively small amount of trophoblast and contain rem-
nants of many blood-vessels. The walls of the free um-
bilical vesicle are dissociated, and numerous strands of
cells radiate from it into the adjacent magma. In addition
to this, another vesicle was found closely attached to and
directly continuous with the chorionic wall. This probably
is a rudimentary amnion.

No. 533.

(1) J. L. Fewsmith, Newark, New Jersey.

(2) A 35X30X30 mm.

(3) The patient missed one period which should have
occurred on May 17. She aborted June 15.

(4) The ovum is pear-shaped and well covered with
villi and some decidua. In general its external surface is
irregular and ragged. The ccelom is well filled with a dense
reticular magma containing two irregular bodies, one
6 mm., the other 5 mm. long. The latter lies in the am-
nion (?), the former in the middle of the exoccelom.

(5) Sections were cut of these bodies and of the chorion,
but they did not stain well. The chorionic wall is macer-
ated and nonvascular and some of the delicate villi aris-
ing from it are macerated and coalesce; others are
extremely degenerate. The trophoblast is scanty. The
round body, which appeared to be abnormal, was cut
into sections and found to be inclosed by a tough membrane
which does not stain. Its interior is filled with a granular
mass uniform throughout. Apparently we have here a
portion of the amnion with remnants of the yolk-sac, but
without any remnants of the embryo. The decidua is
very degenerate. f

(6) Very early hydatiform degeneration.

No. 555.

(1) G. C. McCormick, Sparrows Point, Maryland.
(2) A 302020 mm.
(3) Specimen said to be of a few weeks’ gestation.

Decidua absent.

CHORION WITH AMNION.

(4) The entire mass measures 453030 mm., and
contains a cavity lined with a smooth membrane. i
cavity is separated from the chorion by a delicate reticular

magma.

(5) The chorion and villi are fibrous, and many of the
latter are embedded in blood and disintegrating. The
trophoblast is necrotic, and its nuclei are turning into
dust, while the stroma is being invaded by leucocytes.
The decidua shows marked general infiltration and some
necrosis.

(6) Marked infiltration.

No. 556.

(1) E. J. O’Shaughnessy, New Canaan, Connecticut.
(2) A 3038030 mm.

(3) Patient has one child, 13 months old. Since birth ©

of child menstruated only once, September 3. Coitus
only once, about October 15. Abortion November 28.
Patient induced, or tried to induce, abortion by taking
12 gr. calomel and 20 gr. quinine about a week before.

(4) The mole is the usual fleshy variety, with a cavity
lined by the amnion. The whole mass is 503030
mm., within which is a cavity 30 mm. in diameter. In
this hangs a peculiar mass about 20 mm. wide, with a
ragged ending, which is probably the cord. It appears as
if the ovum had been injured mechanically in some way,
and that the embryo had been broken off.

(5) Sections of the chorionic wall show it to be fibrous,
and many of the villi are also undergoing mucoid degenera-
tion. The trophoblast is scanty and mostly necrotic,
the greater portion containing nuclear dust. Where it
comes into contact with the decidua, however, it appears
to have been growing with some activity. The fibrinoid
substance over the villi is very extensive, and this in turn
is partly covered with a degenerate decidua infiltrated with
leucocytes. :

(6) Slight infiltration of the decidua.

No. 564.

(1) Josiah S. Bowen, Mount Washington, Maryland.

(2) A 35X25X25 mm.

(8) The ovum was found protruding from the uterus
and was removed with the curette. This is the second
time the patient has been curetted.

(4) The specimen was perfectly smooth, but with spot-
ted surface. The larger part of it is solid. In the smaller
end there is a cavity measuring 20X10 mm., which is
filled entirely with granular magma. Deep down on one
side there is a smooth, pear-shaped opaque body, about
1.5 mm. in diameter and about 4 mm. long, which appeared
to represent the head of the embryo. The solid part of
the ovum is composed of an extensive mass of villi.

(5) Part of the chorion containing the suspicious mass
shows no trace of an embryo in serial sections. There are,
however, numerous other large cheesy masses within the
amnion which probably represent the disintegrating em-
bryo, but which are without structure. The chorionic
wall and villi are very fibrous, and some villi show granular
infiltration. There is considerable fresh blood within the
intervillous spaces. The trophoblast is quite abundant
and active. The decidua has a great deal of fibrinoid
substance upon its chorionic side, and is extensively in-
filtrated with leucocytes, showing that the uterus was
markedly inflamed. There is a degenerate, thickened
amnion.

(6) Marked infiltration.

No. 584.

(1) Henry Rohlfing, St. Louis, Missouri.

(2) A 37X31 X21 mm.

(4) About two-thirds of the ovum is covered with long,
irregular villi, branching two or three times, while the
remaining part is denuded. Within there is an extensive
mass of reticular magma. By varying the illumination,
the faint outline of a sac with a transparent body within

was suspected.

121

(5) Sections show the chorion and villi to be somewhat
macerated and hyaline. There is no trophoblast, but a
few buds of syncytium. The ccelom is filled with a dense
reticular and granular magma, and its serial sections
reveal the stub end of the umbilical cord about 2 mm.
in diameter, around the edges of which are attached large
folds of collapsed amnion. The outline of several blood-
vessels within the cord can be followed, and within the
amniotic cavity there is a débris of cells, showing that the
embryo has disintegrated.

(6) Decidua not included.

No. 605.

(1) Charles S. Parker, Baltimore, Maryland.

(2) A 455025 mm.

(3) The specimen was aborted after uninterrupted men-
struation; an unsuspected case of pregnancy, believed
to be illegitimate.

(4) The ovum is covered by a uniform layer of villi
which branch two or three times, and on one side is a
small patch of decidua. The interior is partly filled with
coarse strands of reticular magma, to which are attached
numerous granules. On one side of the specimen is an
umbilical cord surrounded by ragged amnion. The tip of
the cord has what looks like a piece of intestine and stom-
ach attached to it. The larger granules attached to the
reticular magma would seem to be remnants of the embryo,
parts of which appear to be normal.

(5) Sections include part of the amnion and the attach-
ment of the cord to the chorion. The amnion is disinte-
grating, macerated, and the tissues of the chorion are dis-
sociated and also macerated. The chorionic membrane
is somewhat hyaline and contains a few blood-vessles,
around which there is an invasion of round cells. Other-
wise it appears to be normal. The villi are hyaline and
practically non-vascular, with degenerate stroma and
epithelium. Between them there is a great quantity of
necrotic trophoblast. A fibrous, degenerate yolk-sac and
a stump of the cord with the degenerate vessels are the
only embryonic remnants found.

(6) Early hydatiform degeneration. Decidua absent.

No. 611.

(1) V. N. Leonard, Baitimore, Maryland.

(2) A 45X24X20 mm.

(4) The specimen is smooth, has thick walls, and con-
tains a well-defined cavity 25X8 mm. There is consid-
erable reticular magma within this cavity, and a loose
membrane, probably the amnion, is attached to one side
of the chorion. Adherent to this membrane is an irregular
fold, 5 mm. long, which attaches it to the chorion. On
the opposite side a small nodule of irregular shape is
closely attached to the walls of the specimen.

(5) Sections show that the thick-walled mole consists
of a thin chorion encircled by blood and a very hemor-
rhagic decidua, the deeper portions of which show marked
general infiltration. The amnion was not included in the
sections, but can be seen as a crumpled membrane within
the chorion among the blocks of tissue which were not
cut. The chorionic membrane is hyaline, and through it
are scattered numerous nuclei. It is surrounded by villi
of the same structure, radiating through much necrotic
trophoblast, with quite a good deal of fresh blood between
them. The trophoblast shows a little activity where it
comes in contact with the fresh blood. The fibrinoid
shows a curious stratification in some areas not seen in
other specimens. The very degenerate villi are encircled
by a very thick layer of fibrinoid substance, following
which is the very hemorrhagic and infiltrated decidua.

(6) Marked infiltration.

No. 645.
(1) C. A. Bentz, Buffalo, New York.
(2) Ovum 30X30X20 mm.

(4) One end of the ovum is covered with ragged villi.
The chorion is lined with a delicate amnion, and at one

122

end is a small pointed body, 3 mm. long, thought to be the
remnant of the umbilical cord. This is attached to a part
of the chorion which is markedly thickened.

(5) Sections through the chorion include a hemorrhagic
mass about 5 mm. in diameter, and show the amnion
greatly hypertrophied, much folded upon itself, and more
or less adherent to the chorion. What appeared to be the
umbilical cord in the» gross specimen is Eropanry, only a
fold in the amnion. There are few blood-vessels in the
chorion and one large epithelium-lined cavity. The villi
have undergone mucoid NepeuibratiGn and in some of them
there are numerous Hofbauer cells. Where they come in
contact with the blood-clot they are covered with active
trophoblast, which not only forms islands, but also streams
through the blood-clot.

(6) Typical hydatiform degeneration.

No. 651d.

(1) G. C. McCormick, Sparrows Point, Maryland.

(2) A 452525 mm.

(4) The ovum is covered with long, tortuous villi.
Within there is much reticular magma and the remnants
of a disintegrated embryo.

(5) The chorionic wall has lost its sharp contour, and
there are irregular strands of mesenchyme reaching from
it to the celom. This tissue comes in contact with a thin
membrane which seems to be the disintegrating amnion.
The villi have mostly undergone mucoid degeneration,
and there are a few clumps of trophoblast. There are also
buds of syncytium scattered quite equally throughout the
chorion. The villi and exoccelom contain many Hofbauer
sae) which are very large, many of them containing several
nuclei.

(6) Early hydatiform degeneration.

No. 65le.

(1) G. C. McCormick, Sparrows Point, Maryland.

(2) A 25X25X20 mm.

(4) The ovum is covered with regular villi which divide
two or three times and measure from 2 to3 mm. There is
much reticular magma within the exocelom, and within
the amnion a layer of granular magma.

(5) The chorion is fibrous and the villi show mucoid
degeneration. The trophoblast is scanty, but proliferatin
in places, with a stringy mass between the villi, senda
more or less by buds of syncytium. A remnant of the
yolk-sac is present.

(6) Early hydatiform degeneration.

No. 658.
(1) Thomas C. Smith, Washington, District of Colum-

ia.

(2) A 30X20X20 mm.

(3) Patient aged 41 years, married twice; three children
by first marriage, none by second. In this case the patient
says her menses came on time on March 12. On March
6s she had a sharp pain and the specimen dropped from

er.

(4) The smooth vesicle is filled with a jelly-like whitish
mass. On one side of the interior there is a transparent
mound about 3 mm. in diameter. The chorionic wall is
fibrous, covered with a few villi and an inflammatory,
rather fibrous decidua. The villi are mostly fibrous, non-
vascular, and the trophoblast scanty. Within there is a
vesicle embedded in the fibrous amnion.

(6) Mild infiltration.

No. 668.

(1) O. 8. Lowsley, Bellevue Hospital, New York.

(2) A 403020 mm.
: (3) Last period December 26; abortion in March fol-
owing.

(4) Ragged specimen, to which is attached a transparent
vesicle 10 mm. in diameter. The vesicle is attached to a
hollow stem which can be traced into the mass, and there

STUDIES ON PATHOLOGIC OVA.

communicates freely with the amniotic cavity. Within
this cavity is an opaque cylindrical body about 3 mm.
long, possibly the remnant of an embryo. No doubt the
ovum was injured some time before the abortion, causing
the amnion to protrude and leaving it attached to the
chorion. More careful examination of the specimen did
not reveal the presence of an embryo.

(5) Sections were cut through the chorion, but did not
include the amnion. The chorion is degenerate and the
villi large and swollen, most of them having undergone
mucoid degeneration, which is very complete in some cases.
They are matted together by blood, inflammatory exudate,
trophoblast, and many buds of syncytium, and contain
large Hofbauer cells. Marked leucocytic accumulations
are found at the periphery. Decidua is not included in the
sections.

(6) Hydatiform degeneration.

No. 682.

(1) G. H. Hocking, Govans, Maryland.

(2) Chorion with amnion.

(3) The woman had been married 18 years and had
eight consecutive births at term, followed by this abortion.
Syphilis suspected, but a Wassermann test gives a negative
reaction.

(4) The specimen consists of large pieces of decidua and
an ovum with a layer of ragged villi which are more or less
bound together by blood-clots and fibrinoid. The mass
measured in formalin 453030 mm. Upon further
dissection it proved to be a collapsed ovum lined with
smooth membrane, which does not contain an embryo,
The amnion is easily detached from the chorion, and the
remnants of the umbilical cord can be seen. However,
the specimen appears to be an ovum from which the em-
bryo has escaped.

(5) The chorionic wall is somewhat fibrous, and over it
there are degenerating matted villi. The encircling layer
is composed mostly of fibrinoid substance and a small
amount of decidua, which shows some general and con-
siderable local infiltration. There is some active tropho-
blast where the villi come into contact with fresh blood.

(6) Mild infiltration.

No. 689.

(1) Robert B. Slocum, Wilmington, North Carolina.

(2) A 32X28X20 mm.

(3) Patient aged 22 years; married slightly less than a
year. The last menstrual period was March 12 to 18,
abortion following on May 22. Said to be caused by an
automobile accident 2 days before.

(4) The ovum is spherical, measuring 322820 mm.
It is well covered with villi, some of which are larger than
others, showing marked swellings at their tips. At one
pole over 1 em. square, the villi are scanty and poorly devel-
oped. Judging externally, the specimen appears to be
abnormal. The clear area of the chorion was then re-
moved, and it was found that the ccelom was filled with a
very dense reticular magma. Within are opaque granules,
one of which is about 1 mm. in diameter. Upon removing
most of the magma a nodule, about 2 mm. long and evi-
dently representing the embryo, was found near that
portion of the wall of the chorion where the villi were best
developed. On examination of the specimen in this way
it was found that a poraan of the magma was glassy in
appearance and fell out easily, while the remaining part
was fibrillar, the fibrils radiating toward the embryo.

(5) The entire chorion was cut into serial sections,
those containing the nodule being mounted. There are
no blood-vessels in the chorionic wall, and the villi ap-
ane edematous, with a scanty amount of trophoblast.

here are numerous buds of syncytium. The amnion
is sharply defined, well folded upon itself, and attached
to the ss Pcie at one point, but contains no embryo.
There is, however, an umbilical vesicle—the nodule—
which is nearly disintegrated. Its blood-islands are small,

Decidua absent.

CHORION WITH AMNION.

but can still be outlined, and its interior is filled with

round cells.
(6) Hydatiform degeneration. Decidua absent.

No. 701.

(1) George H. Hocking, Govans, Maryland.

(2) A 705030 mm.

(3) Patient 22 years old. Married one year and the
mother of one child. Last period March 8; abortion
June 7, after a slight bloody discharge which had continued
for 2 weeks.

(4) The chorionic mass, which measures 705030
mm., contains a cavity 30X20 mm., lined by the
amnion, in which is a cylindrical mass 2 mm. in diameter
and 20 mm. long. No remnants of an embryo were found.

(5) The specimen consists of a chorion with many well-
developed villi covered with a great quantity of necrotic
trophoblast, blood, and fibrin. In this irregular mass are
growing many buds of syncytium. The mesenchyme of
the villi is somewhat fibrous, and scattered through it are
many Hofbauer cells. Sections through the umbilical
cord show the remains of large blood-vessels, indicating
that the embryo was well developed shortly before the
time of the abortion.

(6) Marked infiltration; early hydatiform degeneration.

No. 72361.

(1) Lawrence L. Iseman, Chicago, Illinois.

(2) A 604040 mm.

(4) Ovum filled with magma. Umbilical cord is normal
in appearance.

(5) The structure of the villi and of the chorionic mem-
brane is quite normal. The mesenchyme of the villi
contains great quantities of Hofbauer cells, and is largely
non-vascular. Between the villi there is a great deal of
fresh blood, and into this are growing numerous buds of
syncytium. The surrounding tissue is markedly inflamed.
Remnants of the amnion are attached to one end of the

cord.
(6) Marked infiltration.

No. 7236.

(1) L. L. Iseman, Chicago, Illinois.

(2) A 50X35X30 mm.

(4) Ovum with smooth, fleshy wall, which is thickened
and lined by the amnion, which has fused with the chorion.

(5) The villi, which are necrotic, have undergone partial
mucoid degeneration and are surrounded by a degenerated,
fibrous decidua. The spaces between the villi are filled
entirely with fibroid which apparently has cut off the
nutrition. There is very little trophoblast.

No. 757.

(1) A. C. Smink, Baltimore, Maryland.

(2) A 50X50X25 mm.

(3) Patient aged 30 years; married in 1909. Two preg-
nancies. Last menstrual period June 20 to 24, 1913, and
abortion September 18 following. Condition of uterus
poral, no venereal diseases. Patient belongs to a prolific
amiliy.

(4) The specimen is disk-shaped and measures
505025 mm. It is covered by a delicate membrane,
which suggests that the ovum has been turned inside out.
Sections of this mass show the interior to be composed
mostly of a stratified blood-clot, intermixed with numerous
irregular villi.

(5) Microscopic examination shows that the outer
layer above noted is composed of the inverted membranes
which surround a blood-clot containing some villi. The
stroma of the latter is decidedly fibrous, non-vascular, and
degenerate, suggesting rapid destruction. The epithelium
is quite well preserved, but the “appendici durate’’ are
necrotic. Hofbauer cells are quite common, and the
stroma in many p! , and even whole villi, have under-
gone coagulation necrosis, In other villi it is fenestrated.

123

The blood-cells are well preserved in many portions of the
clot, but the stroma of both membranes has undergone
hyaline degeneration.

(6) Decidua not included.

No. 771a.

(1) B. T. Terry, Brooklyn, New York.

(3) Patient had a miscarriage in 1900. From that time
until June 28, 1913, she menstruated regularly, then the
periods became irregular, until she was operated upon
September 5, 1913. At operation it was found that the
ovaries and left tube were normal, but that there was a
chronic endometritis. Venereal diseases denied.

(4) The specimen is formed of blood-clot containing a
cavity 13 mm. in diameter.

(5) The sections show very degenerate fibrous villi
which are matted together in hyaline material and necrotic
decidua. Between the villi and the decidua there is fibrin-
oid substance. The chorionic membrane is thickened,
macerated, and degenerated, and neither it nor the villi
contain any blood-vessels. The amnion, which is decidedly
macerated and degenerate, is folded. No evidence of
inflammation.

No. 803.

(1) W. J. Weese, Ontario, Oregon.

(2) A 43X26X23 mm.

(3) First pregnancy of a woman aged 21 years, married
March 23, 1913. Last menstrual period October 15 to 19,
1913, and abortion November 26 following. No infection
of uterus. No venereal diseases. Mother of patient had
one abortion.

(4) The chorion has a very thin, hemorrhagic wall lined
with a smooth membrane. On one end is a small tuft of
villi. There is a considerable reticular magma, and on one
side a nodular embryo 3 mm. long.

(5) The chorionic membrane, which is somewhat fibrous,
is covered with matted villi which have undergone fibrous
degeneration. There is a great deal of fibrinoid and large
hemorrhages. On the outside is a layer of unorganized
clot. The nodule consists of what appears to be a collapsed
amnion. As the sections were not serial, it is impossible
to determine the exact relation of this membrane to the
chorion. The decidua is decidedly necrotic, fibrous,
slightly infiltrated, and hemorrhagic.

(6) Slight infiltration.

No. 813.

(1) H. D. Taylor, Baltimore, Maryland.

(2) A 80X50X25 mm.

(8) First pregnancy of a woman aged 24 years, married
August 10. Last menstrual period June 13 to 17, same
year; abortion December 30 following. No venereal dis-
eases. Family fertile.

(4) The specimen appears ulcerated and is composed of
a flattened oval mass measuring 805025 mm. After
opening it, the chorionic wall was found to be sharply
defined, with numerous hemorrhages between the villi.
The cavity measures 70X35 mm. and is filled with a tough,
clear jelly.

(5) Sections of the chorion show that the wall is very
thick and fibrous, and that at many points it appears to be
composed of two layers. The amnion is closely attached
to the chorion. Some of the villi are completely degen-
erated, and others are fibrous and matted together by a
large amount of fibrinoid substance. There is a necrotic
decidua, the cells of which are arranged in whorls in some
places, and which is markedly infiltrated in some areas.

(6) Marked infiltration.

No. 814.

(1) J. M. Melton, Crozet, Virginia.

(2) A 55X25 X25 mm.

(8) The sixth pregnancy of a woman aged 43 years, mar-
ried 18 years. Fourth pregnancy ended in abortion 7

124

ears before. November and December periods missed
era this abortion, December 26. No venereal diseases.
Family very fertile.

(4) The mole is solid, stratified, and hemorrhagic,
measuring 55 25X25 mm. Upon opening, it was found
to be composed of a slit-like cavity running into the larger
part of the specimen, which upon sectioning proves to be
the amniotic cavity.

(5) Into this there extends the stub of an umbilical cord
containing several very large blood vessels, and also a
large cavity partially filled by a reticular mass. The cho-
rionic wall and villi are very fibrous, and are matted
together into a great mass by blood and quite active tropho-
blast. On the outside are remnants of decidua which are
markedly inflamed.

(6) Severe infiltration.

No. 922.

(1) H. F. Cassidy, Roland Park, Maryland.

(2) A 60X45 X26 mm.

(3) Negro, age 24 years, married in 1908. Two children,
5 and 2 years. This is the only abortion. Last menstrual
period May 20 to 22 and abortion June 24 following (1914).
Four or five days before abortion just a show, then about
a normal flow. Lifted a heavy child and felt some pain
then. No history of infection. Pregnancies not attended
by fever.

(4) The specimen is a pear-shaped abortion mass meas-
uring 60X45X26 mm., and consists chiefly of thick,
blood-infiltrated chorionic walls which inclose a smooth-
lined cavity 20X9 mm. No trace of an embryo can be
seen.

(5) The specimen is very hemorrhagic, with a very thin
chorionic membrane and an amnion which is much folded
upon itself. The decidua is ill-preserved, markedly infil-
trated and hemorrhagic, and near it lie a very few fibrous
villi. The trophoblast is mostly necrotic. The wide space
(5 mm.) between the decidua and the chorion is filled with
fresh blood.

(6) Marked infiltration; some hydatiform degeneration.

No. 960a.

(1) Marcus Ostro, Baltimore, Maryland.

(2) A 90X70 X25 mm.

(3) Patient aged 32 years, married in April 1909. Three
pregnancies, one abortion. Last menstrual period October
3 to 8, 1914; abortion October 16 following. Patient dis-
charged from hospital March 29, 1914, after having had a
post-partum hemorrhage. Menstruated regularly every
month thereafter until abortion, each period lasting 4 to
6 days. Flow free, no pain. Two days after the last period
ceased, bleeding began again and continued up until the
time of entrance to the hospital, October 15. The hemor-
rhage was very profuse during the two days preceding the
abortion, and the patient had become very weak and ane-
mic. On October 16 the specimen was passed. Husband
has triple-plus Wassermann on blood and spinal fluid.

(4) The specimen consists of a mass of clotted blood
907025 mm., but the greater part is separated easily,
leaving a placental mass with torn chorionic sac. No
embryo was found. What was apparently the stump of
the umbilical cord could be recognized.

(5) Sections of the chorion show a leucocytic infiltration
within its cavity which involves the amnion. The villi are
well-developed, largely non-vascular, and have undergone
a peculiar degeneration which is neither mucoid nor fibrous;
they are matted together with inflamed exudate, mucoi
substance, and more or less active trophoblast. There are
also numerous plaques of nuclear dust. A layer of fibrinoid
substance covers the chorionic membrane as well as the
tips of the villi. ‘There are nests of trophoblast cells
within the inflammatory mass, probably within the blood-
vessels. It would appear as though the embryo escaped
some time before the abortion, leaving a normal chorion
which underwent degeneration.

(6) Intense infiltration.

STUDIES ON PATHOLOGIC OVA.

No. 962a.

(1) J. M. Jackson, Pittsburgh, Pennsylvania.

(2) A 35X35X35 mm.

(4) The specimen is covered with decidua and has a
smooth inner surface, to which is attached a delicate cord
about 15 mm. long. This ends in a collapsed bag, measur-
ing 30X5X8 mm., apparently in the amnion.

(5) Sections of the chorion show it to be thin and lined
with a great deal of reticular magma. ‘The villi on the
outside are delicate, the mesenchyme having undergone
mucoid degeneration, and there is some mucoid substance
between them. The individual villi are well covered with
trophoblast, all of which is vascular and very much more
extensive than usual.

(6) Early hydatiform degeneration.

No. 976.

(1) J. C. Bloodgood, Baltimore, Maryland.

(3) Patient a 38 years; married. One pregnancy 2
years before, ending in miscarriage at second month.
Family and past history unimportant. Present trouble
began with nausea about 4 months before curettage.
At first this was slight and intermittent, but for the last
2 months it had been continuous and severe. Patient
noticed no irregularities or abnormalities about her
periods until September, when, although appearing on
time, the flow was very scanty and lasted only 3 days
instead of a full week as previously. After that she be-
came worse, and there was bleeding for 2 weeks before
operation. The hemorrhage was slight, and at no time
did she pass any clots. During that time the patient was
constipated and constantly nauseated, vomiting every-
thing she took. At no time did she have any pain bei
a dull backache. This had been present for 4 mont
and was worse at her periods. No leucorrhea. _

(4) Specimen consists of about 40 c.c. of uterine curet-
tings, a considerable portion of which is chorionic mem-
brane. Attached to one piece of this membrane is a
cylindrical embryo 5 mm. long. Part of the chorion
appears to have normal villi, while sections of another
show its main wall to be very fibrous and the villi quite
edematous, containing many Hofbauer cells. The entire
ovum is encircled by a mass of leucocytes and shows an
extensive inflammatory reaction in the uterus. The part
of the chorion containing the embryo does not seem to
have this inflammatory reaction. é

(5) The piece of the chorion to which the assumed
embryonic mass was attached was cut into serial sec-
tions, but upon examination it was found not to be such.
The overlying trophoblast at this point and the decidua
are very markedly inflamed.

(6) Severe infiltration.

No. 985.

(1) A. F. Ries, Baltimore, Maryland.

(2) A 705035 mm. :

(3) Patient aged 34 years; married about 14 years.
Seven previous pregnancies. ‘This abortion November 19
1914. Endometritis, cystocele, rectocele, and lacerated
perineum. Family fertile. Specimen was passed in two
parts, with 12 hours interval between; first the ovum,
then the decidua. ae

(4) Ovum 70 X50X35 mm., with thick irregular walls.
Apparently it is inverted and contains a fibroid nodule.
3 mm. in length, which, when sectioned, seemed to be
the umbilical cord. ; : een

(5) Sections show the chorion with many villi, with
degenerate nuclear mesenchyme containing some blood-
vessels. There are several enormous Hofbauer cells
scattered through the villi; in fact, they might be called
giant cells. There is a great deal of blood between the
villi, and the trophoblast is fairly active. The overlying
decidua is very hemorrhagic and infiltrated. The embry-
onic nodule was cut into serial sections and proved to be
the umbilical cord, which has undergone fibrous degenera-

NODULAR CYEMATA.

tion. Within the cord there is an epithelial vesicle,

possibly the remnant of the allantois. Besides the cord

there is the amnion, which is thrown into many folds

and which has also become very fibrous and degenerate.
(6) Marked infiltration.

No. 1001.

(1) Geo. Heller, Baltimore, Maryland.

(2) A 65X43X25 mm. (abortus); 423020 mm.
(chorion).

(4) The specimen is composed* of a partially torn
decidua containing a chorionic sac partly filled with clear
fluid, and a small oval mass 1 mm. long which may be the
remains of an embryo. The amnion, which is partially
fused with the chorion, is approximately two-thirds its
size. Where it is separated from the chorion reticular
magma is present. When examined under the binocular
microscope the presence of hydatiform degeneration easily
is revealed. The decidua is only slightly hemorrhagic.

(5) The best examples of hydatiform villi which are
already vesicular in form are found near the basalis, which,
like all the rest of the decidua, has undergone autolysis
and shows a few small areas in which there is an increase
in round cells. Otherwise no evidence of infiltration was
noticed. Some of the villi and membranes contain small
numbers of atypical Hofbauer cells, and the stroma of
all the villi is degenerate. The epithelium is not well
differentiated and shows no evidence of unusual growth.
The trophoblastic nodules also are degenerate and no
remnants of an embryo were seen. A fair quantity of ill-
preserved blood is found between the villi.

(6) Hydatiform degeneration with slight infiltration
and autolysis of the decidua.

No. 1005.

(1) H. B. Titlow, Baltimore, Maryland.

(2) A 48X36 X35. mm.

(4) On cutting the clot, “caseous magma’’ welled out,
clotting immediately in the bichloride in which the clot
had been placed. No embryo was found in the necrotic
contents, which apparently represents the degenerate con-
ceptus.

(5) Microscopic examination reveals nothing but the
very degenerate vesicles with villi and decidua.

GROUP 4.

No. 11.

(1) F. E. Kittridge, Nashua, New Hampshire.

(2) A 10X7X7 mm.; embryo 0.8 mm.; umbilical vesi-
cle 1.5X1 mm.

(3) Patient aged 25; menses regular every 4 weeks,
periods lasting from 4 to 5 days. She gave birth to a
child Spetember 19 and had the first recurrence of men-
struation December 19. The second period followed on
January 25, was very profuse, and lasted until February
1. She missed her next period, concluded she was preg-
nant, and called upon the physician a few days later.
March 1 she fell and hurt herself, and during the
night had a scanty flow. This recurred each day, and on
March 7 she passed the ovum.

(4) The ovum is very large for its age, having a long
diameter of 10 mm. and a short diameter of 7 mm. It is
covered with villi only around its greatest circumference,
having two spots without villi, as was the case with Reich-
ert’s ovum. The villi of the chorion are from 0.5 to 0.7
mm. long, branched and somewhat fibrous in structure.
Upon opening the chorion it was found that the embryonic
vesicle was situated just opposite the edge of the zone of
villi. About it there was a considerable quantity of
magma réticulé which was not removed. The portion
of the chorion to which the vesicle was attached was cut
and from the sections a reconstruction made in wax.

(5) The sections and reconstruction show that the
embryonic vesicle is attached to the chorion by means of

125

astem. The greater part of the vesicle itself is composed
of two layers, ectoderm and mesoderm. In the neighbor-
hood of the embryonic stem there is a third outer layer
which shows all of the characteristics of the ectoderm.
Just beside the attachment of the vesicle to the stem
there is a sharp, deep, and narrow invagination of all
three embryonic membranes. Within the stem a sharply
defined allantois communicates with the cavity of the
vesicle just below the cavity of the ectoderm. The
ectodermal plate of the evagination is very broad, but
not of equal thickness throughout. It extends to the
outside of the vesicle and ends quite abruptly in the
neighborhood of the stem. The blood-vessels of the
mesodermal layer extend to the stem, but do not enter it,
nor are there any blood-vessels in the chorion. Since the
first publication of this specimen our studies, both of
normal and pathological material, have been greatly
extended, and seem to prove even more clearly that this
specimen must belong to the pathological class. The
other pathological specimens in our collection, as well as
the perfect, normal specimen described by Peters, all
speak for this conclusion. Yet the presence of all three
blastodermic membranes, with blood-islands in the meso-
derm and an allantois in the embryonic stem, indicate
that the specimen can not be far from the normal, but
represents the earliest changes in the blastodermic mem-
branes of an ovum of the Peters stage under pathological
conditions. The villi coalesce and are matted somewhat.
The chorion is macerated.

No. 14.

(1) J. Friedenwald, Baltimore, Maryland.

(2) A 30X30X30 mm.; within is a small double vesi-
cle with a short pedicle 1.5 mm. in diameter.

(5) The mesodermal layer of the chorion is thin and
decidedly fibrous, with but few cells scattered through
it. There are groups of cells in the chorion at the base of
the vesicular embryo. The walls of the vesicle are thick,
without blood-islands, and covered with a single layer of
epithelial cells which have fallen off at points. Scattered
throughout the mesoderm are numerous cells. At the
base of the vesicle there are a few blood-spaces containing
blood-cells. At the base of the larger vesicle is a large
closed space. A similar space lies immediately below the
smaller vesicle. The small embryonic nodule shows but
slight differentiation, and the whole specimen is con-
siderably macerated.

No. 24.

(1) C. O. Miller, Baltimore, Maryland.

(2) Chorion 21X16X5 mm., with vesicular nodule.

(4) The ovum was completely covered with villi which
branch a number of times. Upon opening the specimen,
it was found that the celom was filled with magma
réticulé of moderate density; no trace of an embryo could
be found. When placed in direct sunlight a small nodule
became visible. The walls of the vesicle are composed of
three layers, the outer being greatly thickened at points,
but retaining sharp borders. The mesoderm is hyper-
trophic. The inner layer is irregular—thick. and thin—
with a tubular branching process which extends to the
stem of the vesicle. There are blood-islands in the vesicle
and stalk, and the vessels extend to the villi of the chorion.
The trophoblast is very extensive, forming large buds
upon the chorion as well as upon the villi. At points these
buds coalesce to form islands, the centers of which are
composed of a necrotic mass filled with fragmented nuclei.
The amnion is absent, but a remnant of the allantoic
stalk is found in the chorionic membrane. A small mass
of tissue near the yolk-sac, and continuous with it, may
be a remnant of the embryo. This shows but little differ-
entiation. The villi show typical hydatiform degeneration.

(6) Hydatiform degeneration.

126

No. 25.

(1) J. W. Lord, Baltimore, Maryland.

(2) A 252525 mm., with pedicle 6 mm.

(4) The ovum is covered entirely with long villi, and
one side of it is hemorrhagic. The pedicle within
shows all the characteristics of the umbilical cord of an
embryo 5 weeks old. No trace of an embryo, however,
could be found, but at the free end of the pedicle, which
has very ragged edges, are a number of cells. The amnion
lines the entire ccelom and is reflected over the pedicle,
just as it would be over a normal cord.

(5) Sections show that the club-shaped, cylindrical
body is in fact the cord with its blood-vessels and amnion
The free end of the cord is rich in round cells, appearing
much like the granulation tissue of healing wounds.
this point the end of the cord is infiltrated with cells, in
addition to the nucleated cells of the cord. It appears
as if the embryo had gradually fallen off, piece by piece,
leaving the ragged stump of a cord, the blood-vessels of
which are but sparsely filled with blood. At the base of
the cord there is a remnant of the umbilical duct. The
chorion apparently is normal, but macerated.

No. 32.

(1) W. D. Booker, Baltimore, Maryland.

(2) Ovum 303030 mm.; within is a pedicle
9X2 mm.

(3) Patient is a colored woman. Last menstruation
began December 26 and lasted 4 days, the usual duration
being from 4 to 5 days. Cohabitation with husband
December 12 and January 9. Hemorrhage began March
14 and continued until the 18th, when the abortion took
place. Time between beginning of last period and the
abortion, 82 days.

(4) Within the ovum was a large pedicle 9X2 mm.,
which had every appearance of the normal umbilical cord
of an embryo 25 mm. long. The age of the ovum, as
estimated by the menstrual history, calls for a cord of
this size, but the chorion is undersized.

(5) There was no embryo, but at the point where the
cord should be attached to the body is a mass of cells,
making it appear as though the embryo had sloughed
away. At this point the blood-vessels are greatly dis-
tended with blood, which permeates also into the sur-
rounding tissues. Within the cord is a large as well as a
smaller space. The mesoderm of the chorion and villi is
fibrous and the chorion thickened. The stroma of many
of the villi is decidedly dense, suggesting ‘‘granular
hyperplasia.’’ The vessels are degenerate or altogether

absent.
No. 37.

(1) G. M. Gould, Philadelphia, Pennsylvania.

(2) A 25XK18X15 mm.

(4) The entire ovum is covered with villi which appear
normal in form, both to the naked eye and under the
microscope.

(5) The specimen was macerated considerably, but the
thick sections made of it are extremely instructive. The
embryonic mass within proved to be an atrophic cord,
embryo and umbilical vesicle. The cord with its blood-
vessels passes directly over into the head end of the em-
bryo, which contains but a rudimentary nervous system.
The mesodermal tissues are characteristic and the form
of the pharynx and the lower jaw is recognizable. From
this region two branchial arteries pass into the cord. A
single vein, however, extends from the cord directly into
the center of the body and ends just below the lower jaw.
There is no heart, liver, myotomes, or lower end of the
body, these being replaced by the cord. The arteries are
empty and the vein is distended with blood.

No. 58.
(1) W. Howard, Cleveland, Ohio.
(2) A 20X15X12 mm.
(3) The specimen was from the first pregnancy of a
woman who has been married one year. ‘The duration of

STUDIES ON PATHOLOGIC OVA.

the menstrual period was usually 3 to 4 days, the last one
having ended July 25. The August and September periods
were passed, and September 30 she had a hemorrhage
which she believed to be the usual menstruation; this
ended October 1 with abortion of the ovum. The time
between the beginning of the last period and the abortion
is 71 days. Cohabitation July 25 to August 5, and again
on August 15, or several days before the first period lapsed.

(4) The ovum was only partly covered with villi and
filled with a jelly-like mass of magma. Floating within
this mass was a large vesicle, 6 mm. in diameter, with
transparent walls. This vesicle in turn was partly filled
with granular magma.

(5) The trophoblast is excessive. The mesoderm of the
chorion and inclosed vesicle is very fibrous. There are
blood-islands and a cavity lined with epithelium in the
stem of the vesicle. The main portion of the vesicle is
composed of two layers, but near the stem three layers are
present. The mesoderm of the villi is hyaline and edema-
tous, and between them is a stringy mass of fibrin, rich in
leucocytes. Some of the villi have coalesced and the
stroma of others suggests “granular hyperplasia.’ The
amnion is very much larger than the embryo. Both
chorion and amnion show some maceration. The embry-
onic mass at the base of the amnion is well preserved and
contains blood-cells and a small cavity.

No. 78.

(1) A. P. Stoner, Harlan, Iowa.

(2) A36X33 X13 mm.; B 1 mm.

(3) Last menstrual period December 1; abortion took
place February 26 following. The sac was perfectly
smooth when passed. After the abortion two or three
pieces of decidua and placenta were passed, weighing
together about 30 grams, the right quantity, it seemed, for
a 10-weeks’. ovum. The woman’s husband had been
absent for over 10 weeks, making the specimen at least
that old. It appears as if there had been an arrest of
development of the embryo and that the membranes con-
tinued to grow.

(4) When the specimen came to the laboratory the walls
were perfectly smooth, without any villi whatever. The
cavity was filled with a clear fluid, and within this was
attached a small double vesicle, measuring 10.6 mm.
This was embedded and cut in serial sections.

(5) The nodule within is covered with a single layer of
epithelial cells which become thickened over the pedicle.
At one point the thickening is greatly increased, and
immediately below it there are two small vesicles lined
with epithelial cells. The main cavity of the vesicle is
lined with a layer of cubical cells, and is filled with a con-
siderable quantity of round cells. This cavity is hour-
glass in shape and extends to the walls of the chorion.
The mesoderm of the vesicle is increased in quantity. At
the base are several blood-spaces filled with blood. The
chorionic membrane is absent, which accounts for the
smooth nature of the specimen; but a few detached,
degenerated villi are present.

No. 111.

(1) Dr. Gray, Washington, District of Columbia.

(2) B 3mm. long.

(5) Specimen is a greatly dissociated embryo, in which
there are two very large cavities and a remnant of the
central nervous system, entirely filled with cells. The
amnion is present in some of the sections, but in all of
them the chorion is absent. No decidua accompanies
the embryo.

No. 134.

(1) G. N. Sommer, Trenton, New Jersey.

(2) Ovum 17X11 mm., with compressed vesicle measur-
ing in sections 9 x 3 mm.

(3) A number of sections of this unique specimen were
received from Dr. Sommer with the statement that the
ovum had been passed by a young multipara, after con-

NODULAR CYEMATA.

siderable pain and hemorrhage due to the introduction of
a bougie to produce abortion. The monthly period had
been five days overdue when the abortion occurred. The
bougie had been introduced several days earlier.

(5) In stirring up the ovum the woman punctured it,
and it then became filled with maternal blood, which
formed a clot around the embryo. The leucocytes
invaded the walls of the ovum, the stem of the yolk-sac,
and even the blood-vessels of the embryo, and show all
stages of fragmentation within the embryonic tissue. The
yolk-sac itself is most interesting, as it shows the effect
of an infraction upon a very young normal embryo. The
stem of the vesicle is quite extensive, and in it are embry-
onic blood-vessels filled with blood. Many of them extend
into the chorion and some into the villi. The walls of the
yolk-sac are composed of three distinct layers. The inner
is composed throughout of a single layer of sharply defined
cubical epithelium—the entoderm. Immediately next to
this is an extensive mesoderm which continues into the
mesodermal layer of the stem to the chorion. Near the
attachment of the vesicle to the chorion there is a sharp
evagination of the vesicle, which is lined with a thick layer
of epithelial cells—the ectoderm. This layer lines only
the evagination and does not extend over the rest of the
vesicle. Beyond and on the distal side of the evagination
the mesoderm is arranged in five groups of cells which in
every way suggest myotomes. In this region there are
embryonic blood-vessels filled with blood. The syncytium
is very extensive.

The blood-clot from the mother’s blood, within the
ccelom, is recent, as is shown by the fact that many red
blood-corpuscles are present. In the periphery of the
clot, next to the chorion, the red corpuscles are partly
broken down and appear as an imperfect granular detritus
containing a network of fibrin. There are as yet no pig-
mentary changes in the tissues adjacent to the clot. The
latter extends through a tear in the chorion into the celom,
and as this portion is approached it is noticed that its
characters change. The red blood-corpuscles diminish in
number, and the main coagulum consists of leucocytes
which extend through the surrounding tissues. This mass
of leucocytes also extends along the border of the red clot
into the cavity and walls of the vesicle. The blastoderm
cells are intact on one side of the vesicle, whereas on the
other they have suffered desquamation and have retracted
from its walls. A part of the leucocytes composing this
part of the clot are in a very imperfect state of preserva-
tion. They show great irregularities in the forms of their
nuclei and are in a state of fragmentation. Fragmented
leucocytes extend throughout the clot, a great portion of
the chorion, and through the walls of the embryonic vesicle.
The tissue elements of the embryo are for the most part
well preserved. ‘There is no evidence of extensive necrosis.
Occasionally where the clot of red and white corpuscles
and fibrin becomes clearly intermingled with the villi of the
chorion the syncytial cells stain imperfectly. The blood-
vessels of the chorion contain numerous leucocytes, con-
stituting in some instances what appear to be leucocytic
thrombi. One section was stained for bacteria, but none
were found. The process as a whole is to be interpreted
as an acute hemorrhagic inflammation of the embryonic
structures. The large number of leucocytes undergoing
fragmentation indicates that the inflammatory irritant
was of a severe nature and had acted with a considerable
degree of intensity, as is shown not only by the rich immi-
gration of leucocytes, but by the severe retrogressive
changes which they have undergone.

No. 161.

(1) H. F. Cassidy, Baltimore, Maryland.

(2) A 50X25X25 mm.; B 10 mm.

(3) “Last period at the end of August. Abortion
November 17. After missing the next period patient
took medicine and had a rubber tube introduced into the
uterus. Purulent leucorrhea during the past six months.

127

(4) The entire ovum was covered with hard clots of
blood, but on one side the villi appear to be normal. Upon
opening the ovum a mass measuring 10X55 mm. was
found attached to its walls.

(5) Upon sectioning, this proved to be a strangulated
embryo of the fifth week, filled and covered with round
cells. These cells have obliterated the structure of the
head entirely, but as the tail end of the body is approached
the outline of the organs still can be followed. The villi
of the chorion are enveloped in a great mass of blood and
pus, and the syncytium is excessive. Within the stroma
of the villi at many points are numerous round cells which
appear to be migrating cells from theembryo. The vessels
of some of the villi and of the chorionic membrane appear
to be normal.

(6) Decidua necrotic and infiltrated.

No. 162.

(1) A. Wanstall, Baltimore, Maryland.

(2) A 70X30X30 mm.; B 1 mm.

(3) ‘Last period from September 2 to 7, five days being
the usual length of periods. The woman began bleeding
November 9 and passed the specimen on November 22.
She is the mother of five children and states that this is the
only time she has aborted. There is not the slightest
indication of uterine disease.”

(4) Within the specimen is a cavity measuring 35 X12 «12
mm., lined with a smooth wall and filled with a jelly-like
substance, within which is a very small embryo.

(5) The sections show a remarkable atrophy of the
embryo and umbilical vesicle. The chorion is very thin
and composed of mesoderm only. The villi and epithelial
cells are lacking, but in their place is a thick layer of mater-
nal blood. The entire chorion is lined with an amnion, and
into its cavity the nodule-like embryo projects. Its tissues
are not uniform, being thickened at some points, necrotic
at others, and mucoid at others. Throughout the center
of the nodule are some capillaries filled with blood. At the
point of juncture between the amnion and chorion there
are three projections from the embryo into the ccelom:
(1) the umbilical vesicle; (2) the allantois; (3) the heart.
That the second is the allantois is indicated by its cavity
which is multiple at points. The heart is within a pocket
of the ccelom and has an irregular lumen which is well
filled with blood. At the base of the nodule there is a
short tube which communicates with the allantois—the
intestine.

No. 166.

(1) H. F. Cassidy, Baltimore, Maryland.

(2) A 404040 mm.; B 2.5 mm.

(3) Last period October 18; on December 29 there was
a discharge of blood which continued until the 31st, when
the mole was expelled.

(4) The mole is composed of very thick, fleshy walls,
within which there is a cavity with a smooth wall, measur-
ing 30X20X20 mm. On one side there is a small
atrophic embryo 2.5 mm. long.

(5) The sections of the chorion show that its villi are
well formed and are embedded in a mass of blood. Pos-
sibly the syncytial layer of epithelium is increased. The
ccelom side of the chorion is mooth and in contact with
the amnion. Attached to the latter is the embryonic
mass or remnant which does not reach to the chorion. No
umbilical vesicle is to be found. The amnion and embryo
are completely separated from the chorion, which is non-
vascular. The embryo is nodular in form, being at-
tached throughout half its length to the amnion, and
passes through the latter. In the center of the embryo
there is a solid column of cells quite sharply defined—the
remnants of the central nervous system. At the tail end
of the embryo there is a blind tube—the allantois. The
ccelom of the embryo, which lies as a pocket on its ventral
side, contains an irregular sac which may be either the
heart or the umbilieal vesicle, probably the former.

128

No. 189.

(1) T. BE. Oertel, Augusta, Georgia.

(2) A 28X25X15 mm.; B 4 mm.

(4) The ovum, filled with granular and reticular magma
contains a deformed embryo lying within a distended
amnion, 8 mm. in diameter.

(5) The umbilical vesicle and amnion appear to be
normal for an embryo of this size, but the body is greatly
deformed, the central nervous system is open throughout
its extent and partly encircles the dwarfed embryo like a
broad hoop around a ball. A number of the motor roots
of the spinal nerves are developed, more in the region of
the tail than elsewhere. There are no cranial nerves. The
heart is a vesicle filled with blood, hanging into the celom
and slightly attached to the body-wall. Its vascular con-
nection with the body is entirely cut off. The blood-
vessels of the body are irregular in shape and gen’
changed from the normal type. They are filled wit
blood, which extends through their walls into the sur-
rounding tissues. The branchial arches correspond to
an embryo of this size. There are still traces of optic
vesicles, chorda, and possibly allantois, the liver, stomach,
and intestines having degenerated.

No. 198.

(1) R. E. Larsen, Chicago, Illinois.

(2) A 25X25X25 mm. '

(4) The interior is filled with considerable reticular,
and large clumps of granular magma. Embedded in this
is a large cylindrical pedicle, 7 mm. long, bent upon
itself. Sections of the specimen show the pedicle to be
the umbilical cord rounded off at its former juncture
with the embryo. ;

(5) The mesoderm of the cord, thickened chorion,
and villi is fibrous, having also an excess of spindle-
shaped cells. The blood-vessels are all very large, those
of the villi as well as most of those of the main wall being
gorged with blood. The large blood-vessels of the cord
are empty. Within the cavity of the amnion, scattered
throughout the magma, are numerous flakes of tissue of
the embryo and a great many free cells.

No. 244.
(1) M. Brédel, Baltimore, Maryland. (From Dr.
Kelly’s sanitarium.)
(2) B 4mm.

(4) The specimen is inclosed in the amnion, which
measures 25X15X15 mm., and is surrounded by a
mass of granular magma.

(5) The sections show the amnion attached along most
of the ventral side of the embryo, somewhat as it is in
the normal specimen at the end of the second week. The
central nervous system is still quite sharply defined,
being more characteristic in the head than in the trunk.
The heart is composed of a solid mass of cells in the front
of the embryo, and extends as a horn-like process to the
head. Between the heart and the body there is a large
group of epithelial cells, in which are scattered some
small round cells, probably the remnant of the liver.
Otherwise the tissue of the embryo is of even structure,
with an occasional necrotic area. Most of the epidermis
is missing. Neither umbilical cord nor umbilical vesicle is
present, the free embryo being attached to the amnion only.

No. 247.

(1) W. S. Seymour, Trappe, Maryland.

(2) A 404017 mm.; B 2.5 mm. ‘

(4) The ovum was found filled with granular magma,
and in the center, far away from the chorion, there is a
free body.

(5) Sections of the chorion show that it is slightly
macerated, and that the stroma of the villi has undergone
hydatiform degeneration. The villi are without capillaries
and the amnion is missing. At points between the villi the
trophoblast cells form mounds below the epithelium,

STUDIES ON PATHOLOGIC OVA.

which have a tendency to penetrate the mesoderm of the
chorion. The pear-shaped body is probably the embryo.
It contains cavities lined with epithelium and surrounded
by a considerable amount of mesoderm which contains
numerous blood-vessels filled with blood. There are some
accessory vesicles in this layer similar to those found in
No. 78, described above.
(6) Hydatiform degeneration.

No. 253.

(1) M. Brédel, Baltimore, Maryland.

(2) A 353015 mm.; B 4 mm.

(5) Chorion and villi are somewhat hyaline, with only
indications of blood-vessels within them. ‘The amnion,
which measures 19X13X13 mm., is attached at one
point, has hyaline walls, and does not contain the embryo.
The latter is a swollen infiltrated specimen of the third
week, with no brain and little of its spinal cord left. The
rest of the structures (heart, celom, and Wolffian body)
are quite sharply defined, but are well infiltrated with
round cells. Most of the epidermis is intact. The arm-
buds are well defined.

No. 264.

(1) Wm. S. Gardner, Baltimore, Maryland.

(2) A 25X20X15 mm.; B 2 mm.

(3) Last period occurred August 12, but menses had
been irregular for three months before.

(5) The ccelom is filled with a hard hyaline magma,
rich in round cells, in which is embedded the umbilical
vesicle, measuring 2.5 mm. in diameter. The chorion is
thickened, fibrous, and covered with some villi. These
also are fibrous and most of them are non-vascular.

(6) Decidua infiltrated.

No. 275.

(1) W. Tobie, Portland, Maine.

(2) A 403025 mm.; B 8 mm. (straightened).

(4) The chorion of this specimen, which was thought to
be 2 months old, is thin and covered with some villi
embedded in much blood. In structure it is fibrous, with
a diminished amount of epithelium, and contains no
blood-vessels. Within is an amniotic cavity, filled with a
clear fluid, into which the deformed emia projects. The
exoccelom is from 2 to 3 mm. wide and is filled with typical
magma réticulé.

(5) The structures of the embryo form almost a con-
tinuous mass of tissues, in which the irregular central
nervous system can still be outlined. Most of the epider-
mis is still intact. The lenses of the eyes form small
pearls inclosed in capsules lying beneath the skin. In
front of them are two small bodies connected with the
epidermis, which might pass for lenses, but which are prob-
ably olfactory pits. In a number of places the tissues are
fibrous. The decidua shows some infiltration and the
villi are decidedly fibrous, non-vascular, and glued.

(6) Mild infiltration.

No. 291.
(1) A. Wegefarth, Baltimore, Maryland. (Brédel col-
lection.)
(2) B 5mm.

(4) The membranes are devoid of villi and very thin.
The umbilicial vesicle is necrotic and filled with an irregu-
lar mass.

(5) Sagittal sections of the embryo show that the speci-
men is pathological, its head being rounded and the
epidermis having fallen off. The spinal cord is distended
and the brain is solid. Veins and arteries are greatly
distended with blood. The eye-vesicles are atrophic and
the lenses dissociated, but encircled by a sharply de-
fined capsule.

No. 292a.

(1) J. P. West, Bellaire, Ohio.
(2) A 503030 mm.; B 3.5 mm.

NODULAR

(3) ‘Patient 31 years old, married 10 years, but has
never been pregnant before. Last period November 10,
and on December 24, after a hard day’s work, she had a
sudden gush of blood, and since then has been wasting at
times until abortion, February 4.”

(4) Chorion is partly covered with long villi, which are
fibrous in some places and edematous in others. The
amnion within, which occupies the entire cavity of the
chorionic vesicle, is partly filled with granular magma
through which can be seen the outlines of an atrophic
embryo.

(5) Sections show that the brain and most of the spinal
cord have been destroyed. In the middle of the embryo
the aorta and ccelom are sharply defined, but elsewhere
the tissues are entirely obscured by numerous round cells.
The epidermis is intact. The decidua is decidedly infil-
trated and also contains a few large local accumulations
of leucocytes.

(6) Marked infiltration.

No. 304.

(1) G. L. Hunner, Baltimore, Maryland.
lection.)

(2) A 15X7X6 mm.; B 4 mm.

(4) The specimen is surrounded by much decidua, which
is infiltrated with leucocytes.

(5) The stroma of the villi and chorion are decidedly
macerated and degenerate, with remnants of blood-vessels
within them, and are covered with an active trophoblast.
The decidua is encircled with pus and fragments of uterine
mucous membrane. The ovum is partly filled with magma
réticulé, in which is embedded an umbilical vesicle 2
mm. in diameter, attached to the remnants of an embryo
without myotomes. The neural canal is present and the
body runs out into a stem containing a tube (allantois)
which does not attach itself to the chorion. Remnants
of an amnion are present. All in all, the embryo appears
to be much like Graf Spee’s specimen, which is 1.54 mm.
long. No trace of a heart could be found, but there are
numerous blood-islands in the umbilical vesicle and rem-
nants of blood-vessels in the chorion.

(6) Severe infiltration.

No. 309.

(1) H. S. Steensland, Syracuse, New York.

(2) A 232020 mm.; B 4mm.

(4) This specimen, apparently normal, had been in
alcohol for three or four years when received, but was well
preserved. The amnion filled the entire chorion; other-
wise the interior also appeared normal.

(5) Section showed, however, that the dilated amnion
was accompanied by marked changes in the embryo. All
of the tissues are infiltrated with round cells, obliterating,
to a great extent, both the tissues and the organs. The
central nervous system is markedly dilated and filled with
round cells. In front the walls are broken and the round
cells extend into the tissues of the front of the head.
The eye and ear vesicles also are dilated and filled with
round cells. No trace of a lens is seen, and the ear-vesicle
has two sprouts on its ventral side. The whole epidermis
is present.

The specimen is markedly dissociated; only the central
nervous system, the head, and perhaps some hepatic
remnants are present. The embryo apparently was
sessile upon the amnion. All of the chorionic membrane
that was mounted contained a network of vessels, and
some of the villi also are splendidly vascularized. A
continuous network of vessels containing some blood-cells
is found just near the amniotic surface of the chorion, as
shown in figure 82. The epithelium of the chorionic
vesicle is full of syncytial buds and some maceration is
present, but there also is very evident hydatiform de-
generation.

(6) Decidua absent.

(Brédel col-

Partial hydatiform degeneration.

CYEMATA. 129

No. 377a.

(1) J. L. Crawford, Cedar Rapids, Iowa.

(2) A 30X22x14 mm.; B 0.5 mm. long.

(4) The specimen is well covered with villi, which, to
the unaided eye, appear quite normal. The interior of
the ovum contains a considerable amount of reticular
magma, within which is embedded a large sac (5 mm. in
diameter) containing a nodule (0.5 mm. in diameter)—
the embryo.

(5) Upon microscopic examination the villi are found
to be very fibrous and tipped with trophoblast; at points
the latter forms islands with necrotic centers. Sections
show that the whole chorion is lined with the amnion
except at the point of the inclosed sac, which proves to be
the exocelom. The embryo is composed of a mass of
cells which extend into the mesoderm of the chorion. It
may represent the last remnant of the umbilical vesicle
No traces of blood-vessels are seen in any portion of the
embryonic mass, nor in the mesoderm of the chorion.

No. 425.

(1) M. Brédel, Baltimore, Maryland.

(2) A15X12X8 mm.; B1 mm. long.

(4) The ovum, which is covered with a few villi and
some decidua, contains a nodule about 1 mm. in diameter.

(5) Sections show that it is lined with amnion and con-
tains at one point the atrophic nodular remnants of an
embryo which is much degenerated. These remnants
consist of an open neural groove, on either side of which
are two large veins filled with blood. No remnants of
any organs are present. Immediately below the neural
body is a sharp ring of tissue which may represent the
chorda. The amnion is fibrous and adherent throughout
to the chorion, which is covered with thin, fibrous de-
generate villi. ‘The entire ovum is encapsulated in frag-
ments of decidua, which shows very extensive inflamma-
tory changes.

(6) Severe infiltration.

No. 433.

(1) D. S. Lamb, Washington, District of Columbia.

(2) A 23X21X11 mm.; B 4 mm.

(3) Patient is a multipara, 30 years old, whose men-
strual period was one week overdue.

(4) The ovum is well covered with villi, and its anterior
lined by a smooth chorionic membrane, to which is at-
tached an irregular body about 1 mm. in diameter and
4mm. long. There is practically no magma present.

(5) Sections of the chorion show that the villi are practi-
cally normal in form and arrangement, the tips being
covered with a very liberal amount of trophoblast. How-
ever, between the villi there is some fibrinous substance
through which are scattered numerous round cells and
in which are embedded masses of syncytium. The em-
bryonic mass is well preserved, and in it there are several
gland-like bodies, probably the allantois. This embryonic
tissue appears partly like an embryo and partly like a hy-
pertrophic umbilical vesicle. The tip is ragged, indicating
that most of the embryo has fallen off. At its point of
attachment. to the chorion there is a delicate membrane
folded upon itself many times, which no doubt represents
the collapsed amnion. There are but few blood-vessels
within the villi of the chorion.

(6) Very early hydatiform degneration. Decidua ab-
sent.

No. 433a.

(1) D.S. Lamb, Washington, District of Columbia.

(2) A 27X25X15 mm.; B 3 mm.

(3) Patient has one child, 3 years old. Her regular
menstrual period occurred February 1; there was a slight
show March 1, lasting a few hours, and on March 15, after
running to catch a car, the flow came on and continued
until March 21, when the specimen was passed.

130 STUDIES ON

(4) The ovum is well covered with villi which are normal
in form. Within there is a large quantity of reticular
magma encircling several nodules, one of which appears
to be the embryo. ‘This is inclosed with its amnion and
measures 3 mm. in length.

(5) The villi are non-vascular, have undergone mucoid
degeneration, and are stuck together by a very pronounced
mucoid mass, within which radiate numerous syncytial
cells. At certain points these are covered with maternal
blood; otherwise there is no indication of inflammatory
changes. The form of the embryo and amnion appear to
be quite normal, but the former is markedly dissociated.
Its blood-vessels, including those of the chorion, are gorged
with embryonic blood. ‘The dissociation is so marked that
practically all of the organs are involved and more or less
obliterated, although their main form can still be made
out. The lumen of the brain and cord are mostly filled
with cells, which also invade the otic vesicle. The process
of dissociation has involved the eye-vesicles to such an
extent that they are entirely obliterated. At this point the
cells of the brain seem to shade over to the mesenchyme
of the head without any line of demarcation.

(6) Decidua absent. Probable hydatiform degeneration.

No. 436.

(1) J. Park West, Bellaire, Ohio.

(2) A 654030 mm.; B 2.9 mm. long.

(3) “Patient a Russian Jewess, 31 years old, who has
four children, the youngest 18 months old. In July 1907
she aborted at 2 months; in January 1908 at 3 months;
this specimen May 17, 1908, at 2 months. She appears to
be healthy and shows no evidence of syphilis.”

(4) The large fleshy ovum is partly covered by decidua
with atrophic villi. Its wall is thin, and when opened it
was found to contain dense reticular and granular magma.
On one side is a small nodule about 2.9 mm. in diameter,
which encircles an atrophic embryo. The gross appear-
ance of the embryonic mass looks much like a fish embryo.
The yolk-sac is distended, has thickened walls, and is
attached to the chorion by means of a pronounced stalk.
The embryo lies spread upon this vesicle with head and
tail ends protruding somewhat.

(5) Sections of the chorion show that both the chorionic
membrane and some villi are fibrous and stuck together
by a large quantity of mucoid tissue, within which are
numerous buds of syncytium. The chorionic membrane
is very vascular, but few vessels are found within the villi.
Sections of the embryonic mass show that the vesicle is
directly continuous with the body-wall; that is, the body
is distended sufficiently to incorporate entirely the umbili-
eal vesicle. The body-wall is very fibrous and there are
several bundles of these fibers which push up the epithelium
into papille. The central nervous system is more or less
dissociated, but can be followed throughout most of the
length of the embryo, and occasionally a lumen is present.
Its course is interrupted at several points. In the head
end there is an additional body, which may represent the
pharynx, and which does not communicate with the yolk-
sac, but appears to be continuous with the brain-tube; it
may possibly belong to the latter. In the ventral midline
there is a large single blood-vessel which represents all that
is left of the heart. From this other blood-vessels are
radiating into the body of the embryo. In the tail end of
the embryo the neural tube has a very pronounced lumen,
apparently filled with cells. In this region the amnion is
continuous with the lateral sides of the vesicle, showing
the line of demarcation between the body of the embryo
and the yolk-sac. The chorda, eye and ear vesicles are
absent. The decidua is somewhat infiltrated, fibrous and
degenerate.

(6) Decidua slightly infiltrated.

No. 440.

(1) W. Preston Miller, Hagerstown, Maryland.
(2) A 25X20X15 mm.; B 2.5 mm.

PATHOLOGIC OVA.

(4) The chorion, which appears to be normal, is covered
entirely with villi. When opened it is found to contain a
great quantity of reticular magma, within which is buried
an embryo 2.5 mm. long.

(5) The amnion is greatly distended, showing a marked
hydramnios. Sections of the embryo show that it has
undergone extensive dissociation, the central nervous
system being the only structure that can be made out.
Most of it is solid, cells from the wall having completely
filled its lumen. In the anterior end of the embryo the
eye and ear vesicles can still be outlined, although they
are mostly filled with round cells. The chorionic wall and
its villi have undergone fibrous degeneration, and few
blood-vessels are present.

(6) Hydatiform degeneration.

No. 441.

(1) J. T. Haller, Davenport, Iowa.

(2) A 171310 mm.; B 2.3 mm.

(4) A transparent sac, about the size of the ovum, pro-
trudes therefrom, and isno doubt the amnion. The ovum
contains some granules, and near the attachment of the
sac to the chorion there is an embryo, 2.3 mm. long, which
is somewhat curled upon itself. Within the chorion
there is considerable magma. The hydramnios is very
conspicuous.

(5) Sections of the chorion show that its wall is some-
what fibrous, as is also the mesenchyme of the villi. Con-
siderable trophoblast is attached to the tips of the villi,
and between them there is a great deal of fibrinous
substance intermingled with many leucocytes. Into this
substance large buds of syncytium ramify. The tissues
of the embryo are greatly dissociated, the central nervous
system being composed of a uniform layer of round cells.
The spinal cord does not reach to the tail end of the em-
bryo, and the eye and ear vesicles are destroyed. Near
the attachment of the embryo to the amnion there is a
grouping of small round cells which no doubt represent the
heart. In certain places these cells stream into the ccelom,
which can barely be outlined. The umbilical vesicle is
small and atrophic and attached to the lower part of the

embryo.
(6) Hydatiform degeneration. Decidua absent.

No. 504.

(1) H. I. Davenport, Auburn, New York.

(2) A 15X15X15 mm.; B 0.2 mm. long.

(3) Patient 40 years of age; youngest child aged 6
months. Woman menstruated a little about February 3
and missed the next period, which should have come on
about March 3. On March 17 passed some blood, accom-
panied by slight pain in back and over symphysis pubis.
The abortion followed the next day.

(5) The entire specimen was cut into serial sections, and
in several of these the remnant of a nodular embryo, about
0.2 mm. in diameter, was found. The embryo lies isolated
within the extensive magma and contains two cavities. It
is markedly macerated. In the region of the nodule there
are numerous delicate mesodermal processes from the
chorion, pointing towards it and indicating the point of
its former attachement. There also seem to be a few blood-
vessels in the chorionic wall and in some of the villi. The
villi are capped with considerable trophoblast, most of
which is atrophic and macerated. There are also numer-
ous buds of syncytium arising directly from the chorionic
membrane.

Decidua absent.

No. 525.

(1) David Jurist, New York.

(2) A 5035 X25 mm.; B 3 mm. long.

(4) The somewhat solid mole contains a clear vesicle
25 mm. in diameter. Its inner surface is smooth, but
within the vesicle, which proves to be the amnion, there is
considerable granular matter, and attached to one side
is a nodular embryo 3 mm. we On one side of the
chorion is a small tuft of villi. ctions of the chorion

NODULAR

show that its wall is very hemorrhagic, the membrane
somewhat fibrous, and the villi mostly necrotic, the rest
having undergone what appears to be mucoid degenera-
tion The decidua is necrotic and markedly inflamed.
(5) Sections through some tufts of villi show them to
be quite normal in appearance, with a great deal of tropho-
blast between them. The embryo represents a transitional
stage between the nodular and cylindrical forms. It is
still possible to make out the head end upon microscopical
examination. The central nervous system is partly dis-
sociated, but throughout the embryo more or less of the
tube-wall is still indicated. Some portions of this wall are
broken through, and the contents are continuous with the
surrounding mesenchyme. In the other portion of the
embryo the spinal cord is double, but only one eye-vesicle
is present, and that one very atrophic; the other has
entirely degenerated. Lens and otic vesicle are lacking,
as is also the heart. The ccelom is fairly well formed, and
the ventral region of the embryo is filled by a small but
much distended umbilical vesicle. It appears as though
the embryo did not develop after it had reached a growth
of 1.5 mm., but simply distended the cavities laid down
at that time. The amnion is somewhat fibrous, and the
umbilical vesicle does not protrude into the exoceelom, but
seems to be contained within the body of the embryo.
Along the dorsal side of what appears to be the pharynx
are two very large blood-vessels filed with blood, which
extend for a short distance in the middle of the embryo.
(6) Marked infiltration.

No. 528.

(1) G. Ackerman, Wheeling, West Virginia.

(2) A 302020 mm.; B 4 mm.

(4) The chorion is covered partly with normally formed
villi and partly with blood-clot. The ccwlom contains
considerable magma and an amniotic cavity about 13 mm.
in diameter. Within the amnion are large flakes of sticky
magma encircling a knob-like embryo 4 mm. long, which
is attached to the amnion at its point of juncture with the
chorion.

(5) The chorionic wall and its villi are somewhat edema-
tous and fibrous. There is very little trophoblast, put a
small group of quite irregular tufts of syncytium are seen
at the tips of the villi and upon the outside of the chorionic
membrane. The embryo was cut into sagittal sections and
shows extensive dissociation. The only structure which
can be made out with certainty is the central nervous
system, which reaches through the whole length of the
embryo and has a thin-walled tube filled entirely with
round cells. The eye and ear vesicles are absent, but
in their places there is the distended brain-tube broken
through at points, where the cells within the lumen mix
freely with those of the mesenchyme. There are several
large blood-vessels within the embryo, and also an indica-
tion of the heart.

(6) Infiltration.

No. 529.

(1) M. B. Wesson, New York.

(2) A 25X15X15 mm.; B 3 mm. long.

(4) Chorion is partly covered with long, slender villi
and the ccelom entirely filled with dense, irregular reticu-
lar magma. On one side of this were found two small
bodies about 2 mm. apart, at first thought to be the
umbilical vesicle and the embryo.

(5) Serial sections were cut of the entire specimen and
those containing the embryo were preserved. The chori-
onic wall is fibrous, but the villi appear to be more nearly
normal, the larger ones containing many sprouting blood-
vessels. Attached to the villi is a considerable quantity
of syncytium and a small piece of decidua which shows a
marked inflammatory reaction. The two bodies seen
within the ovum before the sections were cut prove to be
two portions of the umbilical vesicle, one of which is
free and the other attached to the chorion by means of a

CYEMATA. 131

very pronounced pedicle. The pedicle contains a marked
allantois and is rich in blood-vessels, which branch out
into the adjacent chorion and villi. The other portion
of the umbilical vesicle contains blood-vessels, the blood-
islands within the pedicle apparently being separated from
the blood-vessels. In addition to these two bodies a
third was found within the specimen, which represents the
lower part of the embryo, having a sharply defined spinal
cord, the chorda, and myotomes. It appears to belong
to an embryo about 3 mm. long.
(6) Marked infiltration; hydatiform degeneration.

No. 543.

(1) G. C. McCormick, Sparrows Point, Maryland.

(2) A 703025 mm.

(3) Menstrual periods irregular; last one occurred on
June 10, but continued for one day only. Abortion
August 24.

(4) Pear-shaped specimen, the stem of which is solid
and comprises about one-half of the entire mass. The
other half contains the chorion, which is about 25 mm.
in diameter and has a cavity 17 mm. in diameter. This
is filled with delicate but pronounced reticular magma,
in the center of which is a nodular embryo 3 mm. long.

(5) Sections show the chorionic membrane to be nor-
mal in structure, but the villi are fibrous and matted
together. They are encircled by a zone of fibrinoid sub-
stance, followed by one of decidua which is extensivel
inflamed. The intervillous spaces are partly filled with
maternal blood, in which there is a very great excess of
leucocytes. In the fresh blood grow numerous buds of
syncytium. What was taken for a nodular embryo
seems to be a free umbilical vesicle, lying near a thin
amnion which is thrown into numerous small folds. Out-
side of this are small remnants of a macerated embryo
which is probably not over 2 mm. long. Where the
umbilical vesicle and the amnion come together there is a
thickening, and therein are several large blood-vessels.
We have here a case of marked hydramnios with dis-
integration of the embryo, leaving the umbilical vesicle.

(6) Marked infiltration.

No. 568.

(1) Solomon Dodds, Baltimore, Maryland.

(2) A 48X36X21 mm.; B 0.5 mm. long.

(3) The patient was 36 years old and had been married
6 years. Pregnant four times; two living children. The
other pregnancies ended in abortion, from one of which
the present specimen came. Last period November 23
to 30. There was some bleeding in February and the
abortion followed on February 6.

(4) The ovum is within the decidua, 64X42 mm.,
and measures 48 X36 21 mm. It is completely covered
with villi which branch two or three times, and lying
free within it is a large, smooth vesicle equally distended,
27 mm. long and 17 mm. wide. Within the vesicle, to
one side and at its point of attachment to the chorion,
there is a small nodule about 0.5 mm. in diameter. This
is the remnant of the embryo. The vesicle is undoubtedly
the amnion.

(5) Sections through the chorion show the tissues to
be atrophic and hyaline, with a small amount of tropho-
blast. The tips of the villi are embedded in a layer of
fibrinoid substance which, in turn, is covered with a thin
layer of decidua showing inflammatory changes. There
is a great deal of reticular magma between the chorion
and the amnion. The small, knob-like embryo has an
irregular shape, and its main portion is taken up with a
large, irregular vesicle filled with cells and lined with
several layers of epithelium. No doubt this is a remnant
of the central nervous system. There seems also to be
present a rudimentary allantois, a body cavity, a few
blood-vessels, and a very small, irregular umbilical cord.

(6) Marked infiltration; some hydatiform degeneration,

132

No. 569.

(1) W. P. Miller, Hagerstown, Maryland.

(2) A 30X26X20mm.; B 2.5 mm. long.

(3) Patient had been married about a month.

(4) The ovum appears to be normal. It is completely
covered with villi which branch two or three times, and
the interior is filled with a dense mass of reticular magma.
At one side is a small nodule 2.5 mm. long and 2 mm. in
diameter, which appeared to be the remnant of the embryo.
There are other opaque granules scattered through the
magma. In order to determine which of these may be
the remnant of the embryo, it was necessary to stain the
entire specimen and cut it into serial sections.

(5) The chorionic wall and the villi are edematous, and
some of the latter have undergone mucoid degeneration.
There is not very much trophoblast attached to the villi.
A great quantity of reticular magma is in the exoccelom.
Sections of the embryo show that the brain is greatly
distended and its ventral wall is disintegrating. This
enlargement seems to be mostly in the hind-brain, the
fore-brain being reduced in size. It ends in two ex-
tremely small eye-vesicles. The ear-vesicles are filled with
cells. The spinal cord can be followed only a short dis-
tance into the body of the embryo. In the neck there are
two very small bilateral blood-vessels. In the body the
ecelom is pronounced, and suspended in it is a very small
atrophic heart. The intestine is not present, but the
lower part of the body is somewhat injured and the
structures here can be followed with precision.

(6) Hydatiform degeneration. Decidua absent.

No. 573.

(1) G. Ackerman, Wheeling, West Virginia.

(2) A 46X17X17 mm.; B 8.5 mm.

(3) Period has been two weeks overdue.

(4) The specimen, fleshy and ruptured, contained a
large cavity, with an atrophic embryo with a knob-like
head, and arm and leg buds missing on the right side.

(5) The chorionic wall is hyaline and covered with
completely degenerated villi which are matted together
with blood-clot and very degenerate decidua, which show
some leucocytie infiltration. The embryo is markedly
dissociated, the brain being practically solid. The fore-
brain is dragged out into a long process, and on each side
there is a very small rudimentary eye with lenses attached
to the skin. The dissociation of the eye-vesicles is so
extreme that it is difficult to separate them from the
surrounding tissue. The limb-buds are very atrophic.
The shape of the organs and body is normal, but the
tissues are much dissociated. There is a large central
space in the umbilical cord filled with débris.

(6) Decidua very degenerate, but probably somewhat
infiltrated.

No. 592.

(1) Abraham Poska, Hobson, Montana.

(2) A 47X33 X26 mm.

(3) The specimen came from an induced abortion.

(4) One side of the ovum is partly covered with blood-
clot, the other with short, apparently normal villi. Its
cavity is filled with very dense reticular and granular
magma containing remnants of an opaque and apparently
disintegrated embryo. After fixation in formalin the
magma is somewhat reticular, being intermingled with a
very extensive and dense jelly-like substance. There are
but few opaque particles to be seen within it.

(5) Sections show the magma to be quite clear, and
scattered through it are large strands of cells representing
the disintegrating embryo. In one of the sections a faint
outline of the peritoneal cavity, encircling the intestine,
can be made out. There are also independent blood-
vessels. It would seem as though the embryo had been
crushed when about 4 mm. long. The chorionic wall is
thickened and badly infiltrated with leucocytes on the

STUDIES ON PATHOLOGIC OVA.

outside, but these do not enter the celom. The wall is
covered with villi partly degenerated and partly normal
in appearance. Between them there is an inflammatory
mass. Where the villi are bathed with fresh maternal
blood they are fibrous, with poorly preserved blood-
vessels; but many of them contain blood-vessels which are
filled with blood, which takes on an intense eosin stain.
Scraps of tissue, which appear to be remnants of the
amnion, reach from the chorion into the cavity of the ovum.
(6) Severe infiltration.

No. 610.

(1) V. Van Williams, Baltimore, Maryland.

(2) A 232020 mm.; B 3 mm.

(3) Patient has a child about 15 years old. Aborted 4
years ago. Period 3 days overdue.

(4) The entire specimen is pear-shaped, the body being
formed by the ovum, covered with a uniform layer of
villi, which branch three or four times. The stem is 13
mm. long and is composed of fibrin, decidua, and blood.
The interior of the specimen is partly filled with reticular
magma, and on one side a small nodule, 3 mm. long and
about 1 mm. in diameter, is embedded. This is not
closely attached to the walls of the chorion, nor does it
appear to be covered by the amnion. It probably is
pathological.

(5) Sections of the chorion show that its walls are
badly disintegrated. The main wall is somewhat fibrous,
and between the villi there is a large quantity of fibrinous
substance well filled with round cells and buds of synecy-
tium. In other portions the trophoblast is necrotic.
There are also a few clumps of it which show an active
owth within the centers. The embryo is almost entirely
sociated. In the sections the head, brain and eye-
vesicles can be made out, but otherwise the embryo is
badly disintegrated.

No. 633.

(1) C.S. F. Lincoln, Shanghai, China.

(2) A 11X11 X11 mm.

(3) The specimen is from a white patient who had gone
1 to 2 weeks overtime.

(4) The ovum is spherical in shape and covered with a
uniform layer of villi which branch once and are 1.5 mm.
long. It was opened carefully but no remnant of an
embryo was found.

(5) Sections show that the chorion is macerated.
Within was found a vesicle, 2 mm. in length, which appears
quite like the umbilical vesicle. This runs out into a
stem, one side of which is directly continuous with the
chorion. At the point of juncture the tissues are full of
blood-vessels; otherwise no structure can be made out.
The specimen is very degenerate.

No. 651g.

(1) G. C. McCormick, Speen ne Point, Maryland.

(2) A 35X30X30 mm.; B 3 mm. long.

(4) The ovum is irregularly covered with ragged villi
and entirely filled with a mass of granular and reticular
magma containing a spherical amnion measuring 12 mm.
in diameter. This latter is filled with clear fluid, and on
one side is an hourglass-shaped body—the embryo—
measuring 3 mm. ;

(5) Longitudinal sections through the body of the
embryo show that it is set upon the flat amnion, which
does not touch the chorion, being separated throughout
by reticular magma. The main body of the embryo
contains a pear-shaped central nervous system. There are
several large cavities which can not be interpreted easily.
One is the exoccelom; a second is the umbilical vesicle.
The heart and a piece of intestine can be identified. The
chorionic membrane and the villi have undergone a
eed dissociation; some are a little fibrous, with small
nuclei.

(6) Some hydatiform degeneration; decidua absent.

NODULAR CYEMATA.

No. 660.

(1) Wm. J. Todd, Mount Washington, Maryland.

(2) Ovum 403530 mm.; B 1 mm. long.

(3) Married woman 17 years old. Last menstruation
January 17, and abortion March 25.

(4) A pear-shaped ovum, mostly covered with decidua.
At one pole a third of the ovum protrudes and is covered
with ragged villi. The interior is filled with a jelly-like,
translucent reticular magma. No remnant of the embryo
was seen at this time, but the search was incomplete.

(5) Sections through the chorion include the decidua,
which shows considerable round-cell infiltration. The
chorionic wall is thin and the villi, which are fibrous and
non-vascular, are attached to the decidua by a thick layer
of fibrinoid substance, the trophoblast having almost com-

letely undergone this sort of transformation. There are,
ae numerous buds of syncytium. The amnion is
markedly fibrous and thickened, and within are numerous
spaces containing some Hofbauer cells. The nodular
embryo is quite completely dissociated, but not macera-
ted. It is impossible to recognize any organs.

(6) Mild infiltration.

No. 674.

(1) Guy L. Hunner, Baltimore, Maryland.

(2) B 3.5 mm.

(3) ‘Patient is 42 years of age; has had 11 children and
one miscarriage. Youngest child 2 years old. Normal
labors. For several months the periods have been profuse,
but she thinks the last period was three weeks ago, when
she bled unusually. For the past six weeks there has been
some bleeding off and on most of the time. She is now
suffering with a great deal of pain in the lower quadrant
and about the umbilicus, and is tender over the appendix
region. I think that whatever pathological condition you
find was due to the threatened miscarriage as expressed
by the recent bleeding. There was no evidence of in-
flammation anywhere except in the appendix, and this was
not of an acute character, and probably had not influenced
the pelvic organs. The extreme retroversion of the uterus
may have had something to do with the threatened
abortion.”

(4) When received the fresh uterus had been opened
in front and a pathological ovum protruded. Ovum was
opened and an atrophic embryo 3.5 mm. long and 2 mm.
wide, was found within. Sections were taken through the
middle of uterus and chorion, then at right angles to it
through the fundus. The ovum is almost entirely de-
tached from the uterus, but we succeeded in getting good
transverse as well as longitudinal sections through it
without disturbing the relation. The transverse section
is near the os. In this region the chorion is fully separated
from the mucous membrane and the latter has practically
degenerated. The longitudinal section shows this de-
generation on one side of the chorion, while on the other
side the villi are still in contact with the uterus.

(5) Over the villi are long strands of decidua reaching
far into the mucous membrane. The villi, which are
closely attached to the uterus, are surrounded in many
places by a large mass of fibrinoid substance. They, too,
have undergone fibrous degeneration, are non-vascular,
and frequently are intermingled with large plaques of
nuclear aie At other points the trophoblast pierces the
glands and blood-vessels, while between the mucous mem-
brane and the greater portion of the amnion there is a
large organized clot composed of stratified fibrin, some
leucocytes and small masses of red blood-corpuscles which
do not serve to nourish the ovum. The chorionic wall is
fibrous and the villi few in number. The specimen repre-
sents well the last stages of an abortion in which the ovum
has gradually become detached and the mucous membrane
is regenerating. However, sufficient nutrition may have
been carried to the embryo to allow it to continue to grow
in an irregular fashion. The embryo is very irregular in
form. Near the sharp tip are two pigmented spots—the
eyes. The embryo is completely dissociated and macer-

133

ated, and entirely covered with a poorly preserved epider-
mis. The pigmented spots are eaion from the brain,
and a pronounced central nervous system does not make
its appearance until the region of the heart is reached, and
even then does not extend very far into the body. It is
eampored of round cells and is sharply separated from
the body of the embryo by a fibrous layer of mesenchyme.
Most of the tissue has undergone a pronounced fibrous
degeneration. Along the ventral side of the body there
are numerous sharply defined cavities, devoid of cells,
which ramify in all directions and convert the body at the
point of its attachment to the umbilical cord into a curious
cavernous mass. It is impossible to determine whether
the system of spaces is vascular or coelomic; probably the
latter. In the neighborhood of the degenerated heart
there are several large blood-vessels, but these do not
communicate with the system of spaces. There are also
numerous wart-like processes extending into this cavity.
The decidua is locally infiltrated, especially in the region
of the implantation site, where the peri-glandular infiltra-
tion is very evident.
(6) Marked focal infiltration.

No. 677.

(1) Thomas Brayshaw, Glenburnie, Maryland.

(2) A 18X21X12 mm.; B 1.5 mm. long.

(3) Patient had been married 3 years, this being her
first pregnancy. The last period was February 15 to 19;
abortion April 17.

(4) The fresh specimen, measuring 182112 mm.,
was brought to the laboratory immediately after the
abortion. It was well covered with villi, having bulbous
tips to which adhered scraps of decidua as well as blood-
clot. The ovum was opened in warm saline solution and
sketches of its contents made under the binocular. It is
filled with a delicate web-like transparent system of
reticular fibers containing the flattened, transparent yolk-
sac and blood-vessels, which lead to a white embryonic
rudiment. This shows four processes, possibly the ex-
tremities. While the specimen was fixed in sublimate and
glacial acetic, the reticular magma immediately became
dense, completely obscuring the nodular embryo.

(5) The latter is completely dissociated, and over its
body are numerous irregular warts which are difficult to
interpret. The whole rests upon a large umbilical vesicle.
There are slight traces of the central nervous system, and
within the body is a curious mass which may represent
the degenerated heart. The brain and spinal cord can
barely be outlined. Towards its lower part the specimen
contains a lumen. The umbilical cord, or what amounts
to the same, passes along one side of the umbilical vesicle
before it reaches the wall of the chorion. The chorionic
wall is somewhat fibrous and contains numerous very
large, almost empty blood-vessels. The mesenchyme of
the villi is mostly degenerated and disintegrated, and
practically all of the trophoblast is necrotic. The villi
are glued together by strands of fibrin, blood, syncytium,
and fine fragments of extremely degenerate decidua.

(6) Hydatiform degeneration.

No. 692.

(1) James L. Huntington, Boston, Massachusetts.

(2) A 20X20X20 mm.; B-3 mm.

(3) Patient aged 40 years; married 6 months. This may
be the second pregnancy, as patient gives a history sugges-
tive of an early abortion February 10, when she was 19 days
overdue and flowed profusely. She had no medical
attendant. Last menstrual period March 10 to 16;
abortion May 19 following. No evidence of syphilis,
gonorrhcea, or endometritis due to other infections.
Uterus involuted normally and well.

(4) Specimen measured in formalin. The ovum is 20
mm. in diameter, and one half of it is covered with ragged
villi, the other half being quite smooth. The interior is
filled with a delicate reticular magma. Within the amnion

134 STUDIES ON

on one side is a small spherical body, without the charac-
teristic form of a degenerate embryo. Further gross
examination was impossible without op hese the specimen.

(5) The villi and chorion are very fibrous, and some of
the mesenchyme is edematous with large cavities. The
trophoblast is quite irregular in shape. There are some
buds of syncytium and strands of a mucus-like substance.
There are many Hofbauer cells in the tissues. The amnion
is fibrous and attached to the chorion by means of a short
cord. The embryo, which is closely surrounded by the
amnion, is turned away from this cord, and on the side
opposite the amnion there is an opening through which
the tail of the embryo protrudes to reach out to and enter
the very small atrophic umbilical vesicle. The back of
the embryo is toward the umbilical cord and adjacent
chorion. The tissues of the embryo are almost completely
dissociated. The heart can still be outlined, as also a few
of the body nerves. The central nervous system forms a
large tube mostly filled with cells, reaching through the
body up into the head, where it is practically lost. In the
forepart of the head is a sharply defined, epithelial pocket,
which may represent the beginning of a lens.

(6) Early hydatiform degeneration. Decidua absent.

No. 708.

(1) N. I. Ardan, Bristol, Tennessee-Virginia.

(2) A 706040 mm.; B 2 mm.

(3) The specimen came from the first tubal pregnancy
of a woman 24 years of age. Dizziness began two weeks
before the abortion and continued with hemorrhage.

(4) The specimen measures 706040 mm. and is
covered with villi which are very markedly developed,
in fact, hypertrophic. It contains a cavity lined with
smooth membrane. This cavity measures 45X20 mm.,
and from it protrudes a small umbilical cord, 10 mm. long
and 2 mm in diameter. At the end of the cord there is a
small opaque knob, a little less than 2 mm. in diameter,
undoubtedly a remnant of the embryo.

(5) The specimen consists of a fibrous chorionic mem-
brane, to which are attached numerous long, irregular
villi, and beyond these large areas of inflamed decidua, the
inflammatory processes often being so extensive as_ to
produce small abscesses. The villi are matted together
with fibrinoid substance, a great deal of blood, and fibrin.
The trophoblast is scanty. The mesenchyme of the villi
contains no blood-vessels. The amnion is closely adherent
to the chorion. The embryo is represented by a small
nodule of largely undifferentiated tissue.

(6) Marked infiltration; hydatiform degeneration.

No. 712.

(1) G. W. Cox, Hartford, Connecticut.

(2) A 303030 mm.; B 2 mm. long.

(3) Patient aged 37 years, married, and the mother of
a child 2 years old. No other pregnancies. Health good,
except recently a neoplasm of the breast. Periods about
regular and normal. No history of venereal infection.
Last period March 21; 36 hours after operation vaginal
hemorrhage started. This increased in severity and pa-
tient was packed 24 hours later. Twelve hours after
being packed she entered the hospital (June 4), and since
hemorrhage had stopped she was curetted. The specimen
was procured at this time.

(4) The chorion is covered entirely with long, ragged
villi, except at one end. Without the stem, which forms
this end, the specimen measures 303030 mm. The
amnion is greatly folded. This cavity contains a trans-
parent body 8 mm. long and nearly 2 mm. in diameter—
the umbilical cord.

(5) The chorionic wall, amnion, and villi are fibrous.
The trophoblast is quite active, producing numerous buds
of syncytium and clumps of trophoblast which have
partially undergone fibrinoid degeneration. The bod
within the chorion consists mostly of an umbilical cord,
which is capped by a clump of uniform round cells, which
no doubt represent the embryo. A highly differentiated

PATHOLOGIC OVA.

group of these cells encircles a cavity in the center, and
ssibly represents the heart. No other structures can
made out.

No. 714.

(1) G. J. Lochboeler, Washington, District of Columbia.

(2) A 302020 mm.; B 2 mm. long.

(3) Patient aged 38 years, married at 26 years. Hight
pregnancies; five normal, one following 18 months after
ovarectomy for cystic disease; since then one miscarriage
at 414 months (macerated fetus), one at 214 months, and
another (the last) at 2 months. All occurred without
assignable cause. Last period April 20 to 25; abortion
June 25. Was infected at the time of abortion from
inflammation of stump of right tube, which had been
removed five years previously with a cystic ovary. Fam-
ily fertile.

(4) The chorion measures 302020 mm., and is
covered with long, delicate villi. It contains a cavity 15
mm. in diameter and lined by an amniotic membrane.
In the bottom are several small nodules, one of which is
pointed and protrudes into the cavity about a millimeter,
while the other two are slightly larger and lie between
the amnion and the chorion.

(5) The chorion, amnion and villi are present, the latter
being stuck together by an irregular mass of fibrin, blood,
and trophoblast, which is scanty. The embryonic mass
is irregular and dissociated, and the ccelom is not sym-
metrical. The spinal cord and brain are dissociated and

_are not sharply defined, and the heart is probably atrophic.

The yolk-sac is degenerate.

No. 723a.

(1) L. L. Iseman, Chicago, Ilinois.

(2) A 22X19X17 mm.

(4) The small chorion measures 221917 mm., and
is covered with long, irregular villi. The specimen,
which had been opened, contained a transparent body
composed of several membranous sacs, which together
measure 4 mm. in diameter. Within these sacs were a
few granules, one more opaque than the rest.

(5) The chorion is covered with but few villi, although
there is a great tuft of them opposite the attachment of
the embryonic mass. Most of the villi have undergone
mucoid degeneration. The trophoblast is plentiful, and
between the villi there is considerable mucoid matter
and blood. The embryonic mass consists of a collapsed
amnion and a degenerated cord, to which is attached a
nodular embryo containing spaces, the calom, an epi-
thelial tube and possibly the alimentary canal.

(6) Hydatiform degeneration. Decidua absent.

Nos. 788 a, b.

(1) Anfin Egdahl, Menominie, Wisconsin.
(a) Ovum 604540 mm.; stunted em-

bryo 17 mm. CR. (See Group 6.)

(b) Ovum 65X55xX40 mm.; nodular em-
bryo 2 mm. long.

(3) Norwegian woman aged 32 years, married 10 years.
Three previous pregnancies. This abortion, which is the
first, occurred July 2, 1913. Condition of uterus normal.
ne history of venereal disease. First twins known in
amily.

(4) b. This specimen measures 65X55X40 mm.,
and is composed of chorion covered with degenerate
villi. The wall is thin and lined throughout with the
amnion. The cavity is filled with transparent fluid,
within which was found floating a small vesicle 3 mm. in
diameter. On one side of this vesicle is a small nodule.
Otherwise no trace of an embryo was found.

(5) The chorion is thickened, and the mesenchyme of
most of its villi is fibrous. The trophoblast is scattered in
large nodules between the villi. The centers of these
iis have undergone fibrinoid degeneration and con-
tain large plaques of nuclear dust. The decidua is some-

(2) Twins

NODULAR CYEMATA.

what inflamed, showing a general infiltration. Its inner
border is formed by a fibrinoid layer. The embryo con-
tains a large cavity, the walls of which are very thick and
fibrous, and the lumen of which is filled almost entirely
with cells. The thickened wall of the cavity passes into
the nodular embryo, which has undergone fibrous de-
generation and contains degeneration areas. Towards the
tip of the embryo the central nervous system is indicated,
but its lumen is entirely filled with cells which grade into
the surrounding mesenchyme. Sections of the central
nervous system are not characteristic. The epithelial
lining is crescent-shaped. The entire epidermis is still
intact, but otherwise no structure can be recognized.
(6) Mild infiltration.

No. 795.

(1) C. 8. Minot, Boston, Massachusetts.

(2) A 4035x115 mm.; B 3 mm. ;

(4) The ovum is pear-shaped and smooth on the outside
and measures 40X35X15 mm. The wall is relatively
thin, and the ovum completely surrounded by a layer of
blood which is covered by a thin layer of decidua. The
interior is lined with a smooth membrane and filled with
blood and magma. On one side, closely attached to the
chorion, is a very opaque nodular embryo, with a sharply
pigmented eye. It measures 3 mm. in length and is
markedly deformed.

(5) The chorionic wall is thickened and lined with the
amnion. The villi are atrophic and buried within a large
mass of maternal blood. The nodular embryo is entirely
dissociated and its cells stain intensely. The free end
contains a vesicle which may represent an eye or the
brain. At the attachment of the embryo to the chorion
there is a semicircular space, and within this is a body
lined with cylindrical epithelium. This may be inter-
preted as representing the alimentary canal surrounded
by eceelom. Below this the body of the embryo is closely
attached to the chorion, and in this region a great many
blood-vessels pass from the embryo into it.

No. 799.

(1) V. Van Williams, Baltimore, Maryland.

(2) A 402525 mm.; embryo 1.5 mm. long.

(3) Patient aged 43 years, mother of 14 live-born
children; 5 miscarriages. Only 3 or 4 children living, and
these are all boys. Last period three weeks previous to
abortion. Both husband and wife use alcohol to excess.

(4) The chorion, which measures 40 25X25 mm., is
covered with long, irregular villi which make the specimen
appear pathological. The wall is thin and closely lined
with the amnion. The latter, which measures 25x18 X18
mm., contains a small white nodule 1.5 mm. in diameter.

(5) The chorion and villi, which are thick, have under-
gone mucoid degeneration and most of the trophoblast
is necrotic. The nodular mass is also completely disso-
ciated and is attached to the amnion, where it is greatly
thickened. At the point of attachment there is a large
vesicle which may represent the alimentary canal. Below
this is a second small vesicle and also numerous spaces
which reach far out into the detached amnion, and appear
to be remnants of distended and degenerated blood-vessels.

(6) Early hydatiform degeneration. Decidua absent.

No. 807.

(1) Raymond Sanderson, Canandaigua, New York.

(2) A 18X12X12 mm.; B 3 mm.

(4) The ovum is partly covered with decidua, which
comes off as a shell and shows the ovum covered with a
broad zone of irregular villi which divide twice. The two
poles are bare and opaque. Through one of these the
ovum was opened. The ccelom is filled with reticular
magma. Near the point of opening is a spherical cavity
5 mm. in diameter containing an opaque, irregular embry-
onic mass 3 mm. long.

(5) The chorion is markedly fibrous and sparsely
covered with non-vascular villi which are also fibrous, and

135

attached to some of them is a small quantity of tropho-
blast. The umbilical vesicle apparently is normal and
somewhat macerated. The wall of the amnion is also
fibrous, and at its point of attachmenf to the embryo it
appears somewhat like the umbilical vesicle. The exo-
ccelom is wide open up to the body of the embryo, and
from the latter a small yolk-duct appears to arise. How-
ever, this can be followed through the free space to the
yolk-sae with which it communicates. The embryo is
markedly stunted and dissociated, but most of the organs
can be made out. The central nervous system has we
lumen filled with round cells, and the heart is fairly still
defined, but dissociated. The eye-vesicles are still present,
although very small.

No. 820.

(1) C. W. Crum, Brunswick, Maryland.

(2) A 45X25 X20 mm.; B 1 mm. long.

(3) Patient aged 38 years; married in 1899; 11 preg-
nancies—10 births at term and this abortion. Began
bleeding 6 days before, which was attributed to lifting.
view not infected; no fever; no venereal disease. Family
ertile.

(4) The specimen is an irregular mole 452520
mm., containing a sharply defined cavity, 257 mm.,
which is lined by a smooth membrane and filled with
reticular magma. On one side is a small nodule, a milli-
meter in diameter, which may represent the embryo. The
wall of this specimen is composed of numerous villi which
have undergone mucoid degeneration, and are matted
together by fresh blood, considerable fibrinoid and tropho-
blast. On the outside is an inflamed decidua.

(5) The chorionic membrane is very fibrous and the
ccelom filled with granular magma. Arising from one
side are small strands of tissue which may possibly repre-
sent the amnion. Lying in the granular magma are
remnants of tissue which probably come from the chorion.
The epithelium of the latter is largely destroyed, and the
infectious process seemed to be attacking the chorionic
membrane from the outside.

(6) Marked infiltration.

No. 830.

(1) Austin Miller, Portersville, California.

(2) A 80X38X35 mm.; B 4 mm.

(3) Woman aged 41 years, married in 1889. Pregnant
10 or 11 times; 8 living children, last child 6 years old.
Last period at end of June, abortion September 26 follow-
ing. Uterus presumably normal. No venereal diseases.
Family fertile.

(4) The specimen is a pear-shaped abortion mass,
measuring 80X38X35 mm. At the larger pole a clear
bluish membrane was exposed through an opening 3015
mm. The mass was opened through this membrane and
found to contain a cavity 603030 mm., lined by a
smooth membrane which crosses it in a large, clear fold.
To this was attached a small opaque white embryonic
rudiment, 4 mm. in length, as well as what seemed to
be a yolk-sac about 1.5 mm. in diameter. The wall of
the oval mass is thin throughout except at the smaller or
upper pole, where it measures about 9 mm. in thickness,
and is very hemorrhagic.

(5) The chorionic wall is composed of non-vascularized
villi matted together by an inflammatory material, a
great deal of fibrinoid substance and inflamed decidua.
The trophoblast is fairly active, and there are numerous
plaques of nuclear dust.

(6) Marked infiltration.

No. 888.

(1) Oliver T. Logan, Changteh, Hunan, China.

(2) A 70X50X50 mm.; B 1 mm. in length.

(3) Chinese woman, age 32 years, married 16 years.
First child born 4 years after marriage; second child still-
born at 7 months. Two children died in infancy of fever.
Three living, healthy children, the youngest 2 years old.

136

No history of lues in either parent. Last menstrual period
October 10. On the following February 21 the patient
flooded badly and was anemic. Came to the hospital on
the 22d, when uterus was emptied.

(4) The specimen consists of an abortion mass 70 X50
50 mm., one half of which exposes villi probably about
9 mm. long, while the other half is covered by decidual
tissue. The ovum was opened freely and a distended
spherical vesicle (amnion) protrudes. It is attached to
one end of the chorion. The structure of the amnion is
very fibrous, and when opened a nodular but irregular
mass, about 1 mm. in diameter, was found attached to one
side of it. The chorionic membrane is very fibrous and
the villi have undergone partly fibrous and partly mucoid
degeneration. There is an overlying trophoblast present.
The decidua is degenerate, but some villi are still well
implanted in it.

(5) The embryonic mass is in the form of a cone with
the entire base attached to the thickened amnion. Below
this base there is a large mass, the débris of which stains
intensely with hematoxylin. This may be a remnant of
the yolk-sac. On either side of this is a large, sharply
cut space which may represent the ceelom. The embryo
itself is composed of two parts, one part forming a large
cavity lined partly with a thickened layer of epithelium;
the other has undergone fibrous degeneration and includes
several round epithelial tubes which may be remnants of
the intestines. The large cavity seems to be the central
nervous system. It lies entirely within the amniotic
cavity; otherwise it might readily be construed as the
yolk-sac, its walls having much the appearance of some
yolk-sacs.

(6) Marked infiltration; hydatiform degeneration.

No. 9150.

(1) C.S. Minot, Boston, Massachusetts.

(2) A 7X7X7 mm.; B 2 mm. GL.

(4) The specimen consists of a clear piece of chorionic
wall about 7 mm. in length, with scanty, thread-like villi
with irregular enlargements. A small, pear-shaped and
opaque, featureless nodule, about 2 mm. in length, is
adherent to the inner surface.

(5) The chorion and villi are very fibrous, and the latter
are covered with a small amount of trophoblast. The
embryo forms a curious crescent-shaped body with a well-
defined neural tube. This on its ventral side spreads out
through the rest of the embryo, so that cells seem to be
directly confluent with the main tube. Between the em-
bryo and its attachment to the chorion there is quite a
plexus of spaces. Numerous villus-like bodies protrude
into the exocelom. Within the embryo there are myo-
tome-like bodies on one side of the cord; otherwise the dis-
sociation is almost complete. In addition to this embryo
there is a well-defined, fibrous vesicle lined by epithelium.
In oe are a few groups of cells which may represent blood-
cells.

No. 930.

(1) F. H. Bacon, Peoria, Illinois.

(2) A 343425 mm.; B 1 mm.

(3) Patient aged 38 years, married 19 years. Six chil-
dren, all living; eldest 17 years and the youngest 14 months.
No previous miscarriages. Missed menstruation in April,
flowed slightly May 23; missed June period. On July 4,
after working harder than usual, began to have abdominal
cramps and started to flow some in the evening. Cramps
and blood increased on the 5th and 6th. On the 7th pa-
tient had severe hemorrhages. Examination showed
uterus to be about the size of a two-months’ gestation.

(4) The specimen is a pear-shaped abortion mass
measuring 553737 mm., the upper portion of which
consists of “fresh’’ deciduous tissue; the lower, of a
spherical ovum, measuring about 343425 mm.
Villi, 7 mm. in length and few in number, are exposed.
On opening, the ovum showed a smooth-walled cavity in
which was found a nodular embryo 1 mm. long.

STUDIES ON PATHOLOGIC OVA.

(5) The chorionic membrane is very fibrous, and at-
tached to it are short fibrous villi matted together by
considerable trophoblast, mucoid substance, and blood.
A decidual mass 2 mm. in diameter has in its center a
large accumulation of leucocytes. The nodular embryo
has undergone degeneration, and only the celom and
several large vesicles which are buried in the chorion can
be made out with precision. Part of the embryonic tissue
looks a little like cartilage, and another portion is com-
posed of small round cells. There is also a small papilli-
form body at the tip of the embryonic mass.

(6) Severe infiltration.

No. 943.

(1) Elizabeth Comstock, New York City.

(2) A 505050 mm.; B 2 mm.

(3) Patient aged 28 years; married in December 1906.
Seven pregnancies: (1) abortion at 6 months; (2) abor-
tion at 4 months; (3) term, child now living; (4) term,
child died at 3 months; (5) term, child died at 4 months;
(6) term, child died at 8 months; (7) this abortion, at 3
months. Last menstrual period May 21 to 23; abortion
August 25 following. There was a slight redness of the
cervix and a blood-tinged, albuminous, glistening dis-
charge the day before the abortion. Syphilis acquired
from husband. Ovaries and tubes in good condition.
Family fertile.

(4) The mass consists of a hard body 804040 mm.,
from which protrudes a chorionic vesicle 50 mm. in diam-
eter, partly covered with relatively small villi. This con-
tained a clear fluid, a few large flakes which float easily,
and a small body 2 mm. long, which appeared to be the
remnant of the embryo.

(5) The chorion is fibrous and the few villi have mostly
undergone mucoid degeneration. These are matted to-
gether with degenerate trophoblast, and there is also con-
siderable blood between them. ‘The amnion lines the
entire chorion. The nodular embryo is greatly degener-
ated and very fibrous, and contains a cavity which ramifies
and seems to be composed of the nervous system. In the
head end there seem to be two rudimentary eye-vesicles,
while at the other end, where the embryo is attached to
the chorion, the tissues have undergone fibroid degener-
ation.

The decidua is well preserved, but shows considerable
local infiltration. Beginning fibrous and obliterative end-
arteritis are evident in certain areas.

(6) Mild infiltration.

No. 1019.

(1) Joseph S. Lewis, Buffalo, New York.

(2) A 70X35X30 mm.

(3) The patient had had three previous abortions—one
at 7 months, two at 3 and 4 months. The last two were
self-induced. The last period occurred about September
15. Hemorrhage began September 27. No infection is
present.

(4) The abortus consists of a chorionic sac almost cov-
ered with clotted blood which adheres firmly to the villi.
The chorionic vesicle is filled with a reddish fluid contain-
ing an embryo 2X4 mm., which is adherent to one side
of the chorionic wall. Subchorial hematomata are pres-
ent, but the chorionic wall is so thin that it is difficult to
identify the villi with the unaided eye.

(5) The clot contains a very degenerate chorionic mem-
brane, villi, and decidua. The stroma of many of the
villi is quite fibrous, and no remnant of the vessels is seen.

No. 1022h.

(1) Ernest C. Lehnert, Baltimore, Maryland.

(2) 35X25 X20 mm.

(4) A little more than half of the chorionic sac is bare.
A small white nodule can be seen on the interior. _ It is
about 1 mm. in diameter, and apparunlly represents the
embryo. The remainder of the chorion is covered by a

CYLINDRICAL CYEMATA.

thick coat of villi. Examination under the binocular
shows the presence of undoubted hydatiform degeneration,
and a small nodule within, which suggests an embryonic
remnant.

(5) Higher magnification shows this to be a specimen
of hydatiform degeneration, with non-vascular, glassy,
fenestrated, and degenerate stroma, with only moderate
epithelial proliferation. A few small vessels still are found
in the chorionic membrane. Some villi contain consider-
able numbers of Hofbauer cells. The decidua was not
included and no embryonic or amniotic remnants were seen
in the sections examined. The trophoblastic nodules are
degenerate.

(6) Hydatiform degeneration.

GROUP 5.

No. 110.

(1) J. P. West, Bellaire, Ohio.

(2) A 463030 mm.; B 8 mm. CR.

(3) ‘The last menstrual period began September 22 and
lasted 5 days. On December 8 there was a slight flow
which continued until the 13th, when the abortion took

lace.””

: (4) The shape of the ovum is oblong and its walls are
fleshy, the villi having all disappeared. Within there is
a clear fluid, with a granular deposit covering the embryo.
The embryo is greatly macerated and is but slightly at-
tached to the chorion. At the point of attachment there
is an elevated mound of necrotie tissue, to which the
embryo is stuck. There is no distinct cord and the am-
nion is absent. Evidently both chorion and embryo have
been dead for a long time.

(5) The chorion is atrophic and the decidua is infiltrated
with leucocytes. The amnion, umbilical vesicle, and the
attachment of the umbilical cord to the chorion are com-
pletely destroyed. The embryo is atrophic, the face not
being developed at all. The central nervous system is
swollen; the outlines of the viscera and body-cavity are
obliterated and filled with migrating cells. The liver is
small; the heart and blood-vessels greatly distended.

(6) Mild infiltration and probably hydatiform degener-
ation.

No. 115.

(1) A. 8. Atkinson, Baltimore, Maryland.

(2) A 30X27X22 mm.; B3 mm.

(3) The abortion took place two months after the begin-
ning of the last period. During the second month of preg-
nancy there was continuous bleeding.

(4) The ovum was brought to the laboratory fresh,
immediately after the abortion. It was opened at once
in formalin and found filled with a gelatinous, transparent
mass, which became fibrous after the formalin had acted
upon it. Later on aleohol made it opaque. The chorion
is practically free of villi and looks necrotic. The embryo
is well in the middle of the ovum and apparently is separ-
ated from the chorion. The head, as well as the tail, is
atrophic.

(5) Sections show that the villi of the chorion are also
atrophic, with but a small quantity of syncytium attached
to them. Both chorionic membrane and villi are wholly
non-vascular, and the stroma of many of the latter is clear.
Except for slight maceration, the amnion looks normal.
It is detached from the chorion and the embryo is prac-
tically sessile upon it. The entire chorion is surrounded
by a mass of decidua filled with leucocytes. The magma
of the ccelom is very dense and has within it but few
migrating cells. Within the greatly distended amnion lies
the embryo, looking much like a chick of the third day.
The peritoneal cavity communicates freely with the exo-
ccelom, in which hangs an atrophic umbilical vesicle. The
lumen of this is filled completely with entodermal cells,
its blood-spaces greatly distended but nearly empty, and
its solid stem ends abruptly after it enters the body of the
embryo. There is no trace of either alimentary canal or

137

liver. Rudimentary Wolffian bodies and ducts are
present. The central nervous system is solid. The heart
and large veins are simple in form and greatly distended
with blood.

(6) Marked infiltration of the decidua; hydatiform de-
generation of the chorion.

No. 141.

(1) J. P. West, Bellaire, Ohio.

(2) A 403030 mm.; B 8 mm.

(3) Specimen obtained from same patient as No. 110,
described above. Woman has had 9 children and has
always been healthy until about 10 years ago. From that
time her health gradually became worse; now she is
extremely neurasthenic. Stomach is dilated, digestion
poor, bladder irritable, and urine scanty. Uterus large,
thick, and retroverted; leucorrhea. The uterus is about
three times its normal size and has a number of cysts in
the cervix. There were several earlier abortions; the one
before this took place December 13, 1897 (No. 110). The
last period began October 27, 1898, and the abortion fol-
lowed on January 13.

(4) The chorion is fleshy, like No. 110, with but few villi,
and within the ccelom there is a great quantity of magma
réticulé and a dissociated embryo about 4 weeks old.

(5) The sections show that the chorion and villi are
matted together and contain but few blood-vessels. The
trophoblast is very extensive, and where it is in large
masses the most central cells are necrotic. The mesoderm
of the chorion is fibrous and hypertropbic. There is a
considerable quantity of mucus or fibrin, rich in leuco-
cytes, between the villi. This condition may have been
more extensive elsewhere, as only the chorion in the neigh-
borhood of the embryo was examined. The great quan-
tity of magma réticulé within the ccelom has numerous
migrating cells scattered through it. The amnion is
partly in contact with the chorion, and at the points of
contact is normal in appearance, but in other places it is
cystic. Where it is separated from the chorion by the
excessive quantity of magma, the walls of the amnion are
greatly hypertrophied. The umbilical vesicle is collapsed
and its walls have undergone complete hyaline degeneration.
The central nervous system of the embryo is greatly di-
lated and dissociated. The body-cavity can barely be
outlined. The large blood-vessels are faintly marked by
the blood within them. The rest of the tissues form one
homogeneous mass of tissue ce!ls infiltrated with round
cells, within which can still be recognized cartilages and
nerve bundles. The boundaries of the heart and liver are
wholly obliterated, due to their dissociation.

we Probably some hydatiform degeneration. Decidua
absent.

No. 142.

(1) G. N J. Sommer, Trenton, New Jersey.

(2) A 50X40X30 mm.; B 15 mm.

(3) “Last period September 28. On January 3 there
were marked uterine pains; free hemorrhage February 1;
abortion February 4.”

(4) Chorion fleshy with some villi. Subchorial hema-
tomata are present. Within is a macerated embryo about
5 weeks old, embedded in a mass of fibrin-like magma.
Between the magma and walls of the chorion is a large
space filled with clear fluid.

(5) Serial sections of the embryo and chorion show most
remarkable changes. The chorion and amnion are greatly
thickened and very fibrous, and appear in every respect
like the membranes in fleshy moles. The very degenerate,
fibrous villi are matted together by necrotic as well as
living cells. The fibrinous mass within the amnion is in
all probability blood which has entered from the exterior.
It has all the appearance of blood-clots found elsewhere
in the body, but in addition it has been invaded by wan-
dering cells from the embryo. The ccelom was partly
filled with a granular magma, into which project numerous
slender villi arising from the walls of the thickened am-

138

nion. The dimensions of the ovum and the length and
degree of development of the embryo indicate that the
pathological changes began not later than the sixth week
of pregnancy, while the menstrual history of the mother
indicates that at least 14 weeks elapsed between the con-
ception and the abortion. In other words, the patho-
logical process has been under way for at least 8 weeks.
The embryo itself has undergone most marked changes,
which also speak for this. The nervous system is mark-
edly dissociated and macerated. Arms and legs, external
features, as well as most of the internal organs, have
vanished. ‘The liver is still outlined but necrotic. Wan-
dering cells have invaded all of the tissues and are also
beginning to attack the cartilaginous bodies of the verte-
bre. Large nests of them are also embedded in the clots
of blood which surround the embryo. The main blood-
vessels of the embryo can still be traced through the sur-
rounding tissues. The cord is filled with embryonic
blood, but likewise is necrotic. From all appearances,
had the ovum remained in the uterus much longer it would
soon have become filled with maternal blood. which in
turn would soon have solidified to make of the specimen
a typical fleshy mole.

(6) Decidua necrotic and infiltrated; chorionic changes
suggestive of lues.

No. 150.

(1) Theo. E. Oertel, Augusta, Georgia.

(2) A 353010 mm.; B 5 mm.

(4) There are but few villion the chorion. The embryo
is distorted and the arm on one side is unusually large.

(5) The chorion and amnion are greatly degenerated.
Villi are not included. The sections of the embryo show
an extreme degree of change. The nervous system is
swollen and solid, and the contour of the viscera is wholly
obliterated. The large blood-vessels are greatly dis-
tended with blood. Round cells are distributed equally
throughout the body of the embryo. ;

(6) Decidua absent.

No. 205.
(1) D. 8. Lamb, Washington, District of Columbia.
(2) A 403030 mm.; B 6 mm. :

(3) “The specimen which is about 4 weeks old is from a
woman who had been married 3 months. Syphilis is
suspected in the case.”’

(5) The chorion is partly encircled by the decidua,
which is more or less necrotic and infiltrated with leuco-
cytes, showing that an inflammatory process was present
in the uterus. The chorion is fibrous at points, and at
others edematous, with but few villi present. These are
irregular and many of them fibrous. Their outlines are
irregular, and they are covered with a dense and very
irregular mass of syncytial cells. The few blood-vessels
present in the villi are all empty. The amnion is com-
pletely adherent to the non-vascular chorion throughout
its extent, making these two membranes appear as one.
On the amnion side there are numerous fibrous tuberosities
which look much like small villiinverted. At other points
the epithelial covering of the amnion builds by itself a
double layer of cells, which often give rise to papilliform
processes much like the syncytium on the outside. In
some places this layer of epithelium is raised, forming a
blister with a fibrin-like substance, possibly magma,
throughout which are scattered transparent round cells
with very small nuclei. The umbilical cord is quite
fibrous, with large, irregular cavities scattered through it.
These are filled with a mucoid substance in which a few
nuclei are scattered. The blood-vessels are all obliter-
ated, except at the point of attachment of the cord to the
embryo, where irregular vessels are filled with blood.
The external form of the embryo is well preserved and
covered entirely with much thickened epidermis. The
brain and spinal cord are swollen, the former being prac-
tically solid in the region of the forebrain. The heart and
large vessels are gorged with blood, which extends from

STUDIES ON PATHOLOGIC OVA.

them into the surrounding tissues, obliterating them almost
entirely. Within this mass of migrating cells can be seen
the outlines of some of the organs of an embryo about 4
weeks old. The liver, stomach, and lungs are riddled
by them, and only the faintest mark of an endoccelom
can be seen. It appears as if all the blood of the speci-
men accumulated within the embryo, the cord and the
chorion being free, the extensive epidermis preventing the
migration of the blood-cells into ra amniotic cavity.

(6) Probably some decidual infiltration; chorion and
amnion suggestive of lues.

No. 228.

(1) J. P. West, Bellaire, Ohio.

(2) A 602525 mm.; B 4 mm.

(3) “The specimen is from the first pregnancy of a
fairly healthy woman. Last period July 1 to 3; abortion,
October 10.”

(4) The solid, blood-red specimen contains a regular
cavity, 301818 mm., which is filled with a granular
magma, on one side of which is attached an embryo shaped
like an hour-glass.

(5) Sections of the mole show that it is composed of
thick walls in which there is much blood, some villi, a
great deal of decidua, and some pus, especially on the
outside. The mesoderm of the villi and chorion is very
fibrous and devoid of blood-vessels. The cavity of the
chorion is lined with a very thick amnion, and the rem-
nant of an embryo indicates that its development was
arrested towards the end of the third week. The vascular
system still is represented by a mass of cells on the ven-
tral side of the embryo, behind which there is a large
vessel full of blood, extending towards the remnant of the
umbilical vesicle. No vessels extend to the chorion. The
central neryous system fills the main part of the embryo,
being much dilated in the head and pretty well filled with
round cells throughout. In front of the brain are two
vesicles which communicate with it through two long
tubes. These no doubt represent the eyes. In the neck
there is a small gland, possibly the thyroid.

(6) Marked infiltration.

No. 246.

(1) A. Wegefarth, Baltimore, Maryland.

(2) A 30X21X14 mm.; B 3 mm.

(3) “The woman from whom this specimen was ob-
tained is the mother of two children, the youngest about
7 years of age. Since then she has had five miscarriages,
all of about the same age as this specimen. No history
of syphilis, but have started to give her iodide of potash,
with the hope that she may give birth toa child. It would
be interesting if the great fire we had recently could have
played any part in this trouble, as she felt well up to that
time, and the fright, due to the fear that the fire would
burn out her neighborhood, kept her in a state of great
excitement for about 24 hours.”

(4) The external surface of the ovum is normal in
appearance, but when opened it was found to contain a
deformed embryo lying beside a very large amnion. Sec-
tions of the chorion show that its structure is somewhat
hyaline and the villi are devoid of blood-vessels. ‘The em-
bryo and membranes were cut together, and the sections
show that the amnion is greatly hypertrophied, folded, and
torn, and that the embryo is deformed and injured, but
lying outside the amnion. The heart and great blood-
vessels are empty, the brain is distended and partly filled
with round cells; together they give the appearance of
an embryo of the beginning of the third week. No liver
can be found, but there are loops of intestine present, as
during the fourth week. The otic vesicles are well de-
fined, but the optic vesicles are absent. No umbilical
vesicle can be found, but this may have been lost when
the amnion was torn. The amnion, however, runs down
in a thickened ridge which contains two large blood-
vessels and an epithelial tube, the allantois, between them.

CYLINDRICAL CYEMATA.

At no place is the amnion attached to the chorion, nor are
there indications that they have been torn apart.

(6) Early hydatiform degeneration and maceration.
Decidua absent.

No. 252.

(1) D. S. Lamb, Washington, District of Columbia.

(2) B 3mm.

(3) ‘First pregnancy in an unmarried woman 23 years
old. Patient missed one month, then had free hemor-
rhage which continued for a month, when the embryo was
expelled.” This would make its age three months, count-
ing from the last period.

(4) This Seakabls specimen shows to what extent an
embryo may grow after its regular development has been
arrested. It came to the laboratory attached to a solid
body and appears to be about 3 weeks old. The free end
of the embryo is bent upon itself, and tapers to a point
where two intensely black spots may be seen.

(5) The membrane or body behind the embryo is un-
doubtedly the thickened, curled-up amnion; for on the
side towards the embryo it is covered with epithelium,
which continues over the body. On the other side the
mesoderm, which is thickened and hyaline, is free, there
being no border cells or villi. The skin is markedly thick-
ened, the epidermis in some places forming small papille
and in others depressions where pearl-like bodies similar
to those of epithelial cancer are found. Within the
body there is a large cavity filled with round cells. Near
its attachment to the amnion several such ‘‘abscess-like”’
masses lie within the embryo. The pigment dots, on
account of their position, undoubtedly represent the eyes.
Each forms a small sac immediately below the skin, filled
with large, free pigment cells. Deeper within the head
a band of pigment cells, which may be the optic nerves,
connects the eyes.

No. 288a.

(1) H. Brille, Baltimore, Maryland.

(2) A 85X35X35 mm.; B11 mm. CR.

(4) On one end of the chorion there is a space (30X30
X< 5 mm.) filled with reticular magma. Within this, and
pushed to one side, may be seen a collapsed ovum. The
intervening space is filled with blood, through which
ramify a few long, slender villi. These are fibrous and
devoid of blood vessels. At points they are invaded by
syncytium and leucocytes. The amnion, which is also
fibrous, is partly filled with magma réticulé and is very
rich in degenerated migrating cells from the embryo.
The disintegrating embryo is pushed to one side of the
chorion and is pretty well dissociated, but the tissues are
sharply enough defined to show that it is not over 6 weeks
old. ‘They are well infiltrated with round cells which extend
into the surrounding magma. The epidermis is absent.

(6) Infiltration.

No. 289.

(1) H. Briille, Baltimore, Maryland.

(2) B 8 mm.

(4) The specimen is distorted, very dissociated, and
macerated. Limb-buds are merely indicated, and the
outlines of the organs are almost entirely obscured.

(6) Decidua and chorion absent.

No. 297.

(1) D. S. Lamb, Washington, District of Columbia.

(2) B 6 mm.

(3) This specimen was removed from the uterus with a
curette and is said to be nearly 3 months old.

(4) The distorted embryo is of the 3-weeks stage and
shows extreme changes in its organs and tissues.

(5) The chorion is thin and atrophic. There is no trace
of an umbilical cord, but instead the embryo sits upon the
amnion. The spinal cord is dilated and the brain is fully
dissociated, filling up the stumpy head entirely. The
blood-vessels are much dilated with blood, and all of the

139

tissues are infiltrated with round cells which deform the
organs and obscure their outlines. The mandible is ne-
coy and the distended medulla reaches almost to the
mouth.

No. 302.

(1) M. Brédel, Baltimore, Maryland.

(2) A 25*20X15mm.; B 4mm.

_ (4) The ovum is normal, apparently, but is covered with
irregular villi. Sections show, however, that these are
fibrous and contain remnants of blood-vessels. The tro-
phoblast is very active and the villi are partly surrounded
by a recticular mass of mucus, rich in leucocytes.

(5) The amniotic vesicle, which is 10 mm. in diameter, is
embedded in much magma réticulé and filled with granular
magia, in which is an embryo about 3% weeks old. The
umbilical vesicle is degenerated and lies in the reticular
magma. The blood-vessels and tissues of the embryo are
gorged with blood and the outlines of the organs are oblit-
erated. The brain is partly solid and the spinal cord dis-
tended and dissociated. The eye vesicle and lens are nearly
destroyed. The umbilical cord is very short and wide,
vieraoel marked blood-vessels, but infiltrated with round
ce!

No. 312.

(1) E. M. Stanton, Albany, New York.

(2) A 25X15X10 mm.; B 8 mm. (straightened).

(3) Abortion followed a blow upon the abdomen.

(4) One side of the ovum is very hemorrhagic, the other
side thin.

(5) The villi are few in number, without a syncytial
covering and possibly invaded by leucocytes. The main
wall of the chorion appears to be necrotic. The embryo
is straight and shows three gill arches and some myotomes.
Its tissues do not stain well, but the spinal cord can still
be outlined. The tissues appear to be infiltrated with
round cells.

No. 321.

(1) A. C. Wentz, Hanover, Pennsylvania.

(2) A 40x40X20 mm.; B 2 mm.

(4) The ovum is covered entirely with villi and contains
some reticular and much granular magma.

(5) The whole chorion is lined by the amnion and the
embryo is attached to it at its middle. Traces of the cen-
tral nervous system can still be seen, and in front of it
there is a structure which may represent the heart encir-
cled by a large space—the cceelom—which extends to the
umbilical cord. The tail end of the embryo is nearly solid.
A large share of the dissociation may be due to the dilute
alcohol (50 per cent) in which the embryo had been placed
10 days before it was received at the laboratory. This,
however, could not alter the general shape of the embryo
and its attachment to the chorion.

(6) A very macerated hydatiform degeneration. Decidua
is absent.

No. 328.

(1) A. G. Pohlman, Bloomington, Indiana.

(2) B 4.5 mm.

(5) The chorion is covered with irregular, fibrous villi,
surrounded by a necrotic decidua more or less infiltrated
with leucocytes. The main wall of the chorion is about
normal in structure and contains numerous blood-vessels.
Within, the amnion nearly reaches the chorion. The de-
generated umbilical cord is attached to the amnion, but
not to the chorion. The umbilical vesicle is well embedded
in magma, is very rich in blood-vessels, and on its outside
has many papilliform processes, some of which seem to
blend with the chorion. In fact, it appears as if the blood-
vessels of the umbilical vesicle passed directly over into
those of the chorion. The embryo is somewhat deformed,
and it is difficult to follow the outlines of some of its
viscera. The central nervous system is dilated and con-
verted into a mass of round cells lying in the mesoderm,
without any epithelial lining; the otic and optic vesicles

140

are likewise filled with round cells. The larger vessels are
filled with blood, and the tissues are fairly well infiltrated
with round cells. The epidermis is intact. Dissociation
of the tissues has taken place to such a degree that it is
difficult to outline the organs with certainty.

(6) Infiltration.

No. 340.

(1) C. S. Minot, Boston, Massachusetts.

(2) B 6 mm.

(5) The embryo is infiltrated with round cells, and the
dissociation of the tissues is quite complete. Large blood-
vessels can still be outlined, but the central nervous system
is practically solid.

No. 347.

(1) C. S. Minot, Boston, Massachusetts.

(2) A 40X35X30 mm.; B 11 mm.

(5) The decidua is hemorrhagic and necrotic at points
and well infiltrated with leucocytes. The scattered villi
and main walls of the chorion are fibrous, and at some
points infiltrated with leucocytes. Very little syncytium
is present, and but few traces of blood-vessels are found
in the chorion. The villi are non-vascular and partly
matted. The embryo is dissociated and macerated, with
dilatation of the central nervous system and extension of
the medulla. The blood-vessels are distended and the
blood-cells are continued through their walls into the
surrounding tissues.

(6) Slight infiltration of the decidua.

No. 366.

(1) A. G. Pohlman, Bloomington, Indiana.

(2) B 9mm.

(5) Sections of the chorion, which is fleshy in appear-
ance, show that its main wall is very thin and lined with
amnion. The villi, few in number, are fibrous or hyaline
and covered with some syncytium, while the spaces be-
tween them are filled with blood. Some of the’villi adhere
by means of the trophoblast to the decidua, which is
fibrous and necrotic. There is no leucocytic infiltration
of the chorion nor of the decidua. The embryo is pretty
well infiltrated with round cells and the tissues are dis-
sociated. The latter are, however, well preserved and
appear to have been very much alive. There is a consider-
able quantity of blood within the cavity of the heart and
in the blood-vessels. The central nervous system is dis-
sociated. The lower jaw is large and adherent to the head
above, and to the trunk below. The arms and legs are
atrophic.

(6) Hydatiform degeneration; specimen very degene-
rate.

No. 398.

(1) C. R. Bardeen, Madison, Wisconsin.

(2) B 5mm.

(5) The embryo is of the 3-weeks stage, but markedly
changed. Most of its organs can still be recognized and
the embryonic ccelom is fairly definite. The front of the
head is adherent to the thorax below, and the face is pretty
well atrophied. The central nervous system is dissociated
and distended, as are also the heart, the blood-vessels, and
the liver.

No. 399.

(1) A. S. Thompson, Mount Horeb, Wisconsin.
deen collection.)

(2) B 4mm.

(3) Patient 20 years old, married 10 months. She is a
marked bleeder; otherwise strong and healthy. The pelvic
organs are normal. The last period occurred during the
ats week in September and the abortion followed Oc-
tober 9.

(4) The external form looks much like that of a chick
embryo.

(5) Sections show that the tissues are generally disso-
ciated and also macerated.

(6) No decidua or chorion.

(Bar-

STUDIES ON PATHOLOGIC OVA.

No. 400.

(1) G. J. Kaumheimer, Milwaukee, Wisconsin.

(Bar-
deen collection.)

(2) B 3.5 mm.
(3) Last menstruation October 21; abortion De-
cember 19.

(4) The external form is that of a normal embryo, but
the sections show that marked changes have taken place.

(5) The central nervous system is distended and partly
filled with round cells. The walls of the brain are disso-
ciated and apparently are giving rise to the numerous
round and fragmented cells which are present. The heart
and large blood-vessels are distended and well filled with
blood. The tissues of the mesoderm are generally filled
with round cells, as well as with numerous fragmented
nuclei, the infiltration including the myotomes and peri-
toneal cavity. The amnion and epidermis are intact.

(6) Decidua and chorion absent.

No. 413.

(1) A. R. Stevens, Baltimore, Maryland.

(2) B 5mm.

(4) The ovum measures 35X25 mm. and is covered
with numerous long atrophic villi. It contains a large
amnion, measuring 17 mm. in diameter, which encircles
a stunted and twisted embryo 5 mm. in length. The
embryo is curled upon itself at the lower end, being sessile
upon the amnion, but the head and neck are straight and
in many respects appear to be normal.

(5) The arm-buds appear very much like those of a nor-
mal embryo of this size, but the brain is completely dis-
sociated, forming an even layer of cells throughout the
neural canal. In fact, the only structure in the embryo
that is pronounced is a very sharp pericardial cavity
containing an atrophic heart. It is impossible to outline
any other organs within the body save the spinal cord.
There is a fairly sharp outline of its cells in the tail of the
embryo, where it spreads out into a wide open plate form-
ing spina bifida. This is a case of stunted embryo with
spina bifida and almost complete dissociation of tissues.

(6) Decidua absent. Hydatiform degeneration.

No. 414.

(1) J. R. Laughlin, Hagerstown, Maryland.

(2) A 30X20X20 mm.; B 6 mm.

(3) Patient is 32 years old and the mother of four living
children. She had one miscarriage at 4 months three
years ago. There is no specific history. The last men-
struation occurred August 28 and the abortion November 8.

(4) The ovum is transparent and entirely covered with
scattered, ragged villi. It contains a deformed embryo
6 mm. in length. The head is normal in shape, but the
body is atrophic. The arm-buds are large, but the leg-
buds are too small for an embryo of this size. The ceelom
is filled with reticular magma.

(5) Sections of the embryo show extensive dissociation
of the tissue. The nervous system is practically solid, the
brain being greatly reduced in size. The eye-vesicles also
are atrophic, reaching from the brain to the skin as delicate,
trumpet-shaped bodies. The optic cups contain vascular
lenses. Within the tissue of the embryo many of the
blood-vessels can still be outlined by the presence of blood
corpuscles within them. The heart is solid and more or
less atrophic, and the ccelom fairly well outlined. The
body is directly continuous with the amnion, there being
no umbilical cord. The ccelom of the embryo communi-
cates very freely with the exoccelom, and at the point of
communication the intestines extend into the latter.
Adjacent to the intestines there is a very small atrophic
umbilical vesicle. There is no lumen, the Wolffian bodies
can barely be made out, and the liver is completely dis-
sociated. The amnion is greatly thickened at points, but
the chorionic wall appears normal in structure and thick-
ness. The villi are somewhat fibrous, the trophoblast
scanty, and there is a small amount of mucoid substance

CYLINDRICAL CYEMATA.

between them. It appears that in this case there was an
arrest of development of the embryo at about the 20-
myotome stage, but the specimen continued to develop
in an irregular fashion, the tissues becoming dissociated
and ultimately undergoing maceration.

(6) Decidua absent.

No. 419.

(1) J. Park West, Bellaire, Ohio.

(2) A 15x55 mm.; B 5 mm.

(3) This is the second specimen from the same woman,
the first being from an abortion in March or thereabouts.
The woman is about 27 years old and very nervous. Last

eriod began on October 5 and was as usual. Before

ovember 5 she decided she was pregnant. November
23 there was a slight show, which increased and continued
until the abortion, November 28. There was no pelvic
trouble, but the uterus was very small, almost of an infan-
tile type.

(4) The ovum has a hemorrhagic wall 4 to 8 mm. thick,
the entire mass measuring 252020 mm. It contains
a cavity lined by an amnion measuring 15X55 mm.,
and a stunted embryo which is somewhat straight and
measures 5 mm. in length.

(5) The chorionic wall is of normal thickness, but very
degenerate. The hemorrhagic mass is also surrounded
with fibrous decidua, more or less infiltrated with leuco-
cytes. The few villi which are embedded in blood are
mostly necrotic, the trophoblast being scanty, but where
it remains in any considerable quantity it has undergone
extensive fragmentation, leaving large plaques of nuclear
dust. Sections of the embryo show extensive dissociation
and maceration. The brain is solid, but the medulla and
spinal cord contain a lumen. The eye-vesicles can barely
be outlined. The branchial organs appear quite normal,
but the two poles of the body are atrophic. The heart,
which appears to be normal in form, lies free within the
pericardial cavity. The tissues of the lower part of the
body are so much macerated that it is impossible to deter-
mine whether or not the organs are normal in form.

(6) Marked infiltration of the decidua; probably hyda-
tiform degeneration.

No. 446.

(1) Elizabeth Morse, Boston, Massachusetts.

(2) B 8.5 mm.

(3) Patient is 33 years of age and the mother of several
healthy children. She is overworked and lives under poor
hygienic conditions. Last period was October 17 and the
abortion December 15.

(5) There is a piece of chorion which, upon section
ing, proved to be very hemorrhagic; otherwise the struc-
ture is poorly defined. However, there are a few necrotic
villi close to the chorion and the embryo. The latter is
markedly dissociated, but some of the organs can still be
made out. The brain fills entirely the head region, and
the spinal cord reaches to the tip of the tail. The heart,
pharynx, and lungs can still be outlined in their proper
positions. The myotomes are well outlined, and between
them are seen various peripheral nerves, indicating that
the embryo had developed normally to about the 5 or 6
mm. stage before the strangulation and dissociation began.
At the tail end of the embryo there is a large accumulation
of round cells which stain intensely.

No. 451.

(1) H. D. Senior, Syracuse, New York.

(2) A 80X45x40 mm.; B 3.5 mm.

(3) Patient aged 23 years; married 6 years. Five years
ago a child born at 8 months died at 3 months. Four years
ago gave birth to a 7-months child, stillborn. Three
years ago had 2 months’ abortion, another the year follow-
ing, at 2 months. One year ago had a child born dead;
said to have been “distinctly syphilitic’; an “unusua
amount of liquor amnii.” This miscarriage was preceded
by one month’s flow. Last period began September 1;
abortion December 4 (?).

141

(4) The surface of the ovum is smooth and covered
with decidua. The very large cavity is lined with a very
smooth membrane which proved to be the amnion.

The decidua is composed of an inflammatory mass. At
points there are abscesses. Between the decidua and the
chorionic membrane the villi are packed together in an
inflammatory exudate. Most of the trophoblast is ne-
crotic, but the mesenchyme of the villi is still sharply
defined. The dissociation of the embryo is quite complete,
although the form of the brain and heart can still be made
out. The umbilical cord is short and distended, and in
the chorion, opposite to its attachment, there is a sharply
defined epithelial tube lined with cylindrical epithelium.
This, no doubt, represents the distended allantois. The
embryo is irregular in shape and filled quite uniformly
with round cells. These are very pronounced within the
cavities of the heart, but do not invade its wall. They
appear to reach the heart by invading it through natural
channels. There is a small remnant of the Wolffian body,
and the eye-vesicles are still outlined by their pigments.
They are detached from the brain and filled with round
cells. The borders of the hind-brain are fairly well pro-
nounced, but those of the fore-brain are entirely oblit-
erated. The anterior tip of the head is pronounced and
extends beyond the brain, which makes it appear as though
the mesenchyme of this region had continued to grow
independently. No ear-vesicles can be found.

(6) Infiltration; probably early lues.

No. 466.

(1) Henry Rohfling, St. Louis, Missouri.

(2) A 292316 mm.; B 4mm.

(3) The patient, who was 35 years of age, never missed
her menstrual flow; always regular, 28 days from the
beginning of last menstruation, the periods lasting 4 days.
On the day of the abortion she bagan to menstruate early
in the morning, and at about 6 o’clock in the evening the
physician was called on account of pains, which patient
asserted resembled labor pains. On examination he found
a slightly dilated os and a protruding mass which felt like
a cyst. After strong bearing down he received the mass,
which proved to be an ovum, in toto. Patient had borne
three children, all in a healthy state.

(4) Somewhat over half of the ovum is covered with
villi, 2 to 3 mm. long, very irregularly shaped, and many
of which show bulbous enlargements. Over the remaining
portion of the ovum are sparsely scattered villi about 1.5
mm. in length, which branch several times, but do not
show enlargements.

(5) The stroma of the villi is non-vascular, fibrous, and
so degenerate in many instances that few nuclei remain.
Degenerate erythroblasts (Hofbauer cells of Minot) lie
between the amnion and chorion, and the chorionic mem-
brane is rather fibrous. The trophoblast lies in necrotic
knots among the villi. A window being cut in the ovum,
it was examined in strong sunlight under the binocular
at every possible angle. There is a small amount of gran-
ular magma. An opaque spot is seen near one end. This
has the general appearance of a small embryo with a groove
along its dorsum. Magma covers it so closely as to prevent
a sharper picture. The embryo is curled sidewise upon
itself, and the camera drawing made of it before it was cut
shows that we have an extensive spina bifida reaching well
up into the head region. In section the embryo shows the
homogenous appearance so characteristic of those speci-
mens in which dissociation has taken place. The outline
of the brain is recognizable and the two optic stalks are
present. Only the anterior end of the brain is inclosed.
In the head region the epithelial covering has fallen off,
and round cells have accumulated around the periphery
of the sections. Caudal to this the central nervous system
opens over the back of the specimen in a broad, shallow
trough. At intervals ventral to this trough in the body of
the embryo are dense accumulations of cells, which
probably represent remnants of both mesodermal and
entodermal structures, most of which are unrecognizable.

142 STUDIES ON

However, the solid heart figures in this way in familiar
outline on the ventral surface. The embryo is attached
along its ventral surface to the amnion, from the anterior
limit of the heart backward. Near its caudal end it is
bent abruptly to one side. In this region the central nerv-
ous system is closed, and its round outline may be seen
twice in the same section, with about 10 somites indicated
in the region between. There is a fragment lying on the
amnion near the embryo, which may represent the umbil-
ical vesicle. It is very small, with practically no vessels.
(6) Some early hydatiform degeneration.

No. 489.

(1) John A. Luetscher, Baltimore, Maryland.

(2) A 45X30X25 mm.; B 2 mm.

(4) The ovum is smooth and partly covered with atro-
phic villi, over which there is an extensive decidua. The
Jarge cavity within measures 30X23 mm. and is lined by
a smooth membrane which proves to be the amnion.
The amniotic cavity is filled with clear fluid, and on one
side, closely attached to the chorion, is a cylindrical
embryo 2 mm. long, shown in section in figure 28, plate 4.

(5) Sections through the chorion show it to be covered,
as was surmised, with a capsule of decidua and mucous
membrane, half of which are infiltrated. Where the mu-
cous membrane comes into contact with the villi there is an
extensive fibrinoid degeneration. The chorionic mem-
brane is closely attached to the amnion, but where they
are separated the gap is filled out with a delicate reticular
magma. The villi are mostly non-vascular and fibrous,
but some seem to have undergone mucoid degeneration.
The latter are filled with Hofbauer cells. The intervillous
spaces contain blood and large necrotic nodules of tropho-
blast. Growing into this substance are numerous processes
of active syncytium. In other words, there is a very
perfect implantation in this specimen. The chorionic wall
contains a number of blood-vessels filled with blood.
The chorion in the neighborhood of the attachment of
the embryo shows a beautiful implantation. The tropho-
blast cells invading the uterine mucous membrane are
capped with fibrinoid substance, and the mesenchyme of
the villi has undergone extensive fibrous degeneration.
The non-vascular umbilical cord is in direct continuity
with the amnion, but not with the chorion. The embryo
itself has undergone extensive dissociation, but the brain,
heart, and liver can be outlined. The round cells of the
embryo extend out into the cord, and where they stop
there are many Hofbauer cells, making it appear as though
the latter arose in the chorion and are invading the embryo.
The dissociation of the brain is quite complete, and within
the embryo it is somewhat difficult to see a line of demar-
cation between the brain and the adjacent mesenchyme.
Unfortunately, we have no clinical history of this interest-
ing specimen, but its morphological study suggests that
the prime difficulty may have lain in the umbilical cord.

(6) Infiltration, probably luetic.

No. 545.

(1) Richard I’. Rand, New Haven, Connecticut.

(2) A 12X9X9mm.; B 5mm.

(3) Patient has one healthy child 14 months old. Last
menses September 2 to 7, normal. Coitus, September 15.
Menstruation due September 30, but failed to appear,
the patient feeling merely “out of sorts.’ Coitus October 6.
October 22, 23, and 24 had a very slight show; October
25, cramps and free flow. Embryo in sae found in clots in
the cervix.

(4) The specimen is well preserved and partly covered
with villi. It contained a cylindrical embryo suspended
upon what at first appeared to be a large umbilical cord.

(5) Sections show the chorionic wall to be very thin
and somewhat fibrous, as are also some of the villi which
have undergone mucoid degeneration. On one side they
are matted together with mucus and fibrin containing
only a few leucocytes. The trophoblast is scanty. The

PATHOLOGIC OVA.

pete Auer mass is closely encircled by an amnion. The
umbilical vesicle reaches from the lower surface of the
embryo almost to the chorion. In this region of the latter
there are but few villi. The umbilical cord is small and
runs around one side of the amnion to reach the chorion
at a point somewhat distant from the tuft of villi. The
vessels then encircle the chorion and finally reach those
villi which seem to have been still active. The embryo
has undergone extensive dissociation. The brain is almost
completely dissociated and entirely fills the atrophic head.
The eye-vesicles can still be made out, and the otic vesicles
are sharp and filled with round cells. The lower part of
the body has undergone less change than the head end.
The eye, spinal cord, and Wolffian bodies are well formed.
The heart has undergone the least change. The pleural
and pericardial cavities are well formed. The arm and
leg buds are just beginning, and in the lower part of the
body the myotomes are sharply outlined.

No. 551.

(2) A 11X6X6mm.; B 3mm.

(3) Last period June 27. Left husband June 7. Abor-
tion August 30, after two weeks of ill health. Pelvic in-
flammatory disease. The whole ovum was expelled, but
opened before fixing.

(4) Amnion with distorted embryo 3 mm. long. Near
the latter is a vesicle 2 mm. long, and on the opposite side
of the amnion a granule 1 mm. in diameter.

(5) The entire mass was cut in serial sections and those
containing an embryo were mounted. The cylindrical
embryo shows extensive dissociation with an early stage
of destruction of the brain. The brain-tube with its eye-
vesicles is distended and the wall partly broken down, the
adjacent mesenchymal cells entering it. The spinal canal
likewise is distended. The heart has collapsed and the
inner walls are partly dissociated. There are several large
blood-vessels well distended with blood. The chorda is
present. The ccelom is sharply defined and passes off into
the umbilical cord, which is attached to the amnion.
In this region the amnion is thickened and fibrous. The
yolk-sac passes through the patent ccelom well into the
body of the embryo. In addition to the attachment of
the embryo to the amnion, there is a special band of tissue
making a second umbilical cord which passes as an isolated
band over the region immediately below the heart and across
the amniotic cavity, to become attached to the amnion at
a point somewhat distant from the embryo. It contains a
blood-vessel filled with a great quantity of blood-cells, which
passes around the amnion behind the embryo and becomes
markedly dilated. In this section of the amnion there is
a capillary plexus encircled by numerous strands of mesen-
chymal tissue, making it appear as though the amnion
had been attached to the chorion in this region. Since the
chorion was not received it is impossible to establish this
point. Within this region there are several larger isolated
cavities having the appearance of diverticula of the amni-
otic cavity, and it may be that they arose from it.

No. 587.

1) F. A. Conradi. Baltimore, Maryland.

2) A 58X38X29 mm.; B 7 mm.

(4) The chorion is pear-shaped, quite smooth, and with-
out villi. The walls are thick and fleshy, and surround a
smooth cavity, 32X23X23 mm., filled with clear fluid.
This cavity appeared also to contain a layer of reticular
magma (2), On one side of it, closely attached to the
amnion, was an oblong embryo shaped like a grain of
wheat, with a small additional knob at one end, probably
aremnant of the head. The length of the embryo is 7 mm.
and its greatest diameter is 4.5 mm.

(5) Sections of the chorion show it to be composed of a
thin chorionic wall somewhat separated from the amnion,
and between the two there is a delicate reticular magma.
The entire mass is encircled by a decidua somewhat infil-
trated with leucocytes, which is separated from the
chorion by a layer of fibrinoid substance. Between the

CYLINDRICAL CYEMATA.

latter and the chorionic wall are small irregular villi, most
of which are degenerated, and which contain a scanty
amount of trophoblast. The stroma of the villi, which is
somewhat hyaline and partly mucoid, is rich in nuclei.
The chorionic wall appears to have EnderEame a gradual
atrophy. The embryo is greatly dissociated. The central
nervous system is practically solid, and attached to the
brain in front are small atrophic, but completely disso-
ciated, eye-vesicles. One of these shows a small amount
of pigment formation. The spinal cord contains a lumen
throughout the greater length of the body. The heart and
blood-vessels are easily outlined by the blood within them,
but their walls are indistinct. A slight indication of celom
where it passes into the umbilical cord, and a remnant of
the intestines can be made out. The cord has undergone
maceration and the extremities are atrophic.
(6) Decidua slightly infiltrated.

No. 621.

(1) George H. Hocking, Govans, Maryland.

(2) A 70X45x40 mm.; B 3 mm.

(4) The specimen is pear-shaped, dark, and well cov-
ered with decidua. The walls are thick, measuring at
points over 10 mm. Within is a cavity 202020 mm.,
filled with clear fluid, in which floats a transparent vesicle.
The amnion is suspended in the ccelom, which is lined with
most delicate and transparent reticular magma. On one
side is an atrophic embryo 3 mm. long.

(5) The chorionic wall is transparent, but may be a
little more fibrous than in normal specimens. The villi
also are somewhat fibrous and non-vascular, with consid-
erable trophoblast attached to them. This in turn has a
fairly normal connection with the decidua. The latter is
somewhat fibrous and hemorrhagic, with very little leu-
cocytic infiltration. The intervillous spaces contain some
blood and considerable stringy matter, the latter being
filled with buds of syncytium. At certain points there are
very large spheres of trophoblast; in some places the tips
of the villi end in them, and others pass through them.
The embryo is markedly dissociated and is partly filled
with round cells. In the head the central nervous system
is distended, although the outline is still preserved. The
eye-vesicles are very atrophic, and the brain reaches only
to the upper part of the body. In this region the heart,
which lies within a well-formed pericardial cavity, begins.
From it arise two vessels which run down to the point of
attachment of the embryo to the thickened amnion, which
divides near this point, forming a very large vesicle noticed
in the specimen before it was cut. One side of this is closely
attached to and directly continuous with the chorion.
In the lower part of the embryo there is a row of cells
running along the dorsal side, probably the dissociated
cord. The ccelom is well formed.

No. 639.

(1) Edwin B. Fenby, Baltimore, Maryland.

(2) A 18X12XK12mm.; B 6mm.

(3) Patient took 8 grains of quinine to break up a cold
and two or three days later had an incomplete miscarriage.
She did not think she could have been pregnant more than
two weeks, and said she did not know she was in that
state. The specimen was obtained through curettage for
an incomplete miscarriage.

(4) The ovum is covered with irregular patches of
ragged villi and filled with a dense mass of granular magma.
Within there is a disintegrated embryo whose greatest
length is 6 mm. There are also two round bodies, about
1 mm. each in diameter, which probably are the arms.

(5) The chorionic wall amd villi are somewhat fibrous,
with practically no trophoblast. Sprouts of syncytium
arise from some of the villi. The embryo is badly macer-
ated, and the brain is completely dissociated, there being
no lumen present. The boundaries of the spinal cord are
indistinct. Only a portion of the embryo was cut into
serial sections.

143

No. 655.

(1) A. G. Singewald, Baltimore, Maryland.

(2) A 30X3010mm.; B 4mm.

(3) White patient, aged 36 years; married 18 years.
Has had nine pregnancies—four abortions and five births
at term. Four children living. Three abortions occurred
within the last three years. The first two took place in an
interval between full-term births. All were induced.
The patient last menstruated January 22 to 27, and the
abortion occurred March 21, having been induced Feb-
ruary 28. Bleeding from the uterus began March 1 and
continued intermittently until March 21. Uterus rather
enlarged. Part of placenta retained. No infection; no
venereal diseases.

(4) The ovum was carefully examined, and a fine retic-
ular magma was found lying so closely about the embryo,
yolk-sac, and belly-stalk that great care was necessary to
obtain a clear view of it without the reticular fibers pulling
on the amnion or yolk-sac. The embryo | to be
normal, with normal amnion; the yolk-stalk lay to the
left, the belly-stalk to the right; the ccelom is wide open
posteriorly. The heart and lungs are most prominent.
In general it might be said that the body below the heart
is unusually short, but it may be flexed. Direct measure-
ment of the embryo through the amnion while in alcohol
gave 4 mm. as the greatest length. The edges of the
ovum opposite the embryo are denuded for a few milli-
meters, but the remainder is covered closely with villi,
which reach 5 mm. in length and branch two or three times.

(5) The sections of the chorion show that the villi are
normal in form, but macerated. All of them contain
blood-vessels and blood. There is considerable tropho-
blast and a peculiar mucoid substance between the villi.
The embryo appears to be normal in form, but badly
macerated, but whether it is dissociated is impossible to
determine. Judging from the history, it was probably
killed some time before the abortion.

(6) Decidua absent.

No. 669.

(1) O. S. Lowsley, New York.

(2) B 7mm.

(3) Patient’s last period two months before abortion.

(4) The club-shaped embryo was attached to a small
piece of fibrous chorion, on which there were no villi.

(5) The dissociated brain almost completely fills the
head of the embryo, and the tissues of the body have under-
gone extreme dissociation. It is difficult to outline any
other organs, although there are indications of the verte-
bre and spinal nerves. In place of the heart there is a
large group of round cells, but these grade over into the
adjacent tissues.

No. 690.

(1) D. V. Adnaine, Williamstown, Massachusetts.

(2) A 40X35X25 mm.; B 7 mm.

(3) The specimen came from a woman 36 years of age,
who has been married 7 years. She is the mother of a
child 6 years old, and had an abortion August 15, 1910.
Last menstrual period October 20, 1911; abortion Jan-
uary 12 following.

(4) The ovum measures 40X35X25 mm. One half
of it is covered with well-developed villi; the other half is
fibrous, with but few ragged villi. The interior is filled
with a clear fluid. Within the amniotic cavity is an atro-
phic embryo 7 mm. long, without any well-defined umbil-
ical cord. From the front the organs are protruding, and
in front of the head is a small, club-shaped nodule, which
it was thought may represent the heart. 5 .

(5) A portion of the ovum was cut into serial sections
to get the rélation of the membrane, and the embryo was
cut sagittally. The sections give its greatest length as
7 mm. Sections of the chorion and villi show that the
mesenchyme is edematous and contains but very few
blood-vessels. The trophoblast is scanty, but at points is

144 STUDIES ON

vacuolated. Otherwise the ovum is undergoing fibrous
degeneration. There are also numerous buds of syncytium.
The exoccelom is filled with a very dense mass of magma,
but a large part of the amnion is so closely blended with
the chorion that it can not be separated from it. Along
this line, as well as in the exoceelom, there are numerous
Hofbauer cells. Although the embryo is cylindrical in
shape, macerated, injured, and dissociated, the organs can
still be outlined. The liver is well infiltrated with round
cells; the heart has apparently broken away, but the larger
blood-vessels are filled with blood. The front of the head
is very small and entirely filled with the dissociated brain,
which protrudes anteriorly.

(6) Very early hydatiform degeneration. Decidua ab-
sent.

No. 704.

(1) Winfred Wilson, Memphis, Texas.

(2) A 20X12X12 mm.; B 6 mm.

(3) Patient aged 26 years; married 1904. Four preg-
nancies: Birth at term 1906, another in 1910; abortion
1912, and the present one, June 8, 1913. Last menstrual
period April 25 to 30. No infection, but bad retroversion
of uterus. Does not belong to a large family.

(4) The specimen, which measures 201212 mm.,
consists of a clean chorion, covered mostly with villi which
divide about twice. On one side there are no villi, but
instead a smooth membrane. The specimen is filled with
reticular magma, in the center of which is a cavity about
3 mm. in diameter. On clearing away the magma it was
found that this cavity contained an embryo which, when
straightened out, measured about 6 mm. in length and
1 mm. in diameter. It has a knob-like head 1 mm. in
diameter, which in form resembles very much a chick of
the same age. No amnion was found.

(5) The chorion is somewhat fibrous, with a scanty
trophoblast, and contains numerous blood-vessels filled
with blood. The embryo is embedded in a granular sub-
stance and an extensive infiltration of round cells which
are largely disintegrated. There is no amnion. The cen-
tral nervous system can still be outlined, and a few periph-
eral nerves recognized. No other organs can be seen.

(6) Early hydatiform degeneration. Decidua absent.

No. 710.

(1) Howard Fletcher, Fairfax, Virginia.

(2) A 955555 mm.; B 13 mm.

(3) Patient aged 31 years; married 6 years. Mother of
three children, this being her first abortion. Last period
October 27 to 30; abortion following June 15.

(4) The chorion measures 95X55X55 mm., has a
rough surface, with irregular and atrophic villi and some
decidua. Within is a cavity of uniform caliber of about
2 mm., which extends throughout the specimen. To one
side of the cavity was a large mass 40 X30 mm., which was
found to be a subchorial hematoma. Opposite this mass,
towards the point of the specimen, was an atrophic, bean-
shaped embryo 13 mm. long and 5 mm. in diameter, with
an edematous umbilical cord.

(5) The chorionic wall and amnion are very fibrous and
thickened, and are encircled by a mass of fibrin, blood, and
coagulum, in which are embedded necrotic fibrous villi and
small masses of dust. The epithelium of the chorionic
membrane is somewhat abundant, but vacuolated and
necrotic. The embryo is almost completely dissociated,
but the organs can still be made out. The ribs are very
evident. ‘There are remnants of the extremities and a
large cavity within the short umbilical cord. A few periph-
eral nerves are present, but the central nervous system
was aio aeriied completely, forming, in fact, an irregular
amorphous mass in which there is seen the pigment of
the eyes.

No. 785.

(1) C. 8. Minot, Boston, Massachusetts.
(2) A 151210 mm.; B 2 mm.

PATHOLOGIC OVA.

(3) Patient aged 27 years; married in 1911. One pre-
vious pregnancy, a birth at term. Last menstrual period
August 5 to 10, 1913, and abortion October 8 following.
Had been menstruating since September 20; occasional
show. Badly lacerated cervix. No venereal diseases.
Family fertile.

(4) When received the chorion had been opened. It
is entirely covered with irregular villi, well matted together,
and eel of them are club-shaped. Within there is a
great deal of reticular magma, in the center of which is an
embryo 2 mm. long, with a knob-like head.

(5) The villi are fairly fibrous, and between them are
considerable trophoblast, blood, and a slimy substance
rich in leucocytes. Some of the villi contain remnants of
blood-vessels and a few have undergone mucoid degenera-
tion. Within the chorionic wall is the amnion, which is
thrown into many folds. The embryo is well disorganized.
The brain-tube has two marked protuberances from the
head end, probably the remnants of the eye-vesicles. At
the junction of the head with the body the solid nervous
system communicates freely with the exterior of the body.
Otherwise, no structures can be recognized in the head or
in the upper part of the body; but as the lower part is
approached a free communication between the amnion
and the yolk-sac takes place through the dorsal midline.
That is, there is a spina bifida, or probably an open blasto-
pore. The lower part of the body is closely attached to
the yolk-sac, there bee no true umbilical cord. The tis-
sues throughout the body are dissociated, and only at its
lower end is there any indication of blood-vessels.

(6) Probably very early hydatiform degeneration. De-
cidua absent.

No. 839.

(1) W. 8S. Miller, Madison, Wisconsin.

(2) A 503030 mm.; B 5 mm. long.

(4) The specimen consists of a beautiful white egg-
shaped ovum, 503030 mm., about one-half of which
is covered with slender, thread-like villi, as much as 9 mm.
in length. The other half of the surface is bare and trans-
parent. Through the clear chorionic membrane and in
the middle of the bare area a small white embryonic rudi-
ment could be seen. On one side of this bare area the
ovum was opened and found to be free of magma. The
embryonic rudiment, measuring 5 mm., lay within a large
amniotic cavity. Stretching from the embryo to the
chorion, opposite the well-developed villi, was a white
cord about 17 mm. long (magma?).

(5) Sections through the embryo include also the cho-
rionic wall, which is found to be somewhat fibrous and
covered with atrophic villi which have undergone mucoid
degeneration. Most of the trophoblast is degenerate.
The entire cavity of the chorion is lined by the amnion
which contains a very thick-walled cavity. Within, an
closely attached to it, lies a nodular embryo. The tissues
are markedly dissociated. The central nervous system,
although nearly obliterated, can be followed throughout
the body. At one point there is a remnant of the ccelom,
and the region of ihe heart can still be outlined.

(6) Some hydatiform degeneration. Decidua absent.

No. 842.

(1) G. C. Ney, Baltimore, Maryland.

(2) A 76X34X27 mm.; B 5mm.

(4) The knotty, fleshy abortion mass measures
76X34X27 mm. Cross-section near one end discloses
what is apparently a collapsed chorionic cavity, measuring
about 10 mm. across. The next slab shows a dimension
of almost 20 mm. for the cavity. A remnant of the mass
was then opened cautiously by a longitudinal incision, and
disclosed a large flattened oval space, 50X20 mm., lined
by a smooth membrane and containing at one pole a com-
pact, deep-red clot, 25X15xX15 mm. At one point
there is a small cylindrical protuberance about 5 mm. in
length and 2 mm. in diameter—the embryonic rudiment.

CYLINDRICAL CYEMATA.

(5) Sections were cut longitudinally through the em-
bryo attached to the chorion. The amnion and chorion
are fibrous, and the non-vascular villi are matted together
by an inflammatory exudate; the whole being covered
by a very thin, inflamed decidua. Between the amnion
and the thick, macerated, degenerate chorion there is a
very dense reticular magma containing a small collapsed
and dissociated umbilical vesicle. The embryo is pear-
shaped, with the stem attached to the amnion, there
being no umbilical cord. It is composed of a mottled mass
of round cells, so that only the central nervous system
can be made out with precision. The latter is a small
mass of cells located in the dorsal midline and in the head.
pom: eye-vesicles are present, but not connected with the

rain.

(6) Mild infiltration.

No. 856.

(1) C. O. Henry, Fairmount, West Virginia.

(2) A 57X31X26 mm.; B 5mm.

(3) Polish woman aged 17 years; married August 30;
first pregnancy. Last menstrual period December 24-28
(same year); abortion February 11 following. Condition
of uterus good; no infection. No venereal diseases.
Family fertile. ¢

(4) The specimen consists of a pear-shaped, thin-walled
transparent vesicle measuring 57 X31*26 mm. The sae,
which seems to be the denuded chorion, is sharply pointed
atoneend. An opaque, white, and comparatively straight
embryonic remnant was found protruding from one side
of the wall of the sac, near the base. The embryo measures
about 5 mm. and somewhat resembles an embryo with 15
somites.

(5) The non-vascular chorion and amnion are thin and
fibrous, and covered by a single layer of degenerated cells.
There are no villi. The embryo is completely dissociated;
the central nervous system, which appears as a solid mass,
reaches through its whole length. There is an indication
of the ccelom, and in the lower part of the embryo the
myotomes can just be made out. In this region the tissues
are dissociated. The cord is short and attached directly
to the chorion, which here contains a few islands of blood-

cells
No. 874b.

(1) Homer Scott, Little Rock, Arkansas.

(2) A 35X30X30 mm.; B 3 mm.

(3) Patient aged 32 years; married September 9, 1906.
Four pregnancies. Last menstrual period January 23 to
28, 1914; abortion April 13 following. No infection of
uterus. First abortion in her family.

(4) The chorion, which is transparent and spherical,
measures 353030 mm., and is partly covered with
atrophic villi. It contained clear fluid, within which the
amnion, 10 mm. in diameter, was floating. The celom
was filled with delicate reticular magma. The embryo,
which is cylindrical in form, was attached to the amnion.

(5) The chorion is closely covered with villi, which have
a reasonable amount of trophoblast and some mucoid
substance between them. ‘The mesoderm is somewhat
fibrous. The embryo is closely attached to the amnion,
and at the point of attachment the eelom communicates
freely with the cavity of the chorion. It appears as though
there was an arrest of development at this point. The
ccelom is distended, but the greatest distention is in the
central nervous system, in which it is so pronounced that
it might be called “hydrocephalus.” The eyes are very
small and atrophic.

(6) Hydatiform degeneration.

No. 885.

(1) Robert Dodds, Chicago, Ilinois.

(2) B 10.3 mm.

(3) Patient aged 33 years; married April 1906. Three
pregnancies—two births and one abortion. Last menstrual
period September 5, 1910; abortion January 11 following.
Condition of uterus normal. No venereal diseases. Fam-
ily fertile.

Decidua absent.

145

(4) The specimen consists of a small cylindrical em-
bryo 10.3 mm. The head is rounded and the extremities
are barely marked. The cord is long, running out to a
slender point at its attachment to the chorion, and has
undergone mucoid degeneration.

(5) The tissues are markedly dissociated, but the skin
and epidermis are intact. The brain is converted into a
kind of unformed mass, and the front of the head has grown
over into the thorax, concealing entirely the lower jaw.
The heart is represented by a mass of round cells. The
liver and intestines can be outlined.

No. 915a.

(1) C. 8. Minot, Boston, Massachusetts.

(2) A 26 X24 X15 mm.; B 4.6 mm.

(4) The specimen consists of a flattened spherical ovum,
measuring 262415 mm., covered over most of its
extent by villi which reach 9 mm. in length. It was opened
freely so as to completely expose the chorionic cavity, in
which are a moderate amount of reticular magma and a
collapsed spherical amniotic sac about 10 mm. in diameter.
Through the walls of the latter an opaque white embryo,
apparently free in the amniotic cavity, can be seen. It
measures 4.6 mm. in length and is distinguished by a
marked dorsal concavity. The head is represented by a
practically featureless nodule in which one may make out
the mouth. An extension of anterior limb-buds may be
seen.

(5) The amnion and chorionic wall are somewhat fibrous,
as is also the mesenchyme of the villi. The trophoblast is
scanty. The embryo has been almost completely disso-
ciated and only the central nervous system can be made
out with precision. It forms a solid strand which is en-
larged within the head region, and ends in front in a very
small solid mass to which are attached two rudimentary
eyes. There are no lenses.

(6) Hydatiform degeneration. Decidua absent.

No. 933.

(1) Gilbert M. Elliott, Brunswick, Maine.

(2) A 37X32 X40 mm.; B 4.5 mm.

(3) Patient aged 32 years; married in 1904 or 1905.
Four pregnancies. First ended at term, 1906; second in
abortion at three months, 1910; third at term, 1912;
fourth, this abortion, August 5, 1914. Last menstrual
period supposed to be about the middle of June. Condition
of uterus normal. Patient has slightly contracted pelvis.
Family fertile.

(4) The specimen consists of a spherical ovum measur-
ing 373240 mm., about one-half of which is covered
with villi, normal in form, and reaching 9 mm. in length.
The remainder of the ovum is devoid of villi. In the
denuded area the chorion was carefully opened, disclosing
a beautifully transparent spherical amniotic sac, about
20 mm. in diameter. Although separated by a considerable
distance, the amnion is bound to the chorion by many
invisible magma strands. The spherical yolk-sae is 8.5
mm. in diameter. Within the amnion an opaque white
embryo, measuring about 4.5 mm. long, could be seen.
It is clearly malformed.

(5) Sections of the chorion show that the tissues appear
to be quite normal, but the trophoblast is scanty. ‘There
also are strings of mucus in the intervillous spaces. The
embryo was cut with the chorion and amnion around it.
The tissues are markedly dissociated, but the organs can
still be made out. The eye-vesicles are very small and
atrophic, and the lenses still attached to the skin. The
central nervous system is practically solid. The blood
from the blood-vessels extends over into the tissues.

(6) Early hydatiform degeneration. Decidua absent.

No. 937.
(1) Gilbert M. Elliott, Brunswick, Maine.
(2) A 30X11X7mm; B4mm.
(3) Patient aged 27 years; married in 1907. Three
pregnancies First and second at term, June 1908 and

146

December 1912, respectively, and this abortion, August
15, 1914. Last menstrual period June 24 to 27. Condition
of uterus normal. No venereal diseases. :

(4) The specimen consists of a small oblong abortion
mass, measuring 30X11X7 mm. On opening, it is found
to consist chiefly of fibrous chorionic tissue so infil-
trated with blood as to be very fragile. Within is a pear-
shaped chorionic cavity 11 mm. in length by 5 mm.
greatest width, which contains a clear coagulated substance.
This substance broke easily and could be lifted out, and
proved to be a very interesting pathological embryo,
4 mm. long, with a transparent yolk-sac 3.3 mm. in
diameter.

(5) The chorion is fibrous and covered with small de-
generate villi, matted together and surrounded by a de-
generate and inflamed decidua. Most of the trophoblast
is necrotic, and there is considerable nuclear dust, as well
as an invasion of leucocytes. The embryo is mostly disso-
ciated and is attached to the chorion at the lower end.
In its middle there is an accumulation of cells which appear
to be the remnants of the heart, and towards the upper
end the nervous system can be outlined. No eyes, ear-
vesicles, or extremities are present. The amnion is almost
completely destroyed, while the embryo is embedded in a
mass of granular magma which is being invaded by cells
from the embryo at a point where the two come in contact.

(6) Mild infiltration, probably luetic.

No. 1004.

(1) E. Plass, Baltimore, Maryland.

(2) A 2565268 mm.

(3) The patient was the mother of 9 children and had
one abortion four years ago. Last menstrual period oc-
curred on October 1 to 5, and the abortion, which was
spontaneous, on December 4.

(4) The decidual cast, which was open at one end, con-
tains a chorionic cavity 20 mm. in diameter. The latter
contains nothing but a portion of an umbilical cord 18
mm. long and 2 mm. in diameter. Since the amniotic
fluid had been drained off, remnants of the embryo may,
however, have escaped through the opening.

(5) The membranes arefused and have undergone hyaline
degeneration. The villi are fibrous and degenerate. The
decidua also is degenerate and infiltrated slightly, with local
intensification. Portions of it have undergone fibrosis.
Except in a few places, only moderate syncytial prolifera-
tion is present. No remnants of the embryo were seen.

(6) Decidua slightly infiltrated.

No. 1022a.

(1) Ernest C. Lehnert, Baltimore, Maryland.

(2) A 623324 mm.

(3) The last menstruation occurred on January 2.
Hemorrhage began March 6 and abortion occurred
March 25. Abortion was said to probably have been me-
chanical.

(4) The chorionic vesicle contained a blighted embryo
3 mm. in diameter. Examination of the former under the
binocular microscope shows the presence of splendid par-
tial hydatiform degeneration.

(5) Histologic examination confirms the presence of
hydatiform degeneration, although the histologic speci-
men was not taken from the portion which showed the
hydatiform degeneration present in most pronounced
form. The stroma of the villi is degenerate and fenes-
trated and contains numerous atypical Hofbauer cells.
The epithelium is not increased and syncytial buds are
practically absent. The chorion and embryo also are de-
generate. Many of the oval and elongated degenerate
decidual casts show a finely granular cytoplasm, but the
decidua as a whole is too degenerate to enable one to judge
of the question of infiltration. However, since the villi
are embedded in large, dense masses of leucocytes, infec-
tion undoubtedly was present.

The tissues of the embryo are dissociated and its devel-
opment was apparently normal for only the brain and cord.

STUDIES ON PATHOLOGIC OVA.

Possibly the optic cups and the ccelom are present. Al-
though an area of ponnenretion is found in the more caudal
portion, it is impossible to identify this with the develop-
ment of any particular organ.

(6) Partial hydatiform degeneration.

GROUP 6.

No. 54.

(1) J. M. MeMorris, Belle Plaine, Iowa.

(2) B 11 mm.

(4) Only the embryo was received at the laboratory.
The head is atrophic, but otherwise the specimen has the
appearance of a normal embryo of 414 weeks.

(5) In the sections it is seen that the central nervous
system is solid, with the exception of the midbrain, whose
ventricle still communicates with the exterior of the body
through an open neuropore. Some of the vertebra are
fairly well developed; the liver is large, but the heart,
other organs, and ccelom are difficult to outline because of
the presence of marked disintegration.

(6) Decidua and chorionic vesicle absent.
and disintegration of fetus.

No. 69.

(1) G. Henry Chabot, Baltimore, Maryland.

(2) A 705020 mm.; B 13 mm. CR (from mounted
section).

(4) The chorion is smooth, not being covered with villi.
The head of the embryo is atrophic and club-shaped, the
body fairly plump. The arms are well developed, of the
5-weeks stage, and appear normal.

(5) The central nervous system is distended and the
brain is macerated. The outline of the organs and of the
peritoneal cavity are not distinct, and the entire body is
filled with migrating cells. The main bundles of nerves
are filled with spindle-shaped cells, making them look like
the nerves of amphibian embryos. The epidermis is
hypertrophied, and at many points forms papille. Some
of these have a short pedicle and could justly be called
appendices. The embryonic end of the umbilical cord is
atrophic, invaded by migrating cells, and its blood-vessels
are greatly distended. The whole chorion and part of the
cord have undergone fibrous degeneration. Twenty-five
vertebre are present and quite well preserved.

(6) Decidua and chorion absent.

No. 81.

(1) J. H. Branham, Baltimore, Maryland.

(2) A 65X55X35 mm.; B 20 mm.

(3) ‘Abortion took place just three months after the
beginning of the last menstrual period.”

(4) The apparently macerated embryo was broken in
its middle. The crest of necrotic tissue on the head, the
stumpy leg, the distended cord, and atrophic chorion, all
indicate that it is pathological. The two parts were cut
in serial sections and different portions of the chorion also
were examined.

(5) Macroscopic as well as microscopic examination of
the chorion shows that it has undergone extensive degen-
eration. Subchorial hematomata are present, and the
chorionic membrane is non-vascular, fibrous, greatly
thickened, and fused with the amnion. The villi are
fibrous, wholly non-vascular, decidedly clubbed in some
areas, and coalescing. The umbilical cord is extremely
edematous near the abdomen, and contains only a trace
of the vessels. The embryo is somewhat atrophic. Its
central nervous system is macerated, and there is a marked
cyst-like dilatation at the tip of the spinal cord, which
incloses double cavities filled with mucoid reticulum.
This tissue is similar in appearance to the normal noto-
chord of the amphibian embryos. All the tissues, including
the cartilages, show more or less dissociation. A necrotic
crust covers the top of the head; the ectoderm is destroyed
and the mesoderm covering the brain is greatly thickened

Maceration

STUNTED CYEMATA.

and pigmented with round cell infiltration of the sur-
rounding tissue.

(6) Decidua locally infiltrated. This and the chorionic
changes suggest lues.

No. 104.

(1) J. P. West, Bellaire, Ohio.

(2) A 85X35X15 mm. Embryo elongated, 12 mm.;
if curled upon itself, CR about 7 mm.

(3) Last menstrual period began May 7, and abortion
took place June 11.

(4) The villi of the chorion appear to be atrophic, and
are absent on one side of the ovum. After carefully cutting
in half, the ovum was found to be filled with magma,
partly reticular and partly granular. On one side is an
embryo with straightened head and atrophic extremities.
This, with a piece of chorion to which it was attached,
was cut into serial sections.

(5) The main walls of the chorion are fibrous; the
amnion is intact. The brain and spinal cord of the embryo
are dilated and dissociated, probably macerated also.
The outlines of the organs and body-cavity are obliterated.
The boundaries of the liver can no longer be determined.
The tissues of the body are generally dissociated, and they,
with the umbilical cord and magma, are infiltrated with
migrating cells. The heart, large veins, and aorta are
greatly distended with blood. The head is atrophic.

(6) Hydatiform degeneration. Decidua absent.

No. 122.

(1) J. W. Williams, Baltimore, Maryland.

(2) A 20166 mm.; B 5 mm.

(3) ‘Last period began April 19, and the abortion took
place June 23. Continuous bleeding for eight days before
the abortion.”

(4) The thin transparent and fibrous chorion is covered
with a few scattered villi of irregular length. The embryo
is atrophic, with club head, large heart, stump tail, and
no limb-buds.

(5) The nervous system is greatly distended and disso-
ciated. The front of the head and the branchial arches
are atrophic. The liver is small, the Wolffian body well
marked, and the body-cavity sharply defined. The large
veins of the body and of the liver are greatly distended
with blood, the aorta being much enlarged and empty.
The tissues of the entire embryo are partly filled with loose
round cells. The amnion is macerated.

(6) Decidua and chorion absent. Hydatiform degenera-
tion of chorion.

No. 1382.

(1) R. Munson, Washington, District of Columbia.
(Sent by Dr. Lamb.)

(2) A 42X30 mm.; B 15 mm.

(3) The woman menstruated last between August 15
and 20, and aborted November 12.

(4) The chorion is atrophic, with but few villi. The
embryo has a stub head and the extremities on the right
side are atrophic, while those on the left appear to be
normal.

(5) The organs of the embryo are about normal in
form and structure. The cord and brain are slightly dis-
sociated. There is a small number of migrating cells in
the tissues of the body, as well as within the peritoneal
cavity.

(6) Chorion and decidua absent.

No. 135.

(1) Wm. E. Moseley, Baltimore, Maryland.

(2) A 1056565 mm.; B 9 mm.

(4) The ovum is fairly smooth, its walls very thin and
lacking in villi. It was completely filled with a gelatin-
like mass, neither fibrous nor granular. Within this mass
there is an atrophic embryo attached to a thin umbilical
cord. The entire chorion is lined with amnion. The head
of the embryo is atrophic and the body shaped like a grain

147

of wheat. The extremities are more rudimentary on the
right than on the left side.

(5) Sections of the embryo show the cord distended,
the brain almost completely destroyed, and the mesoderm
of the top of the head converted into a mass of mucoid
tissue. The head end of the chorda is greatly hypertro-
phied, being converted into a mucoid tumor. On either
side of this tumor are two large cartilages of normal struc-
ture. Farther cranialward, buried deep in the mesoderm,
are two additional pearl-like bodies, which, on account of
their appearance, as well as by the fact that they are
encircled by an oval zone of pigmented cells, are identified
as the lenses of the eyes. These bodies have within them
lens fibers, making them appear much like the lenses of
amphibians. The front end of the head is necrotic.
The heart is convoluted, its outline obscure and distended
with a mass of blood-cells. The outline of all of the ab-
dominal organs and of the peritoneal cavity can be deter-
mined, although the tissues are considerably obscured by
the great quantity of round cells within them. The
entire wall of the chorion is very thin and lined throughout
with a delicate fused amnion. The villi have almost dis-
appeared, and in their place are islands of necrotic syn-
cytium covered with a hyaline layer of fibrin. The whole
chorion and decidua are infiltrated with leucocytes, which
form small abscesses at points.

(6) Marked decidual infiltration and fibrosis; marked
hydramnios.

No. 137.

(1) William T. Watson, Baltimore, Maryland.

(2) A 655030 mm.; B 16 mm.

(3) ‘Last period commenced September 26. Abortion
December 21.”

(4) The ovum is nearly covered with long and well-
developed villi, having a bare area on one side. The
ceelom contains no magma. The embryo is broken from
the cord and is macerated on its ventral end. The head
is atrophic, but the arms and legs are normal. At the
middle of the umbilical cord there is a marked swelling
seen in other specimens of this kind.

(5) Sections of the chorion show the villi to be normal
in form, but somewhat hyaline in structure and without
blood-vessels. There is a considerable quantity of tropho-
blast. The thickened umbilical cord has within it a
cavity partly filled with a reticular substance, homog-
enous in appearance and more intensely stained than the
surrounding tissues. Within the cord there are large
blood-vessels, greatly distended with blood-cells, which
extend through the walls into the surrounding tissues.
10 mm. from the attachment of the cord to the chorion
is the umbilical vesicle. It measures 3X2 mm.; its walls
are degenerated and its cells, which are necrotic, fill its
cavity. The stem of the umbilical vesicle reaches but
halfway to the umbilical cord. The central nervous
system of the embryo is irregularly distended and dis-
sociated, the spinal cord being roughly segmented to
correspond with the vertebre. ‘The liver is necrotic and
filled with blood. The heart is collapsed and dissociated.
The large blood-vessels are collapsed and empty, while the
small ones are filled with blood. The outlines of the
abdominal organs are pretty sharp, the tissues fairly free
from migrating cells. Most of the epidermis has fallen
off the embryo, but where it remains intact it shows areas
of irregular thickening.

(6) Early hydatiform degeneration. Decidua absent.

No. 174.

(1) E. C. Gibbs, Baltimore, Maryland.

(2) A 35X25X25 mm.; B 13 mm. :

(3) Last period January 11, and bleeding five weeks
later, which continued until the eighth week, when the
abortion followed. oo

(4) The ovum is smooth, having but few villi, and is
filled with granular magma.

148 STUDIES ON PATHOLOGIC OVA.

(5) Sections of the chorion show a marked degeneration
of its stroma and walls, nearly all of its villi having been

destroyed. The few fragments of villi that remain are |

embedded in blood and riddled with cells of the syncytial
layer. The mesodermal layer of the chorion no longer is
sharply defined, and is more or less filled with cells with
fragmented nuclei, the origin of which can not be de-
termined. The embryo is of the five or six weeks’ stage,
with pretty sharply defined organs and tissues which are
more or less dissociated and infiltrated with round cells.
Most of the epidermis has fallen off. In the region of the
olfactory pit, which is almost obliterated, the epidermis
forms two marked horn-like elevations. The central
nervous system is swollen and dissociated more than the
remaining tissues of the body, the change being greater
in the brain than in the cord. The vascular system is
gorged with blood, which is beginning to invade the
surrounding tissues. This is most marked in the umbilical
cord, which appears edematous.
(6) Decidua absent; not enough chorion present.

No. 177.

(1) R. G. Harrison, Baltimore, Maryland.

(2) B 12 mm.

(5) The sections show, well outlined, all the organs of
an embryo at the end of the fifth week, but they are dis-
sociated and swollen. The head is beginning to become
stumpy, and the frontal process is necrotic and commencing
to fall off. So extensive is the dissociation of the head
that the brain has become practically solid, the vesicles
being nearly obliterated. The process is not so extensive
in the spinal cord. Most of the epidermis has fallen off.
The vascular system is greatly distended with blood, which
is infiltrating the tissues, especially those surrounding the
larger arteries and veins. In general the tissues show the
changes always seen in embryos which have been grad-
ually strangulated before the abortion. In this speci-
men there is one marked variation in the changes usually
found. The precartilage outlines all of the vertebra and
ribs, but no true cartilage is yet formed in them. Back
of the eyes in the occipital region on either side of the
head, there are two cartilages which are too well developed
for an embryo in this stage. A more advanced stage of
cartilage was found in embryo No. 135, described above.

(6) Decidua and chorion absent.

No. 188.

(1) G. N. Sommer, Trenton, New Jersey.

(2) A 45X40X40 mm.; B 17 mm.

(3) ‘Last menstruation began January 6; bleeding
began March 19, and ended in a few hours with the
abortion. The unopened ovum was immediately placed
in 95 per cent alcohol.’’

(5) The eccelom is filled with granular magma, the
chorionic membrane is absent, and the villi very fibrous
and mostly lacking. The organs of the embryo are all
normal in form and approximately of the degree of develop-
ment for an embryo of this size. The tissues are dis-
sociated somewhat, the most marked being that of the
brain. The veins of the body are all gorged with blood,
with but little migration of blood-cells into the surrounding
tissues. The decidua is somewhat fibrous and degenerate.

(6) Slight infiltration of degenerate decidua.

No. 200.

(1) Max Brédel, Baltimore, Maryland.

(2) A 352520 mm.; B 14 mm.

(5) The central nervous system is dissociated and
macerated very much, the form of the brain and spinal
cord being lost entirely. The organs are all disintegrated,
the liver being necrotic. There is ulceration of the front
of the head, but the epidermis is intact over the rest of
it, in spite of the extensive internal change. The walls
of the umbilical vesicle are broken down entirely and its
lumen is filled with a mass of necrotic cells. The amnion,

chorion, and villi are more fibrous than normal. The villi
are non-vascular and show “granular hyperplasia.’’ The
nodules of trophoblast are quite necrotic and some of the
villi are glued.

No. 201.

(1) Max Brédel, Baltimore, Maryland.

(2) A 806050 mm.; B 20 mm.

(4) The ovum was received without villi, and when
opened was found to be filled with a fluid which had
hardened into a jelly in formalin. The embryo is atrophic
with a necrotic mass on top of the head.

(5) The fleshy chorion proved to be a mixture of true
chorion, villi, blood, fibrin, decidua, pus and syncytium.
The layers show all stages of disintegration. The meso-
derm of the villi is fibrous and at many points is invaded
by leucocytes and syneytium. At other points the syney-
tium invades the blood-clot and frequently maternal
blood sinuses are filled with leucocytes and syncytium.
Within the embryo most extensive changes have taken
place. The brain is greatly deformed and severed, through
a growth of tissue from the spinal cord in the region of
the medulla, back of the deformed ear. In fact, the brain
is included within the cap-like body on top of the head.
The spinal cord begins quite abruptly in the upper cervi-
cal region and ends in the same way in the upper lumbar
region. At its end there is a curious fibrous tumor meas-
uring half the diameter of the cord. The cord, so far as
it is developed, appears to be normal, but somehow dis-
sociated. Below the upper lumbar region the spinal cord
is wholly lacking, the spinal canal being filled with meso-
dermal tissue rich in blood-vessels. Where it is missing,
most of the spinal nerves appear to remain, and many
dorsal ganglia can be made out. This all indicates that
the changes in the central nervous system took place
after the spinal nerves were developed. The eyes are
united into a single one with a double retina, two lenses,
a single choroid, and a single optic nerve; back of this they
are double. It certainly appears as if the two eyes had
wandered together and united in the middle line. The
epidermis is quite complete, but is broken through at the
back of the head. The extensive ulcer which is found here
is very rich in blood-vessels, involves the walls of the brain,
but does not reach into its ventricle. At the highest point
of the head the epidermis has developed into a papilli-
form body; below this there is a large necrotic area in
which is found a great quantity of yellow pigment gran-
ules. The mouth is closed, although the alimentary canal
from there to the stomach is open and appears normal.
The intestine is matted together, the cloaca and anus
being obliterated. The epithelium of the upper portion
of the intestine shows marked growths into this matted
mass. The thoracie region, liver, and vascular system
have undergone practically no change. The extensive
growth of mesodermal tissue throughout the embryo has
caused an extensive destruction and arrest of further
development of the muscular system. This is shown by
secondary changes in the connective tissue, especially
that of the skin, which is markedly fibrous. Here the
change is so great that it obliterated the external auditory
canal entirely.

(6) Marked infiltration of the decidua.

No. 207 a, b.

(1) Max Brédel, Baltimore, Maryland.

(2) A 704545 mm.; B 16 mm.

(4) The specimen is smooth, with small villi at one of
the poles. Within are two embryos, both macerated with
atrophic heads. The larger measures 16 mm.; the other
is a little smaller, but as it is broken an exact measure-
ment could not be made. The cords of both embryos are
atrophic. There is some granular magma within the
amniotic cavity, with several large clumps in the ccelom
where the two amnions meet.

(5) Sections of the membranes show that the chorion is
denuded of most of its villi, except over the point of

STUNTED CYEMATA.

attachment between the cord and the broken embryo.
The villi are non-vascular and fibrous, with a clear stroma
in some. The entire chorion is covered with its decidua,
which is rich in blood-sinuses and infiltrated with leu-
cocytes. But few remnants of the syncytial layer of the
chorion remain. The whole embryo is still covered by
epidermis, except on top of the head, at the tail end of the
body, and at the attachment of the umbilical cord. At
these points there is a marked destruction of the tissues,
which are beginning to disintegrate. The top of the head
is ulcerated, and in front it is necrotic and pigmented, as
is frequently noted. The nervous system shows the usual
changes seen in strangulated embryos. The vascular
system is gorged with blood, but none is within the vessels
of either the cord or the chorion. Within the body there
is quite an extensive migration of blood-cells in the tissues,
obliterating them in part. The majority of the organs
can still be outlined. We have here a rapid infiltration
with migrating cells of an embryo of 40 days, with cytol-
sis rather than dissociation of the tissues. The changes
in the broken embryo are practically the same as in the
unbroken one, although they are more advanced. Only
the head extremities and cord remain entire, and in these the
changes are more marked than in the corresponding parts
of the unbroken embryo. In the former it is practically a
mass of individual cells, while in the latter the brain is
swollen and quite solid.
(6) Marked decidual infiltration; chorionic changes
somewhat suggestive of lues.

No. 216.

(1) A. Wegefarth, Baltimore, Maryland.

(2) A 35X35X25 mm.; B 17 mm.

(3) This specimen was entered as pathological, but later
was transferred to the normal group. The original note
is dated January 28, 1903.

(4) On further consideration, it appears that this is
really a pathological embryo, as the head is somewhat
rounded and the extremities are not well developed. The
cord has two enlargements, and there is considerable
granular matter within the amniotic cavity.

(5) Sections show the embryo to be both macerated and
dissociated, the dissociation being especially marked
around the cartilage and in the extremities. The blood-
vessels are gorged with blood, and in the lower part of
the body their walls are well defined. They seem to be
normal within the head. The small segment of the chori-
onic vesicle which was cut is thin and only slightly vascu-
lar. The slender villi also are non-vascular and fibrous,
and the thin amnion is fused with the chorion.

(6) Decidua absent; not enough chorion.

No. 232.

(1) M. Brédel, Baltimore, Maryland.

(2) A 45X25X25 mm.; B 14 mm. CR.

(4) Most of the chorion is devoid of villi, except im-
mediately over the attachment of the cord, which appears
to be normal. The villi are somewhat fibrous, with less
numerous blood-vessels than usual, and are covered with
a rich layer of syncytium. The amnion reaches the
chorion.

(5) The embryo is atrophic and embedded in a mass of
granular magma containing numerous round cells. Most
of the epidermis has fallen off. The head is cylindrical in
form, containing a solidified brain and dissociated eyes.
The lenses are composed of broken cells surrounded by a
very thick hyaline capsule. The organs of the body are
not sharply defined, being filled with many round cells.
Even the nerves and cartilages have lost their sharp
borders. The extremities are stubby, being composed of
densely packed round cells which show no differentiation.
The blood-vessels are mostly empty.

(6) Endometritis.

149

No. 251.

(1) A. H. Ritter, Brooklyn, New York.

(2) A 30X25X25 mm.; B 9 mm.

(3) Last period January 16; abortion April 3.

(4) Half of the chorion is covered with villi; the other
half is bare, thickened, and hemorrhagic. The amnion
lines the entire chorion and the cord is very thin.

(5) Sections show that the mesoderm of the villi is
rich in cells, fibrous, and devoid of blood-vessels. The
main wall of the chorion apparently is normal, with a
large number of vessels containing blood scattered through
it. The head of the embryo is atrophic and is nearly filled
with a distended, dissociated, and macerated brain,
which protrudes from the back of the head. The eyes are
solid and the lenses have become dissociated, but are en-
circled with sharply defined and thickened hyaline cap-
sules. The heart and blood-vessles are distended and
filled with blood. The organs and tissues of the body are
not well defined and are filled with round cells. The
epidermis is lacking. The extremities are stubby, without
structure, and filled with round cells. The cartilages are
sharply defined and the liver appears to be about normal.
The decidua is very hemorrhagic and contains a large
number of abscesses. Apparently there was an extensive
endometritis.

(6) Decidua necrotic and infiltrated; probably early

lues.
No. 262.

(1) H. F. Giering, Baltimore, Maryland.

(2) A 801515 mm.; B 14 mm.

(4) The interior of the specimen is filled with a large
amount of granular magma, in which was embedded a
necrotic embryo 14 mm. long.

(5) The decidua is filled with small abscesses, the
leucocytes invading the villi as well as the main walls of
the chorion. The changes in the embryo are extreme, the
nervous system being solid and filling the stumpy head.
The outlines of the organs are hazy, they being filled more
or less with round cells. The embryo is falling to pieces,
but some of the epidermis is still intact.

(6) Marked infiltration of the decidua.

No. 263d.

(1) Albert B. Lyman, Baltimore, Maryland.

(2) A 27X27X27 mm.; B 17mm.

(4) The villi apparently are normal in form.

(5) In structure they possibly are a little fibrous and
some are macerated. The blood-vessels appear to be
normal. The cord is dilated, showing the double enlarge-
ments, which are mucoid in structure. The brain and
spinal cord are dissociated, the brain protruding into the
mouth, but the other organs are fairly well outlined. The
heart and large blood-vessles are filled with blood, and
there is some infiltration of the surrounding tissues with
round cells. The epidermis has fallen off. The changes
within the embryo may be due to maceration, but on
account of the sharply defined tissues of the chorion and
slight amount of fibrous changes in the villi and the mucoid
dilatations in the cord, with some wandering cells in the
tissues, it is probable that this specimen represents the
earliest stage of a strangulated embryo of the sixth week.

(6) Decidua absent. Maceration of chorion and prob-
ably early hydatiform degeneration.

No. 270.

(1) L. R. Wilson, Baltimore, Maryland.

(2) A 403020 mm.; B 14 mm.

(5) The chorion is only partly covered with villi, which
are atrophic and fibrous in structure but contain some
blood-vessels. The main wall of the chorion is also fibrous
and of irregular thickness, but contains some blood-
vessels. The amnion has reached the chorion and is
filled with granular magma, which completely envelops
the embryo. The central nervous system is distended,
dissociated, and macerated. The large blood-vessels and

No chorion.

150

heart are distended with blood, and the tissues of the

body are somewhat infiltrated with round cells. The out-

lines of the organs are slightly obscured, and the tissues

macerated. The villi are fibrous and largely non-vascular.
(6) Decidua absent.

No. 276.

(1) Dr. Stanley, Portland, Maine.

(2) A 70X35X35 mm.; B 13.5 mm.

(3) Time between the jast menstrual period and abor-
tion 80 days.

(4) The walls of the chorion are partly infiltrated with
blood, and on one side are closely adherent to a fleshy
mass—the decidua.

(5) Sections through these regions show that the decidua
contains large blood-sinuses and numerous small ab-
scesses. The villi of the chorion are embedded in a mass
of blood and covered with a normal amount of syncytium,
but in structure they are fibrous and partly devoid of
blood-vessels. In addition, they are invaded at numerous
points by the syncytium, which forms in them small
vesicles lined with two layers of cells, and which are often
filled with dense masses of small round cells. These
vesicles sometimes communicate with the surface of the
villi by means of bands of epithelial cells. The chorion is
in apposition to the amnion, but neither is invaded by
syncytium.

The changes within the embryo are equally remarkable.
The spinal cord is dilated and dissociated; the medulla is
solid, fills the entire head, and protrudes from an opening
formed by the destruction of the forepart of the head.
In front of this opening the atrophic upper jaw, containing
nerves, may be seen, and behind the epidermis it has grown
into a small ridge encircling the opening. The outlines
of the organs are not sharp, but those of the precartilages
are very definite. The blood-vessels are greatly dilated
and filled with blood-cells. They are especially well
marked along the line from the umbilical cord to the
heart. In their immediate neighborhood there is more or
less infiltration with round cells. The smaller veins and
arteries are still filled with blood.

(6) Marked infiltration of the decidua; early hydati-
form degeneration of chorion.

No. 285.

(1) T. W. Keown, Baltimore, Maryland.

(2) A 453535 mm.; B 8 mm.

(3) “Last menstruation October 9 to 12; abortion
December 20. The specimen came away unbroken, was
washed in water, and placed in alcohol. There is reason to
believe that conception did not take place until the time
for the period which lapsed. The mother insists that this
is the case, and inasmuch as all three of her children had
diphtheria at that time, this date probably is correct.”

(4) The chorion is mostly bare, with some hemorrhage
in its walls.

(5) The villi that are left are fibrous and contain few
blood-vessels. The syncytium over them is very active
and at numerous points it is heaped up in small mounds
which form depressions, making it appear as if they were
about to invade the mesoderm of the villi as well as that
of the main wall of the chorion. The amnion fills the
entire chorion, which is non-vascular. Between the villi
there is a reticular arrangement of blood and mucus in
which are found numerous leucocytes. The trophoblast
enters this reticular mass at numerous points and makes
a very remarkable picture. The embryo has an atrophic
head and cord, showing, however, enough structures to
fix its age at 4 weeks. The spinal cord is dilated and
dissociated, and the brain is solidified, filling the entire
head. ‘The eyes are destroyed. The blood-vessels are
enormously distended with blood, which also fills the
tissues of the body, obscuring them to a great extent.
The epidermis is intact.

(6) Decidua absent. Early hydatiform degeneration.

STUDIES ON PATHOLOGIC OVA.

No. 311.

(1) Wm. T. Watson, Baltimore, Maryland.

(2) A 363030 mm.; B 12.5 mm.

(4) The wall of the chorion is thin and covered with a
few scattered and irregular villi.

(5) Sections show the villi to be in all stages of degenera-
tion, the large ones with blood-vessels and a rich syney-
tium, the small ones, which are fibrous, devoid of syney-
tium and infiltrated with leucocytes. The spaces between
them contain considerable blood, and where this comes
in contact with an active syncytium the nuclei of the
leucocytes are fragmented; elsewhere they are not. Por-
tions of the main wall of the chorion are very thin, fibrous,
and devoid of epithelial covering. The amnion is in con-
tact with the chorion and at many points blended with
it. Within the amniotic cavity there is a mass of granular
magma which could be seen through the thin walls of
the chorion before it was opened. The umbilical cord is
enlarged in its middle and very thin at its attachment to
the chorion, which also is atrophic at that point. Sections
show that the center of the cord is fibrous, and that the
enlargement is due to the extreme mucoid degeneration.
Near its attachment to the body the cord is infiltrated with
round cells, and the intestine within the eelom of the
cord is irregular and gorged with them; the lumen of the
intestine is destroyed entirely. The embryo is embedded
in the granular magma and approximately normal in
form. Within, however, most radical changes have taken
place. The blood-vessels and heart are distended enor-
mously with blood and the tissues are gorged with round
cells. Liver, heart, intestine, and mesenchyme are un-
dergoing destruction. The precartilage is more sharply
defined than in the normal embryo. ‘The spinal cord is
dilated, the brain and eye are nearly solid, and the ear-
vesicle is destroyed. The ganglia and nerves are dis-
integrating. The epidermis is partially lacking, and in the
head region the din is studded with numerous papil-
lomata. The face is adherent to the thorax.

(6) Decidua absent. Early hydatiform degeneration.

No. 320.

(1) E. C. Gibbs, Baltimore, Maryland.

(2) A 705040 mm.; B 18 mm.

(4) The chorion is fleshy and thick, with irregular spots
of villi covering its surface. Some of the villi are fibrous,
others are swollen, and all are deficient in syncytium.
The decidua is fibrous and well filled with leucocytes.
The entire chorion is lined by the amnion, which contains
no magma. The umbilical cord is thin at its attachment
to the chorion, but swollen in its middle. This swelling,
upon microscopic examination, proves to be a vesicle
filled with a hyaline, stringy mass tinged with carmine.
Otherwise the cord is fibrous, with remnants of blood-
vessels in its center. These are practically obliterated.
The tissues of the embryo are pretty well dissociated, the
cord and brain are nearly solid, with occasional irregular
ieee representing the central canal. The outlines of
the alimentary canal are obscure, and its epithelial lining
is nearly lost. The blood-vessels are distended with
blood in an irregular fashion. The liver is necrotic and
free from blood. The tissues of the body are all disso-
ciated, which condition obscures the muscles and nerves
and sharpens the outlines of the cartilages. The epidermis
is intact.

(6) Slight infiltration of the decidua; probably early
hydatiform degeneration.

No. 325.

(1) E. K. Ballard, Baltimore, Maryland.

(2) Ovum 555535 mm.; B 13 mm. CR.

(3) “Last menstrual period September 15; abortion
November 27. Periods regular.”’

(4) The specimen was clean, well covered with villi,
and hardened in formalin. The amnion and celom are
filled with magma réticulé, in which is embedded the

STUNTED

trunk of an embryo attached to the chorion by a thin
cord. On the opposite side of the ovum the head is located,
also embedded in magma. Over the body of the embryo
there is a greenish-colored nodule 4 mm. in diameter,
which proves to be the degenerated umbilical vesicle.
The legs are poorly formed and stubby.

(5) Sections of the chorion show that the mesoderm of
the villi is hyaline, and therein remnants of blood-vessels
may be seen; a normal number of round nuclei are scattered
through it. The trophoblast also appears to be normal.
Between the villi may be seen some mucus containing
leucocytes. No decidua is attached to the villi. The cord
is thin at its attachment to the chorion, and is slightly
enlarged midway between the chorion and the embryo.
Here it contains large mesodermal spaces, which at points
are infiltrated with round cells. The umbilical vesicle
is present only in outline and its lumen is partly filled
with débris. However, some beautiful multipolar meso-
derm cells may be seen. The epidermis covers the embryo
only in part; a shell of granular magma covers the rest
of the body. The tissues are greatly dissociated and
macerated, which has caused almost complete oblitera-
tion of the outlines of the epithelial lining of the alimentary
eanal. The central nervous system is nearly solid, and
the large blood-vessels are gorged with blood. The liver
is necrotic. The mesodermal tissues are obscured,
with the exception of the cartilages, whose outlines are
sharpened.

(6) Hydatiform degeneration. Decidua absent.

Nos. 330 a, b.

(1) J. Park West, Bellaire, Ohio.
(a) A 60X55X50 mm.; B 12 mm.
(2) Twins| (b) A 55X50X45 mm.; B 12 mm.

(3) “The woman from whom these twin specimens
were obtained is about 25 years of age. Fifteen months
ago she gave birth to an 8 months child which lived for 2
days. Her last regular menstrual period took place
during the middle of September. The October and
November periods were missed. About the middie of
December, at her regular time, bleeding began, which
continued until January 21, when these two ova were
aborted. I am quite positive, but not certain, that the
woman has syphilis.”’

(4) Both ova have smooth surfaces, being composed of
thin walls, upon which there are occasional villi.

(5) In both specimens the villi are irregular, fibrous,
non-vascular, and embedded in a mass of pus, in which
may be found much necrotic syncytium, fibrin, and blood.
Many leucocytes are found in the mesoderm of the villi.
The chorion and amnion of both specimens are of irregu-
lar thickness and well blended with each other. The
changes in the two embryos are very similar. In both the
epidermis is intact and the dermis thickened. In front
of the head, in the region of the deformed mouth, there
are peculiar thickenings of the epidermis. Both spinal
cords are markedly dissociated. The dissociation of the
brains is so extensive that the cerebral vesicles and mid-
brains are nearly destroyed, and the hind-brains occupy
spaces in the centers of the deformed heads. The large
vessels and heart are gorged with blood. In 330b the wall
of the ventricle is well infiltrated, and in 330a nearly
destroyed by the migrating cells. The outlines of the
organs and tissues are very obscure, the whole being more
or less filled with round cells. Some of the liver tissue is
necrotic.

(6) Decidua necrotic and infiltrated; chorionic changes
suggestive of lues.

No. 334.

(1) B. J. Merrill, Stillwater, Minnesota.

(2) A 50X40X30 mm.; B 5 mm.

(3) ‘Last period 4 weeks before. About 10 days before
abortion there was some bleeding, which repeated itself
at intervals, and was finally followed by the abortion.”

CYEMATA. 151

(4) Examination of the mass proves that it is made u
mostly of uterine mucous membrane, decidua, and blood,
and that it contains a cavity 15 mm. in diameter.

(5) The chorion can still be made out as a very macer-
ated, fibrous band. The amnion is almost completely de-
generated, the villi are macerated, the non-vascular stroma
clear and wavy, but the epithelium and trophoblast
fairly well preserved.

(6) Decidua and mucosa infiltrated; hydatiform de-
generation.

No. 336.

(1) J. Park West, Bellaire, Ohio.

(2) A 35X25xX15 mm.; B 8 mm.

(4) The ovum is smooth, one end being covered with
well-developed villi.

(5) Their mesoderm is hyaline, with scattered nuclei
containing some remains of blood-vessels. The main wall
of the chorion is fibrous and infiltrated with blood-cells

from theembryo. Within, there is a cavity (15X10 mm.)
filled with granular magma and containing the umbilical
vesicle and the embryo, which is closely encircled by the
amnion. The embryo is somewhat distorted, with large
blood-vessels filled with blood and tissues infiltrated with
round cells. What is especially noteworthy is that the
circulation within the chorion has been cut off, the cord
being atrophic and infiltrated. The large omphalo-
mesenteric vessels are filled with blood and spread over
the yolk-sac, the walls of which are necrotic.
(6) Decidua absent. Hydatiform degeneration.

No. 339.

(1) C.S. Minot, Boston, Massachusetts.

(2) A 503030 mm.; B 16 mm.

(4) The chorion is thin, covered by only a few villi and
hemorrhagic at one end.

(5) In structure it is somewhat hyaline at points and
at others somewhat fibrous. The villi are largely non-
vascular, fibrous, and hyaline. The cord is thickened and
fibrous. The walls of its blood-vessels are dissociated, and
the blood from them is infiltrating the surrounding tissues.
The embryo is somewhat distorted, but normal in form.
Within, the tissues are dissociated and macerated. The
large blood-vessels are distended with blood, and within
the liver and heart the blood-cells from them have ex-
tended into the surrounding tissues.

(6) Decidua absent.

Nos. 341 a, b.

(1) C. S. Minot, Boston, Massachusetts.

(2) A 70X60X50 mm.; B 14 mm.

(4) The ovum is pear-shaped and smooth, being covered
with some decidua and at points with hemorrhagic masses.
Its tissue does not stain well, but some of the villi appear
to be fibrous and others edematous. There is not much
syncytium present. Possibly there are masses of leu-
cocytes in the decidua. Within the ovum are two stumpy
embryos, both of which have dilated cords which come to a
point where they are attached to the chorion.

(5) These dilatations show the usual mucoid changes
with cavity formation. The embryos are dissociated and
macerated. The large blood-vessels are filled with blood,
and it appears as if the migrating cells had infiltrated
much of the tissues.

(6) Decidua too necrotic; probably some hydatiform
degeneration.

No. 343.

(1) C. S. Minot, Boston, Massachusetts.

(2) A 55X45X35 mm.; B 11 mm.

(4) The chorion is mostly smooth and of unequal
thickness. The decidua is necrotic and infiltrated with
numerous leucocytes. Below it there are distorted villi
with fibrous, non-vascular mesoderm. The amnion is in
contact with the chorion. Between the villi there is a
tringy mucoid mass rich in leucocytes. The stumpy

152 STUDIES ON PATHOLOGIC OVA.

embryo is attached by means of a fibrous umbilical cord.
Its tissues are dissociated and infiltrated with round cells.
The blood-vessels and heart are greatly distended with
blood. The liver is necrotic. In front of the head the
tissue is broken away, leaving a pocket which contained
the forebrain, and above this the brain protrudes. The
cord and fourth ventricle are distended and dissociated.
The epidermis is intact.

(6) Marked infiltration of the decidua; insufficient
chorion.

No. 344.

(1) C.S. Minot, Boston, Massachusetts.

(2) A 45X45X45 mm.; B 16 mm.

(5) The wall of the chorion is very thin and non-
vascular, with a few fibrous villi scattered over it. The
long, thin umbilical cord is fibrous and shows remnants
of blood-vessels. The embryo has a rounded head and
stumpy legs. Its tissues are dissociated, the brain being
distended and macerated as well. The medulla has
expanded towards the mouth. Heart and blood-vessels
are distended. In many places the walls are destroyed
and the blood-cells extend into the surrounding tissue.
This condition is very marked in the liver. The legs are
filled with an even mass of round cells, 7. e., the tissues
are dissociated. Some of the epidermis has fallen off.

(6) Decidua absent. Chorion suggestive of lues.

No. 346.

(1) C. S. Minot, Boston, Massachusetts.

(2) B 13 mm.

(4) A piece of hemorrhagic chorion, which may have
been 50 mm. in diameter, is attached to the embryo.

(5) Its tissues are macerated, but preserved well
enough to show that there is mucus and pus between some
of the villi. The latter are matted, very degenerate, non-
vascular, and fibrous. The chorion has undergone hyaline
degeneration and contains remnants of blood-vessels only.
The decidua is markedly infiltrated. The umbilical
vesicle is filled with a necrotic mass. The embryo is
dissociated and macerated. The central nervous system
is dilated and the heart is distended with blood, some of
which infiltrates the surrounding tissues.

(6) Marked infiltration of the decidua.

No. 348.

(1) R. M. Pearce, Albany, New York.

(2) A 50X30X25 mm.; B 12 mm.

(4) The specimen is smooth, being covered with numer-
ous small hemorrhagic spots and irregular masses of
small villi.

(5) Sections show that the decidua is infiltrated with
leucocytes, with a consequent fibrous degeneration of the
villi of the chorion. Some of the villi, as well as the very
degenerate portions of the wall of the chorion, have under-
gone invasion by leucocytes and syncytial cells. The
stroma of the villi is largely non-vascular and shows
“‘oranular hyperplasia.’”” The epithelium and tropho-
blast are fairly well preserved. The dissociation of the
tissues of the embryo is extreme, the blood from the blood-
vessels having passed through their walls to infiltrate the
surrounding tissues. This is especially well marked in
the heart and liver. The nervous system is pretty well
broken up and the epidermis has fallen off.

(6) Marked infiltration of the decidua and changes
suggestive of lues.

No. 357.

(1) E. J. Russell, Baltimore, Maryland.

(2) A 904040 mm.; B 17 mm.

(3) “The specimen came from an unmarried woman 22
years old. er menstruation was irregular, sometimes
every two weeks, sometimes every six weeks. The last
period occurred about the middle of January. On March
29 she began to bleed and aborted April 19. Apparently
her uterus is normal.”

(4) The unruptured specimen was inclosed in a layer
of decidua and covered with villi of unequal size, some
being very large. Within it was a stumpy embryo with-
out a neck and with atrophie leg-buds. The cord was
transparent and partly filled with granules, indicating
that the embryo had been dead for some time before the
abortion.

(5) The main wall of the chorion is very thin, being
composed in many places of epithelial cells only. The
mesoderm of the villi is unusually fibrous and contains no
blood-vessels. The very large villi are degenerated, often
hollow, and do not stain. The syncytium is very de-
ficient in quantity, but at points invades the mesoderm.
Over the villi there is a mass of fibrin and disintegrated
blood. Leucocytes are not numerous, even in the decidua,
which appears to be normal. The tissues of the embryo,
which are dissociated and macerated, do not stain well.
The sharp boundaries are lacking, showing that adjacent
tissues have begun to coalesce. In fact, the whole head,
down to the thorax, seems to have been converted into a
bag in which fragments of cartilage and nerve tissue may
be seen. The front of the head is adherent to the thorax
immediately over the heart. The contour of the cartilages,
liver, heart, and adrenals can be made out, but that of the
blood-vessels is obscure. According to the menstrual
history, this embryo was in the seventh week when bleeding
began, which was followed by the abortion three weeks
later. However, the degree of development of the car-
tilages and other structures places the embryo in the
sixth week. The continued bleeding may have been the
primary difficulty, being followed by death and degen-
eration of the embryo.

(6) Decidua is very degenerate and possibly infiltrated; -

hydatiform degeneration of the chorion.

No. 364.

(1) B. J. Merrill, Stillwater, Minnesota.

(2) A 905040 mm.; B 16 mm.

(3) ‘Last menstruation April 7, abortion July 5. The
first flow and pain appeared on the night of July 4. The
woman has been married four years, but this was her
first conception. Both she and her husband are very
anxious to have a child, so the miscarriage could not have
been aided. There was no incident, accident or other-
wise, to give cause for the abortion. The woman is
unusually healthy and the miscarriage took place without
chill or rise of temperature. She had been operated upon
several years ago for appendicitis. She has not been
altogether regular with her menstrual periods, and there
is some pain connected with them. She had been treated,
some time before I saw her, for vaginal discharge; there
may have been edometritis. Prior to her conception I
gave her some treatment for leucorrhoeal discharge, and
also made some slight dilatation of the cervix. She had a
long cervical os with a narrow canal. There was some
vaginitis and, as I remember, some endocervicitis rather
than endometritis, none of them very marked. Probably
there was enough uterine trouble to cause the delayed
development of the embryo and the abortion. The
husband is ordinarily healthy, but about a year ago, his
wife states, he had some trouble with his genital apparatus.
He has night emissions and I judge took medicine for
them. As far as I can ascertain from her outline, he has
not had venereal disease. If so, he did not contaminate
her. If he has, as she states, night emissions, perhaps the
virility of his semen is below par.”

(4) The ovum is covered with a few ragged villi, over
which there is some decidua more or less detached.

(5) Seetions of the chorion show that the villi are far
more numerous than was suspected from the simple
unaided eye inspection. The main wall of the chorion is
thin, atrophic and lined with the amnion, which is full
detached where it connects with the umbilical cord.
However, it must have been attached at one time, as
remnants of blood-vessels from the embryo are seen in the
villi of the chorion. The mesoderm of the villi is very

STUNTED CYEMATA.

fibrous and the villi are matted together by a slimy mass
rich in blood and leucocytes with fragmented nuclei. The
syncytium is well developed and extends into the blood and
slime. The decidua over the chorion has large sinuses
within its walls, is quite hemorrhagic, and at points has
large islands of luecocytes, usually situated along the
course of the blood-vessels. The embryo has hare-lip and
displaced ears. The viscera protrude in the front and
there is spina bifida. The large blood-vessels and heart
are still filled with blood, and there is quite a general
infiltration of the tissues with round cells. The vessels
of the embryo end in the cord and do not reach to the
chorion. In general, there is mainly a destruction of the
tissues possibly due to the irregular growth of the embryo.
The central nervous system has been converted in great
part into a mass of connective tissue, with remnants of
the cord below and a rudimentary brain above, which
forms a shield upon the protruding mass. A portion of
this shield has grown into the connective tissue below,
forming a gland-like structure. The clavicle, mandible,
and maxilla have begun to ossify, and some of the muscles
are fairly developed.
(6) Slight infiltration of the decidua.

No. 365.

(1) A. G. Pohlman, Bloomington, Indiana.

(2) B 14mm.

(4) This embryo, with spina bifida, iniencephaly, and
anencephaly, but the extremities of which are normal in
form, has a straight body and is attached to the end of a
very large umbilical cord.

(5) Sections show that the spinal cord is absent, but
there is a solid brain which is more or less infiltrated with
round cells at its periphery. The same is the case with
the eyes. The mouth is closed by the tongue, which has
become adherent to the lips. The nodules in front of the
body are composed of necrotic epithelial cells. Some of
the other tissues of the body also are necrotic, but most
of them are infiltrated with round cells. Those of the
head are quite fibrous in character. The walls of the
alimentary canal and the lungs are also pretty weli filled
with irregular patches of round cells. Especially well
marked is this change in the region of tendons and peri-
chondrium, showing that there is an irregular growth of
the mesodermal tissues. The clavicle, maxilla, and man-
dible are well ossified, which should not be the case in
so small an embryo.

No. 375.

(1) Simon H. Gage, New York.

(2) B 13 mm.

(4) A piece of chorion, accompanied by the mutilated
embryo. Both appeared quite normal.

(5) Sections of the chorion, however, show that the
mesoderm of the villi is non-vascular, somewhat degene-
rate, and very fibrous. That of its main wall also is non-
vascular, edematous, and macerated. The syncytium
seems to be deficient in quantity and the epithelium
degenerate. The mesenchyme of the cord is very de-
generate and the vessels have disappeared completely.
Sections of the embryo indicate that it is nearly normal,
with some dissociation of tissues. The larger blood-
vessels are gorged with blood, and some of the tissues,
especially those in front of the head, are infiltrated with
round cells. The central nervous system is swollen and
dissociated, as is so frequently the case in many of the
other embryos.

(6) Decidua absent. Chorionic changes suggestive of

lues.
No. 401.
(1) Dr. Hay (Bardeen collection).
(2) B 5.5 mm.

(5) Much of the chorion and many of the villi and the
syneytium are necrotic and infiltrated with many leu-
cocytes. The umbilical vesicle is necrotic and filled with

153

a mass of broken-down cells. The tissues of the embryo
are dissociated, macerated, and infiltrated with round cells.
(6) No decidua, but evidences of infection are present.

No. 402.
(1) Edmund J. O’Shaugnessy, New Canaan, Connecti-

ut.

(2) A 402520 mm.; B 4 mm.

(3) “The woman, aged 30, is strong and healthy. She
was married 3) years before she became pregnant, and
menstruated regularly. After the birth of the first child
she had a slight discharge, which was diagnosed by her
attending physician as an ulcerated cervix, and which he
treated by local applications. Since the birth of the
second child patient has had some discharge, but again
became pregnant, this time aborting at 6 or 8 weeks. She
has never done anything to prevent pregnancy, and both
she and her husband are anxious for a large family.”
At the time the specimen was sent the patient was men-
struating and still had a chronic discharge.

(4) The villi of the ovum are well developed and
regularly distributed over its surface. Within, the ccelom
is well filled with reticular magma. The embryo is club-
shaped, its head being much too large for the body.
Umbilical vesicle normal in size and shape, and the heart
is well outlined. Extremities beginning to develop. The
embryo is lying free within the celom and is attached
but slightly to the amnion, some distance from the latter’s
attachment to the chorion.

(5) Sections of the chorion show that the villi are
matted together with a fibrinous mass extending more or
less between them. Within this mass there is quite an
active trophoblast, which at numerous points forms large
nodules, many of which haye necrotic centers. The
chorionic membrane appears to be normal in texture, and
from it arise great masses of reticular magma which are
brought out well by the Van Gieson method of staining.
The mesenchyme of the villi is partly fibrous and partly
mucoid, and many villi contain numerous Hofbauer
cells. The nervous system of the embryo is completely
dissociated, the cells forming a uniform layer throughout
the canal. It is impossible to outline the different por-
tions of the brain. The spinal cord has a lumen at its
lower end. The vascular system is also destroyed almost
completely, only a portion of the heart being recognizable.
The ccelom is more or less filled with round cells. No
myotomes can be outlined. Small remnants of the
pharynx and the ccelom are present at different points.

(6) Marked infiltration of the decidua and hydatiform
degeneration.

Cc

No. 450.

(1) John Girdwood, Baltimore, Maryland.

(2) A 604545 mm.; B 18 mm.

(3) Patient had missed two periods. She is the mother
of several healthy children, and has also had several
preylous miscarriages.

(4) The unopened specimen came with its decidua
partly stripped off. The portion of the chorion which is
exposed is covered with very long and extremely delicate
villi, with an unusually thin chorionic membrane. The
embryo’s head is nearly detached, and is atrophic, with
rounded atrophic forehead. The body of the embryo is
normal in shape. The cord is sharply dilated in its middle
and very small and pointed at its attachment to the
chorion.

(5) The decidua appears to be normal in form and
thickness, but shows a very extensive inflammatory re-
action. At points there is such an accumulation of leu-
cocytes as to form small abscesses. The villi are small
and fibrous, with practically no trophoblast attached to
them. The main wall of the chorion also is thin and
fibrous. Serial sections through the umbilical vesicle
indicate that it is necrotic and undergoing disintegration
on one side, while on the other its wall is fibrous and
seems to be growing quite actively, tufts appearing upon

154

its surface like small warts. The tissues of the embryo
show marked dissociation, the shape, border of the car-
tilages, and practically all of the organs being obliterated.
These changes extend to the extremities. The specimen
may be viewed as typical of general dissociation of the
tissues in an embryo of this size. It appears as though
the tissues grew independently for some time after the
strangulation of the embryo.
(6) Slight infiltration of the decidua.

No. 465.

(1) H. W. McComas, Oakland, Maryland.

(2) A 70X70X50 mm.; B 13 mm.

(4) The ovum is pear-shaped, with a pedicle 40 mm.
long, representing, no doubt, the portion that was pro-
tring from the uterus. Parts of the decidua are hanging
to the chorion. Other portions of the specimen are covered
by very large villi, while the greater part of it appears to
be Pea. The amniotic cavity is very large, filling
almost the entire specimen. It contains a clear fluid and
a pathological embryo the head of which is broken off
from the body. The extremities are stunted and the cord
is 20 mm. long. The united portions of the embryo
measure together 13 mm.

(5) Sections show that the villi are matted together
and covered with decidua. The mass between the villi
and the decidua consist of fibrin, mucus, blood, irregular
masses of trophoblast, and pus. The chorionic wall
appears to be normal in structure. Many of the villi
are fibrous and the trophoblast is scanty. The embryo is
dissociated and macerated. The lower part of the embryo
and the tips of the extremities are infiltrated with round
cells, making it appear like sections of the lymphatic
glands. The structures of the head are very much macer-
ated and appear to have succumbed before the lower end
of the embryo. The cord is degenerated, jelly-like in
consistency, and contains a cavity. ‘

(6) Slight infiltration of the decidua and hydatiform
degeneration.

No. 499.

(1) H. H. Arthur, Baltimore, Maryland.

(2) A 454540 mm.; B 17 mm.

(3) “‘The specimen is from a frail girl, weight about
110 pounds. Gave birth several years ago to a premature
child at 7 months. Child now living and in robust health.
The last pregnancy, about 6 months ago, terminated in
abortion at about 8 weeks. Could get no information as
to its being induced, so presume it was spontaneous. The
specimen was delivered to me, and, besides considerable
clots, was partially surrounded by a sac containing intact
embryo. In the absence of any evidence to the contrary,
from an obstetric standpoint I consider it to be a case of
habitual tendency to abortion, as there was no history of
traumatism or interference in either instance.”

(4) The ovum is composed of a thin white membrane
which is covered quite evenly with delicate long villi, meas-
uring on an average about 17 mm. long. Attached within
is a much deformed embryo, with kinked arms and legs,
protruding abdominal wall, very thin umbilical cord, and
complete spina bifida. There is also an exencephaly.

(5) Sections of the chorion show that its walls are
somewhat fibrous, thick, and rarefied. The non-vascular
stroma of the villi is very degenerate and fenestrated.
There is very little trophoblast present. It appears as
though the chorion had macerated before we received it.
Sections through the umbilical cord show a marked dis-
sociation of tissue, and the intestines, which normally
pene into it, seem to have dissociated completely.

he same is true of the walls of the large blood-vessels.
These are filled with blood, which, not being circum-
srcibed, penetrates into the surrounding tissues. Sections
through the embryo, which were much too thin, show
that, with the exception of the liver, the tissues are dis-
sociated, the processes being most marked in the intestines,
along the aorta, and in front of the head. The dissociation

STUDIES ON PATHOLOGIC OVA.

is well marked around the cartilages of the vertebra
column. The tissue of the brain is almost entirely de-
stroyed, and in it there is a mixture of nerve-fibers, con-
nective tissue, and blood-vessels. It has undergone almost
complete vascularization. The large blood-vessels are
gorged. Some of the nerves run almost to the surface
of this tissue, which would indicate that the brain had
been well formed before it degenerated into this vascular
mass. Within the tip of the tail the cord is still covered
by the skin of the embryo.
(6) Decidua absent.

No. 510.

(1) H. G. Steele, Keystone, West Virginia.

(2) A 60X45 mm.; B 10 mm.

(4) Scattered over the ovum are long, slender villi
which do not branch much, and over the top of these is a
large piece of decidua.

(5) Sections were cut from two portions of the chorion.
In one the decidua is found to be very vascular, with a
great deal of fibrinoid substance on the side adjacent to
the villi. Large arms of decidua extend between the villi.
It appears as though the decidua had tried to make up
for the defective villi by growing towards the chorion.
In this region the chorion has undergone extensive mucoid
degeneration, with cavity formation. Some of the villi
contain many Hofbauer cells and very little trophoblast.
Sections from the other side of the chorion show the
chorionic membrane to be very thin, with an extensive
mucoid degeneration of the villi, some of which are mere
shadows, and are outlined by fibrinoid substance which
also reaches between them. There are a few masses of
necrotic trophoblast, otherwise the spaces between the
villi are practically empty. The tissues of the embryo have
undergone very extensive dissociation, but the liver,
heart, and stomach can still be made out. Most of the
myotomes and vertebre are distinct. The umbilical cord
contains numerous large cavities, with plenty of Hofbauer
cells scattered through its tisses, as it is undergoing mucoid
degeneration. The dissociation of the lower part of the
embryo is almost complete, it having been converted into
a fairly uniform layer of round cells. The brain and spinal
cord seem to be more macerated than dissociated. The
brain protrudes through the skin in front, and at the
lower part the spinal canal is open. In this region there
is quite a tumor covering the spina bifida, which is com-
posed of a necrotic mass of tissue invaded by round cells.
Between the tumor and the cord, partly blocking the
opening between its lumen and the outside of the body,
are several small nodules of transparent tissue which have
the appearance of being made up of nerve fibers. In this
region, immediately below the epidermis, is a lens-like
body. The otic and optic vesicles are obliterated. There
is no branchial region, as the face has grown firmly to the
body, and at the juncture there are several pronounced
papillomata.

(6) Slight infiltration of the decidua and hydatiform
degeneration.

No. 512.

(1) W. G. McCallum, New York.

(2) A 30X27X18 mm.; B 10 mm.

(4) The chorion is thin and covered with irregularly
grouped villi. On one side a tuft of villi appears to be
normal in size and branching, but elsewhere they are
scattered and atrophic. The chorion is lined entirely by
the amnion, the two being very closely attached. The
stunted embryo is attached to the chorion by means of a
short, thin umbilical cord. The head is atrophic and
transparent, being partly broken from the body. It
appears as though the embryo had been broken for a
considerable time before the abortion.

(5) Sections through the chorion at the point of attach-
ment show that the cord is attached directly to the amnion,
which is only in apposition with the chorionic wall. The
villi are thin, with a clear, non-vascular stroma, not rich

STUNTED CYEMATA.

in nuclei and practically devoid of trophoblast. The
tissues of the embryo have undergone extensive disso-
ciation and maceration. The brain is nearly solid, as
are the eye-vesicles, the lens forming small, solid bodies
immediately below the skin. The heart, as well as the
structure of the lower part of the body and the lumen of
the spinal cord, appears to be normal in form. The dis-
sociation is most pronounced in the stunted extremities.
(6) Decidua absent. Early hydatiform degeneration.

No. 516.

(1) J. M. Hundley, Baltimore, Maryland.

(2) A 655040 mm.; B 15 mm.

(3) “The patient missed her menstrual period February
a, Hee had a slight show of blood March 15, and aborted

pril 15.

(4) The chorion is thin and transparent and covered
with long, ragged atrophic villi which accumulate in
tufts on one side. Attached to the villi are numerous
opaque bodies about a millimeter in diameter, which no
doubt represent clumps of necrotic trophoblast. The
amniotic cavity lines the entire chorion and contains a
transparent fluid with a small granular deposit.

(5) Sections of the chorion do not include the amnion.
The chorionic wall is thin, fibrous, and degenerate. The
villi are non-vascular, fibrous, and hyaline, with a fenes-
trated stroma in some. Small clumps of trophoblast and
small mounds of fibrin bind a few of the tips together.
In this region there are buds of syncytium, some of which
have undergone nuclear fragmentation. Sections of the
amnion which include the attachment of the cord show
that it is thick and fibrous. The tissues of the embryo
are dissociated and macerated, the dissociation at the
tips of the extremities being typical and pronounced.
The brain and cord are badly macerated and folded, the
former protruding from the front of the head through what
appears to be an artificial rupture. The face is atrophic
and round, and there is no well-formed neck. The veins
are gorged with blood, the cells of which radiate more or
less into the surrounding tissues. The umbilical cord
contains numerous large spaces quite characteristic of

specimens of this kind.
(6) Decidua absent. Possibly early hydatiform degen-
eration.
No. 521e.

(1) Francis Carpenter, Baltimore, Maryland.

(2) A 40X30 mm.; B 15 mm.

(4) The specimen is badly macerated and the embryo
broken. It has a round head, atrophic legs, and a very
atrophic umbilical cord.

(5) The tissues of the embryo are dissociated and
extremely macerated. The chorionic wall is thin and
fibrous, and the non-vascular villi are more or less hyaline
and fenestrated. Very little trophoblast is present.

No. 521f.

(1) Francis Carpenter, Baltimore, Maryland.

(2) A 50X70 mm.; B 22 mm.

(4) The embryo shows a thick ridge along the dorsal
midline of the trunk. The head is smaller than usual.

(5) Sections through the chorion show that the tissues
are macerated and necrotic in places, nor do they stain
well. However, this much can be made out: the chorionic
wall at the attachment of the cord is fibrous and the villi
have undergone fibrous, mucoid, and hyaline degeneration.
They are matted together with a mass of fibrin, mucus,
and necrotic trophoblast, and are capped by a layer of
degenerated decidua. A thick layer of fibrin and de-
generate blood covers the maternal surface of the decidua.
Sections of the embryo show extensive maceration, as
well as dissociation of the tissues. The spinal cord is
disintegrated, the fragments being mixed up throughout
the main cavity of the spinal canal. The distended
macerated cord accounts for the ridge seen in the dorsal
midline before the embryo was cut,

No. 566.

(1) A. F. Fuchs, Loyal, Wisconsin.

(2) A 241919 mm.; B 6.5 mm.

(2) Patient gave birth to a healthy child 5 months
before. This specimen came away spontaneously in what
appeared to be the first menstruation after pregnancy.

(4) A beautiful white specimen, completely covered
with villi, somewhat more dense on one side than the
other. The villi are about 2 mm. long and divide once or
twice. The ccelom is filled completely with granular and
reticular magma. The amnion is filled partly with a clear
fluid and contains a nice white embryo, 6.5 mm. in length
(CR), slightly bent towards the right immediately below
the arms, and apparently normal. The internal surface
of the amnion is smooth, the ccelom large, and filled with
dense reticular magma. The umbilical vesicle is spherical,
2.5 mm. in diameter.

(5) The chorionic villi seem to be capped with a layer
of blood which filters down between them. They are
macerated, almost wholly non-vascular, and the stroma
has undergone mucoid degeneration. The trophoblast is
abundant and well preserved. The chorionic membrane
also is degenerate and macerated. The embryo and um-
bilical vesicle show extensive dissociation of the tissues,
but the myotomes and peripheral nerves, as well as other
organs of the body, can still be made out. The blood-
vessels are gorged with blood and the brain and spinal
cord are macerated. The tissues of the wall of the heart
appear quite normal.

(6) Decidua absent, but the coagulum is infiltrated;
early hydatiform degeneration.

No. 595.

(1) Caleb Athey, Baltimore, Maryland.

(2) A 33X27X25 mm.; B 9 mm.

(4) The entire specimen is club-shaped, with an ovum
at the larger end. The latter is vesicular and covered
entirely with villi which branch several times. Upon open-
ing, it was found to be lined with a smooth membrane.
The embryo is nearly normal in form, but injured.

(5) The thin chorion appears to be normal in structure
and surrounded by a layer of matted villi intermingled
with blood and covered with decidua, showing a consider-
able degree of inflammatory change. The villi are non-
vascular and have undergone fibrous degeneration. The
trophoblast is scanty and disintegrating, but certain of
the villi and part of the chorionic wall contain blood-vessels.
The embryo is greatly dissociated and somewhat macer-
ated, and the blood-vessels and heart gorged with blood.
The central nervous system is folded, indicating macer-
ation, and a macerated and dissociated brain fills the
entire cavity of the head. The front end of the latter is
atrophied, and what remains is growing down, to later
become attached to the thorax. Such organs as can be
outlined show a marked dissociation of tissues.

(6) Marked infiltration of the decidua.

No. 601ec.

(1) Charles K. Winne, Jr., Albany, New York.

(2) A 44X41X20 mm.; B 10 mm.

(3) Patient is 39 years old; married 7 years; two chil-
dren, 34% years and 21 months respectively. First two
pregnancies miscarried, at 6 and 3 months, respectively;
cause unknown. Last menstruation April 20. Two days
before the physician saw her she had been working very
hard, packing and closing her house in Washington. Heat
intense. She came to New York June 27, and from there
to Albany on the night boat, arriving there next morning.
While on the boat she was nauseated and vomited, and
had slight vaginal bleeding, which continued. Despite
appropriate treatment, the threatened miscarriage pro-
ceeded to full completion a few hours later, early in the
morning of June 28._ This history can be relied upon, as
both the patient and her husband were anxious for the
child and distressed at the outcome of the pregnancy.

156 STUDIES ON PATHOLOGIC OVA.

(4) The vesicular ovum, which is covered with long,
ragged villi, is filled with clear fluid. The walls are trans-
arent and contain a broken embryo, probably patho-
ogical, measuring approximately 10 mm. The entire
embryo, with its attachment to the chorion, was cut into
serial sections.

(5) The chorionic membrane is thin and fibrous, and
the villi consist of long, delicate fibrous strands with prac-
tically no vessels or trophoblast, except occasional small
nodules which appear to have undergone degeneration.
There are a few remnants of blood-vessels in the villi,
showing that at one time they must have had a circula-
tion. The umbilical cord also is thin and fibrous, with
degenerating vessels and cavity formation. The amnion
is partly separated from the non-vascular chorion. The
tissues of the embryo are somewhat dissociated and slightly
macerated. The blood-vessels are well distended with
blood, and there is a large extravasation in the peritoneal
cavity. Sections which pass through the leg-bud indi-
cate that it is slightly stunted in its growth.

(6) Decidua absent.

No. 604.

(1) J. M. Jackson, Pittsburgh, Pennsylvania.
(2) A 705050 mm.; B 17 mm.
(4) This vesicular specimen is constricted in the middle

and its surface is not uniform, being covered partly with -

fibrin clots and partly with decidua and some ragged villi.
The walls are 3 or 4 mm. in thickness, and the interior is
filled with a jelly-like magma of uniform consistency.
On one side, lying free within the magma, is an embryo
with an atrophic head, arms, and legs. The head is not
bent as it should be at this stage, but is erect.

(5) Sections show a fibrous chorionic membrane sur-
rounded by a few very degenerate villi, much blood, and
fibrinous substance. This layer is capped by an inflamed
decidua. The trophoblast is thickened, and it, as well
as the mesenchyme of the villi, are infiltrated with round
cells. The embryo shows considerable maceration, and
the dissociation of the tissues is so great that only the
cartilages can be made out with certainty. The liver is
necrotic, and the walls and cavities of the heart are prac-
tically obliterated, the whole organ being converted into
a mass of round cells. The same is true of the neck,
and the entire skull and spinal canal are filled with the
dissociated and macerated brain and spinal cord. In the
latter the cells of the floor-plate still hang together, show-
ing the characteristic structure of this region as seen in
normal embryos.

(6) Marked infiltration of the decidua.

No. 635c.

(1) A. C. Pole, Baltimore, Maryland.

(2) B 18 mm.

(5) Sections of the embryo show that all the tissues are
macerated. The outline of some of the blood-vessels is
not sharp, some of the cells have migrated into the adjacent
tissues, and the periphery of the cartilages shows disso-
ciation. Hence it is probable that this embryo died some
time before the abortion.

(6) Decidua and chorion absent.

No. 651a.

(1) G. L. MeCormick, Sparrows Point, Maryland.

(2) A 704545 mm.; B 27 mm.

(4) The embryo, which is normal in form, with the pos-
sible exception of the lower part of the body, came within
the amniotic sac, which measures 70*4545 mm. No
chorion is present. The lower part of the spinal canal
is opened, the opening being 1 mm. in width and 4 mm.
in length. Both legs appear deformed, the left less so
= the right, the latter having a marked bend at the

nee.

(5) Sections through the amnion show it to be fibrous
and macerated. Where the vessels pass through it there

is some dissociation. The embryo was cut into serial
sections which show that the tissues are greatly macer-
ated. The brain and what is left of the spinal cord are
practically solid, the latter filling the spinal canal incom-
pletely in the thoracic region. The skin forms a groove
in the lower lumbar region in which the cord is really
absent. The skin is fairly intact, but the tissues are
markedly dissociated; that is, the boundaries of the organs
and cartilages are obliterated by an irregular wandering
of the cells. This is especially marked at the beginning
of the umbilical cord.
(6) Decidua and chorion absent.

No. 65lc.

(1) G. C. McCormick, Sparrows Point, Maryland.

(2) B 17 mm.

(4) A deformed embryo with an atrophic head and
injured cord, rounded in form. The arms and legs appear
atrophic.

(5) The tissues are dissociated, macerated and largely
necrotic. The central nervous system is solid.

(6) Decidua and chorion absent.

No. 653.

(1) Ira L. Fetterhoff, Baltimore, Maryland.

(2) A 80X50X35 mm. B 11 mm.

(3) Patient is a young woman who has been married
about 2 years. First pregnancy. Apparently healthy,
and in this ease had gone the normal course of a woman
4 months pregnant. Physician was called to attend
her for bleeding, without pain; an hour later he was re-
called to attend her in severe pain, when she passed this
specimen. :

(4) The fresh specimen was brought to the laboratory
and fixed in 10 per cent formalin. Care was taken not to
injure the embryo, and on opening the chorion a rudi-
mentary body, uninjured, and markedly deformed, was
found. The ovum is covered with a few irregular, ragged
villi and scraps of decidua. It contains a large cavity
and an embryo 11 mm. long.

(5) Sections through the chorion show it to be composed
of an irregular mass of blood, decidua, fibrinoid substance,
degenerated villi, and a curious combination of chorion
and amnion, forming in several places processes which
extend into the amniotic cavity. There is only a slight
amount of inflammatory reaction on the outside of the
specimen. A considerable amount of nuclear dust is
present. The embryo is markedly dissociated, but the
organs can be outlined within it. The cartilages are fairly
sharp, but dissociated. The liver is the only organ retain-
ing any of its normal structure. The extremities are
rounded off and dissociated, but there is no central ner-
vous system, and it is impossible to find any canal for it.
The vertebrx and ribs can be outlined, and in this region
the tissues are not broken. The heart is almost completely
areceintes and protrudes through an opening in the
thorax.

No. 675.

(1) John Woodman, New York City.

(2) A 50X30X25 mm.; B 10 mm.

(3) Patient has had several previous miscarriages.
Hemorrhage began on February 10 and was profuse.
There was another hemorrhage a month later, which
became very severe at the time of the abortion, April 14.

(4) The ovum measures 50X30X25 mm. and is
covered with a few atrophic villi. On opening, it was
found to contain a very large amniotic cavity 30 mm. in
length. The embryo (10 mm. GL) is opaque and its
extremities are atrophic. The chorionic membrane is
fibrous and separated from the decidua by considerable
fibrin. The decidua shows considerable inflammatory
reaction. The space between these two structures is
filled with degenerate, fibrous villi, a few buds of syney-
tium, plaques of nuclear dust, and a great deal of fibrin.

STUNTED CYEMATA.

(5) The tissues of the embryo are well dissociated.
The heart is represented by a large mass of cells, its walls
being practically destroyed. The liver and intestines still
are sharply defined. The brain is almost completely dis-
sociated and forms an irregular mass which fills the entire
pointed front of the head. The form of the brain is ab-
normal, and the midbrain protrudes as a solid mass be-
hind. Between it and the medulla there is a curious car-
tilaginous body which encroaches upon the hindbrain.
The lower part of the spinal cord is greatly enlarged, and
the cells have encroached upon and destroyed the vertebra.

(6) Slight infiltration of the decidua; probably luetic.

No. 681.

(1) George H. Hocking, Govans, Maryland.

(2) A 454545 mm.; B 20 mm.

(3) Patient is a Bavarian, 42 years old, who has had
10 children and 2 abortions. Last period January 20
to 25; abortion April 25. No evidence of uterine disease.
Interference suspected in this as well as in the previous
abortion (No. 621, group 5).

(4) The specimen was found to consist of two parts,
one a portion of the decidua and blood clots, the other a
pathological ovum with a hemorrhagic wall. The ovum
measures about 45 mm. in diameter and contains a cavity
30 mm. in diameter, in which there is an atrophic embryo
20 mm. GL. The cord is short and transparent, and
attached to the embryo.

(5) The chorionic wall is fibrous, and the umbilical cord,
within which is a large cavity, is undergoing mucoid
degeneration. The villi are fibrous and mucoid, without
any active trophoblast, and are well embedded in blood-
clot. The decidua also looks degenerate and even necro-
tic in places. The tissues of the embryo are dissociated
and macerated, most of the blood-vessels being well filled
with blood. The dissociation is best shown in the hands
and feet. The brain and spinal cord are characteristic
of this type of macerated embryo.

(6) Decidua not infiltrated.

No. 699.

(1) Emil King, Fulda, Minnesota.

(2) B 13 mm.

(3) ‘‘Patient aged 24 years. Previous history nega-
tive; always very good health. Married 8 months.
Menses regular until 10 weeks ago, then ceased; 4 weeks
ago felt unwell, though not in bed. Traveled some dis-
tance 2 weeks before abortion, June 2. As the patient
was in agonizing pain a hypodermic of morphine and atro-
pine was given and the vagina packed with gauze. When
the pain ceased the packing was removed and the fetus
and membranes were found free in the gauze. The sac
had been ruptured, there being a small tear in it. The
chorion seemed poorly developed, being very dark in
color and thin.’”’ It was the physician’s opinion that the
fetus had been dead 4 weeks.

(4) The specimen consists of a piece of chorionic wall
about 30 mm., one side of which is covered with degener-
ate villi in a layer of uniform thickness. Within isa patho-
logical embryo, CR 13 mm., attached to the chorion by
means of a short cord. The front of the head is atrophie.
The right arm and lower part of the body seem to be
normal, while the left arm and legs are stubby.

(5) The chorionic wall is thick and non-vascular. The
villi are necrotic and encircled with an inflamed decidua.
There is considerable blood between them, and most of
the nuclei of the trophoblast have been converted into
nuclear dust. The embryo is dissociated and the head
end is filled entirely with the brain. The heart, which
protrudes on the chest, is represented by a small mass of
blood. The liver is swollen. The two poles of the body
are rounded off, and in the legs the dissociation is quite
complete.

(6) Slight infiltration of the decidua; probably luetic.

157

No. 705.

(1) C. E. Caswell, Wichita, Kansas.

(2) B 18 mm.

(3) Patient aged 39 years; married at 19. Two preg-
nancies—normal delivery about 20 years ago, and this
abortion, June 8. Last normal period March 12 to 16.
Scanty flow April 12 and 13; Ae a show on May 10.
Examination on May 12 showed the uterus very slightly
enlarged (woman is stout) and cervix blue. Uterus about
size and depth of a 10-weeks’ pregnancy. At that time
pus in urine; no casts.

(4) Head and probably legs of embryo are atrophic.

(5) Most of the structures appear to be normal, but
the central nervous system has undergone quite extensive
dissociation. The medulla and forebrain encroach upon
the pharynx. The large blood-vessels and heart are filled
with blood. The tissues, especially those of the tips of
the extremities, are dissociated.

(6) Decidua and chorion absent.

No. 711.

(1) G. W. Cox, Hartford, Connecticut.

(2) A 35X25X 25 mm.; B 12 mm.

(3) “Patient aged 31 years; married 8 years. Mother
of three children, two living. Last child born 3 years ago.
Periods were regular and about 28 days apart; last one
March 31. In April period was missed. On April 25
patient had slight vaginal hemorrhage lasting only a
moment. On May 9 severe hemorrhage; patient was
packed a few days. May 9 she came to the hospital,
bleeding slightly and with some pain. May 21 she passed
the specimen, after which she was curetted.”

(4) Part of the chorion was cut away. What remains
measures 35 X<25mm. The amnion, which measures about
20 mm. in diameter, is much thickened, fibrous, and con-
tains an atrophic embryo with a round head and a very
short cord.

(5) The wall of the specimen consists of a thick and
infiltrated chorionic membrane encircled by fibrous villi
which are covered with curious spherules of trophoblast
undergoing fibrinoid degeneration. Some of these have
the appearance of sections of cartilage. There are also
small nests of nuclear dust and considerable infiltration
with leucocytes. The embryo is markedly dissociated,
the tips of the extremities being mostly disintegrated.
Round cells invade the cartilages. The outline of the
viscera appears to be normal, but the brain is greatly dis-
sociated and occupies almost the entire head. The tissue
in front of the brain is infiltrated with round cells and not
sharply separated from the dissociated brain.

(6) Intense infiltration of the decidua with abscess for-
mation, probably luetic.

No. 715.

(1) M. Warren, Roosevelt Hospital, New York.

(2) A 55X25X25 mm.; B 10 mm.

(3) Patient aged 40 years; married 214 years. First
pregnancy. Last menstrual period March 28 to April 1,
abortion June 22 following. No infection of uterus, but
multiple fibroid tumors, varying in size from a lime to a
small orange. No history of previous pelvic trouble.
Patient belongs to a healthy, fertile family.

(4) Specimen consists of a smooth vesicular mole
552525 mm. The cavity, which extends throughout,
is lined by the amnion and contains a macerated and dis-
torted embryo about 10 mm..long. The cord is very
short and thick, and the arms and legs, as well as the
head, are atrophic. , . }

(5) The wall of the chorion is relatively thin and is
composed of a macerated, fibrous amnion and chorionic
membrane. It is covered with scattered necrotic villi
stuck together with blood and decidua. The embryo is
markedly dissociated. :

(6) Decidua very necrotic.

158

No. 72304.

(1) Lawrence L. Iseman, Chicago, Illinois.

(2) A 40X25X25 mm.; B 12 mm.

(4) The ovum has very thin walls, and attached to one
pole are a few atrophic villi. It contains an embryo 12
mm. long. The form of the chorion appears normal.

(5) The mesenchyme of the villi is almost wholly non-
vascular, has undergone marked mucoid degeneration and
contains some Hofbauer cells. The trophoblast is not
well defined, and between the villi there are strands of
mucoid substance inclosing many buds of syncytium, some
of which are vacuolated. The embryo is macerated and
markedly dissociated. The front of the head is atrophic;
the large blood-vessels are distended with blood, but their
walls are indefinite. The same is true of the heart.

(6) Decidua absent. Hydatiform degeneration.

No. 727.

(1) B. J. Merrill, Stillwater, Minnesota.

(2) A 55X35X33 mm.; B 9 mm. CR.

(8) Patient 36 years old; married 9 years. Three chil-
dren, born May 9, 1906, March 15, 1908, and August 4,
1910. ‘This is her first abortion. Last menstrual period
April 18 to 21, 1913; abortion June 12 following. Patient
thinks conception could not have taken place until the
last of April or the first of May. Condition of uterus
normal. No venereal diseases. Family fertile.

(4) The specimen is a smooth vesicular mole with ragged
villi, and measures 55X35X33 mm. The amnion,
which measures 3020 mm., fills nearly the entire cho-
rionic cavity. Hanging within it is a stunted embryo
with knob-like arms, legs, and tail. The front of the
head is round, and the embryo is well bent upon itself.

(5) Attached to the chorionic membrane are a few
fibrous villi with Hofbauer cells and considerable blood
and mucoid substance between them. The fibrinoid sub-
stance over the villi is thickened with overlying decidua,
thin and markedly inflamed. The embryo shows exten-
sive dissociation. The front of the head and extremities
are atrophic, and the latter markedly dissociated. There
are numerous epithelial warts protruding from the skin.
The organs can be fully outlined, and the peripheral
nerves are well formed. The heart and blood-vessels are
filled with blood.

(6) Marked endometritis and early hydatiform degen-

eration.
No. 732.

(1) T. W. Harvey, Orange, New Jersey.

(2) A 804545 mm.; B 19 mm.

(3) Patient aged 29 years; married December 1911.
Two pregnancies—normal birth September 1912, and this
abortion. Last menstrual period April 26 to 28, 1913,
and abortion July 23 following. Condition of uterus
normal.

(4) The specimen is a pear-shaped mass, measuring
804545 mm., the “pointed” end consisting of placental
tissue and blood-clot covering the ovum wall, while the
bulbous end consists of the unruptured chorionic sac,
which is covered with delicate villi about 10 mm. long,
except in the somewhat denuded areas, over which they
are scattered irregularly. The wall of the mass is about
2 mm. in thickness and lined throughout with amnion.
Upon opening the chorion at the denuded area, the dis-
tended amnion was seen as a separate sac, containing a
macerated embryo with rounded head and possibly atro-
phic arm and leg.

(5) The chorionic wall, which appears quite normal in
structure, is surrounded PF a mass of coagulated blood
containing a few fibrous villi. The fibrinoid substance is
greatly increased in thickness and is separated by blood
from the surrounding decidua, which shows slight general
and more decided local infiltration. The embryo is both
macerated and dissociated, and the front of the head and
abdominal wall are missing. The viscera are embedded
in a mass of magma, showing that the abdominal wall was

STUDIES ON PATHOLOGIC OVA.

destroyed before the abortion. In the lumbar region the
vertebral column is bent forward towards the protruding
viscera. The tissues of the extremities and heart are
markedly dissociated.

(6) Slight general infiltration of the decidua.

No. 739.

(1) F. B. Bowman, Hamilton, Ontario.

(2) A 70X70X70 mm.; B 17 mm.

(3) The patient was a Polish woman, who was in the
hospital only 4 or 5 hours.

(4) The chorion, which measures 70 mm. in diameter,
is spherical and covered with patches of irregular villi
over one-half of its surface. The interior is taken up by
a large amniotic cavity, leaving a wall only 3 mm. thick.
Floating free within this cavity was a macerated embryo
from which the viscera had fallen out. The embryo,
straightened, measures 17 mm. long, and has a round,
knob-like head and knob-like extremities.

(5) Sections of the chorion, which include the amnion,
show that it is surrounded by fairly well formed villi,
from which numerous buds of syncytium extend. The
stroma of the villi is degenerate and mainly non-vascular.
There also are large clumps of trophoblast which have
undergone almost complete fibrinoid degeneration. Sur-
rounding the villi is a layer of fibrinoid substance which
in turn is followed by an inflamed decidua. Otherwise
the intervillous spaces are filled with a clear fluid. The
embryo, which is distorted and macerated, shows marked
dissociation in the extremities and vertebral column. The
epidermis contains some warts of epithelial cells.

(6) Marked infiltration of the decidua; some hydatiform
degeneration.

No. 752.

(1) Thomas J. Simms, Baltimore, Maryland.

(2) A 65X40 mm.; B 21 mm.

(3) Patient aged 31 years; married October 15, 1902.
Eight pregnancies; last confinement February 17, 1912.
Previous abortion in January 1910. Menstruation regu-
lar, lasting 5 to 6 days. Did not know she was pregnant.
Abortion August 29, 1913. No infection of uterus; no
venereal diseases. Patient belongs to a small family.

(4) Ovum turned inside out, and measures 65X40 mm.
Its wall is very thin, with smooth, hermorrhagic protuber-
ances on the inside. An embryo 21 mm. long (CR), with
an atrophic head and face, is attached to the chorion by
means of a thickened umbilical cord.

(5) The chorionic wall is thickened, somewhat fibrous,
and only a few necrotic villi ramify through the blood-
clot. Most of the trophoblast also is necrotic. On the
outside is a small layer of necrotic decidua which shows a
marked inflammatory reaction. The tips of the villi are
encircled with old fibrin clots, while fresh hemorrhages are
in the intervillous spaces, causing protuberantes of the
chorionic membrane into the chorionic cavity. The
amnion and chorion are closely adherent, and where far
apart are bound together by an excessive mass of magma
fibrils. The embryo shows considerable dissociation, espe-
cially within the extremities. The macerated brain almost
entirely fills the head, which is reduced in size.

(6) Intense infiltration of the decidua.

No. 771b.

(1) B. T. Terry, Brooklyn, New York.

(2) B 8 mm. long.

(3) Patient aged 29 years; married in June 1910. Three
pregnancies—two births, September 1911 and December
1912, and this abortion, September 11, 1913. Last men-
strual period July 7 to 12. Conception must have taken
place July 15. Condition of uterus apparently normal.
No venereal diseases. Family fertile.

(4) The embryo is a curious nodular mass, 8 mm. long,
with a round head running to a knob in front, atrophic
arms and legs, and a distended umbilical cord.

STUNTED CYEMATA.

(5) The embryo is markedly dissociated. The head is
small, being filled entirely by the brain-tube, and on the
dorsal side there is a curious vesicle under the skin, prob-
ably the otic vesicle. The heart can be outlined, but the
abdominal organs are almost completely dissociated. The
peripheral nerves are seen in the trunk.

No. 776.

(1) William Kirk, Troy, New York.

(2) A 453025 mm.; B 13 mm.

(4) The chorion, which had been opened, measures
453025 mm. The embryo, which is 13 mm. (CR)
long, has atrophic arms and head, displaced eyes, and was
eviscerated.

(5) The chorion is thickened and hemorrhagic, and is
composed of a fibrous membrane and a few long, fibrous,
degenerate villi radiating through the blood-clot. The
periphery of the clot shows marked inflammatory reac-
tion. At points where the villi protrude into the spaces
there is a fairly active trophoblast. The macerated and
dissociated brain fills the entire head; the vertebral column
is markedly kinked and the extremities are dissociated.
The right eye is encircled by a thickened layer of round
cells which also invade its lens. The left eye is placed in
front and on top of the head over the midbrain, lying
directly under the skin. It communicates with the brain
through a short optic stalk. The lens contains a cavity
into which its posterior layer projects.

(6) Marked infiltration of the decidua.

No. 788 a, b.

(1) Anfin Egdahl, Menomonee, Wisconsin.
(a) Ovum 604540 mm.; stunted em-

bryo CR 17 mm.

(b) Ovum 655540 mm.; nodular em-

bryo 2 mm. long, group 4.

(3) Norwegian woman, aged 32 years, married 10 years.
Three previous pregnancies. This abortion, which is the
first, occurred July 2, 1913. Condition of uterus normal.
No history of venereal disease. First twins known in
family.

(4) a. This specimen measures 60X45X40 mm.
Half of its surface is formed by a transparent membrane,
which was found upon opening to be the greatly distended
chorion and amnion, containing an atrophic embryo 17
mm. CR.

(5) The chorion and amnion are thickened and fibrous,
the villi irregularly formed, non-vascular, and undergoing
mucoid degeneration. They are encircled by consider-
able fibrinoid substance and a hemorrhagic and inflamed
decidua. The intervillous spaces have within them con-
siderable trophoblast, some of which is necrotic. There
is a fair amount of activity in the syncytium, some of
which has been converted into nuclear dust. The embryo
is dissociated, but all the organs can be outlined. The
front of the face is attached to the thorax.

(6) Mild endometritis.

No. 802.

(1) W. G. Sexton, Baltimore, Maryland.

(2) A 19X26X16 mm.; B 6 mm.

(3) Patient aged 29 years; has had four normal preg-
nancies and two miscarriages. One week before operation
patient began to have abdominal pain and slight bleeding.
The bleeding continued until the time of admission to
the hospital. At times she passed large clots. At the
operation the entire placenta was removed and the uterus
curetted.

(4) The ovum is well covered with villi, excepting at
one pole, which is bare. It was carefully opened through
this area, and a well-formed embryo CR 6 mm. was found
encircled by a somewhat opaque amnion.

(5) The villi are well defined, and the chorionic wall is
normal in structure. The villi are matted together and
do not have the usual clear mesenchyme. The stroma,

(2) Twins

159

which is somewhat macerated, contains degenerating ves-
sels. The trophoblast is very irregular, most of it necro-
tic, and numerous small buds of syncytium are attached
to the villi. The body of the embryo is normal in form,
and sections indicate that its organs are well defined and
apparently normal, with the exception of some dissocia-
tion, which is especially well marked in the cells of the
large blood-vessels; that is, the blood appears to be dif-
fusing through them. The head is atrophic, the brain
badly dissociated and very small, and the eyes are round
and reduced in size.
(6) Decidua absent.

No. 872.

(1) Charles E. Brack, Baltimore, Maryland.

(2) A 38X28X30 mm.; B 13 mm.

(3) Woman aged 40 years; married in 1896. Eight
term pregnancies and three miscarriages. Abortions be-
tween second and third child, between sixth and seventh,
and after the eighth. Last menstrual period January 18
to 25; abortion April 17 following. Patient was ill after
the middle of February with nausea, languor, and chilly
sensations. Size of specimen did not correspond with
period of amenorrhea. Condition of uterus normal. No
venereal diseases. Family fertile.

(4) The specimen consists of an abortion mass, measur-
ing 55X35X35 mm., and seems to be mainly decidual
tissue from which the spherical and distended ovum has
freed itself. The ovum measures 382830 mm., and
is covered on one side by luxuriant villi which attain a
length of 12 mm. On the other side it is bare and
transparent. Opened in the denuded area, an opaque,
stunted embryo and yolk-sac are seen. The embryo is
still attached to the chorion by a short, clear umbilical
stalk. It measures 13 mm.GL. The neck has been torn
ventrally, so that the head is somewhat more extended
upon the body than previously, and therefore the length
recorded is too great. The head, arms, and legs are
atrophic. Lying about 8 mm. distant from the embryo
is a thin-walled but opaque yolk-sac, measuring 4X6
mm. The amnion lines the entire chorion. The villi are
irregular in size, ragged, and suggest the presence of hydati-
form degeneration.

(5) Upon microscopic examination the hemorrhagic de-
cidua shows the presence of considerable autolysis. Some
portions are composed wholly of the usual large polygonal
zells, but in other areas cells of the fibroblast type prevail.
These not infrequently show a tendency to streaming or
arrangement in whorls. No indication of infection is
present.

The chorion, amnion, and villi, though macerated, are
relatively well preserved and the latter distinctly hydati-
form in structure. Considerable epithelial proliferation is
present and the nodules are degenerate. Epithelial mi-
grations are present in some villi, but only relatively
small syncytial buds are present on the chorionic mem-
brane. In many regions the epithelium is still distinctly
two-layered. Hofbauer cells, especially transitional in
type, are quite common.

(6) Hydatiform degeneration.

No. 880.

(1) B. F. Terry, Brooklyn, New York.

(2) B 10.5 mm. : 1a

(3) Patient 34 years old. Has two children, both living.
No former abortions. Menstruated last November 5;
suddenly developed “cramps” February 3 following.
Expelled membranes containing fetus the same day. She
did not suspect her condition because of menstrual irregu-
larity. At times she does not menstruate for several
months. This is probably due to anemia. Age of embryo
estimated at 8 weeks. ;

(4) The specimen consists of a pathological embryo,
measuring 10.5 mm. CR, 11.2 GL, and 11.2 NL. The
left side of the body has suffered grave mechanical injury,
the legs having been removed, the muscles, ribs, and nerves

160

being exposed. The embryo is stunted, as disclosed by
the featureless head and face and poorly developed brain.

(5) The specimen is somewhat macerated and markedly
dissociated. The ear seems to be displaced and the face
is partly adherent to the body, but most of the structures
are normal in form. ‘There are curious warts on the sur-
face of the skin, one on the side of the head being especially
prominent. The walls of the blood-vessels are not sharply
defined.

(6) No decidua or chorion.

No. 936.

(1) John A. Leutscher, Baltimore, Maryland.

(2) A 804015 mm.; B 9 mm.

(4) The specimen consists of a pear-shaped abortion
mass measuring 804015 mm., covered almost com-
pletely with a decidual cast, except at the lower pole,
where the chorion is exposed. Here the villi measure 6
mm. in length. The cavity, which is circular, measures
about 35 mm. in diameter, and shows only delicate shreds
of amniotic tissue; otherwise, no amnion is to be seen.
Projecting into the cavity is an irregular embryonic rudi-
ment 9 mm. long, with a thick, white umbilical cord about
the same length; 7 mm. distant from its point of attach-
ment to the chorion is a flattened opaque sac, 3 mm. in
diameter. The embryo was evidently badly macerated,
as well as seriously hurt mechanically. On the left side
the stump could be distinguished; on the right only the
leg could be made out.

(5) The chorion and amnion are fibrous, and the yolk-
sac is a solid mass of necrotic material. The villi are
fibrous and covered with large clumps of trophoblast.
There is considerable trophoblast substance and a stringy
substance in the intervillous spaces. The head of the
embryo is missing, and sections show that the upper
part of the body ends in a ragged stump. ‘The tissues are
markedly dissociated, but most of the organs can still be
made out. The dissociation is especially pronounced in
the tips of the extremities, as well as in the vertebral col-
umn. In place of the spinal cord there is a slit extending
throughout the length of the embryo, on either side of
which are two strands of round cells in the position of the
dorsal ganglia. These appear like blood-vessels filled with
blood rather than nerve cells. In the lower part of the
body one of these strands has undergone a peculiar fibrous
degeneration. It appears much like a small neuroma.

(6) Intense infiltration; probably some hydatiform de-
generation.

No. 958.

(1) Frederick J. Beitler, Baltimore, Maryland.

(2) A 312220 mm.; B 13 mm.

(3) Patient married about 4 years. Three pregnancies,
first and second ending at term, and this abortion. Con-
dition of uterus normal, no infection, no venereal diseases.
Five children on maternal side of family and 3 on paternal.

(4) The chorionic mass measures 312220 mm.
and is covered with villi and enmeshed blood-clot, except
for a denuded area 10 mm. in diameter. On opening the
chorionic sac there appears a mass of semi-solidified
magma, removal of which revealed a well-preserved embryo
showing signs of arrested development.

(5) The degenerate chorion is entirely lined by the
amnion. Its main wall is thin and covered with clumps
of degenerate, fibrous villi which are matted together
with trophoblast and mucoid substance. Within there
is a great deal of granular magma. The embryo is
stunted and greatly dissociated. The head is closely
adherent to the body, the face atrophic, and the spinal
cord open below, with the cord protruding. The organs,
however, can be fairly well outlined. Most of the blood-
vessels are filled with blood, but all the tissues are disso-
ciated.

(6) Decidua absent.

STUDIES ON PATHOLOGIC OVA.

No. 962.

(1) Joseph M. Jackson, Pittsburgh, Pennsylvania.

(2) A 842824 mm.; B 10 mm. (est.).

(3) A patient aged 32 years; married 12 years. Six
pregnancies.

(4) The specimen consists of a chorionic sac covered
almost entirely by villi, and measuring 342824 mm.
On opening it, a cloud of fine, opaque particles exuded;
otherwise the chorionic cavity was filled by a reticulated
semitransparent network which bridges it from wall to wall.

(5) A piece of chorionic sac, thicker than the rest, was
cut into serial sections, and in this was found a macerated
embryo of about the 10 mm. stage. The wall of the cho-
rion and its well-developed villi are fibrous and macerated.
Some of them are closely matted together with necrotic
trophoblast, and most of them contain degenerating ves-
sels. The stroma of the villi also seems to be invaded by
a great deal of nuclear dust and also many sprouts of tro-
phoblast. The embryo is closely encircled by the amnion
and greatly macerated, the organs and cavities being prac-
tically obliterated. Marked autolysis of the decidua.

(6) Some (?) local infiltration.

No. 983a.

(1) J. F. Hempel, Baltimore, Maryland.

(2) A 705030 mm.; B 18 mm.

(4) The specimen consists of a thickened and discolored
chorionic sac 705030 mm. On opening it, a yel-
lowish, watery fluid, with brownish, fragile clumps, es-
caped. After this was drained off an embryo 18 mm.
long and apparently badly macerated, was found attached
by an umbilical cord 11 mm. long.

(5) The villi are mostly atrophic, and at certain points
the intervillous spaces are distended with blood. The
tissues do not stain well, and the organs, which can
barely be outlined, are badly macerated. The head is
somewhat atrophic.

(6) Decidua very necrotic.

No. 993.

(1) L. W. Haynes, Detroit, Michigan.

(2) A 484115 mm.; B 7 mm. (est.).

(3) Patient aged 42 years; has 3 children living, 8, 6,
and 3 years, respectively. About 10 years before the
abortion she had a bad fall and miscarried at 3 months.
That was the only miscarriage except the present one.
On May 38 she fell down a short flight of steps, sustaining
a large bruise on the right hip. Several hours later she
began to flow. At that time the patient was two weeks
overtime for her period, but had none of her usual symp-
toms of pregnancy. The flow continued until May 5,
when the specimen passed.

(4) The specimen consists of a partially collapsed amni-
otic sac measuring 484115 mm. The villi are thin
and transparent, and divide several times. On opening
the sac there was an escape of turbid fluid containing a
very fine precipitate. On rinsing this out the fragments
of an embryo were found, consisting of an atrophie head
and the tail portion of an embryo about 7 mm. long.

(6) No decidua. Sections include the chorion, amnion
and villi, but do not stain well. Histolysis is almost com-

plete.
No. 1022e.

(1) Ernest C. Lehnert, Baltimore, Maryland.

(2) 332215 mm.

(4) Specimen is a portion of an inverted chorionic sac
with peculiar, long, branching villi, some of which measure
16mm. The embryo is stunted and the arms are atrophic.
Under examination with the binocular scattered hydati-
form villi are seen, although the vesicle is degenerate.

(5) Examination under igher magnification confirms
the presence of undoubted hydatiform degeneration, al-
though there is no unusual increase in epithelium. The
dean is extremely degenerate.

(6) Partial hydatiform degeneration.

FETUS COMPRESSUS.

GROUP 7.

No. 60.

(1) G. W. Dobbin, Baltimore, Maryland.

(2) B 8mm.

(4) The mutilated body and extremities of the embryo
appear normal in form. :

(5) The tissues are considerably macerated and the
specimen may benormal. The spinal cord issolid. There
are large islands of blood-cells in the very degenerate
liver. The umbilical vesicles are completely destroyed a
little distance from the abdomen, and near the latter the
cord is distended and the stroma almost completely
destroyed.

(6) Probably a normal mutilated and macerated embryo.
Decidua absent. “4 es

0. 79.

(1) David K. Briggs, Blackville, South Carolina.

(2) A 505050 mm.; B 32 mm.

(3) Abortion took place 91 days after the beginning of
the last menstrual period.

(4) The specimen was received with all of the mem-
branes intact. When opened, it was found that the am-
nion was filled, and the embryo entirely covered with a
layer of firmly coagulated granular magma.

(5) The chorion is very necrotic, thick on one side and
thin on the other. Many of the villi also are necrotic
and others have undergone mucoid degeneration. All are
non-vascular. There is much degenerate trophoblast.
The decidua is very degenerate. Serial sections of the
embryo show that it must have been strangulated long
before the abortion took place. The central nervous sys-
tem is greatly macerated, the liver has disintegrated, and
the aorta is very much distended. The rest of the embryo
appears normal. The intestine is almost entirely within
the peritoneal cavity, but a single loop of it still remains
in the opening communicating with the ccelom of the cord.
The vessels of the latter are still present. The embryo is
completely covered with a layer of magma which contains
but few cells. Below this the epidermis is lacking at many
points, while at others it appears fairly normal.

(6) Decidua absent. Early hydatiform degeneration.

No. 94.

(1) Edwin G. Knill, Detroit, Michigan.

(2) A 504030 mm.; B 20 mm.

(4) The ovum is smooth, with villi on one side only.
The amnion measures 30X20 mm., and does not fill the
chorion completely. Within it there is much coagulated
matter which entirely envelops the embryo, but which
can be picked off easily in large flakes. The embryo
thus exposed is bent upon itself more than usual and ap-
pears macerated, as if it had been dead for a number of
days. The features are not clear, nor are the tips of the
hands and feet well defined. The lower part of the body
is necrotic and the spinal cord is protruding.

(5) The sections show that the villi of the chorion are
degenerate and non-vascular. The decidua is infiltrated.
The mesoderm of the chorion and amnion clearly show
marked degeneration. The embryo itself is normal in
shape, but the brain is greatly dissociated; the liver is
cloudy and projects into the cord. All of the epidermis
is exfoliated, and great masses of degenerate nuclei lie
between the embryo and the envelope of magma. _

(6) Decidua infiltrated; early hydatiform degeneration.

No. 97.

(1) Gustav Goldman, Baltimore, Maryland.

(2) A 33X30X15 mm.; B 7 mm.

(3) Beginning of last menstrual period March 8; abor-
tion May 8. :

(4) The ovum appeared normal, with the villi distributed
equally over it. Upon opening, it was found filled with
dense magma _ réticulé, in which could be discerned the
faint outline of a 4-weeks’ embryo. The embryo, amnion,
and umbilical vesicle are all normal in form.

161

_ (5) The amnion is filled with cells; the umbilical vesicle
is filled with migrating cells, but its blood-islands and
entoderm appear fairly normal. The chorion is fibrous,
rarefied, and macerated. The outer covering of the
vesicle is composed of a short layer of columnar epithelial
cells. The magma of the ccelom is filled with wandering
cells. On one side of the embryo the epidermis is missing.
The nervous system is greatly dilated and dissociated, and
the liver tissue obscured and filled with migrating cells.
The contour of the abdominal viscera is obliterated, and
they, likewise, are filled with migrating cells. Pharynx,
heart, large veins, and aorta are greatly dilated.
(6) Decidua absent. Some hydatiform degeneration.

No. 124.

(1) H. F. Cassidy, Baltimore, Maryland.

(2) A 90X75 X50 mm.; B-35 mm.

(4) The ovum was received fresh and unopened. It
appears as a transparent cyst with a crescent-shaped
placenta on one end, measuring 60X50 mm. Within
it was a second sac, 50X37X35 mm., with tough,
fibrous walls, which proved to be the amnion. Within
this was an embryo, with club hands and feet, pointed
ears, and a very thin, twisted umbilical cord.

(5) Sections of the placenta show that the villi are
matted together and covered with a thick layer of decidual
cells. The wall of the chorion is considerably thickened
immediately below the placenta and fibrous in structure.
Between the villi at their bases there is a quantity of fresh
blood, and between their distal ends there is a great quan-
tity of trophoblast which does not stain well and appears
to be necrotic. Masses of granules, which stain intensely
with hematoxylin, can be seen. Sections of this interest-
ing specimen do not reveal very much, for the tissues do
not stain well. The form of the organs and skeleton,
with the exception of that of the extremities, appears to
be normal. However, the skin appears more fibrous than
usual, being somewhat infiltrated with round cells. In
the deformed extremities this infiltration is very pro-
nounced and involves all of the structures of the hands
and feet, with the exception of the cartilages. Syndactyly
is present.

(6) Marked decidual infiltration; changes in chorion
suggest lues.

No. 133.

(1) J. M. Hundley, Baltimore, Maryland.

(2) A 32X32X32 mm.; B 12 mm.

(3) Patient’s last period began September 15 and con-
tinued 8 days; bloody discharge began November 11, and
abortion occurred on the 19th. Both parents perfectly
healthy.

(4) When received, the specimen was thought to be
normal, but after a piece of the chorion had been cut the
ccelom was found to be completely filled with a dense mass
of magma réticulé. In taking off the piece of chorion the
attachment of the umbilical cord was cut and thus the
embryo located. The mass of magma and a portion of
the chorion encircling the embryo were removed and cut
into serial sections.

(5) The villi of the chorion are fibrous and macerated,
but normal in shape, with little trophoblast at their tips
and with poorly preserved vessels. The epithelium of
the chorion is greatly macerated. The ccelom is filled
with magma and migrating cells. The amnion is present
but necrotic. The umbilical vesicle is filled with des-
quamated entoderm cells. The embryo is distorted and
cramped; epidermis exfoliated at the points where the
amnion contains masses of migrating cells. The nervous
system is distended and dissociated, and the organs and
peritoneal cavity fairly well outlined. The liver is filled
with blood, which forms large islands at points. The
front end of the head is distorted greatly, the eye macer-
ated, and the whole head gorged with round cells.

(6) Decidua absent. Long retention.

162 STUDIES ON
No. 152.

(1) H. J. Boldt, New York.

(2) A 70X42X38 mm.; B 31 mm.

(3) “The specimen is from a woman suffering with
endometritis, this being her third successive abortion,
which took place in each instance during the third month
of pregnancy. The beginning of the last period preceding
this abortion took place on April 16; conception April 20 (?),
and abortion June 25.”

(4) The chorion was smooth and apparently devoid of
villi. The cavity of the amnion was filled with a mass of
granular magma covering entirely an embryo over 2
months old. The umbilical cord was much twisted and
thin, measuring 0.5 mm. in diameter.

(5) Microscopic examination shows that the chorion and
amnion are fibrous, thickened, and degenerate. The villi
of the chorion are matted together with fibrin and a mass
of cells which have undergone hyaline degeneration. The
epithelium is absent or necrotic; stroma of villi very
fibrous, being invaded at many points by syncytial cells
and leucocytes. At numerous points there are large nests
of leucocytes forming abscesses. It is a plain case of
endometritis infecting the chorion. The embryo is em-
bedded in a large quantity of magma and presents just
such a picture as No. 79, described above. The organs
are dissociated and macerated and the tissues stain poorly,
indicating that the embryo had died a considerable time
before the abortion took place. Again, the central ner-
vous system is swollen and dissociated. Migrating cells
are found in clumps or scattered in all of the tissues. In
general, the connective tissues are more fibrous than
normal, the dermis showing considerable hypertrophy.
The epidermis is lacking.

(6) Infiltration of the decidua; long retention.

No. 182.

(1) D. S. Lamb, Washington, District of Columbia.

(4) Head and upper end of the body of an embryo about
5 weeks old.

(5) Sections show an extreme degree of disintegration.
The brain is converted into a mass of cells filling the central
canal entirely and extending into the surrounding tissues,
the line of demarcation being obliterated. The large
veins of the body are gorged with blood, which also ex-
tends into the surrounding mesoderm. On the frontal
side of the head there is a straw-colored, necrotic mass con-
taining some migrating cells. On the dorsal side the meso-
derm is thin and blistered. The cartilages alone are still
well defined.

(6) Decidua and chorion absent.

No. 212.

(1) J. Park West, Bellaire, Ohio.

(2) B 15 mm.

(3) The macerated embryo is from a large ovum which
was aborted October 9. Last menstrual period began on
April 3, 189 days before the abortion.

(5) The tissues show that its development was arrested
during the sixth week. The central nervous system is
completely dissociated, being but a mass of cells. The
face and top of the head have been converted into a thick-
ened mass of degenerated tissue, in which may be seen
large veins filled with blood. The eyes are immediately
below the skin, thoroughly dissociated, but the vesicular
lenses can still be outlined.

(6) Decidua and chorion absent.

No. 215.

(1) D. I’. Unger, Mercersburg, Pennsylvania (Brédel
collection).

(2) A 454040 mm.; B 17 mm.

(4) The specimen is smooth and fleshy and filled with
granular magma, in which were found the remnants of a
macerated embryo.

PATHOLOGIC OVA.

(5) Sections of the chorion show that it corresponds with
its history, which states that the specimen is about 12
weeks old. The amnion lines the whole ovum. The cho-
rion is thickened locally and degenerate. The villi are
matted together, and the stroma is non-vascular and
fibrous, with necrotic epithelium. The two sections of the
decidua present show no infiltration, but the appearance
of the sections and of the gross specimen suggests very
strongly that infection must have been present.

No. 226.

(1) J. Park West, Bellaire, Ohio.

(2) A 60 X60X30 mm.; B 24 mm.

(3) “The woman, mother of three children, menstruated
last on March 3 and aborted on May 29.”

(4) The ovum is covered with a few large villi, 2 mm.
in diameter at their base, and irregular clots of blood;
elsewhere it is smooth. The amnion is filled with a
granular mass which was easily removed.

(5) Between the amnion and chorion there is an irregu-
lar mass of maternal blood. The tissues of the villi and
the chorion are somewhat fibrous with only a few degener-
ated blood-vessels in some of them, indicating that the
circulation had ceased some time before the abortion.
This is confirmed by a study of the embryo. The exter-
nal form of the embryo indicates that it was nearly 50 days
old when it died; for, with the exception of the head, its
form is practically normal. The menstrual history makes
it 87 days, and if 28 are subtracted, 10 days are still left,
which is time enough in which to bring on the internal
changes found. In general, the organs are sharply de-
fined, but do not stain well. The cartilages also are well
formed, and the maxilla, mandible, clavicle, humerus
ulna, radius, femur, and tibia have begun to ossify. All
this indicates that this embryo died quite suddenly, and
that the changes within it are to be viewed as post-mortem
changes. The vascular system is well developed, the
heart-muscle being normal in shape, but very fibrillar,
and does not stain well. Most of the large vessels are
empty, the blood-cells being scattered throughout the
tissues of the embryo and the cord. The muscle-fibers
are unusually well marked, and the connective tissue
seems to be thickened. The most marked changes are
seen in the head. Much of the epidermis is still in place,
but some of it has fallen off. At the back of the head the
destructive process has included the back of the brain
and the upper part of the spinal cord. The forebrain
midbrain, and spinal cord of the trunk are still intact and
dissociated. The eyes are normal in shape and position
but much macerated. The nerves of the head can sti
be outlined, which shows quite conclusively that the dis-
integration of the medulla is of recent date.

(6) Decidua absent.

No. 230.

(1) J. Park West, Bellaire, Ohio.

(2) A 75X60X59 mm.; B 57 mm.

(3) “The patient has had 3 children and 3 miscarriages.
She always menstruates regularly during pregnancy, and
hence has been undecided during the past 7 months
whether or not she was pregnant.”

(4) Upon opening the ovum it was found that the fetus
was greatly cramped and embedded in much granular
magma. The cord is thin and knotted. The right leg
has a club-foot and the left a dislocated knee-joint. Evi-
dently the embryo had been dead for a long time.

(5) The chorion and amnion are very degenerate, fused,
fibrous, and thickened. The vessels of the chorion are
largely obliterated. The stroma of the villi is fibrous and
non-vascular, and the epithelium necrotic. The villi are
matted into a solid mass by fibrin and coagulum, together
with the degenerate decidua and trophoblast. ‘The dislo-
cated knee and club-foot of the embryo show that the car-
tilages are markedly deformed. ‘The liver, brain, spinal
cord, and eye are macerated, converted into a pulpy mass,
and do not stain. All of the epidermis has fallen off.

ware

i

FETUS COMPRESSUS.

Apparently the embryo died suddenly, for there are prac-
tically no tissue reactions to suggest the contrary, and
the changes must have taken place after death.

(6) Decidua very necrotic; changes in chorion sugges-
tive of lues.

No. 261.

(1) W. H. Lewis, Baltimore, Maryland.

(2) A 1207070 mm.; B 90 mm.

(4) The distorted fetus, which no doubt had been dead
for a long time, is embedded in a mass of granular magma.

(5) Sections of the placenta show that the villi and cho-
rion are very fibrous and almost devoid of epithelium.
The stroma of the villi is clear and non-vascular. Numer-
ous degenerate syncytial buds are present. The vessels
in the decidual septa, and some of those in the chorion,
are obliterated or are being obliterated. The umbilical
cord is somewhat fibrous, but contains blood-vessels filled
with blood. The decidua contains large sinuses and is
infiltrated and fibrous. The tissues of the hand and the
skin are somewhat infiltrated with round cells, but other
changes within them are not marked. It appears as if
the embryo died quite suddenly.

(6) Decidua is infiltrated.

No. 286.

(1) John Girdwood, Baltimore, Maryland.

(2) A 1005040 mm.; B 60 mm.

(3) This specimen must have been dead in the uterus
for about 5 months, the last period having taken place
during the latter part of May and the abortion on Janu-
ary 4 following.

(4) The chorion thickens as it passes into the large,
fleshy placenta on one side and is very thin on the other.
The thin, twisted cord enters the chorion at the border of
the placenta. The embryo is well-embedded in granular
magma.

(5) Sections from the placenta at the point where the
cord enters it show a most remarkable reaction. The
amnion is thickened, fibrous, folded upon itself, and has
undergone hyaline degeneration. The chorion aiso is
hyaline, thickened, and infiltrated with leucocytes and
syncytium. The villi are fibrous, with numerous spots
of hyaline matter scattered through them. The lining
cells of the large blood-vessels of the villi show remarkable
growth, forming small pearls of endothelial cells. They
are also invaded by syncytial cells at some points, and at
others by masses of leucocytes. Between the villi there
is a great mass of necrotic syncytium mixed more or less
with fresh blood. Throughout this general mass numerous
small islands of active trophoblast may be seen; there are
also a great number of scattered leucocytes. The decidua
is decidedly fibrous and degenerate in some places, and
infiltrated in others. Sections of the cord, of the abdomi-
nal viscera, and of the hand show that the embryo must
have died quite suddenly. However, the tissues do not
stain well and the epidermis has fallen off, although the
large blood-vessels are filled with blood containing the
usual number of leucocytes.

(6) Decidua infiltrated, fibrous, and degenerate.

No. 316.

(1) Thomas J. Simms, Baltimore, Maryland.

(2) B 44 mm.

(4) There are peculiar patches upon the skin, the cord
is atrophic, feet and hands club-shaped, and one hand is
adherent to the side of the head.

(5) Sections of the cord show that it is fibrous and infil-
trated with round cells along the course of the blood-ves-
sels. The skin is thickened locally and much of the epi-
dermis has fallen off. At points the epithelial cells form
mounds without any horny changes. The muscles, blood-
vessels, and nerves of the extremities are converted into
a mass composed of spindle-shaped cells, giving much the
appearance of myomatous tissue, infiltrated at points
with round cells. The cartilages are still hyaline, but

163

richer in nuclei than is normal. Bone formation is present,
and at the border-line between it and the cartilage the
latter shows police changes. There is a mass of this
changed cartilage in the os calcis, without any surround-
ing bone formation. In general the cartilages are de-
formed, a condition in part producing distorted joints.
Where the hand is adherent to the side of the head the
epidermis of the two is blended. The skin and subcu-
taneous tissue are thickened, being composed of a mass
of round cells. At some points of the body there are
thickened areas in the skin. The form and structure of
the brain are pretty well preserved, while the tissues of
the liver and intestine are necrotic and macerated. It
appears as if the growth of the embryo had been retarded
by a continued growth and change in the connective tissue,
and that, after its death, it was retained in the uterus for
some time.
(6) Decidua and chorion absent.

No. 345.

(1) C. 8. Minot, Boston, Massachusetts.

(2) A 605050 mm.; B 19 mm.

(4) The fleshy ovum is composed largely of decidua in
which are buried plugs of mucus and necrotic villi of the
chorion. The embryo is normal in shape.

(5) Its tissues are greatly macerated, but on account
of the distended medulla, which encroaches upon the
mouth, it is probable that the tissues were dissociated
before they became macerated.

(6) Slight general infiltration of the decidua; chorionic
membrane absent.

No. 379.

(1) A. W. Meyer, Baltimore, Maryland.

(2) A 35X25X15 mm.

(3) Last menstrual period early in August; abortion
October 20.

(4) The specimen is well covered with villi and filled
with a considerable amount of reticular magma. The
amnion measures 10 mm. in diameter and contains a
granular mass, which, when floated from alcohol into water,
revealed an embryo of the fourth week. No internal struc-
tures could be seen, and in handling the embryo it fell
to pieces. No doubt it had been dead for some time.
The wall of the amnion is composed of two layers of cells
and appears to be normal.

(5) Sections show that the mesoderm of the umbilical
cord, the wall of the chorion, and the villi are fibrous,
with a curious growth of blood-vessels in some places.
The stroma of most of the villi is clear, non-vascular, and
has undergone mucoid degeneration in some. Maceration
changes also are present. Within the vessels of the villi
are numerous fragmented cells which may have come from
the blood of the embryo. The syncytium is very exten-
sive and necrotic at points. In many places it dips deep
into the mesoderm of the villi and forms islands of epi-
thelial nests. The wall of the amnion is composed of two
layers of cells and appears to be normal.

(6) Decidua absent. Very early hydatiform degener-

ation.
No. 445a.
(1) J. L. Fewsmith, Newark, New Jersey.
(2) B 60 mm.

(3) “Patient first menstruated at about 14, and as far
as she can recall was pretty regular at first. At 19 the
periods became rather irregular. She could count upon
skipping two months in summer, usually July and August.
This irregularity has continued up to the present time,
though not so marked during the last two years since she
has been under treatment. Each period, as a rule, is
accompanied by severe pain lasting for the first 12 to 14
hours. This has been so severe at times as to need small
doses of morphine or cocaine. The flow, when established,
has usually lasted for about 5 days. During the last 2
years it has been less in amount and has ceased on the

164 STUDIES ON

third or fourth day. When about 15 or 16 years of age
she had a great deal of pain over the ovaries, and her
physician made her stop A cet tennis, ete. When about
18 there was a mild attack of chlorosis, with cessation of
menstruation for several months. She became pregnant
about a year after her marriage, 6 years ago. The fetus
was carried for 6 months, when she miscarried. Develo)

ment apparently had not gone.much beyond 3 to 315
months. The pregnancy was accompanied by a great
deal of pain in the sacral region. As she did not become
pregnant again, she was, about 3 years ago, put under the
doctor's care. He finally decided to dilate the cervix,
curette, and put in a glass plug. At the operation he
found the cervix to be very brittle; he could feel it give
under the dilators, so that he had to give up dilating and
merely do a slight curettage. She became pregnant again
about 4 months after the operation. This time the fetus
was carried 4 months. The pregnancy was accompanied
by some pain in the back, often with bearing-down pains
and pains along the thighs. She became pregnant again
last September and miscarried at the end of January.
This is the specimen in which the sac was unruptured.
The same pains were present, but even more severe, mak-
ing her extremely uncomfortable and miserable. This last
miscarriage was hard, the severe pains lasting about 8
hours, as the cervix would not dilate. Each miscarriage
has been preceded by a bloody discharge lasting from 5
days to a week. Dr. (the physician under whose
care she had been) can tell you better the condition of
the uterus and appendages. He considers the uterus, I
believe, to be rather fibrous and the ovaries to be some-
what smaller than they should be, but says he can not
explain the pains, nor why, having become pregnant, she
should miscarry. There has never been any leucorrhea.”

At that time it was recommended that the uterus of this
patient be thoroughly scraped a number of times, if neces-
sary; but, as the following will show, it seemed to be of no
value in preventing this particular disease of the fetus and
subsequent abortion. Five years later we wrote to Dr.
Fewsmith again, asking for more details regarding the
ease. He replied that during the interim the patient had
been pregnant twice, each time aborting at about the
same period of gestation—that is, about the fifth month.
In his opinion the fetuses aborted were about the 3-months’
stage.

(5) The chorion is small, hemorrhagic, and atrophic,
and contains an embryo which, although somewhat dis-
torted, is normal in form. The villi are very fibrous and
some of them are edematous. The trophoblast is scanty
and at many points has invaded the stroma of the villi.
There are also numerous Hofbauer cells. The intervillous
spaces are pee with an inflammatory mass consisting
of mucus, fibrin, disintegrating blood, and numerous leuco-
cytes. Intermingled with this mass are many small buds
of syneytium. ‘The chorionic wall does not seem to be
any thicker than usual, and between it and the amnion
there is a dense layer of reticular magma, through which
are scattered numerous Hofbauer cells. The decidua
appears to be atrophic, but there is the usual fibrinoid layer
between it and the villi.

(6) The decidua is markedly infiltrated and contains
small abscesses; hydatiform degeneration of the chorion.

No. 445b.

(1) See No. 445a.

(2) B 85 mm.

(3) (See No. 445a, just described.)

(4) The chorion is somewhat hemorrhagic and covered
with well-formed villi' The fetus is normal in shape,
well bent upon itself, and the cord is very much twisted;
being extremely thin at some points. The amnion is
filled with a large quantity of granular magma which forms
large cakes, many of which are closely adherent to the
embryo.

(5) The chorion shows all the reactions of 445a but in
a more marked degree. A hand from each embryo was

PATHOLOGIC OVA.

cut into serial sections and appears to show slight changes,
more pronounced, however, in 445b than in 445a. The
decidua is infiltrated intensely in some places.

(6) Marked infiltration of the decidua.

No. 502.

(1) A. Shelley, Baltimore, Maryland.

(2) A 906050 mm.; B 85 mm.

(3) Said to be a fetus of the third month.

(4) The pear-shaped mass is quite solid, being hemor-
rhagic, with only a few villi protruding. It contained a
compressed, dried fetus, which seemed to be normally
developed but much shriveled, with a greatly twisted and
flattened umbilical cord.

(5) Sections through the chorion at the point of attach-
ment of the ampbilioal card show that the mesoderm of the
villi is very fibrous, and that the chorion is covered with
an inflammatory, hemorrhagic mass composed of blood,
fibrin, numerous leucocytes, fibrinoid substance, and villi
which have undergone extensive degeneration. There is
very little trophoblast present, but a number of syncytial
buds radiating into this mass, many of which are being
converted into nuclear dust. Surrounding each villus is
a space filled with fresh blood, indicating that in some way
the trophoblast has the pore to prevent coagulation.
Serial sections were cut of the right hand of the embryo
and show dissociation of its tissues. At points the epi-
dermis is lifted from the underlying structures, and the
cleft thus formed is filled with small round cells.

(6) Decidua absent. Very long retention; chorionic
membrane infiltrated.

No. 549.

(1) J. M. Jackson, Pittsburgh, Pennsylvania.

(2) A 403520 mm.; B 12 mm.

(4) The specimen is covered mostly with a layer of
decidua and the ccelom is filled with a mass of reticular
magma, within which is a ruptured amnion containing
the remains of an embryo of about the 12 mm. stage.

(5) The tissues of this remnant are macerated and partly
dissociated. The chorionic wall is normal in structure
but is encircled by villi which have undergone fibrous and
mucoid degeneration. There is very little trophoblast,
and some of that has undergone nuclear fragmentation.
There is also considerable fibrinous exudate between the
villi. The layer of villi is encircled by considerable fibri-
noid, decidua, and fresh hemorrhages. The decidua shows
leucocytic infiltration. The magma of the exocelom is
very rich in cells, especially in small round cells. The
embryo is dissociated and macerated.

(6) Some infiltration of the decidua.

No. 586.

(1) F. A. Conradi, Baltimore, Maryland.

(2) A 90X55X40 mm.; B 30 mm.

(3) Patient is said not to have menstruated for a year.

(4) A cavity extends throughout one side of the mass.
This is lined with a smooth amnion in which was found a
compressed, extremely macerated, and somewhat muti-
lated embryo, measuring about 30 mm. CR. Accordin,
to the shape of the arms and legs, the specimen is norm
in form. However, on account of the color and consis-
tency of the tissue, it appeared to have been dead a long
time before the abortion.

(5) Sections of the chorion show that its wall is ex-
tremely macerated and greatly thickened on one side,
measuring 25 mm., on account of a large hemorrhage.
This thickened area is composed of degenerated villi
intermingled with fibrin, pus, and fresh blood. The tro-
phoblast is mostly necrotic, and at points there are large
masses of nuclear dust. ‘The villi are de nerate, and
many of them are invaded by leucocytes. The nuclei of
the chorionic wall do not stain well, and i aye are
disintegrating. The specimen appears to be like some of
those obtained from tubal pregnancy; that is, after the

FETUS COMPRESSUS. 165

chorion is detached it keeps on growing in an irregular
fashion, for the villi are in fresh hemorrhages. Sections
of the embryo show that cartilages have been well formed.
In some places the ossification centers stain with hema-
toxylin; otherwise the tissues are markedly macerated.
Since none of them gives a differential stain, the embryo
no doubt had been dead for a long time before the abor-
tion.
(6) Some infiltration of the decidua; long retention.

No. 622.

(1) H. T. Collenberg, Baltimore, Maryland.

(2) A 804015 mm.; B 70 mm.

(3) Patient aged 30 years, with three children living and
apparently healthy. ‘This is the third miscarriage. The
others were early and likely not induced. Fetus was
expelled after 24 hours of pain. No menstruation for 9
months.

(4) The specimen consists of an unopened membrane
with placenta. The contents of the amniotic cavity con-
sist of a dark-brown fluid and the macerated fetus. The
latter measures CR 70 mm., is very much distorted and
slender, with a head greatly reduced in size. The extremi-
ties are very much deformed, with club hands and feet,
and the left forearm is adherent to the shoulder. The
cord is nodular and atrophic.

(5) The placenta, which was cut at the attachment of
the cord, was found to be fibrous. The villi are packed
together with an almost continuous mass of necrotic
trophoblast and show considerable invasion by leuco-
cytes. Occasionally some activity is shown in the tropho-
blast. Most of the villi are fibrous and others do not
stain well. They are all degenerate, even necrotic, and
are glued by degenerate blood, epithelium, and tropho-
blast. Throughout the entire specimen large plaques of
nuclear dust indicate that the tissues had been dead some
time before the abortion.

(6) Marked infiltration of the decidua; long retention.

No. 627.

(1) H. F. Cassidy, Roland Park, Maryland.

(2) A 80X50X35 mm.; B 45 mm.

(4) The specimen consists of a solid mass, 403025
mm., to which is attached a large vesicle, measuring
805035 mm., and undoubtedly representing the
distended amnion. Within the latter, which is filled with
clear fluid, there is a distorted embryo with an extremely
small and very much twisted umbilical cord. Over the
legs, on one cheek, and on the back of the head there are
large vesicles which seem to involve only the skin. The
one over the back of the head is 15 mm. long and 8 mm.
wide. Caudal to this and running down the middle of
the back there is a marked fibrous ridge. The hands,
especially the fingers, appear as if deformed.

(5) Sections made in the neighborhood of the attach-
ment of the umbilical cord show the vessels of the latter
with indistinct walls but filled with blood. The villi have
largely undergone fibrous degeneration, and most of the
trophoblast has been converted into nuclear dust, although
some have fibrinoid substance only within their centers.
There also are left rounded islands of trophoblast.

(6) Marked infiltration of the decidua; changes sug-
gestive of lues.

No. 646.

(1) G. C. MeCormick, Sparrows Point, Maryland.

(2) A 906050 mm.; B 85 mm.

(4) The chorion, which measures 906050 mm.,
was empty, the amniotic sac having slipped out. Within
the latter was a macerated, edematous fetus, with a dis-
torted head from which the brain is protruding. There
are marked contractions in the forearms, and the fingers
of the right hand are nearly amputated. From their
knob-like stumps extend numerous delicate fibrils. As
they strip off so easily, it is probable that they are com-

posed exclusively of macerated epidermis. The umbilical
cord is very thin and greatly twisted. The chorion is
covered with large, shaggy villi, showing that implanta-
tion had been well established before the abortion.

(5) Sections through the cord show that it has under-
gone degeneration; sections through the hand show the
dissociation of the periphery of the cartilages and muscles.
In other words, there is an infiltration of cells between the
muscle-fibers.

(6) Decidua and villi absent.

No. 649.

(1) G. C. McCormick, Sparrows Point, Maryland.

(4) The body and extremities of this specimen are much
out of proportion. There is a large tumor on the back of
the head, the spinal column is bent upon itself, and the
viscera hang out in an enlarged bag in front. From one
side of this bag the umbilical cord arises.

(5) The most marked abnormalities of this specimen are
total spina bifida and defective posterior portion of the
cranial vault. The spinal column consists of 31 verte-
bral bodies. This includes the coceyx, but not the atlas,
which could not be traced. Along the sides of the verte-
bre there are present rudimentary, cartilaginous neural
processes. The spine is in sharp dorsi-flexion in the upper
cervical and lower thoracic regions, with a more rounded
and probably compensatory kyphosis below these areas.
All that remains of the spinal cord is a strip of thin mem-
brane into which the spinal nerves run fairly regularly
ventrally. The anterior vault of the cranial cavity is
flattened so that it is reduced to a narrow slit, and the
defective contents of the cranium project backwards into
a sac which lies over the spinal column. This sac con-
sists of several layers of membranes.- The remains of the
nervous system which it contains are quite elongated
nerves and shreds of much-folded membranous tissue.
(Wheeler.) The ribs are very crowded and show a ten-
dency towards fusing. In the forearms both ulnz are
present; 4 metacarpals and 4 phalanges; the radii and
thumbs are lacking. In the legs the bones are all present,
but the positions are anomalous. There is extreme exter-
nal rotation, with the soles of the feet directed backward
and inward (equino-varus). There is ectopia viscerum,
the liver, intestines, stomach, spleen, and pancreas pro-
jecting outward into arounded sac. Several subcutaneous
blebs are scattered over the surface of the sac, and the
stumps of the cord attached to it show marked mucoid
degeneration. There is a Meckels diverticulum; the dia-
phragm is bilaterally defective; the lungs are abnormally
formed and lie next the kidneys. The adrenals could
not be traced.

No. 717.

(1) Max Emmert, Atlantic, Iowa.

(2) A 50X45X35 mm.; B 14 mm.

(3) Patient is 34 years old: married June 1907. First
abortion February 1908, at 3 months. Last menstrual
period April 7 to 10, 1913; abortion June 5 following.
No infection of uterus; no venereal diseases. Patient is
one of two children.

(4) The specimen measures 50X45X35 mm., and
consists of a vesicular chorion covered partly by a few
ragged villi and partly by infected decidua. The cho-
rionic wall is very thin, and the cavity contains a clear
fluid and a granular deposit. There also is a small mass
of granular magma on one side, a macerated cord 10 mm.
long, and a floating remnant of an embryo 14 mm. long.
The latter can barely be outlined. One arm and the
atrophic legs are still intact. A slight amount of shaking
would cause the entire specimen to fall to pieces.

(5) The chorionic membrane and amnion are thin and
fibrous. The villi are atrophic and some are fibrous.
Between them there is a considerable amount of mucoid
substance and blood, containing numerous buds of syn-
cytium. The entire mass is surrounded by a thin layer

166

of decidua marked off on the inside by a pronounced
zone of fibrinoid substance.
(6) Decidua not infiltrated.

No. 735.

(1) J. R. Blackman, Hastings, Nebraska.

(2) A 50X40X30 mm.; B 4 mm.

(3) First pregnancy of a woman, aged 30 years, who
was amet January 10, 1912. Last menstrual period
May 29 to 31, and abortion July 20 following. Cervix
dilated July 19 and a strip of gauze inserted in the uterus.
Abortion induced for pernicious vomiting. Last periods
were less profuse. Right ovary adherent and tender over
McBurney’s point. Frequent pain in appendix region.
Uterus not infected.

(4) Pear-shaped mole 504030 mm., with very
thick walls and well filled with granular magma, which
peels out in the form of large clumps. The cavity con-
taining the magma measures 25X20 mm. On one side
was seen a small whitish, amorphous body, about 4 mm.
in length, the remnant of the embryo.

(5) The chorionic wall is thin and lined with a dense
mass of granular magma containing embryonic fragments.
It is surrounded by necrotic villi which are embedded
in a mass of fibrin, mucoid substance, and some blood.
The surrounding fibrinoid substance and decidua are very
thin. There are numerous syncytial buds at points;
otherwise most of the trophoblast is necrotic. 'The embry-
onic mass proved to be a macerated fragment of an embryo.
It includes a section of precartilage and spinal cord, and
is closely embedded in granular magma. No amnion was
found. The decidua is necrotic, but not infiltrated.

(6) Decidua very degenerate, but apparently not infil-

trated.
No. 740.

(1) Ira L. Fetterhoff, Baltimore, Maryland.

(2) B 56 mm. .

(3) Patient 44 years old; married in 1890. Six preg-
nancies: First ended at term; second and third in abor-
tions; fourth, twins; fifth at term; sixth, this abortion.
Menstruation in April 1913, continued 6 weeks; again
July 16 to 23; abortion August 8 following. After careful
examination uterus found to be apparently normal.

(4) The embryo has a clubfoot, but otherwise is nor-
mal. It is encircled by a mass of magma which has
cemented the extremities together, making it look like
amummy. ‘The cord is very thin and twisted. No mem-
branes were received with the specimen.

(6) Decidua and chorion absent.

No. 743.

(1) John H. Groshans, Baltimore, Maryland.

(2) B 105 mm.

(3) Patient 34 years old; married June 1, 1907. One
birth at term, July 1908; abortion at 4 months, June 1910.
Last menstrual period March 8 to 16, 1913, and abortion
August 17 following. Patient supposed to use abortives,
but denies it. No venereal diseases. Patient is a second
wife. Husband's first wife had 7 children and 3 abortions.

(4) The specimen is shriveled, as if it had been in
alcohol for some time, but the body and extremities are
normally formed. The frontal bone is greatly retracted
and the parietal bones overlap. The ears are flattened
out and the eyes are sunken, all of which make it appear
as an early stage of fetus compressus.

(6) Decidua and chorion absent.

No. 797.

(1) George T. Tyler, Greenville, South Carolina.

(2) A 653535 mm.; B 35 mm.

(3) Woman aged 29 years; married one year. Always
has had painful menses, which have been profuse. This
was especially so in the last period, 4 weeks before the
present one, November 9. History of exertion just before
this period began. The patient did not know she was

a ae

STUDIES ON PATHOLOGIC OVA.

pregnant, as she had missed no periods. Physician called
on November 9 because of pain and bleeding, and he found
specimen presenting at vaginal orifice. No previous
history of importance.

(4) The specimen is covered with a few atrophic villi,
and its wall is thin on one side and thick on the other.
The interior is filled with a jelly-like magma and contains
an atrophic embryo 35 mm., which is markedly deformed,
having atrophic hands and feet and a very thin umbilical
cord. The ae is also reduced in size.

(5) Sections of the chorion show that it is hemorrhagic
and inflamed. The chorionic wall is fibrous and degenerate,
and the villi mostly necrotic, only a few of them being
fairly preserved. ‘They are bound together by fibrin and
a great deal of fibrinoid substance. There is also con-
siderable nuclear dust.

(6) Marked infiltration of the decidua; probably luetic.

No. 805.

(1) Morris A. Birley, Thurmont, Maryland.

(2) A 1006045 mm.; B 50 mm.

(3) Woman aged 31 years; married 16 years. Seven
births at term, this being her first abortion. Last period
September 2 to 5; abortion December 5 following.
lacerated os. Patient belongs to a very fertile family.

(4) The chorion, which measures 1006045 mm,.
has a smooth wall, the greater part of which is thickened
and hemorrhagic. One end, however, is thin and trans-
parent. When the specimen was halved it was found to
contain a cavity 705025 mm., lined by a smooth
amnion containing a fetus CR 50 mm., normal in shape
but macerated, with numerous edematous blebs of skin.
The umbilical cord is very thin and extremely twisted.

(5) Sections show that the amnion and chorionic wall
are fibrous, and surrounding the latter are numerous villi
packed together and intermingled with a great quantity
of fibrinoid substance, organized blood, decidua, and
inflammatory patches. There also is a great deal of
nuclear dust. The spheres of trophoblast so frequently
seen in these specimens have undergone fibrinoid changes.

(6) Marked infiltration of the degenerate decidua.

No. 809.

(1) O. S. Lowsley, New York.

(2) A 503030 mm.; B 22 mm.

(4) The abortion mass, which is composed mostly of
chorion, measures 50X3030 mm. The amnion pro-
trudes and contains a badly macerated embryo 22 mm.
GL. This is distorted and bent upon itself, but when
straightened appears to be normal in form.

No. 811.

(1) George H. Hocking, Govans, Maryland.

(2) A 1008060 mm.; B 120 mm.

(3) Patient aged 40 years; married 1896. Six preg-
nancies, five at full term and one abortion. Last men-
strual period May 12 to 17; abortion December 26 fol-
lowing. Beginning about October, there were slight
losses of blood at intervals for several weeks, and it is
fair to assume that gestation ceased even earlier than this.
Patient one of 6 children. The specimen is bent markedly
upon itself; the epidermis is mostly lacking and the cord
is greatly twisted. The fetus measures 120 mm.

(5) The amnion and chorion are very fibrous and
closely connected by a thick layer of reticular magma.
The chorionic wall is closely covered with decidua, there
being no villi in the portion cut. One of the hands of the
satel was cut into sections. The tissues do not stain
well.

adly

No. 828.
(1) Austin Miller, Porterville, California.
(2) A 503016 mm.; B 8 mm.
(3) Patient aged 28 years; married 3 years. One
previous pregnancy, which ended at term. Last men-

FETUS COMPRESSUS.

strual period about November, and abortion January
following. No venereal diseases. Family fertile.

(4) This specimen consists of a compressed oval mass,
measuring 523016 mm. On being opened, the
firm hemorrhagic wall disclosed a smooth-lined cavity
from which some blood-stained fluid emerged. It was
filled with reticular magma, in which was embedded a
macerated embryo GL 8 mm. The chorionic cavity
measures 301210 mm. Theembryois in fragments,
two of the limbs being free; these, however, preserved
their form well. The umbilical vesicle measures about 5
mm. in diameter and appears normal.

(5) Sections of the chorion show that the chorionic
membrane is macerated, well infiltrated with leucocytes,
and covered with matted villi, together with an inflam-
matory exudate. There is much fibrinoid substance and
many buds of syncytium. The embryonic mass is com-
posed mostly of a well-developed cord and portions of a
macerated and disintegrated embryo, more or less en-
circled by the amnion. In the cord there are indications
of dissociation, as the walls of the distended blood-vessels
are not sharply defined.

(6) Severe intervillous infection.

No. 831.

(1) Austin Miller, Portersville, California.

(2) A 85X85X85 mm.; B 115 mm.

(3) Patient aged 29 years. Two pregnancies ending at
full term. Last menstrual period July 21 and abortion
January 20 following. Uterus normal as far as known.
No venereal diseases. Family fertile.

(4) The specimen consists of a fetus compressus well
curled upon itself and inclosed in its membranes, with
placenta attached. The whole mass, which is spherical,
measures about 85mm. in diameter. On opening the mem-
branes, the amnion could be separated from the chorion; on
opening the amniotic cavity, a white, cloudy fluid poured
out. The inclosed fetus is somewhat macerated, the
epidermis being off in places and the head compressed.
The umbilical cord is about 30 mm. long and very much
beited upon itself. Otherwise the specimen is normal in

‘orm.

(5) Sections were made through the chorion at the
attachment of the umbilical cord. The chorion and villi
are fibrous and matted together by a great quantity of
fibrinous substance, more or less invaded by tropho-
blast cells, making the substance look like cartilage.
There are numerous buds of trophoblast undergoing con-
version into nuclear dust. The decidua is atrophic and

ed.
(6) Slight infiltration of the decidua; probably luetic.

No. 868.

(1) E. H. Egbert, Washington, District of Columbia.

(2) A 75X48X22 mm.; B 39 mm.

(3) Patient aged 26 years, with no specific family or
penal history on the part of patient or her husband.

th are in good health. Miscarriage March 1911, at
21% months; May 1912, stillbirth at term; miscarriage at
21% months, with curettage, May 25, 1913. Last men-
strual period September 26, 1914; all symptoms of preg-
nancy. Flowed November 1 to 15 (a few clots); abortion
April 7, 1914.

(4) The specimen consists of a pear-shaped abortion
mass, measuring 75X48X22 mm., and the fetus which
was inclosed therein measures CR 39 mm. It appears
unquestionably pathological, both regarding the shape of
the head and the extremities, which are club-like. The
lining of the chorion (amnion) presents a remarkable
sight, being profusely covered with small thickenings in
the form of minute tubercles in rings.

(5) The chorionic membrane is very fibrous, and the
overlying villi are firmly matted together by fibrinoid
substance and some trophoblast. There are also numerous
plaques of nuclear dust. Upon examining the amnion, it

167

is seen that the minute tubercles are due to local thicken-
ings in the fibrous layer.

(6) Decidua absent. Probably luetic.

No. 869.

(1) G. C. McCormick, Sparrows Point, Maryland.

(2) B 150 mm.

(3) Negro, age 30 years, married April 24, 1907. Six
pregnancies: first, 7 months: second, 6 months; third, 6
months; fourth, 8 months; fifth, 4 months; sixth, 6 months.
Last menstrual period October 1-4, 1913; abortion March
28 following. Condition of uterus good. Syphilis. Fam-
ily fertile.

(4) The specimen is normal in form, but badly macer-
ated. Most of the epidermis has falien off, and the ex-
tremities, as well as the head, are compressed in an irreg-
ular fashion.

No. 896.

(1) Edwin B. Fenby, Baltimore, Maryland.

(2) B 88 mm.

(3) Patient aged 25 years; married nearly 7 years.
Four pregnancies, but this is the first abortion, all the
others at term and living. Uterus apparently normal.
No history of venereal diseases. Family fertile.

(4) The abortion mass, consisting of placenta and fetus
intact in its amnion, was sent to the laboratory 214 hours
after being passed. It was opened under salt solution, and
much brown fluid with “débris” poured out. In this were
epidermal casts of hands and feet, and a badly macerated
fetus, length CR 88 mm., weight 26 grams, with a long,
twisted umbilical cord, 150 mm. The head is shrunken,
making it appear as an early stage of fetus compressus,
perhaps from strangulation due to the extreme twisting
of the cord.

(5) Sections of the placenta at the attachment of the
cord show that the villi, though well formed, are practi-
cally non-vascular, and the stroma degenerate and cellular.
The intervillous spaces are filled with some blood, tropho-
blast, and a great deal of fibrinoid substance. There are
also numerous plaques of nuclear dust.

(6) Slight infiltration of the decidua.

No. 903a.

(1) J. H. Bacon, Peoria, Illinois.

(2) B 66 mm.

(4) The embryo is greatly macerated, distorted, and
decerebrated. It weighs 11.5 grams in formalin, which
indicates that it is somewhat under weight. The umbilical
cord is very thin and twisted.

No. 921.

(1) J. L. Genella, New Orleans, Louisiana.

(2) B 16.5 mm.

(3) Patient aged 35 years. Mother died in childbirth
and father of dementia. About five years after a diagnosis
of malignancy was made the patient gave birth to a normal
child. Several recent abortions. Coitus March 9.
Beginning of last menstrual period February 28; abortion
March 30. Pathologists had made a diagnosis of chorio-
epithelioma and hysterectomy was advised. It appears
that the patient has syphilis.

(4) The specimen consists of a rather poorly preserved
young fetus, measuring 16.5 mm. CR. The ventral
abdominal wall had been seriously injured. It is difficult
to be sure whether or not the specimen is normal, the left
hand plate being somewhat abnormal in outline. The
head is smaller than usual, being round in front. Macera-
tion is so complete that a depression is present over the
lower part of the spinal cord.

No. 9296.

(1) N. H. D. Cox, Baltimore, Maryland.

(2) A 80X70X50 mm.; B 75 mm.

(3) Patient aged 22 years; married 6 years. Four
pregnancies; one abortion and three births at term.

168

Had no menstrual period after the birth of last child,
November 10, except one day in January, and once,
April 14, after a fall downstairs. After this a slight flow
every two weeks. Nausea February 28 and March 22;
abortion June 3. Accidental abortion from fall and there-
fore no infection. No venereal diseases.

(4) The chorion, which measures 80X70X50 mm.,
is entirely covered with well-formed villi, and appears to
be normal. The contained fetus, measuring 75 mm., is
badly macerated. It has a much-twisted and very slender
umbilical cord, and there are large blebs on the right leg
which appear to be abraded over the knee.

No. 960.

(1) G. C. McCormick, Sparrows Point, Maryland.

(2) B 190 mm. : y

(3) Negro woman, aged 31 years; married April 6,
1914. Has been pregnant six times; no abortions. Last

riod February 18 to 22, 1914; abortion October 17
ollowing.

(4) An encephalic fetus apparently at term. Crown of
head devoid of scalp, exposing an area 40X60 mm. of
blighted brain and its membranes. Over the sacral
region there is an area devoid of integument.

No. 964.

(1) Henry F. Cassidy, Roland Park, Maryland.

(2) B 115 mm. .

(3) Negro patient, aged 24 years; married March 20,
1911. Two pregnancies, both ending in abortion; the
first in 1913 at 3 months. Last menstrual period March
22 to 25; abortion October 19, 1914. Bled September 3,
and intermittently after October 6, apparently a natural
flow in time and amount. No history of venereal disease.
Family fertile.

(4) The specimen consists of a macerated, flattened,
and distorted embryo with umbilical cord 280 mm. long,
and detached placenta 806535 mm. On section the
uterine surface of the placenta presents a firm white
marginal layer of decidua, 2 mm. thick, thrown in ruge.

(5) The villi of the placenta are normal in shape, but
closely packed together with trophoblast, and nearly all
of them have undergone fibrinoid changes. The mesen-
chyme is fibrous and there are many plaques of nuclear
dust. There is some blood in the intervillous spaces. This
stains black with the Heidenhain method. The tropho-
blast in contact with it shows no activity whatever.

(6) Slight infiltration of the decidua; probably luetic.

No. 971.

(1) G. C. McCormick, Sparrows Point, Maryland.

(2) B 92 mm.

(3) Patient aged 26 years; married December 31, 1903.
Three pregnancies—two births at full term and this
abortion. Last menstrual period May 24 to 27, 1914,
abortion October 29 following. Condition of uterus good.
No venereal diseases. Family fertile.

(4) The specimen consists of a placenta, amnion, and
a compressed, greatly macerated, attached fetus. The
placenta is very firm. The cord is about 130 mm. long and
not greatly twisted. The extremities are flattened and
contorted, the legs being badly bent upon themselves.
Most of the epidermis has fallen off, and the fetus in
general is shrunken.

(5) Sections through the placenta at the attachment of
the cord show the villi to be very fibrous, degenerate, and
matted together by a uniform mass of fibrinoid substance,
in which there are numerous plaques of nuclear dust.

No. 979.
(1) James A. Melvin, Baltimore, Maryland.
(2) B 210 mm.
(4) The specimen consists of a badly macerated fetus
attached to a placenta which measures 130X100 mm.

The fetus is discolored and distorted and the cord greatly
twisted.

STUDIES ON PATHOLOGIC OVA.

(5) The chorion is very fibrous and most of the tropho-
blast necrotic. The villi are matted together with exten-
sive masses of fibrinoid substance, within which are large
plaques of nuclear dust. The decidua is thin and some-
what inflamed, and the placenta itself is practically dead,
there being no buds of syncytium at the point where the
trophoblast comes in contact with the fresh blood.

(6) lig general infiltration of the decidua; some sug-
gestion of lues.

No. 983c.

(1) J. F. Hempel, Baltimore, Maryland.

(2) B 103 mm.

(4) The specimen consists of a naked fetus with flat-
tened and distorted extremities. The eyes are recedin
and the face has the appearance of a mummy. The ae
is irregularly shaped, thin and fibrous at some points and
thick and mucoid at others. Most of the epidermis has
fallen off.

No. 983d.

(1) J. F. Hempel, Baltimore, Maryland.

(2) B 97mm.

(4) Specimen consists of pisces with unopened mem-
branes, 1007455 mm. On opening the latter there was
found a shrunken and distorted fetus.

(5) The villi are well formed and appear to be fibrous;
between them there is some blood and occasional clumps
of nuclear dust. The decidual layer is thin and is attached
to the tips of the villi by means of a fibrinoid substance.
No active trophoblast is present in any portion of the
sections.

(6) Decidua not infiltrated.

No. 996.

(1) H. B. Titlow, Baltimore, Maryland.

(2) A 726030 mm.; B 100 mm.

(4) The specimen consists of placenta, membranes, and
fetus. The uterine surface of the placenta is pearly white
hard, and corrugated. On cutting this surface it was found
to be covered by an external layer about 1 mm. thick, of a
firm cartilaginous substance. The cord was twisted
excessively, and the extremities flattened and distorted.

(5) Sections through the chorion at the attachment of
the cord show that the villi are fibrous, and that large
nodules of trophoblast have undergone fibroid degenera-
tion and contain plaques of nuclear dust. Some of the
villi are attached to the decidua, which contains several
well-defined small abscesses.

(6) Decidua infiltrated.

No. 1014.

(1) M. Ostrow, Baltimore, Maryland.

(4) The specimen is an unopened conceptus about 8
inches in diameter. The uterine surface of the placenta
was gristle-like in consistency and the membranes opaque.
The amniotic fluid was brownish and the fetus contorted
and macerated. The cord is decidedly tortuous.

(5) The villi are non-vascular and very fibrous, with
an especially degenerate epithelium which shows begin-
ning calcification. Some of the larger vessels in the chorion
are represented as solid fibrous areas, their lumina being
entirely obliterated. Some fairly preserved blood is
found between the villi, the stroma of which is represented
by a translucent coagulum only. The decidua is too de-
generate for further comment.

No. 1020.

(1) W. F. Twigg, Cumberland, Maryland.

(2) CR. 260 mm.

(3) The last menstruation occurred April 26 to 30 and
abortion December 11. The patient declares she felt life
September 30. No infection. Abortus is estimated to
have been dead 10 days at least.

(4) Specimen is a macerated fetus with marked abdomi-
nal distention, suggesting ascites. It must have been

DESCRIPTIONS OF PLATES.

dead for some weeks, and this is indicated also by the
relation of the menstrual age of 32 weeks and 5 days
to the anatomical age of 2914 weeks.

No. 1027.

(1) H. B. Titlow, Baltimore, Maryland.

(2) 1308050 mm.

(4) The placental area of the chorion is firm and partly
converted into a gristle-like substance. The remnant of
the chorion is opaque and thickened, except for an area
4050 mm., which is translucent. The chorion contains
a brownish fluid and a brownish, macerated fetus with
several turns of the umbilical cord around the neck. The
extremities are very distorted.

(5) Microscopic examination of the placenta presents
the picture typical of long retention. The vessels are
largely degenerate. The epithelium is necrotic or wholly
absent and the stroma fibrous and degenerate. In places
growths of villi are matted and fused into a solid mass,

169

forming the so-called “‘infarcts.’’ The decidua also is
very degenerate, but some fairly well-preserved blood
still is contained in the intervillous spaces and also in
some of the dilated villous vessels.

No. 1028.

(1) G. J. France, Baltimore, Maryland.

(3) Last menstruation occurred September 25 to 27,
and abortion December 18.

(4) The specimen is a very badly macerated and dis-
torted fetus with compressed and twisted extremities, and
portions of the body barely recognizable.

(5) One of the umbilical vessels (apparently an artery)
is almost completely obliterated, while the other two
vessels show little change. Perivascular infiltration is
absent. In spite of the marked maceration and disin-
tegration, the subcutaneous vessels still show in some of the
digits, and the striations and voluntary musculature are
splendidly preserved.

DESCRIPTIONS OF PLATES.

Puate 1.

Fig. 6. Old retained hydatiform. degeneration.
Fia. 7. Abnormal conceptus. No. 1843. X6.
Fie. 8.

Fic. 9. Festoons of chorionic epithelium. No. 1324.
Fic. 10 No. 1224.
Fra. 11

. Detached conceptus, still in utero.

No. 323.

Decidual cast containing remnants of conceptus.
300.
x6.

. Almost total lysis or gossamer form. No. 606. X69.

1.25.

No. 698. X1.

PLATE 2.

Fic. 12.
Fig. 13.
Fia. 14.
Fia. 15.
Fic. 16.
Fic. 17.
Fig. 18.
Fig. 19.

Villi showing hydatiform degeneration.
Hydatiform tubal twins in situ.
A fine hydatiform villous tree in section

An unusual nodular form. No. 2288. X6.
Reniform nodular cyema. No. 1369. 4.

Cross-section of a nodular cyema, showing simple structure.
External appearance of chorion containing small nodular twin. No. 788b.

Same specimen as fig. 10.

No. 825. X3.

No. 367. X10.

Full-term nodule accompanying a twin donated by Dr. Slemons. No. 1682.

X1.1.

No. 651g. X10.

X1.15.

PuaTE 3.

Fig. 20.
Fia. 21.
Fic. 22.
Fig. 23

Fies. 24-26. Illustrating variation in form of cylindrical cyemata.
Fia. 27. Longitudinal section showing structure of cylindrical cyema.

Cross-section of No. 788b, shown in fig. 19. X45.
Macerated normal cyema, No. 788a, companion to 788b.
Divergence in external form of cylindrical cyemata. No. 885. 4.

Illustrating marked changes in form and structure of cylindrical cyemata. No. 446. X6.

X1.

Nos. 2236 (X9), 2222 (<6), and 1776 (<6).
No. 150. X15.

PLATE 4.

Fia. 28.
Fig. 29.
Fia. 30.
Fig. 31.
Fig. 32.
Fia. 33.
Fig. 34.
Fia. 35.
Fig. 36.
Fig. 37.
Fia. 38.
Fig. 39.
Fia. 40.
Fig. 41.

Longitudinal section of cylindrical embryo.

Illustrating stunting. No. 2233. 4.5.

Section of a similar fetus, to show structure.

Macerated, rolled-up, older fetus. No. 1041.

External view of No. 2473, showing stunting in an older specimen.
No. 675.
Sagittal section illustrating fusion of mandibular margin with chest.
Sagittal section showing internal maceration changes and gaping of the mouth. No. 988a.
Macerated, firmly rolled-up, young fetus. No. 921.

X0.75.
Cyema classed as fetuses compressus. No. 1245. X3.

No. 489. 37.5.

A cyema in the pre-gossamer stage of lysis. No. 2197. 6.75.

Twin conceptus with larger chorion opened and location of smaller indicated. No. 587. 0.75.
Part of the same conceptus in section, showing the cavities of both chorionic vesicles. 1.5.
Side view of cyema, showing so-called stunting. No. 2173.
Front view of same specimen, showing maceration and stunting. 3.

X3.

X<3.

4.5.

No. 788a. X4.5.

4.5.

X2.25.

170 DESCRIPTIONS OF PLATES.

Puate 5.

Fras. 42-50. Various forms of cyemata classed as fetus compressus: Nos. 1463 (X2), 1806 (X1.5), 1301 (8.5),
1513 (X0.58), 1495¢ (0.58), 896 (X.55), 1925 (X.65), 1239 (0.55), 1515 (0.58).
Fig. 51. Distortion due to maceration and retention in utero. No. 1931. Xl1.
Frias. 52-63. Illustrating the absence of fundamental differences between the group of fetus compressus and grade
3 of the normal specimens.
No. 12956 (fig. 52) pathological. 1.5.
No. 532 (fig. 53) normal. X1.8.
No. 1475 (fig. 54) pathological. 1.5.
No. 852 (fig. 55) normal. X2.
No. 1750 (fig. 56) normal. 1.5. (To be compared with No. 1806, fig. 43.)
No. 1779 (fig. 57) normal. X1.
No. 65la (fig. 58) pathological. 1.
No. 1513 (fig. 59) pathological. 0.58.
No. 1350 (fig. 60) normal. 0.58.
No. 1474a (fig. 61) normal. 0.58. (To be compared with No. 896, fig. 47 )
No. 1758 (fig. 62) pathological. 0.5.
No. 1532 (fig. 63) normal. 0.5.
Fic. 64. Fusion of epidermis on lower extremities during maceration. No. 1859. 0.5.
Fic. 65. Epidermal thickenings. No. 316. 7.5.
Fic. 66. Early drooping and distortion of extremities. No.1710. X1.
Fic. 67. Showing diversity in position and distortion of extremities. No. 1751. X05
Fia. 68. A similar but younger specimen. No. 1931. X1.
Fic. 69. Distortion of digits. No. 1751. X1.
Fic. 70. Unilateral maceration bleb on cord. No. 1523. X0.5.
Fic. 71. Bleb formation on neck, same specimen. X1.
Fia. 72. Bleb formation in whole nuchal region. No. 2261. X1.5.

Puate 6.

Fic. 73. Nodular fibrosis of the amnion. No. 868. 1.35.

Fig. 74. Nodular fibrosis of the amnion. No. 1048. 0.66.

Fic. 75. Large, clear, normal decidual cells. No. 1599. 200.

Fic. 76. Maceration, hemorrhage, and lysis, with early transformation of the decidua. No. 872. 200.

Fic. 77. Further transformation of the polygonal decidual cells into the spindle and fibroblast type of cells. Same
specimen as figure 76. 200.

Fic. 78. Longitudinal section of right ovary, showing carcinomatous nodule to the right. No. 865. X2.

Fic. 79. Same specimen. Portion of carcinomatous nodule. X27.

Fic. 80. Left ovary from same case in longitudinal section, showing disk-shaped teratoma in section. X2.

Fia. 81. Teratoma in section, same case. 11.5.

Fic. 82. Remarkable vascular proliferation in the chorionic membrane. No. 309. 120.

AND MEYER

MALL

MALL AND MEYER

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MALL AND MEYER

MALL AND MEYER

MALL AND MEYER

MALL AND MEYER

PLATE 6

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ts

CHAPTER V.
THE RELATION OF CYEMIC TO CHORIONIC SIZE.

The occurrence of hydramnios indicates that in some specimens the relation
of cyemic to chorionic size must vary considerably for this reason alone. This
could fail to be the case only if hydramnios could be recognized in its beginning,
so that such specimens could be excluded. Moreover, since we are as yet
unable to recognize the earliest regressive changes in the cyema, this fact too would
increase the range of variation in specimens which might be regarded as normal,
at present. If we consider specimens classed as pathologic in the Carnegie Col-
lection, the disproportion between cyemic and chorionic size would of course be
very much greater. This variation, in fact, is over 800 per cent. Since the eyema
may be extremely abortive and evidently also disappear entirely, disproportion
between cyemic and chorionic dimensions might be extremely great in these speci-
mens also. But even aside from these considerations, the relation between chori-
onic and cyemic size can not be constant throughout gestation unless the shape of
the conceptus were invariable. But we know that such is not the case, for the
greater growth in length of the fetus, placental development, the formation of
the chorion leve, and other matters, all tend to change the form of the conceptus.
It is true that regression of the villi in the region of the chorion leve would be
compensated for to some extent by placental formation on the other side of the
vesicle, but in such large specimens the extrauterine change in form will be con-
siderable and thus increase the fluctuation in the measurements. However, it is
very probable that the closest correlation exists between cyemic and chorionic
size, during the early stages of development, when the conceptus probably is still
more nearly spherical. During this time the conceptus also undergoes but little
change in form during measurement under proper extrauterine conditions; but
even at this time the villi always will be a decidedly variable factor in all external
measurements of the chorionic vesicle. Hence it would seem that satisfactory
results for a comparison of chorionic and cyemic dimensions probably can not be
obtained without taking those of the chorionic vesicle regardless of the villi. Such
measurements, however, can not be made accurately without bisecting the vesicle.

I do not know whether the increase in amniotic fluid is very constant or not,
but if its volume changes disproportionately, even if not independently of the
length of the cyema, this fact would introduce another variable and so further
obscure the real correlation in size between the cyema and its chorionic vesicle.
In addition to all these things, there are, of course, the normal variations in growth
and the changes in form effected during parturition and fixation, for very few
abortuses are obtained and measured when fresh. Besides, the vesicle and the
cyema no doubt vary independently of each other in growth, so that a very broad
basis becomes necessary before a reliable comparison between the two can be
made. For all these reasons, then, it would seem that the volume, or, better still,

171

172 STUDIES ON PATHOLOGIC OVA.

the weight, of the empty chorionic vesicle and that of the eyema would be more
reliable data for a determination of a correlation between the two.

Very few data on this matter are available to us in the literature and we must
bear in mind that it is not yet possible to distinguish between the early normal and
the abnormal. Whether or not the relationship between the dimensions of the
eyema and the chorionic vesicle can be used, as suggested by Giacomini (1894),
for distinguishing between the normal and abnormal, it is impossible to say at
present. But even if such a criterion can not be obtained, a comparison between
the size of the cyema and the chorionic vesicle nevertheless ————-——-—————_
may reveal fluctuations in the one or the other, or in both, | Embryo. | Chorion.

which might otherwise be overlooked. mm. cm.
Without reference to the excellent older observations tee ee
of Velpeau (1855), His (1882) concluded that chorionic was | 121233 | 22 to4

related to amniotic size in early specimens, as shown in the 20 to 25 4.0 to 6
accompanying table.

Giacomini stated that embryos with a length of 2 to 4 mm. are contained in
vesicles 1.5 em. long; embryos 4 to 10 mm., in vesicles 1.5 to 3 em.; embryos 10
to 18 mm., in vesicles 2.5 to 4 em.; embryos 15 to 20 mm., in vesicles 3.5 to 5
em.;and embryos 18 to 20 mm., in vesicles 4 to 6 em. long. Giacomini also stated,
as did His (1882), that the amnions of embryos less than 10 mm. long invest the
latter closely and His further stated that the amnion is 1 to 3 mm. distant from
embryos 11 to 15 mm. long and that it had fused with the chorion when the embryo
had gained a length of 2.56 em. Schaeffer (1898) stated that embryos 1.15 mm.
long are contained in vesicles of 2.5 to 2.7 em.; embryos 3 mm. long in vesicles of
2.5 em.; and embryos 8 mm. long in vesicles 7.5 to 8.5 em. J. Kollmann (1898)
gave the relation of chorionic to embryonic size the same as His. Since His and
Kollmann give only one chorionic measurement, it is impossible to surmise what
their conception of the form of the chorionic vesicle was, but His’s table suggests
that the relation between embryonic and chorionic length varies from 1-5 to 1-2
by the time the embryo has reached a length of 2 cm.

Eternod (1909*) emphasized the fact that the conceptuses described by
Reichert, Ahlfeld, and by himself, all were lenticular in form and also flattened
somewhat upon one of their faces. The same thing is true of those reported by
Bryce and Teacher, Peters, von Spee, and also of some other specimens. Eternod
stated that while early conceptuses are lenticular, they later become ovoid, and
still later more spherical. According to Eternod, the portion toward the basalis
is flattened the most, while that toward the capsularis is more curved.

Since some of the conceptuses called lenticular by Eternod are so very small,
their shape scarcely can be attributed to the influence of the surrounding mus-
culature. Hence it would seem that the human conceptus soon loses the inherent
sphericity undoubtedly possessed by the ovum. If, as Eternod thought, the villi
of early conceptuses are zonal or annular, with two free surfaces which he desig-
nated as dorsal and ventral, a further source of variation in the measurements of
young specimens would be introduced.

RELATION OF CYEMIC TO CHORIONIC SIZE. 173

Evans, in an undated circular issued by this laboratory, gave the length of
the embryo and the size of the chorionic vesicle as indicated in table 5. Such
tabulations as these are very helpful and suggestive and are bound to gain much
in value with enlargement of the data upon which they are based. This table from
Evans indicates that the conceptus of the third week practically is spherical, that
it then rapidly becomes oblong so that its greatest diameter is almost twice that
of the second dimension by the fourth week, and that it returns to a more spherical
condition in the sixth, seventh, and eighth weeks, during which time its greatest
‘dimension is indicated as only one-sixth longer than the second dimension. Upon
comparing the length of the cyema with that of the conceptus as given in table 5,
we find that the greatest dimension of the latter is 10 times that of the former in
the third week. The greatest dimension of the chorionic vesicle is approximately
6 times that of the embryo in the fourth week; 4.5 times in the fifth week; 3 times
in the sixth week; 2.2 times in the seventh; and 1.4 times in the eighth. From
this it is seen that there is a rapid and early approximation between the greatest
dimension of the chorionic vesicle and the length of the cyema. This might be
expected from the fact that growth in length of the cyema is so much greater than
growth in the other two dimensions. The irregularities evident in this table
probably are attributable to the small series available for the tabulation, to the
fact that all measurements of necessity had to be made postpartum, and that they
were not made by the same individual.

The exact form of the human conceptus in its early stages still remains un-
known, but as indicated by specimens from the literature, it is probably spherical.
This sphericity, however, must be lost as soon as the conceptus extends across the
uterine cavity or when the cyema reaches a length which brings its cephalic and
caudal extremities closer to the chorionic membrane than are the rest of its sur-
faces. From this time on we might expect the form of the conceptus to become
more and more elongated and ovoid. It may be recalled that one of Leopold’s speci-
mens of early conceptuses was represented as ovoid or as almost cylindrical even,
but one must bear the possibility of molding during abortion and of postpartum
distortion in mind. However, it often is difficult to detect elongation attributable
to molding during labor, even in conceptuses of considerable size. Conceptuses
up to 4 and 5 cm. in greatest dimension usually assume a flattened, ovoid form
when placed in fluid of approximately the same specific gravity. One might, I
presume, suppose that after the first weeks all conceptuses have a more or less
cylindrical form, in consequence of the shape of the uterine or tubal cavities, but
the form of early guinea-pig conceptuses throws doubt upon this supposition.
They are quite spherical, and the same thing is true of young rabbit conceptuses,
even when they have considerably distended the thin-walled cylindrical uterine
cornua by reaching a size of one centimeter.

What is needed, however, is a careful series of measurements on selected
material, although even such material will not be ideal as long as we remain unable
to differentiate early normal from abnormal forms and as long as not all measure-
ments are made either on fresh or on fixed material. Hence it is evident that the

174 STUDIES ON PATHOLOGIC OVA.

field and graph shown in Chart 1, although made upon the basis of selected normal
material from the Carnegie Collection, supplemented by data from the literature,
probably can not give us anything more than a very rough approximation of a
portion of a curve illustrating the relation between cyemic and chorionic size
during the first month.

Among the cases used for this graph there are a few in which the cyemic
length is somewhat greater than the greatest chorionic measurement. This may
be due to the fact that the chorionic vesicle was measured after it was opened and
fixed. It is always diffeult to restore the form of opened chorionic sacs in fluid,
even with the greatest care, unless they are coated with blood and decidua so that
their walls are stiffened.

rl ae
30

kes 1
20

eye ame =

Greatest dimensions of chorion in millimeters.

Cuart 1.—Field and graph showing correlation between cyemic and chorionic size, based on the 255
selected normal specimens. Uterine specimens indicated by dots, tubal by circles.

In some instances conceptuses with different menstrual ages have the same
size, a fact which not necessarily finds its explanation in the existence of normal
growth differences, but rather in the earlier death of one cyema or conceptus. Other
discrepancies between the length of the cyema and the dimensions of the
chorionic vesicle may be due to distention of the latter after death of the former,
or possibly to actual growth of the chorionic vesicle after the death of the embryo.
It is fortunate that we possess a double check on our data, for we can consider
the relation of the size of the ovum and the eyema independently, and also can
compare each with the menstrual age.

RELATION OF CYEMIC TO CHORIONIC SIZE. Nie

Since the number of conceptuses with embryos of the first month which have
been measured is exceedingly small, any curve based on these data necessarily
must remain largely conjectural. However, if we regard it as purely tentative,
even such a curve nevertheless may be of value. Moreover, its obvious incom-
pleteness will prompt to improvement. As will appear from Chart 1, only 16 cases
were available for the construction of the curve for the first month; 8 of these were
from our own collection, 8 from the literature. One of the two embryos, 2.5 mm.
long, belongs to a vesicle which is entirely too large and hence falls high on the
chart. On consulting the history of the case it was learned that the conceptus was
decidedly collapsed and hence very probably distorted. But this is not the only
specimen which shows considerable disproportion between the size of the eyema
and the conceptus. I do not imply, however, that these disproportions represent
wholly normal variations, although until a large series is available for study it will
remain impossible to determine the deviation from the average of normal speci-
mens in a given state of development.

The field represented in Chart 1 was plotted from measurements of chorionic
vesicles and cyemata below the fourth month, which are listed as normal in the
Carnegie Collection. It includes both uterine and tubal specimens; the former
are represented by dots and the latter by circles. In addition to these specimens
the measurements of 12 young conceptuses from the literature have also been
added; these are represented by crosses. Since scrutiny of the fields made by the
use of other than only the greatest dimension of the chorionic vesicle made it
evident that the other dimensions were quite useless as criteria, only the greatest
measurement was used for the construction of the field as here represented. The
greatest dimension of both cyema and chorionic vesicle is represented in milli-
meters-—the former on the ordinate and the latter on the abscissa.

Reference to the location on the field of the cases from the literature, and
also an inspection of the beginning of the curve, show that the chorionic vesicle
forges ahead of the cyema in its growth. This is what one would expect, for
embryonic differentiation naturally must be delayed at the start. However, the
specimens of conceptuses with a measurement of less than 10 mm. are too few to
enable one to regard this part of the curve as more than an approximation of the
actual. Between a length of 10 and 20 mm. a considerably larger number of cases
are found, and here the curve is more reliable, although considerable scattering
of the cases nevertheless is present. To what extent this scattering is due to
variations to growth, and to what degree to the fact that the material was perhaps
not strictly fresh or normal, it is impossible to say; probably both factors are
involved. Moreover, since the chorionic measurements were external, the con-
dition and length of the villi introduce a further factor of fluctuation; for although
the average dimensions of normal villi may fluctuate very little in length when
large series of conceptuses are concerned, they do vary considerably, not only in
different but also in the same specimen. This is especially true when the period
of placental differentiation is reached. Hence measurements of the cavity of the
chorionic vesicle or those taken from the wall of the bisected vesicle would give

176 STUDIES ON PATHOLOGIC OVA.

far more reliable data, because the variations in thickness of the membranes are
slight and one has then to contend only with the question of distention from hy-
dramnios or other causes.

Since the curve is fairly regular throughout, and the disproportion of the
cases but slightly greater as the older conceptuses are reaehed, I think it can be
assumed that it is approximately correct in its general relations. With advancing
age it is seen that the length of the fetus more and more approximates the greatest
dimension of the chorionic vesicle. This is in agreement with common observa-
tion and shows that the greatest chorionic dimension no longer can be of any
special value for determining the fetal age. Moreover, in older conceptuses the
vesicle no longer retains its form.

Since the majority of the tubal specimens fall considerably below the curve,
it is evident that development of the fetus was considerably retarded in these
specimens. Only a few fall above the curve, but one of these is so very far above
that one is compelled to conclude that the greatest dimension of the chorion was
not obtained in this case, or the chorionic vesicle must have been torn and the
amniotic fluid drained off. As will be noticed, the length of the fetus in this case
exceeds that of the membranes in which it was contained.

From the curve it is seen that the relations apparently existing between the
chorionic and cyemic dimensions are approximately those shown in table 6.

Tasie 5. (From Evans.) TABLE 6.

Approxi-
Chorion.}| Embryo. Chorion.| Embryo.

Greatest external
dimensions of
the ovum.

Probable
age in
full weeks.

Standing
height.

m. mm,

5 by 4
14 by 9
24 by 17
34 by 29
42 by 36
52 by 44

0.0
6.6
5.0
3.3
3.0
2.8
2.7
2.5

we eee ett
Aaonrnwaormw

oo

A comparison of the estimates on the accompanying graph (Chart 1) with
the estimates of other investigators previously referred to shows that those of
Evans agree most closely with these. However, the present curve can be regarded
as provisional only, for it is based upon but 255 cases and upon external measure-
ments alone.

CHAPTER VI.
SEX-INCIDENCE IN ABORTIONS.

By Apouex H. Scuutrz.

The numerical proportion of the sexes has always been a subject of great
interest. The question whether man produces males and females in equal or un-
equal numbers bears a close relation to the problem of sex determination and must
be studied in connection with the death-rate in different periods of life and the
comparative sex-mortality. While sex-ratio is conditioned originally upon sex-
determination, mortality may change it in the course of time. It will be shown
herein that sex-ratio is not constant, but varies in the different periods of life and
under manifold influences. Most of the information at hand concerning it is
derived from statistics of the new-born and adult, but as regards intrauterine life,
as far back as conception, our knowledge is limited to a few incomplete statistics
and conflicting estimates. The main purpose of this study is to elucidate as far
as possible this problem of the proportion of the sexes in utero, both living and
aborted. The short review of the sex-ratio after birth, given herein, is intended to
show the fluctuations in the numerical proportion of the sexes throughout life and
may serve for a comparison of the relative mortality before and after birth. The
last part of the study is a compilation from the literature of factors which may
possibly have an influence on the original sex-ratio and of conditions which may
change it during the course of prenatal life.

In view of the generally accepted supposition that sex is determined either
before or at the time of fertilization, one may speak of a sex-ratio at conception
or a sex-ratio of fertilized ova. This may also be called an original, physiological,
or primary sex-ratio; the sex-ratio of the new-born may be termed secondary
and, finally, that of adults is the tertiary sex-ratio. The latter term, in contrast to
the preceding ones, does not apply to a definite time, such as conception or
birth, but may be used collectively to designate the changing numerical proportion
of the sexes after they reach maturity.

TERTIARY SEX-RATIO.

The consideration of sex-ratio in adults will be limited to generalities. Accord-
ing to Biicher (1892), for Europe the sex-ratio,’ including all ages, is 97.6; for
Asia 104.5; for Africa 103.3; for America 102.8; for Australia 117.4. However
imperfect these computations may be, they nevertheless show that Europe, with
its excess of females, occupies a unique position. There are only a few European
countries with a greater proportion of men than women. Among the American
negroes there is an excess of females, and among the American Indians an excess
of males (Cummings, 1918). According to Brooks (1887), the Australasian colonies

1 The most common method in use for representing the sex-ratio is to determine a number which indicates the pro-
portion of males to every 100 females. Unless otherwise stated, this is the method used herein. The sex-ratio is also fre-
quently termed masculinity.

177

178 STUDIES ON PATHOLOGIC OVA.
had in 1881 a sex-ratio of 143.7 for the aborigines, and one of 118.6 for the popula-
tion of foreign descent.

TaspLe A.—Number of females per 1,000 males. Tasie B.—Changes in sez-ratio with advancing age.
(From Rauber.) (From Prinzing.)

Age Austria, | England and} France, | Germany, Age Females per Age Females per
in years. 1869. | Wales, 1871.| 1872. 1875. in years. 1,000 males. in years. 1,000 males.

25 to 30 1,087 ’ 1,017 1,059 Oto 5 993 40 to 45 1,045
30 to 40 1,074 991 1,046 5 to 10 998 45 to 50 1,067
40 to 50 1,089 , 996 1,052 10 to 15 995 50 to 55 1,121
50 to 60 1,033 : 1,008 1,081 15 to 20 995 55 to 60 1,140
60 to 70 1,022 1,033 1,114 20 to 25 1,008 60 to 70 1,189
80 to 90 1,052 ; 1,359 1,240 25 to 30 1,008 70 to 80 1,259
30 to 35 1,014 80 to 90 1,338
35 to 40 1,020 90 to — 1,751

Table A, taken from Rauber (1900), represents the number of females to
every 1,000 males in some of the European countries. As will be noted, the excess
of females increases with age. This is still more clearly shown in table B, from
Prinzing (1905), taken from the census of 1900 in Germany. Inasmuch as in
Europe sex-ratio at birth favors males, its subsequent decrease must be the result
of a greater mortality among the latter, and also, in some countries, of a greater
emigration of males. The unequal mortality is shown in table C, from Ploss (1887).

The sex-ratio of mortality may differ with age and under various conditions
of life. For example, between the ages of 25 and 40 years (according to Knopfel,
1907) in rural districts it is below, while among urban population it is above 100.
A difference in the comparative death-rate of the sexes in city and rural populations
is shown by table D (Baker, 1910, compiled from the United States census of 1900)
to exist throughout life, but to vary at different ages.

Taste C.—Sez-ratio of mortality in European countries. TaBLE D.—Ezcess of male death-rate (per 1,000 popula-
(From Ploss.) tion) over female death-rate. (From Baker.)

Country. Ratio.

107

Russia (Europe). 108
Holland 108
Germany 109

England Greece lll
France 116

Bell (1918), in his studies on the Hyde genealogy, found that during the years
covering the child-bearing period the death-rate was greater among females than
among males. His conclusions were based, however, upon comparatively small
statistics. In opposition to this we have the more reliable conclusion of Willcox
(1904) that, according to the life tables of several entire countries, the death-rate
of women between 20 and 30 years of age (a period during which probably four-
fifths of the child-births occur) was less than that of males of the same age.

SEX-INCIDENCE IN ABORTIONS. 179

SECONDARY SEX-RATIO.

The sex-ratio of the living-born for all European countries is, roughly averaged,
105 to 106, but this may vary markedly even in comprehensive statistics. Mani-
fold explanations for these variations have been offered and these will be con-
sidered briefly farther on. In the individual countries small differences in the
secondary sex-ratio may exist, as shown by table E, taken from a table by Ploss.

We have very little data concerning the sex-ratio of new-born among races
other than white. Newcomb (1904) states that in Japan the excess of males in
over 1,000,000 births was practically the same as in European countries. Accord-
ing to the same author, it seems probable that among the negroes of the United
States there is a slight excess of female births. In a table by Nichols (1907) one
finds the following sex-ratios among the living-born of primitive races: Japan
(1877-1902), 104.7; India (1891-1900), 107.5; negroes of United States (1900),
99.8; and an average since 1880 of 100.9.

TasLe E.—Secondary sex-ratio. (From Ploss.) Taste F.—Sezx-ratio of mortality during first year of life.
: (From Prinzing.)

Country. Ratio. Country. Ratio.
ae es eee Country. Ratio. Country. Ratio.

Russian Poland..
England and

Connecticut... .

As a result of the unequal mortality of the sexes, this secondary sex-ratio
becomes reversed early in life. Kroon (1917) states that in Holland the sex-ratio
of mortality during the first year of life is 119; that is, the mortality among male
infants is greater by one-fifth than among females; also, that during the first two
months of life this ratio reaches even 139. Analogous numbers for the first year
of life are given in table F (Prinzing, 1906).

Kroon’s statistics show that this high ratio of mortality of the first year of
life soon undergoes a decrease, reaching its minimum (approximately 80) between
the fourteenth and fifteenth year. According to Prinzing (1905), and also Willcox
(1904), the mortality from the ages of 5 to 20 years is greater in females, and indeed
in the latter part of this period it is the result chiefly of tuberculosis, for which
disease the common occurrence of anemic and chlorotic conditions at the time of
puberty furnishes an excellent soil. After this age the sex-ratio of mortality in-
creases rapidly and results in the reversion from an excess of males to an excess of
females, and the higher the death-rate the earlier will this reversion take place,
the death-rate being influenced by various factors. It can be said, for instance,
that as a general rule the death-rate of infants is especially high in countries with
a high birth-rate, such as Russia and China. This, in connection with the high
sex-ratio of infantile mortality, will tend to decrease very rapidly the sex-ratio of
the surviving infants.

180 STUDIES ON PATHOLOGIC OVA.

PRIMARY SEX-RATIO.

The sex-ratio of fertilized ova can not be determined directly; however, there
is an indirect method of solving the problem of the original sex-ratio by means of
computing the mortality of cyemata.’ In case the sex-ratio of fetuses dying in
utero is equal to the secondary sex-ratio, then only will the latter and the primary
sex-ratio be equal. If the number of males and females that were aborted or
still-born were absolutely the same, then the primary would be lower than the
secondary sex-ratio. If, however, the sex-ratio of mortality during pregnancy
exceeds the sex-ratio of the living-born, then the primary sex-ratio must of neces-
sity be greater than the secondary, and indeed increasingly so as the total intra-
uterine mortality becomes relatively greater. It is necessary, therefore, to consider
two factors in order to deduce the primary sex-ratio from the secondary: (1) The
sex-incidence in abortions, and (2) the relative frequency of abortions. Both of
these factors—1. e., the sex-ratio and the relative rate of mortality—differ in the
various periods of pregnancy, thus complicating the calculation of the primary
sex-ratio. I have endeavored to gather from the literature estimates and statistics
concerning the intrauterine mortality, beginning with the relative frequency of
still-births and abortions.

The relative number of still-births differs to some extent according to the
various authors. This is in part explained by the fact that the statistics are taken
from different countries and at various times. Von Winckel (1903) reported that
in Berlin, during a period of 70 to 80 years, the number of still-born males varied
from 3.2 to 7 per cent of all births, that of females from 2.5 to 5.5 per cent. Rauber
states that in Germany the still-births amount on an average to 4 per cent of
1,800,000 annual births. According to Carlberg (1886), the proportion of still-
births to the total number of births in Livland lies between 2.58 and 2.90 per
cent, while the percentage for western Europe lies between 4 and 4.5. According
to Prinzing (1907), from 1891 to 1900 the following proportions of still-births
occurred in every 100 births: Austria 2.9, Switzerland 3.6, Italy 3.9, Holland 4.3,
Belgium 4.5, France 4.6. These figures are somewhat increased when expressed
in percentage of the living-born. Computing from Auerbach’s (1912) statistics
of over 100,000 births in Budapest, the still-births amounted to 3.3 per cent of the
living-born. Bucura (1905) found that among 40,169 births in the Clinic Chrobak
in Vienna, 5.8 per cent were still-born; Le Maire (1906) found 5.7 per cent among
40,339 births in Copenhagen. Both of these figures are too high, inasmuch as
these authors did not use the term still-born in the usual sense, a small number of
abortions being included. Nichols (1907) quotes the following figures from regis-
tries of vital statistics: 3.6 per cent of total births of whites in the United States
are still-births, and among the negro births of the District of Columbia 13.8 per
cent are still-born. The percentage of still-births in Japan is 8, according to the
same source. These figures from Nichols also include abortions, but inasmuch as
these are not nearly so regularly reported as miscarriages in the last few months
of pregnancy, they do not considerably increase the percentages.

+ I use the term cyemata as a collective name for fertilized ova, embryos and fetuses. (See Meyer, 1919.)

SEX-INCIDENCE IN ABORTIONS. 181

The relative number of abortions is extremely difficult to determine, inasmuch
as everywhere large numbers of them, especially of the earlier months, remain
unknown, and even the most careful statistics will always be far from complete.
The most reliable source of information is probably the estimate of the experienced
obstetrician. Williams (1917) expresses himself on the question of frequency of
abortions as follows:

“A conservative estimate would indicate that about every fifth or sixth pregnancy
in private practice ends in abortion, and the percentage would be increased considerably
were the very early cases taken into account, in which there is profuse loss of blood
following the retardation of the menstrual period for a few weeks.”

Other authors give different estimates. Franz (1898) found 15.4 per cent of
pregnancies ending in abortion; Malins (1903) found 19.23 per cent; Taussig
(1910) estimates that one abortion occurs to every 2.3 labors; Pearson (1897) one
_ to every 2.5 labors; Mall (1910) calculates that there is one abortion to every 4
births at term; Ahlfeld (1898) estimates the same proportion; Whitehead (1848)
assumes that every seventh pregnancy is interrupted by abortion, and states
later on that only 13 per cent of married women who reach the end of the child-
bearing period escape having an unsuccessful pregnancy. Auerbach (1912) reports
that, according to estimates for Berlin, abortions amount to one-sixth to one-tenth
of the number of living-born. According to the same author, in Budapest, from
1901 to 1905, there were 111,139 living born, and from 1903 to 1905, 7,702 abortions.
Assuming an approximately equal number of living-born for each year, they would
amount to 66,678 for the years 1903 to 1905, the proportion of abortions to this
number of living-births being 11.55 per cent. This percentage is doubtless too
small. Auerbach himself assumes that many abortions of the earlier months are
concealed. Under certain circumstances the proportion of miscarriages and
abortions may increase tremendously. Bluhm (1918) reports that among working
women in Berlin in 1915 and 1916 there were 190 abortions to every 100 full-term
births, and attributes this partly to the harmful occupations in factories.

From these quotations it would seem most probable, on a rough average, that
out of every 100 fertilized ova only 78, or even less, develop to term, the remainder
being aborted. This intrauterine mortality may appear to many to be very high,
but if we consider that during infancy this waste of life continues unabated the
above estimate will not seem so improbable. Infant mortality during the first
year of life varies in different countries; according to Phelps (1910), from slightly
below 10 to 27 (in Russia) per 100 living-born; 7. e., the number of infants dying
within the first year of life may be more than one-fourth the number of living-born.’

It appears that the frequency of abortion is greatest in the first three months
of pregnancy. Auerbach, in considerable material, found that half of the abor-
tions fell within that period, yet it is for this period that our statistics are most
incomplete. In reality, therefore, more than half the number of abortions must
occur in the first three months. According to Franz, 42.6 per cent, and according

1 In the registration area of the United States in 1900 there were the following death-rates for infants under 5 years

of age (Billings, 1904): White: males 5.33, females 4.43; negroes: males 11.85, females 10.58 per 100. In the negro race
infant mortality is more than twice as high as in whites.

182 STUDIES ON PATHOLOGIC OVA.

to Diihrssen, even 59 per cent of abortions occur in the third month alone. Nichols
tabulated the relative frequency of abortions and still-births at different periods
of pregnancy from extensive statistics of Paris, Brussels, and the District of Colum-
bia. Table G is based on this table by Nichols, the figures representing the per-
centages of the total number of abortions and still-births. These statistics are
quoted for the sake of completeness and not because the writer believes that they
represent the actual conditions; all that they show is that the farther back we go
into fetal development the less regularly are abortions reported. There can be no
question, for instance, that the abortions occurring in the third to the fifth month
inclusive amount to very much more than 11.6 per cent of all the intrauterine
deaths, and yet this percentage is given for the whites of the District of Columbia.

Taste G.—Percentage distribution of abortions in differ-
ent months of pregnancy. (Adapted from Nichols.) Taste H.—Sez-ratio of still-born. (From Morgan.)

District of Columbia.
Month. Paris. |Brussels.

Country. Ratio. Country.

Denmark
Belgium
Austria

Seattered through the literature are reports on the sex-ratio of abortions.
Those concerning the numerical proportion of still-births are more numerous and
more reliable than those relating to younger fetuses and embryos that have been
aborted. The sex-ratio of the still-born is much higher than that of the living-born.
Table H, taken from Morgan (1913), gives the sex-ratios of still-born for some of
the European countries. According to Nichols, the sex-ratio in over 11,000,000
still-births in Europe was 134.2, being highest in Spain (152.3). In Japan ample
statistics of still-births yielded the unusually low sex-ratio of 107, a proportion
which is only a little higher than that for living-born. It should be mentioned
that in the statistics used by Nichols still-births comprise “in the main fetuses of
more than six months’ gestation.”’ Such high sex-ratios of still-born as that of
Walter (260) or that of Tschuprow (400) are probably based upon relatively
limited material and do not represent true ratios.

Auerbach gives detailed information concerning the sex-ratio of abortions.
His material is distributed among the different months of pregnancy as shown
in table I. The sex-ratio of abortions during the first three months he assumes
to be at least equal to that of abortions in the fourth month, 7. e., 229. It seemed
to him more probable, however, that it increases in constant proportion, and he
therefore estimates 322 for the third month and 452 for the second month. Nichols
tabulated, by sex and period of gestation, large statistics of “still-births’’ com-
prising almost 60,000 cases from Paris (1891-1902), and 4,400 whites and 7,500
negroes from the District of Columbia (1874-1902). In these statistics neither

SEX-INCIDENCE IN ABORTIONS. 183

sex nor age determination is any too reliable, and the ratios in the different
periods have therefore to be taken for what they are worth. Nichols’s figures,
in abstracted form, are given in table J. His conclusion is that the “ratio of
male fetuses born dead is much the highest from the third to the fifth month;
much lower from the sixth to the eighth month; and at term the ratio again rises.”
According to Carvallo (1912), the sex-ratio of abortions up to the fourth month
is 250; this figure he calculated from the statistics of Paris in 1908. Ké6résy (1898)

TasBLe I.—Serz-ratio of abortions in different months.
(From Auerbach.)

Month.

Males. Females. | Sex ratio.

Wourth cn os.2isio0 >< 928 405 229
Milthep oon e ose 645 396 163
Sixth seni sees 506 437 116
Seventh: ......... 402 348 116

erate perc ini= 1,586 156.4

found the sex-ratio in 3,781 abortions to be 152.4 Pinard and Magnan (1913)
report on 1,229 abortions, the ages of which are not stated. This material showed a
sex-ratio of only 101.1. Rust (1902) also found the sex-ratio in 454 abortions
from the first six months to be very low, 7. e., 101.8. It is apparent how greatly
these figures vary. A new contribution towards the knowledge of the sex-incidence
in abortions is therefore not valueless, especially as great care has been taken to
determine age and sex.

TaBLE J.—Sex-ratio of abortions and still-births in differ- Taste K.—Sez-ratio of 1,410 fetuses from different
ent months. (Adapted from Nichols.) months.
‘ District of Columbia. : Total material. Whites only.
Month. Paris. ae aaa a

Whites. Negroes.

121.0 110.7

117.5 122.0

Third and fourth. . 176 145 122 i 109.6 107.0

TERE Ss. bic Saat 121 148 152 i 87.5 88.4

SIKGMe ens te ctace 117 lll 124 108.5 112.1

Seventh Peso ceoac 119 114 122 i 133.3 123.5

WapPhth. 52 lens ewe 123 106 112 Ninth and tenth . 167.6 156.5

Ninth and over ... 134 129 127

Average...... 134.8 123 124.9

The last paper of the writer on this subject (1918) was based upon a relatively
small amount of material; since then it has been more than doubled, increasing
correspondingly the dependability of the conclusions drawn from it. The material
in all consists of 1,410 fetuses, 1,249 of which are from the embryological collection
of the Carnegie Institution of Washington. For data on 32 fetuses, I am indebted
to Dr. Ingalls, and in addition I have made use of 57 fetuses published by Rauber
and of 72 Filipino fetuses tabulated by Ruth (1918). Of this material only a
small percentage is derived from induced abortions; the great majority were spon-

184 STUDIES ON PATHOLOGIC OVA.

taneous ones and therefore represent the inevitable mortality. Age classification
was based upon the sitting height (Keibel and Mall, 1910). Both normal and
pathological fetuses were used in this study. These were for the most part white.
In a limited number of cases no parental history was available; however, it is
certain that a great majority of these also were white. Among the specimens other
than white there is a preponderance of negroes, with a total of 201. The sex-ratios
of these fetuses in the various months of pregnancy are given in table K. The
pathological fetuses alone show a sex-ratio of 103.7, a proportion which indicates
that the two sexes become pathological with about the same relative frequency.
The sex-ratio of all the negro fetuses is 105.1, and of all the Filipinos 182.1. The
material on which these latter ratios are based is, however, too small to draw any
safe conclusion from them.

The greatest deviations in the ratios obtained by Auerbach and by Carvallo,
on the one hand, and by the author on the other, occur in the third and fourth
months, in which Auerbach found the ratios to be 322 and 229, and Carvallo 250.
The author’s corresponding figures are very much lower, namely, 121 and 117,
respectively. The great excess of male abortions in the early months of pregnancy,
as found by Auerbach and Carvallo, may find its explanation in the fact that in
the statistics used by them the sex was determined by different individuals. who
had not the specialized knowledge necessary for such determination on young
fetuses. The same source of error exists in case of statistics of abortions throughout
whole countries as used, for instance, by Nichols." Early in the differentiation
of the external genitalia only the expert can state the sex with certainty. At this
time, and even later, the inexperienced, misled by the size of the clitoris as well as
by other factors, may erroneously determine the female fetus as male. Fewer
errors would be made on specimens from the latter part of the third and the fourth
months if only those definitely male were reported as such, and all the doubtful
ones were designated as female. Even granted that larger statistics might raise
the sex-ratio of abortions, the latter would never reach the high figures stated by
Auerbach, by Carvallo, and assumed by others. Just as the sex-ratio of mortality
following birth varies according to age, so it is found to be true during the pre-
natal period. The author’s material showed a high sex-ratio in the third and
fourth months. In the fifth to the seventh month it became very much lower, to
rise again in the eighth to the tenth month, attaining a higher figure than in any
previous period. An analogous changing of the sex-ratio of intrauterine mortality
was found by Auerbach and by Nichols with only slight differences in the duration
of the periods of high and low ratios, but with considerable differences in the ratios
themselves. Nothing is known in regard to the sex-ratio of abortions during the
first two months of pregnancy; however, that of the third month might be used
hypothetically for this period. The author’s material from the fifth to the seventh
month shows an average of 101.9, but owing to the variability in the individual
months it is quite probable that the number of male and that of female fetuses

! The writer had an opportunity to compare the death certificates of a large number of abortions and still-births with
his own findings on the specimens themselves, and found a surprisingly high percentage of errors in sex determination in
the certificaies, sometimes even on full-term fetuses.

SEX-INCIDENCE IN ABORTIONS. 185

perishing during the period from the fifth to the seventh month is relatively, not
absolutely, equal. At any rate, it is apparent that during the middle third of
intrauterine development the excess of male abortions is much lower than at
the beginning and at the end of pregnancy.

In order to make use of the above citations and figures in computing the
primary sex-ratio, rough and approximately average values must first be estab-
lished. The following appear to be most probable: For each 100 living-born, with
a sex-ratio of 105.5, there occur in the eighth to the tenth month 4 still-births with
a sex ratio of 130; in the fifth to the seventh month 7 abortions with a sex-ratio
of 106; in the fourth month 2 abortions with a sex-ratio of 120; and from con-
ception to the end of the third month 15 abortions with a sex-ratio of 125. This
makes altogether 28 abortions and still-births to every 100 living-born; 7.e., 100
living-born to every 128 fertilized ova." The primary sex-ratio found from these
averages by simple mathematical operations is 108.74. The writer’s last calcula-
tion of the primary sex-ratio (1918) resulted in 108.47. The very small increase
in the corresponding value of the present study serves as a confirmation of the
previous finding. The sex-ratio at conception was estimated by Bernoulli as 108.2.
Slightly higher (108.7) is the ratio computed by Jendrassik (1911) from statistics
collected by Bodio. Both of these figures are strikingly similar to that of the
author. Lenhossék (1903) estimates the primary sex-ratio as 111, Auerbach as
116.4, but the latter believes that it would reach at least 125 if corrections were
made.

Even if these approximate averages, which will become more exact only when
based upon more extensive, careful statistics, must be accepted cwm grano salis,
it may nevertheless be stated with certainty that more males (not exceeding
10 per cent) are conceived; that at certain periods of pregnancy the relative mor-
tality of males exceeds that of females by as much as one fourth or more; and that
this, in connection with the very high intrauterine mortality, especially at the
beginning of pregnancy, serves to lower the primary sex-ratio considerably through-
out prenatal life.

DETERMINATION AND CHANGES OF THE PRIMARY SEX-RATIO.

The question now arises as to what determines the sexes and their unequal
distribution at conception. Its discussion dates back into antiquity; since Aris-
totle, philosophers and physiologists searched in vain for the key to this problem.
The most fantastic theories were advanced, one of the oldest being that sex is
correlated respectively with the right or left ovary or testicle (Hippocrates, Galen).
In recent times much work has been done in trying to solve this problem. Among
the most interesting theories stands the idea of the possibility of two distinct
varieties of spermatozoa. Wilson (1905) distinguishes between male-producing
and female-producing spermatozoa. This might lead to an unequal distribution
of sexes at conception. Morgan (1913) suggested that it may be due to a difference

1 The relative number of fertilized ova, estimated by Rauber to be 100 to 76 living-born or, calculated as above,
131.6 to 100 living-born, is somewhat larger than that obtained by the author.

186 STUDIES ON PATHOLOGIC OVA.

in the rate of travel of the two types of sperm, or that a disease process, or a factor
such as alcoholism, might affect one type to a greater degree than the other.
Hertwig (1912) attributes sex determination to the ovum or the degree of its
maturation, an advanced stage of maturation producing males. In this way he
attempts to explain the difference in sex-ratio according to social class. Thury
(1863) proposed the idea that ova which are fertilized late may produce more
males. Thus he explained the high sex-ratio among Jews who, on religious grounds,
refrain from intercourse for 7 days following menstruation. Here may also be
mentioned the recent investigations by Siegel on the relation of menstruation to.
sex, according to which coitus from the first to the eighth day after menstruation
yields 86 per cent males; from the ninth to the fifteenth day it results in 65 per
cent females; from the sixteenth to the twenty-second day, 85 per cent of con-
ceptions are females, and in the remaining premenstrual period woman is prac-
tically sterile. Pryl and Jaeger, working independently, have confirmed Siegel’s
observations.’ These findings contradict, in a way, those of Hertwig and Thury.
Lorenz (1898), Lenhossék (1903), and Orschansky (1903) are of the opinion
that sex is sujbect to hereditary influences, inasmuch as they found families in
which males predominated and those in which females appeared in excessive
numbers. Newcomb (1904), Woods (1906), and Heron (1906) deny this and show
that inheritance plays no part in the sex-ratio. Numerous authors attribute its
variation to the absolute and relative ages of the parents. According to Rosenfeld
(1900), there is a decided preponderance of male children born to young and old
fathers, as compared with those of middle age. Francke, from the statistics of
Norway, found this to be true in respect to young fathers, but reached an opposite
conclusion as regards old ones. Dumont (1894) found for Paris a sex-ratio of
101.9 when the fathers were from 18 to 25 years, 104.2 when the fathers were
between 25 and 50 years, and 97.5 when they were over 51 years. According to
E. Bidder (1878), the sex-ratio of births by mothers under 18 and over 40 years
is especially high, and Specht (1916) reports that the large majority of births
by mothers under 16 years are male. Sadler (1830) stated that the relative ages of
the parents determine the sex-ratio. The latter is 86.5 when the father is younger
than the mother, 94.8 when both are of equal age, and reaches 163.2 when the
father’s age exceeds that of the mother by 16 or more years. Kollman (1890) ob-
tained an opposite result, drawing the conclusion, which was based on extensive
material, that the sex-ratio is high when the father is younger and low when he is
older than the mother. At the same time he opposes the view that the absolute
age of the mother has any influence whatever upon sex-ratio. Stieda, on the basis
of his investigations, came to the conclusion that any influence on the part of the ab-
solute ages of the parents is out of the question, as he noted the highest sex-ratio
when the parents were of equal age. Numerous other authors have occupied
themselves with the question of parental age as an influence upon sex-ratio, but
only two additional ones will be mentioned, Boudin (1862) and Stadler (1878).
The conflicting views which have been presented suffice to show that nothing

‘These papers could not be obtained by the author, but are discussed by Nilsson.

SEX-INCIDENCE IN ABORTIONS. 187

definite is known concerning a correlation between the age of the parents and sex
determination; in fact, such a correlation is hardly to be expected.

Pear] (1908), in a very careful study, demonstrated that there are more males
produced when the parents are of different racial stock. The same effect of hy-
bridization on the sex-ratio has been found by King (1911) for rats and by Guyer
(1903) for birds. The well-known assertion that the sex-ratio rises after wars
has evoked various attempts at explanation. The following few examples show
best how little the different authors agree on this improbable relation. Ploss
(1858, 1861) ascribes it to malnutrition of the mothers. Berner (1883) believes
it to be due to the decreased competition which follows wars and which brings
about an increased prosperity. Diising sees the cause in the increased sexual
demands upon the male, which is also said to increase the sex-ratio in polygamy.
According to Newcomb, following the American Civil War of 1861-65 no increase
in sex-ratio was observed. Nichols found no effect of war upon the sex-ratio in
France from 1806 to 1872. On the other hand, Henneberg (1897) claims to have
found such an influence; he reported that in Holstein, between 1835 and 1845,
the sex-ratio was 105.76, and after the period of the war, from 1846 to 1853, it
was 106.67. In the few cases where such a difference was confirmed, it was so
slight as not to exceed the normal variations of the secondary sex-ratio (it is in
the latter that any difference would be found) and therefore is to be considered
as such. These natural variations were shown by Lehr (1889), Carlberg, Nichols,
and others; they may be very considerable, as reported by von Winckel (1903),
according to whom the sex-ratic of new-born in Berlin showed extremes in a
period of 100 years of 104.79 and 100.64. Variations of sex-ratio have been de-
termined not only for individual years and groups of years, but also for the seasons.
According to Goehlert (1889), in autumn and winter relatively few conceptions
take place, but of these a higher percentage is male. The same conclusion was
reached by Sormani (1883). Inasmuch as the studies of these authors were based
upon statistics of births, without consideration of the relative frequency of abor-
tions, their conclusions in regard to the sex-ratio at conception must be treated
with caution.

CHANGES IN THE SECONDARY SEX-RATIO.

The primary sex-ratio, as shown above, becomes transformed by an unequal
intrauterine mortality of the two sexes into a different secondary ratio, and it is
obvious, from a mathematical consideration, that the greater the proportion of
abortions and still-births the lower will be the sex-ratio of living-born. Attempts
have been made by a number of authors to explain the great mortality of males
during certain periods of prenatal life. Carvallo simply says “les garcons sont plus
fragiles”; Auerbach, also, considers the male fetus less resistant. Grassl (1912)
gives as an explanation the supposition of a difference in the viability of the germ
plasma. Jendrassik speaks of hereditary reduction of vitality among the excess
of males. Ewart (1918) suggested that “‘it is possible—here, of course, we have
no data—that the female conception may graft itself on the lining membrane of

188 STUDIES ON PATHOLOGIC OVA.

the uterus more easily than the male.”’ Rauber explains the greater mortality of
males by the greater demands of the larger fetuses upon the mother, the latter not
always being able to meet them; the production of a female does not require
as much from the mother. Lillie (1917) offers the suggestion that the greater
mortality among male fetuses is a result of disturbance of the equilibrium that
protects the male from the sex hormones of the mother. These are all more or
less plausible hypotheses lacking in proofs. As to any real understanding of the
unquestionably higher mortality of male fetuses we are still at a loss; attention
may be called, however, to the fact that this sexual difference in vitality and power
of resistance against disease is not restricted to the period of intrauterine life, but
is found also in the first few years of postnatal life, at which time occupation,
child-bearing, and other factors can not be held responsible for the difference
between the male and female death-rate.

The excess of male still-births is ascribed by most authors to the more diffi-
cult labor attendant upon the greater size of the male,’ especially the circumference
of the head. Dutton (1910) is of the opinion that at the time of birth the bones
of the male skull are, as a rule, more firmly ossified than those of the female. He
states also that with the advance of civilization the pelvic development in women
is not proportionate to the cephalic development in infants. This perhaps explains
the conclusion reached by Bluhm (1912), that the relative number of therapeuti-
cally induced premature births is increasing. That labor in case of male children
more often demands artificial aid from the obstetrician than in case of females
is shown by Prinzing, according to whom 6.18 per cent of male births in Wiirttem-
berg called for operative measures, as compared with 4.67 per cent of the female
births. This, however, is not due alone to the greater size of the male infant.
Von Winckel found that in 566 new-born infants of over 4,000 grams weight
operative aid was necessary in only 3 per cent more cases than in births of lighter
babies. Furthermore, the more difficult labor of the larger male child can not in
itself be held responsible for the high sex-ratio of still-born infants, inasmuch as,
according to Treichler (1895), 29.6 per cent, and, according to Prinzing (1907),
32.6 per cent, of all still-births are premature, and in the sex ratio of these size
plays but little part. According to Ladame (1904), in Switzerland the number
dying during labor constituted only 36.4 per cent of the total still-births. Finally,
Von Winckel found that the death-rate among 1,000 new-born of over 4,000 grams
weight was only 4.17 per cent.

Sex-ratio has frequently been studied in relation to the pelvic diameters
of the mother. The results are somewhat conflicting. Hoffmann (1887), Dohrn
(1888), and Orschansky (1894) may be mentioned, according to whom the sex-
ratio in children of mothers with narrow pelves is low. In contrast to this, Linden
(1884) states it to be 133 in 360 births in which the mothers had narrow pelves.
In case the size of the pelvis really has an influence, this can be exerted only upon
the secondary sex-ratio in the way of elimination. In the same manner it seems
evident that many of the factors which apparently affect the sex-ratio do not

* Von Winckel found among 1,000 new-born, of over 4,000 grams weight and 52 cm. length, a sex-ratio of 226.

SEX-INCIDENCE IN ABORTIONS. 189

influence it at the time of conception; that is to say, they do not have any sex-
determining effect, but by their influence upon intrauterine mortality they change
only the sex-ratio of the living-born. The well-known fact that the secondary
sex-ratio among Jews is relatively high is explained by Diising on the ground of
incest, blood marriages being of frequent occurrence in that race. Schultze (1903),
on the other hand, concluded that inbreeding has no effect upon sex determination
and the same conclusion was reached by King (1918). Diising, in his conclusions,
failed to make a distinction between the sex-ratio at birth and that at conception;
the latter is probably not different in Jews from what it is in other white races,
but changes less by reason of the relatively fewer abortions and still-births among
Jews, resulting in a higher secondary sex-ratio. The relative infrequency of abor-
tions among Jews has been shown, for instance, by Auerbach. One finds frequently
the assumption that the negro produces fewer sons than other races—another
conclusion drawn from statistics of the new-born alone. Nichols pointed out that
in the District of Columbia still-births and abortions among the colored popula-
tion amount to 13.8 per cent of the living-born, whereas in the white it is only 6.5
per cent. This difference is responsible for the different secondary sex-ratios of
the two races (103.1 in negroes and 106.2 in whites). Punnett (1903) and others
have shown that the births among classes of lower social status present a lower
sex-ratio than those of the rich. The explanation lies again in the fact that the
greater frequency of abortions among women of the working classes, who can spare
themselves less during pregnancy and in whom pregnancies occur in more rapid
succession, results in a corresponding reduction in the sex-ratio, which probably
was originally equal in the two classes. In addition, this greater reduction of the
primary sex-ratio in the poorer classes is due to their higher percentage of still-
births. According to Conrad in Halle, among laborers it was 5 per cent, while
among the upper classes it was only 2.1 per cent; and according to Verrijn Stuart
(1901), in Holland, among the poor, it was 3.16 per cent and among the rich 2.5
per cent of all births.

A further example illustrating how the primary sex-ratio was erroneously
thought to be influenced is shown in its difference in legitimate and illegitimate
children. Heape (1909) states that the sex-ratio of legitimate births among the
white population of Cuba is 109.0, still-births included; that of the illegitimate
only 105.95. There is even a greater difference among negroes, the sex-ratio being
97.91 for illegitimate children and 107.73 for legitimate ones. Heape immediately
draws the conclusion that illegitimate unions result more often in the conception
of females than do legitimate ones. According to Diising, the sex-ratio of legitimate
births in Prussia, between the years 1875 and 1887, was 106.37; that of illegitimate
only 105.54. The still-births in legitimate unions amounted to 3.91 per cent, in
illegitimate ones to 5.32 per cent. A corresponding difference was demonstrated
by Bertillon (1896) in the frequency of legitimate and illegitimate abortions. The
greater mortality of illegitimate fetuses reduced the sex-ratio to a greater degree.
The rule that the sex-ratio is greater in legitimate than in illegitimate births is

1 According to Dusing (1884), the longer the intervals between births the higher is the sex-ratio.

190 STUDIES ON PATHOLOGIC OVA.

not, however, without exceptions. Srdinko (1907) found that the sex-ratio of
legitimate births in Austria was lower than that of the illegitimate, and explains
this by the fact that the illegitimate are for the most part Jewish, in which race
abortions are less frequent. Further exceptions are reported by Nichols in the
case of England and Scotland. According to the last-mentioned author, there is
an especially high sex-ratio in legitimate births as compared with illegitimate ones
in Rhode Island (104.7 to 98.8), Portugal (107.1 to 100.5), and Greece (114.0 to
96.9). He, too, found a greater frequency of still-births and abortions in illegiti-
mate pregnancies. Obviously, in such cases there is more concealment and con-
sequently still less complete statistics are available than in the case of legitimate
pregnancies ending in abortion.

According to a number of authors, the sex-ratio of first-born is greater than
that of subsequent births, as demonstrated, for instance, in a table by Newcomb
(1904). Lewis and Lewis (1906) report that in Scotland the sex-ratio of the first-
born was 105.4, and that of subsequent births 104.8. The secondary sex-ratio is
especially high as regards older primiparae, as shown by Ahlfeld (1872, 1876),
Janke (1888), and Bidder (1893). That this is also due, in part at least, to different
intrauterine mortality may be supported by the citation from Franz that abortions
are more than twice as frequent in multipare as in primipare. Moreover, the
first-born children are appreciably smaller than subsequent ones, as demonstrated
by Schaetzel (1893)’ and others, a condition which might suggest a lower rate of
mortality during labor. According to Duncan and Duke (1917), however, still-
births are more frequent among first-born than among second and third-born, in
spite of their smaller size; only in the case of children from the sixth pregnancy
does the percentage of still-births exceed the one of the first-born. However,
inasmuch as abortions are much more frequent than still-births, comparatively
little importance can be attached to this. The number of children in a family has
also been correlated with the sex-ratio; Geissler (1889) found that in families with
seven or more children there is a greater proportion of sons than in families with
2 to 7 children. Punnett (1903) reached just the opposite conclusion. The former
result was confirmed by several other observers (von Kérésy, Janke, and Nichols);
Nichols considers it very probable that in large families the higher proportion of
sons is due to a smaller number of abortions, leaving a larger number of children
to be born alive, and thus their sex-ratio more closely approaches the primary
sex-ratio.

Besides the above-mentioned causes for the variations found in sex-ratio,
many more have been discussed in the literature in an effort to throw light on the
question of sex determination. Only a few, if any, of these factors actually exert
any influence upon the primary sex-ratio. The changes have all been found in the
secondary sex-ratio and the probability is great that the factors causing them
affected only the intrauterine death-rate. This is especially true in regard to

? Hansen (1913) reports that in Denmark the first born weigh on an average 3,457 grams; the second born 3,607
grams; the third born 3,698 grams, the difference between the first and second being much greater than between subsequent
ones. The figures for weight at birth, given by Heiberg (1911), show an analogous relation.

SEX-INCIDENCE IN ABORTIONS. 191

changes resulting from locality, from age, nutrition, and health of the mother.
Sormani (1883) reported that in Italy the sex-ratio of births in urban districts was
104.9 and in rural districts 107.0. Nichols, in contrast to this, states that in Paris
the sex-ratio of new-born was 103.7 and in the remainder of France 104.3; while
in Paris the mortality in utero was 7.7 per cent of births, in other parts of France
only 4.4 per cent. In regard to the alleged influence exerted by the age of the
mother on the sex-ratio of her children, the finding of Dempsey (1919) may serve
as proof that this influence does not concern the primary sex-ratio. This author
finds that still-births in women of 30 years of age and over were more than four
times as numerous as in women under 30.

To briefly sum up the results of this study, the author believes he has succeeded
in correcting two errors frequently found in the literature:

First, that the relation of the sexes at conception does not, as frequently
stated, show an extremely high preponderance of males, but a surplus of 10 per
cent at most.

Second, that a great number of factors claimed to influence the sex-ratio at
conception, if playing any réle at all, are only sex-eliminating during intra-
uterine life and have no effect upon sex determination.

Further results of interest are the marked fluctuations in the sex-incidence
of abortions and still-births in different periods of development and also the great
changes in the death-rate during intrauterine life. These facts may serve as a help-
ful guide in the search for the cause of the greater mortality among male fetuses.”

1 Schenk (1898) asserts that diabetic mothers bear more female than male children.
1 This is not restricted to man, but has been found also for the rat. (King, 1921.)

ned
»

CHAPTER VII.

THE OCCURRENCE OF LOCALIZED ANOMALIES IN HUMAN
EMBRYOS AND FETUSES.

In a paper on the causes underlying the origin of human monsters (Mall,
1908), I made the assertion that localized anomalies were more common in embryos
obtained from abortions than in full-term fetuses, without, however, adducing
conclusive evidence in support of this theory.

In a footnote on page 27 of that publication I gave a list of embryos with their
chief defects, comparing them with the percentage of frequency of monsters
born at term. Objection might be raised to such a statement on the ground that
there is not a complete correspondence between anomalies in the embryo and
those found in the fetus at the end of pregnancy. For instance, spina bifida in
young embryos is always complete, while at full term the open canal is covered
over with skin. Cyclopia and exomphaly are the same in the embryo as at birth,
but the deformities of the head and neck of the embryo are of such a nature that
it can not survive long enough to admit of comparison with similar malformations
found at term. With these difficulties clearly before me, I have made an effort to
sharply define the anomalies in embryos, so that a satisfactory comparison might
be made with those found in monsters at the end of pregnancy, as described in the
literature.

Cyclopia is, perhaps, the type of anomaly which is now best understood, due
largely to the excellent experimental work of Stockard, and also partly to the fact
that the cyclopean state can exist quite independently of other marked deformities.
I have already discussed the question of cyclopia in a separate publication (Mall,
1917*), and it is not therefore necessary for me to dilate further upon it at present.
Hare-lip is also sharply defined in the embryo and is as readily distinguished as
exomphaly. Other anomalies, however, are more difficult to recognize in the
embryo as sharply defined malformations.

The pathological specimens of the first 400 accessions to our pallection were
reported in my paper on the origin of human monsters mentioned above. Since the
embryological collection has been taken over by the Carnegie Institution of Wash-
ington it has grown at a very rapid rate, about 400 specimens being added to it
each year. At present, however, only the first 1,000 will be considered, the re-
mainder not having been sufficiently tabulated to be of statistical value. The
specimens can clearly be divided into two groups according to their origin, 2. e.,
uterine and ectopic. In both of these the embryos which are normal in form are
catalogued according to their sitting height, which we call crown-rump (CR). The
chief difficulty, however, is to determine what constitutes a normal embryo, and
here we must rely largely upon our experience in human and comparative embry-
ology. A sharply defined, well-formed, white embryo, with blood-vessels shining
through its transparent tissues, is considered normal. If it is partly stunted and
opaque or disintegrating it is considered pathological. A further study of the

193

194 STUDIES ON PATHOLOGIC OVA.

so-called normal embryos, however, shows that in many of them the membranes
are decidedly pathological. For instance, the villi may be deformed, diseased,
atrophic or hypertrophic, or the contents of the amnion and the exocceelom may
be unusual. Nevertheless, in all of these cases we still classify the embryos as
normal, although fully cognizant of the fact that the surrounding membranes are
pathological; otherwise it would be difficult to account for the great number of
spontaneous abortions. The theory is that the embryo was developed under
pathological conditions, but that the chorion was not sufficiently affected to cause
any apparent change in the embryo. If an embryo included in this group is ap-
parently normal in all respects save one, we still consider it normal with a localized
anomaly. In fact, we are gradually forced into this position, as an embryo, at
first regarded as normal, may later prove to have a localized anomaly, such as
spina bifida or cyclopia. As far as we can determine, such an embryo would have
been able to survive longer had not something happened to its membranes, thus
causing its expulsion. I am inclined to believe that pregnancies of this sort, if
carried to term, would produce the ordinary monsters described by teratologists.

The second group of specimens, which are termed pathological, are in a way
more interesting, and their study justifies our method of classifying localized
anomalies with normal embryos. We have in this group a variety of changes
ranging from those found in fetus compressus down to complete disintegration of
the ovum, leaving only a few villi.

Having made numerous efforts to classify these specimens, I have finally
resolved them into seven groups, which have been considered in a previous chapter.
It can be readily seen that this classification into sub-groups is arranged some-
what in the order of the age of the ovum when it began to degenerate. Gener-
ally the changes are so pronounced that the embryo could not have lived through
the duration of pregnancy, and this accounts for the abortion.

We naturally do not find localized anomalies in specimens from the first four
groups, while in the remaining three groups we encounter only such as are very
pronounced and stand out clearly in spite of other changes. Thus, for instance,
with fetus compressus we frequently recognize club-foot; in stunted forms, hare-lip
and spina bifida; and in cylindrical forms, spina bifida. If eyclopia is encountered
in any of these forms, it is looked upon as a localized anomaly in a pathological
embryo. On the other hand, a single anomaly in an embryo called normal can
easily be recognized, and it is from this group that we should expect the develop-
ment of monsters had the pregnancy progressed to term.

A few illustrations of localized anomalies are given here in order to show that
they are identical with those found in infants at birth. Figures 83 and 84 represent,
respectively, a cyclopean and a double monster, the embryos being otherwise
normal. Figures 85 and 86 show hare-lip in an embryo and a fetus. Figures 87,
88, and 89 have pronounced localized anomalies and need no further explanation.
Finally, figures 90 to 93 show anomalies of the hands. The first and last are of the
hereditary variety, while figures 91 and 92 are acquired anomalies—that is, they
were subsequently formed in an embryo whose development began normally.

OCCURRENCE OF LOCALIZED ANOMALIES. 195

It is proper to remark here that these illustrations are mostly from specimens
from the second 1,000 of our collection. This is because we have recently made
many more photographs, and, furthermore, many of the specimens in the first
thousand have already been figured in my paper on monsters.

In order to render possible a comparison between localized anomalies found
in pathological, and those found in normal embryos, six tables have been con-
structed. Table 7 gives the classified distribution of the first 1,000 embryos in the
Carnegie Collection. The primary division comprises two classes—pathological and
normal. The pathological specimens in turn are arranged in the seven groups just
described. The normal are arranged in groups to correspond as nearly as possible
to the ages of the embryos in lunar-months. In order to define clearly which
embryos belong in a given month, I have inserted their probable lengths for each
month in table 12. Thus, for instance, the second month includes all specimens
from 2.6 mm. to 25 mm. in length, ete. (Data upon the estimated ages of embryos
may be found in my chapter on that subject in the Manual of Human Embryology,
vol. 1.)

TABLE 7.—Showing the distribution of first 1,000 accessions.
Pathological, in groups. Normal, in months.

Cen- | Catalogue
tury. No.

lto 98

99 to 205
206 to 295
296 to 380
381 to 476
A477 to 571
572 to 652c
652d to 729
730 to 8165
817 to 900g

1
2
3
4
5
6
7
8
9
0

i

to
oO
o

It will be noted in these tables that the specimens are arranged in centuries;
that is, each line in the table includes exactly 100 specimens. The first century
includes specimens Nos. 1 to 98, the second, Nos. 99 to 205, and so on. ‘This
adjustment was necessary for the reason that frequently a single number is given
to 2 or more specimens. Sometimes the first is called a and the second }; or the
first may be given the number and the second the letter a, ete. The second century,
passing from Nos. 99 to 205, includes more than 100 numbers, because specimens
which are given a number are frequently found upon further examination to contain
no remnants of an ovum, and for this reason they have to be discarded. In our
catalogue they are later marked as ‘‘No pregnancy.”’ Finally, the tenth century
ends with embryo No. 900g. The individual entries are percentage records. Thus
in the fifth century there are 41 normal specimens of the second month; that is,
of this hundred specimens 41 per cent are normal embryos of the second month,
whereas the total for the full 1,000 has brought down this percentage to 24.5.

196 STUDIES ON PATHOLOGIC OVA.

In determining normality, the criterion used was the shape of the embryo,
judging this as best we could by our own knowledge of human and comparative
embryology, as well as by the experience of other students of human embryology.
We have also used freely the atlases of His, Hochstetter, and Keibel and Else in
making our decisions on this point. However, many of these specimens are inclosed
in membranes which have undergone very marked changes. Thus, an embryo
normal in form may be found to be surrounded by an excessive amount of magma
and the chorion may have undergone very pronounced changes; but for purposes

TaBLe 8.—Distribution of uterine specimens.

Pathological, in groups. Normal, in months.

Cen- | Catalogue
tury. No.

lto 98
99 to 205
206 to 295
296 to 380
381 to 476
477 to 571
572 to 652¢
652d to 729
730 to 816b
817 to 900g

o
a

Catalogue
No.

lto 98
99 to 205
206 to 295
296 to 380
381 to 476
417 to 571
572 to 652c
652d to 729
730 to 816b
817 to 900g

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of classification we have found it necessary to arrange them all according to the
shape of the embryo. A fairly large number of our specimens were obtained from
hysterectomies. We believe with Hochstetter that we shall ultimately have to
determine what constitutes a normally formed human embryo from specimens
obtained in this way; but among about 25 hysterectomy specimens, we never-
theless found 3 which were markedly pathological and undergoing abortion.
Table 8 includes all uterine and table 9 all ectopic specimens. In comparing
these three tables it will at once be noted that among the entire 1,000 nearly 40
per cent are pathological embryos and ova. Of this number 31 per cent were

OCCURRENCE OF LOCALIZED ANOMALIES. 197

obtained from the uterus, while slightly more than 8 per cent were ectopic. The
comparative frequency of pathological and normal embryos can be ascertained,
however, by comparing them within a given century, or for the whole 1,000 to-
gether. In the uterine specimens about one-third of the ova and embryos are
pathological, as compared to two-thirds in the ectopic. In other words, patho-
logical specimens are twice as frequent in ectopic as in uterine pregnancy.

Table 10 includes all the specimens in which there are pronounced localized
anomalies. The character of the anomaly for the individual specimens recorded
is given in tables 11 and 12. From these tables it would appear that there are
about as many anomalies among the normal as among the pathological specimens,
but when these figures are compared with the total number of specimens, both
normal and pathological, it becomes evident that localized anomalies occur about
twice as frequently in the pathological as in the normal embryo. Thus, 38 out of

TaBLE 10.—Distribution of specimens with localized anomalies (to be compared with table 7).

Pathological, in groups. Normal, in months.

Cen- | Catalogue
tury. No.

206 to 295
296 to 380
381 to 476
477 to 571
572 to 652¢
652d to 729
730 to 816b
817 to 900g

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396 pathological specimens, or about 10 per cent, exhibit localized anomalies, as
against 6 per cent in 604 normal specimens. The 38 pathological specimens with
localized anomalies listed in table 10 were aborted in the early part of pregnancy,
and only one of them (No. 649) grew to a sitting height of 90 mm., that is, to
about the middle of the fourth month.

The number of normal embryos with localized anomalies tends to decrease
before the fifth month, there being but 1 in the sixth, 1 in the eighth, and 4 in the
tenth month, the end of pregnancy. In other words, all pathological specimens,
either with or without localized anomalies, are aborted in the first half of pregnancy,
as are also nearly all so-called normal embryos with slight malformations, very
few of them reaching full term.

We have made an especial effort to collect specimens of full-term monsters
as well as abortion material from all months of pregnancy. Only the first 100
specimens of the collection show an unusually large percentage of normal embryos.
Although at first an effort was made to collect only good, normal specimens, the
last 900, including all sorts of material, carry about the same percentage of
normal specimens throughout. Among the first 1,000 specimens of our collection
there are not many fetuses from the second half of pregnancy, but we are now

198 STUDIES ON PATHOLOGIC OVA.

endeavoring to collect material covering all months. One monster at term, a
sympus belonging in about the third 100, was not recorded in our catalogue, and
should be added to the four full-term specimens given in table 10. This means that
among 1,001 specimens there were 5 full-term monsters, while among 1,000 speci-
mens there were 71 with localized anomalies, most of them being aborted early
in pregnancy.

TABLE 11.—Localized anomalies in pathological embryos.

Length Men- " henegh ee : ae
Cata- of |Dimensions| strual T ata- ° imensions| strua
a x ype of - ri Type of
a Ma pp ata 88° | localized anomaly. aue pte cae “ne | localized anomaly.
in mm. days. in mm. days.
Group 5, cylindrical embryos. Group 6, stunted embryos.—Continued.
785 2 15X12X10} 64 | Spina bifida. 124 35 90X75X50]...... Club-foot and hand.
8745 3 353020) 80 | Hydrocephalus. 797 35 65X35X35)...... Club-foot and hand.
189 4 2EX2b 1G). ss Spina bifida. 649 O00 Meee ee ralles erm Spina bifida; exompha-
228 4 60 25X25) 99 | Hydrocephalus. ly; without radii and
302 4 252016153 so. Hydrocephalus. without thumbs.
466 4 29X23X16)]...... Spina bifida.
328 28 Sooo Soos Boone Hydrocephalus. : Group 7, macerated and fetus compressus.
842 Oe ea ras cae Actes Eye detached from brain: || 2 = Bose Sk ee ee
753 ll 80X50X35]...... Amyelia; ectopiaofheart. a .
710 13 95X55X55| 228 | Amyelia. 182 Eo aaosousens ooarc Hed dees: spina
365 a dersping 4 oeinac Een ceE nae spina bi- 802 6 19X26X16|...... apiennentnies
: 212 1 Dg tee er hee Head atrophic.
732 TD* (Fsbo Stee 88 | Exomphaly.
Group 6, stunted embryos. 94 OP ANS. acceso ced ters ete Spina bifida.
226 24 606030} 87 | Anencephaly; spina bi-
433a 3 27X25X15| 49 | Hydrocephalus. fida.
413 5 35X35]...... Spina bifida. 65la | 27° |7OXK45X465)...... Spina bifida.
510 10 60X45}...... Spina bifida. 868 BOL Wilt Acele ats 193 | Club-foot.
338¢ RE) Weicte noerscacste 35 | Spina bifida. 316 pT ee RAR eae Heer Club hand and foot;
276 13.5 |70X35X35|} 80 | Anencephaly. hand adherent to head;
81 15 65X55X35)...... Anencephaly. skin nodules.
344 16 45X45X45)...... Rounded head; club-leg.|| 627 45 80X50X35]...... Club hand and foot.
364 16 90 50X40} 89 | Exencephaly; hare lip;|| 740 BS: ail cen eee ee Club-foot.
exomphaly; spina bi-|| 230 57 75X60X50)...... Club hands and feet.
fida. 622 ZOE ucareratetele lee etesnte re Club-foot.
499 17 45X45X40)...... Hare-lip; spina bifida. 646 85 90X60X50}...... Exencephaly.
201 20 80X60X50]...... Cyclopia.

According to the table on the frequency of abortions, given in my monograph
on monsters (Mall, 1908), there are 20 abortions to every 80 full-term births;
therefore, the 1,000 abortions under consideration were probably derived from
5,000 pregnancies.

As we have calculated that there should be approximately 30 full-term mon-
sters in 5,000 pregnancies, and as 5 of these were observed in our 1,000 specimens,
it is apparent that the remaining 25 should be encountered in 4,000 additional
full-term births. When these figures are considered in connection with the fact
that 75 localized anomalies occurred in 1,000 abortions (7.5 per cent) it becomes
apparent that in any similar numbers of abortions localized anomalies should
occur twelve times as frequently as monsters at term. A similar result is obtained
if the number of localized anomalies of the tenth month, as given in table 10, is

compared with all of the localized anomalies of previous months, as given in the
same table.

OCCURRENCE OF LOCALIZED ANOMALIES. 199

Our studies seem to justify the conclusion that pathological embryos, as well
as those which are normal in form, are very frequently associated with localized
anomalies and that abortion usually follows as a result of serious lesions in the
chorion, as well as in its environment. Should the alterations in the embryo and
in the chorion be very slight and the condition of the uterine mucous membrane,

TaB1e 12.—Localized anomalies in normal embryos.

Length Men- Length Men-
Cata- of |Dimensions} strual Cata- of |Dimensions} strual
logue | speci- | of chorion| age logue | speci- | of chorion| age
No. men in mm. in No. men in mm.
in mm. days. in mm.

Type of
localized anomaly.

Type of
localized anomaly.

1 month, 0 to 2.6 mm. 4 months, 69 to 121 mm.

10X 9X 8 Cytolysis. 768c | 80 Stub coccyx.

18X18X18} 41 | Anencephaly; spina bi- || 768) 85 Left forearm and hand
fida. lacking.

306a | 100 Only 2 fingers on right

2 months, 2.6 to 25 mm. hand.
295 110 Rounded head, thick-

.78|16X 14X12 Spina bifida. ened scalp.

.5 |17X17X10 Spina bifida.

.5 |25X20X15 Anomalous tracheal di- 5 months, 122 to 167 mm.
verticulum.

Hydrocephalus. No specimens.

Spina bifida.
24X18X 8 Deformed tail.
40X 28X28 Spina bifida.
35X 20X17 Spina bifida.
30X 20X15 Leg hypertrophic; head || 335 | 190 | Seperate eae | Beans Anencephaly.

atrophic.

Hydrocephalus. =

Spina bifida. 7 months, 211 to 245 mm.
20X 15X12 Cyclopia. =
38X32X32 Spina bifida. No specimens.

Constricted cord.

Spina bifida. 8 months, 246 to 284 mm.
50X50 70 Double monster.
50 50X70 Double monster. 5 5
40X40 40 Cyst of spinal cord. 558 | 250 | So soe eg | wrolotayere | Spina bifida.

Hernia of liver.

Hernia of liver.

eaanienead! 9 months, 285 to 316 mm.

Hernia of liver.

6 months, 168 to 210 mm.

No specimens.

3 months, 26 to 68 mm.
10 months, 317 to 336 mm.

Double monster.

Double monster. 370 Enormous tail.

Extremities deformed; || 862 i Ectopia of bladder.
left radius probably || 862a i Spina bifida.
absent; head atrophic.|| 8626 i Stunted eyes.

which may be expressed by the term inflammation, be overcome, the pregnancy
in all probability would go to term and end in the birth of a monster or an infant
presenting a well-recognized malformation.

I have already pointed out the difference in frequency of malformations and
destructive changes, as observed in the ovum, in tubal and in uterine pregnancies.
Since the publication of my monograph on monsters I have reconsidered the ques-
tion of tubal pregnancy and the specimens mentioned in the present paper are
recorded in detail in a volume on tubal pregnancy (Mall, 1915).

200 STUDIES ON PATHOLOGIC OVA.

It seems to me that the studies based upon our collection, as well as recent
investigations in experimental embryology, set at rest for all time the question
of the causation of monsters. It has been my aim to demonstrate that the em-
bryos found in pathological human ova and those obtained experimentally in
animals are not merely analogous or similar, but identical. A double-monster fish
or a cyclopean fish is identical with the same condition in human beings. Monsters
are produced by external influences acting upon the ovum; as, for instance, varnish-
ing the shell of a hen’s egg or changing its temperature, traumatic and mechanical
agencies, magnetic and electrical influences, as well as alteration of the character
of the surrounding gases, or the injection of poisons into the white of an egg. In
aquatic animals monsters may be produced by similar methods. Whether in the
end all malformations are brought about by some simple mechanism, such, for
instance, as alteration in the amount of oxygen or some other gas, remains to be
demonstrated. The specimens under consideration show such marked primary
changes in the villi of the chorion and in the surrounding decidua that the con-
ditions in the human may be considered equivalent or practically identical with
those created artificially in the production of abnormal development in animals.

It would be quite simple to conclude that the poisons produced by an inflamed
uterus should be viewed as the sole cause, but when it is recalled that pathological
ova occur far more commonly in tubal than in uterine pregnancy, such a theory
becomes untenable. Moreover, monsters are frequently observed in swine and
other animals without any indication of an inflammatory environment. For this
reason I have sought the primary factor in a condition buried in the non-committal
term, faulty implantation. It would seem to be apparent that lesions occurring in
the chorion as the result of faulty implantation can and must be reflected in the
embryo. For example, before circulation has developed in a human embryo,
pabulum passes from the chorion to the embryo directly through the exoccelom,
and probably on this account we always encounter, as a first indication of patho-
logical development, a change in the magma. In older specimens, before any other
changes are noticeable in the ovum, the magma becomes markedly increased and
a variety of changes are found between the villi. I shall not dwell further upon
magma, as I have already dealt with the subject in detail (Mall, 1916).

It is perfectly clear that, in general, monsters are not due to germinal or
hereditary causes, but are produced from normal embryos by influences which are
to be sought in their environment. Consequently, if these influences are carried
to the embryo by means of fluids which reach it either before or after the circulation
has become established, it would not be very far amiss to attribute these condi-
tions to alterations in the nutrition of the embryo. Probably it would be more
nearly correct to state that change in environment has affected the metabolism
of the egg. Kellicott (1916), who has discussed this question, seems to be dis-
inclined to accept such an explanation, but I do not see that he has added materially
to it by substituting the word disorganization for nutrition, as one might as easily
say that the altered nutrition causes the disorganization.

OCCURRENCE OF LOCALIZED ANOMALIES. 201

In my paper on monsters I stated that on account of faulty implantation of
the chorion the nutrition of the embryo is affected, so that if the ovum is very
young the entire embryo is soon destroyed, leaving only the umbilical vesicle
within the chorion; this also soon disintegrates, and the chorionic membrane in
turn collapses, breaks down, and finally disappears entirely. In older specimens,
on the other hand, the process of destruction takes place more slowly, and thus
we many account for a succession of phenomena which correspond to the seven
groups of pathological ova referred to above.

Kellicott, in his discussion of monsters, dropped the subject by stating that
the embryo is a monster simply because it is disorganized. In my original study
I really went, I believe, a step farther than Kellicott, for I attempted to analyze
the process of disorganization more thoroughly and demonstrated that in the
beginning it is accompanied by cytolysis, but as it progresses more rapidly it
results in histolysis, and that these two processes do not act with equal severity
on all parts of the embryo. When we consider the ovum as whole, it is the embryo
itself which is first destroyed, while within the embryo the central nervous system
or the heart is the structure first affected. Morphologically, these changes are
accompanied by a destruction of certain cells and tissues, leaving other portions
which continue to grow in an irregular manner. For this reason I speak of the
tissues which are first affected as being more susceptible than the others. The
entire process of disorganization, resulting in an irregular product, I have termed
dissociation. In a general way this explanation is accepted by Werber (1915,
1916), but he employs the term blastolysis instead.

At the time I prepared my paper on monsters, Harrison was just beginning
his interesting experiments in tissue culture in our laboratory. Since then this
method of study has given us clearer insight into the independent growth of tissues.
I was fully convinced from the study of pathological embryos that tissues con-
tinue to grow in an irregular manner, thus arresting normal development; but since
we are more familiar with the growth of tissues, as revealed by Harrison’s method,
we can understand a little better the process of dissociation. In fact, we have in
our collection two striking examples of tissue culture in human embryos. In one
the cells had formed an irregular mass which was growing actively, but the contour
of the organs had been entirely lost. In the other, from a tubal pregnancy, for
some unknown reason the ovum had been completely broken into two parts,
which in turn had cracked the embryo, and from each piece there had been a
vigorous independent tissue growth, or,as we may now say,a tissue culture. Accord-
ingly, when an embryo is profoundly affected by changed environment the develop-
ment of one part of the body may be arrested, while the remaining portion may
continue to grow and develop in an irregular manner. In very young embryos,
tissues or even entire organs become disintegrated, as can be easily recognized
by the cytolysis and histolysis present, and the resultant disorganized tissue can
not continue to produce the normal form of an embryo. If this process is sharply
localized, for instance, in a portion of the spinal cord or in the brain, spina bifida

202 STUDIES ON PATHOLOGIC OVA.

or anencephaly results. To produce a striking result, as in cyclopia, a small portion
of the brain must be affected at the critical time, and I think the work of Stockard
has shown clearly that this is before the eye primordia can be seen. Consequently,
in order to produce a human monster which is to live until the end of gestation,
the effect of the altered environment must be reflected from the chorion to the
embryo, so that the tissue to be affected is struck at the critical time in its develop-
ment. It is inconceivable that cyclopia should begin in an embryo after the eyes
are once started in normal development. Moreover, the same is true regarding
hare-lip, for after the upper jaw has once been well formed, the abnormality can
not develop. We may extend this statement to include club-foot, spina bifida
occulta, and other types of malformation. In fact, in discussing the origin of mero-
somatous monsters, hardly more has been stated by most authors than that there
has been an arrest of development, but I have attempted to point out that the
primary cause is in the environment of the egg and that the arrested development
is associated with destruction of tissue.

DESCRIPTION OF PLATE.

PLATE 7.

Fic. 83. Normal embryo with cyclopia; in front of the eye is seen the cyclopean snout. No. 559. 3.75.

Fic. 84. Normal double monster. No. 249. 0.75.

Fic. 85. Specimen with hare-lip and exencephaly. No. 364. 2.25.

Fic. 86. Specimen with hare-lip. No. 982. X1.5.

Fic. 87. Stunted fetus with large hernia in umbilical cord. No. 1330. 0.9.

Fie. 88. Normal embryo with exencephaly and spina bifida (the latter opposite the arrow). No. 1315. X1.5.

Fic. 89. Normal fetus with hernia of mid-brain. No. 1690. 6.75.

Fic. 90. Anomaly of left hand of No. 306a. Only the thumb and little finger are normal.

Fic. 91. Left hand, which is club-shaped, from No. 230, a fetus compressus 57 mm. CR. X0.75.

Fic. 92. Deformed wrist with atrophic radius in a normal embryo. No. 789, 50 mm. CR. X3.

Fic. 93. Right hand with six fingers from macerated specimen. No. 1749. There were six digits on each of the
four extremities. X83.

Fic. 94. Hydatiform villi. (After Gierse.) See Chapter VIII.

Fic. 95. Hydatiform villi showing vacuolation. (After Gierse.) See Chapter VIII.

MALL AND MEYER

CHAPTER VIII.
HYDATIFORM DEGENERATION IN UTERINE PREGNANCY.

To read even the titles of articles on “molar’’ pregnancies which have appeared
during the last few decades is a rather wearisome task. The great majority
of the articles concern themselves merely with the report of “a case’’ or (rarely)
of ‘‘several cases” of hydatiform moles. The recent cancer literature stands
in marked contrast to this, for not even the general practitioner would think
of reporting a routine case of cancer of the breast, let us say. The significance of
these facts is self-evident, and whatever else they may mean they do imply that
hydatiform mole is still regarded quite generally as a rare condition. ‘ Indeed, many
of those reporting ‘‘a case’’ frankly say so, and although the incidence of hydati-
form degeneration is estimated variously by different authors and investigators,
there seems to be entire agreement among them that it is a rare, even if not an
extremely rare condition. This opinion seems to be shared also by those general
practitioners whose long practice runs high up into the hundreds or even into the
thousands of obstetrical cases. Indeed, many general practitioners declare that
they have not seen a single case of hydatiform mole during the practice of a
long life.

This prevailing opinion can not be attributed solely to the influence of the
schools or to books, but is based upon the actual experience of the individual
practitioner and upon his conception of what constitutes hydatiform degeneration.
This is illustrated, for example, by Menu (1899), who said that a small hydatiform
mole weighs 300 grams, a large one 8,000, with an average weight in his series of
cases of 1,700 grams. But even specialists in charge of hospitals have reported
experiences similar to that of the general practitioner. Pazzi (1909), for example,
stated that although he had observed more than 6,000 cases of labor in his private
and hospital practice, he never met with a case of hydatiform mole. Moreover, it
would seem that only some specialists have come to regard the condition as some-
what less rare than was heretofore supposed. This is well expressed by Williams
(1917), who wrote: ‘‘Hydatiform mole is a rare disease, occurring, according to
Madam Boivin, once in 20,000 cases. On the other hand, the statistics of William-
son would indicate that it may be found but once in 2,400 cases.”’ Williams adds,
however, that in his own experience it occurred even more frequently than stated
by Williamson; and Essen-Moller (1912), on the basis of 6,000 cases treated
between 1899 and 1908, gives the incidence at the Frauenklinik at Lund as 3
per 1,000. My former colleague, De Lee (1915), in commenting on hydatiform
degeneration, also stated that he “frequently found in aborted ova one or more
villi degenerate and forming vesicles”; and similar remarks were made also by
others, notably by Miiller (1847), Marchand (1895), Veit (1899), van der Hoeven
(1900), Hiess, and according to him also by von Hecker, Langhans, Weber, and
Frankel. Findlay (1917) also regards “‘it as fair to conclude with Veit, Freund,

203

204 STUDIES ON PATHOLOGIC OVA.

and Dunger that abortive types of hydatiform mole are commonly overlooked,”
and although he gave no evidence for his opinion, Weber (1892) insisted that
hydatiform mole ‘‘occurs much oftener than we are led to believe from books
or other literature.’”’ Essen-Méller says K6nig gave an incidence of 1 per 728
cases. Pazzi (1908”) stated that Dubisay and Jennin found in 1903 that hydati-
form degeneration occurs once in 2,000 pregnancies, and that Cortiguera in 1906
declared that the frequency of hydatiform mole has a discouraging variation of
from 1 in 3,000 to 1 in 700 labors, but that in his personal experience Cortiguera
saw one case in every 300 labors. The latter incidence is only slightly higher
than that given by Essen-Moller for the clinic at Lund, and somewhat below that
of Kroemer (1907), who found 15 hydatiform moles in 3,856 births, or one in every
257 cases. Mayer (1911) reported 10 instances among 3,105 cases of labor, an
incidence of 1 in 310 cases, and it is only necessary to add that Donskoj (1911)
stated that the incidence of hydatiform mole in 28,406 cases at the Frauenklinik
at Miinchen, between the years 1884 and 1910, was only 1 for every 4,058 births,
to emphasize the discouraging variation of which Cortiguera spoke. Donskoj
also stated that Engel gave the incidence as 1 in 800, and Korn as 1 in 1,250 births.
Such a surprising fluctuation in the apparent incidence in adjacent communities
points to differences in conception of what constitutes a hydatiform mole, and
also to differences in character of the material upon which the calculations are
based.

The existence of hydatiform degeneration in far greater frequency than com-
monly supposed is indicated also by the records of the Department of Embryology
of the Carnegie Institution of Washington. However, the material covered by
these records is not identical with that upon which the above opinions or those of
other obstetricians are based. The opinion of the obstetrician is based upon
material belonging very largely in the later months of pregnancy, while that in the
Carnegie Collection, on the other hand, belongs very largely in the earlier months.
Hence this material is not truly representative of the entire period of gestation.
But the same thing is true of the material upon which the general practitioner, the
obstetrician, and the gynecologists have based their opinions, for these are based
largely upon material from the last months of pregnancy. Hence, the cases of
hydatiform degeneration which survive mainly come to their attention.

But unless we can assume that the incidence of hydatiform degeneration is
constant during the whole period of gestation, its incidence at any particular time
of this period may very incorrectly express that at any other time. This could fail
to be true only if the incidence of death of the conceptuses and their susceptibility
to hydatiform degeneration were exactly uniform throughout every period of
intrauterine life. But we know that neither is true, for it is common knowledge that
by far the great majority of the cases of uterine hydatiform degeneration recorded
in the literature are mature specimens of total or partial degeneration obtained in
the later months of pregnancy. Although such specimens may contain villi in
various stages of degeneration, they nevertheless represent end or near-end

HYDATIFORM DEGENERATION IN UTERINE PREGNANCY. 205

results. Like the fetuses which rarely accompany them, they are full-term or
near-term products when regarded as hydatiform degenerations, and unless we are
to assume that conceptuses once affected by hydatiform degeneration always survive
to near-term, statistical deductions based upon the cases that do survive can give
us little idea of the actual frequency of the condition throughout the entire period
of antenatal life.

That the specimens upon which past and also present opinion is based usually
were large is confirmed by the belief in the prevailing clinical criterion of the
existence of a disproportionately large uterus in cases of hydatiform mole. The
emphasis laid on this by clinicians is well illustrated by Seitz (1904°), who said
that cases in which the uterus is too small are the exception. Indeed, it seems
that the validity of this clinical dictum has been questioned only very recently
by Briggs (1912). Since most early conceptuses showing hydatiform degeneration
have been inhibited in growth before being aborted, it probably is only the speci-
mens which continue to grow that produce a uterine enlargement greater than
could normally be expected. However, since, as emphasized by Gierse (1847),
Storch (1878), Hiess (1914), and others, most hydatiform moles are expelled early
and spontaneously, it is evident that these can not have been adherent—that is,
have penetrated very deeply—or they would not have been expelled early and
spontaneously. Furthermore, maceration changes so commonly present in
aborted hydatiform moles indicate very clearly that a large percentage of them,
together with the decidua, had been more or less completely detached from the
uterine wall some time before abortion occurred.

As far as one can gather from the literature, the present opinion regarding the
incidence of hydatiform degeneration would be paralleled quite correctly if, in the
case of measles, we assumed that it was as common in octogenarians as in children.
Measles, indeed, is an extremely rare disease in advanced age, but it nevertheless
is very common in infancy. This is exactly the mistake we have made regarding
hydatiform degeneration. It may be and undoubtedly is a rare disease at or near
term, as Gierse also stated, but it probably is the commonest of all diseases during
the earliest months of gestation. The typical large hydatiform mole is an end-
result which it has taken long months to develop. No one seems to have followed
its evolution, although hydatiform degeneration, whether total or partial, is, of
course, gradual in its advent.

The records of the Carnegie Collection contained 8 cases of hydatiform mole in
the first 2,400 accessions, showing a frequency eight times as great as that given by
Williamson, or an excess of 700 per cent. Since the first 2,400 accessions contain
309 cases of tubal and 2 of ovarian pregnancy, only 2,089 uterine specimens
remain. Hence the recorded incidence in the uterine specimens really is 8 in 2,089,
or 1 in every 261 cases. This incidence is only slightly lower than that of Kroemer,
and somewhat higher per 1,000 than that given by Essen-Moller for the Frauen-
klinik at Lund, or than the personal experience of Cortiguera.

The highest incidence of hydatiform degeneration previously reported is that
of Storch, who estimated it as 50 per cent, but he unfortunately did not give a

206 STUDIES ON PATHOLOGIC OVA.

record of his cases. However, he emphasized that the typical, completely hydat-
iform mole is a relatively rare form of the disease, and that all manner of
transition forms between the normal chorionic vesicle and the completely degen-
erated one can be shown to exist. Storch further emphasized the commonness of
hydatiform degeneration, especially in the early months of pregnancy, but as
Veit (1899) well said, Storch somehow has not received sufficient credit for his
investigations and Gierse was forgotten completely. This seems strange, especially
in view of the fact that Storch’s work was done in Copenhagen, where Panum (1860)
had done and still was doing such fine and very suggestive, indeed epochal, work on
the origin of monsters. Although Storch devoted part of his paper to myxoma
fibrosum, and reported only 5 cases of hydatiform mole, one of which, however,
accompanied a living fetus, his opinions on the whole were far ahead of his time.
In order to make this clear I shall quote a very significant passage, which, in the
main, needs but slight changes to serve as a conclusion for my own investigations:

‘‘Nun sind aber bekanntlich Eier mit blasiger Degeneration der Zotten und fehlerhaft
oder nicht entwickeltem Fdétus ein sehr hiufiger Befund bei Aborten aus den ersten Schwan-
gerschaftsmonaten. Mehrere solche Hier sind schon in den bekannten Arbeiten von Dohrn
und Hegar beschrieben worden. Ich habe im Laufe des letzten Jahres eine gréssere Anzahl
von Aborten untersucht und derartige kranke Eier in mehr als der Halfte der Fille gefunden.
Nicht selten ist die Amnionblase vollig leer und enthalt nur eine klare serése Fliissigkeit.
In anderen Fiillen sitzt an der einen oder anderen Stelle der Innenfliiche des Amnion ein
kleiner rundlicher oder unregelmiissig geformter, 144-1 Mm. grosser Korper, welcher aus
Nichts als aus runden, schwach conturirten, zum Theil fettig entarteten Zellen und einer
hellen, fast homogenen Zwischensubstanz besteht, und der durch einen feinen, 1-3 Mm.
langen Strang von ihnlicher Natur mit dem Amnion verbunden ist. In noch anderen
Hiern ist der Embryo zwar etwas weiter entwickelt, aber von den verschiedensten Formen
von Missbildungen befallen. Seltener ist der Embryo einigermaassen wohl gebildet und
von bis zu 2 Cm. Liinge, wie dies auch Hohl nur einmal gefunden hat. Sehr gewoéhnlich
ist fettige oder lipoide Entartung des Embryo vorhanden; derselbe ist dann eine kiirzere
oder lingere Zeit vor der Geburt abgestorben. Als die fiussersten Glieder dieser Reihe
von kranken Hiern stehen endlich die sehr seltenen Fille, in welchen der Embryo seine
Entwickelung ziemlich ungestort fortgesetzt zu haben scheint, und von denen die Faille
von Martin und der oben beschriebene dreimonatliche abort Beispiele sind.

“Die blasige Entartung der Chorionzotten kann demnach neben den verschiedensten
Zustiinden des Embryo gefunden werden. Sehr hiufig ist letzterer der Sitz von mehr oder
weniger eingreifenden Krankheitsprozessen gewesen, die in demselben verschiedene Miss-
bildungen hervorgerufen und ihn in seiner Entwickelung gehemmt haben. Es sind diese
Krankheitsprozesse wahrscheinlich immer sehr friih im Ei entstanden, und miissen mit
Panum zuniichst als entziindliche Vorgiinge aufgefasst werden, welche nach ihrer Intensitit
und vielleicht nach dem Zeitpunkte, zu welchem sie im Keime auftreten, bald eine theil-
weise Verédung der Keimanlagen der meisten wichtigeren Organe mit Verkriippelung
des ganzen embryonalen Kérpers, bald mehr locale Missbildungen einzelner Kérper-
theile hervorrufen kénnen. Das Erstere ist in den hier besprochenen Aborten sehr
hiufig der Fall; der Embryo ist zu einem unférmlichen Klumpen umgewandelt, dem die
meisten Organe deren Keime durch Entziindung zerstért worden sind, giinzlich fehlen.
Von diesen verkriippelten Amorphi finden sich in anderen Hiern alle Uebergangsformen zu
mehr oder weniger entwickelten Missbildungen was auch Panum an einigen Beispielen
nachgewiesen hat. Es Scheinen in der That die nicht zerstérten Keimzellen der ver-

HYDATIFORM DEGENERATION IN UTERINE PREGNANCY. 207

schiedenen Organe, nach dem ablaufe des Krankheitsprozesses, ihren urspriinglichen
Entwickelungsplan mit einer oft merkwiirdigen Hartnickigkeit, so gut sie es konnen,
festzuhalten. Von diesem Verhiiltnisse liefern die bekannten herzlosen Amorphi, die durch
einen Zwillingsbruder ernihrt werden und dadurch zu einer oft bedeutenden Grésse
heranwachsen kénnen, ein schlagendes Beispiel. In unseren Aborten sind zwar diese
Amorphi, die keinen Zwillingsbruder zur Erhaltung ihres Kreislaufes gehabt haben, friih-
zeitig zu Grunde gegangen, und ihre Gewebsteile sind einer fettigen (lipoiden) Entartung
anheimgefallen; sie haben jedoch ihre Entwickelung eine Zeit lang fortgesetzt.

‘“‘Est is von den verschiedenen Verfassern vielfach von einer Auflésung der Embryonen
in der Amnionfliissigkeit und von einer nachherigen Resorption derselben gesprochen
worden. Ich glaube indessen, dass diesen Vorgiingen eine sehr geringe Rolle beizulegen ist.
Man findet in der That gewohnlich Nichts, was auf eine solche Resorption deuten kénne.
Es scheinen vielmehr die abgestorbenen Embryonen auch lange nach ihrem Tode eine
grosse Wiederstandfihigkeit gegen die Einwirkung, von Amnionfliissigkeit beizubehalten.
Ich habe mehrmals ganz kleine, verkrippelte Embryonen zwar fetig entartet, in ihrer Form
aber vollig wohl erhalten, in Eiern gefunden, die bis zu 10 Monaten im Uterus zuriickge-
halten worden sind. Zudem ist die Amnionflissigkeit in diesen Eiern meist ganz klar, oder
sie enthilt nur losgestossene, hinfillige Amnionepithelzellen suspendirt. Wenn daher
die Eier ganz leer gefunden werden, so riihrt dies gewiss am Haufigsten daher, dass der
Primitivestreifen seiner Zeit véllig destruirt worden und somit gar kein Embryo zur En-
twickelung gekommen ist. . . . Im Allgemeinen erreichen sie kiene bedeutende Grésse
und werden zudem oft friihzeitig aus dem Uterus ausgestossen, in dem sie, wie oben
besprochen, ein sehr betrichtliches Contingent zu den Aborten iiberhaupt liefern.

“Die Traubenmole und die verschiedenen Uebergangsformen derselben, die an pones
sehr hiufig vorgefunden werden, ist als Hyperplasie und secundire cystoide Entartung des
(von Allantois nicht herstammmenden) Chorionbindegewebs vorzugsweise charactertisirt.
Die Krankheit wird von pathologischen Zustiinden der iibrigen Eitheile, Amnion und
Embryo (Missbildungen, Verkriippelungen und friihzeitigem Absterben des letzteren) sehr
hiufig begleitet. Seltener ist der Embryo regelmiissig entwickelt, stirbt aber meist auch
dann wegen mangelhafter Vascularisation der (Chorion) Placenta friihzeitig ab. Sehr
selten scheint der Embryo ungestért bis zur Geburt sich fortenwickelt zu haben.”

But the unregarded observations and also the illustrations of Gierse, a few of
which are reproduced in figures 94 and 95 (plate 7, Chap. VID), are still more
startling than these opinions and observations by Storch, who knew of Gierse’s
observations published posthumously by Meckel. The latter quite correctly
stated that such careful observations as those made by Gierse always introduce
new points of view. If it be remembered that in these days, almost a century
later, specimens of hydatiform degeneration which are 4 em. in diameter still
are reported separately as examples of early hydatiform degeneration, the great
merit of Gierse’s observations in this regard alone will be clearly evident upon
recalling that he pictured a hydatiform villus from a chorionic vesicle the size
of a hazelnut (about 12 mm.), the largest hydatids on which were only one-third
of a line large. Moreover, Gierse added:

“Dergleichen geringe krankhafte Veriinderungen finden sich an auserordentlichen vielen
Abortus, und sie scheinen die haufigste Ursache des Abortus in den ersten Monaten zu
sein.”

How such an epoch-making conclusion not only could be forgotten, but abso-
lutely overlooked or disregarded, by all but a few of the scores upon scores who

208 STUDIES ON

PATHOLOGIC OVA.

have written on hydatiform degeneration, it is difficult indeed to understand.
Gierse, who also took steps to ascertain what normal villi look like, stated that
villi with marked irregularities, as described by Desormaux, Breschet, Raspail,
and Seiler, undoubtedly were abnormal, surmised that villi in abortuses seldom
are normal, and added that between the slight pathologic changes in the caliber
of the villi and the most evident hydatiform moles the plainest transitions can
be found. Among other important things, Gierse also recognized the early fenes-
tration of the stroma and pictured such a villus under a magnification of 250

diameters.
still wait for general recognition.

Although reported very briefly, his findings, wholly confirmed here,

Just as the great majority of specimens described in the literature are large,
so 4 of the 8 specimens originally classed as such in the Carnegie Collection also
are large, and none of the 8 is very young, as the following protocols show:

No. 70 (Dr. Charles H. Ellis) is a small, firm,
degenerate-looking, almost solid mass 40 by 30
by 28 mm., composed of small cysts, degenerate
decidua, exudate, and degeneration products.
It is very similar to a very much larger specimen,
No. 323 (Dr. V. Van Williams), a large, firm,
felt-like mass 120 by 90 by65mm. The individ-
ual cysts, which vary from 1 to 20 mm., are
packed together rather firmly, though a few large
ones are free. The exterior of the specimen is
formed by a thick layer of degenerate decidua
and gives only a slight indication of its true
nature upon closer inspection or upon examina-
tion of the cut surface. No fetal remnants were
noticed, and microscopic examination shows that
the specimen is composed merely of a large
hydatiform mass which was retained for a long
time and then aborted in toto with the surround-
ing decidua and exudate.

No. 749 (Dr. G. C. McCormick), on the con-
trary, is a fresh, loose, typical hydatiform mass
composed of loose hydatids of various sizes.
As the specimen floats loosely in fluid, it fills a
half-liter jar about two-thirds. A considerable
portion of the hydatid cysts are glued into a solid
mass by blood, exudate and decidua, which form
a layer on the exterior.

No. 1323 (Dr. J. W. Schlieder) is also a large
mass very like the preceding, and completely
fills a liter jar. It is accompanied by much
clot and composed mainly of a large, thick-
walled, hemorrhagic, necrotic mass 80 by 50 by
45 mm., containing a large, thin-walled cavity
65 by 30 by 25 mm., which is broken at one end.
This cavity, which apparently is that of the
chorionic vesicle, is empty, smooth, and thin-
walled, except where it is composed of a char-
acteristic hydatiform mass.

No. 1325 (Dr. Fred R. Ford) is a small,
irregular mass 40 by 33 by 20 mm., the exterior
of most of which is formed by a thin layer of
decidua. Within this is a small group of quite
typical hydatid cysts, the largest of which

measures about 10 by 5mm. The appearance
of the specimen suggests that it is merely a
fragment, though the amount of decidua present
indicates that the entire specimen probably was
not much larger. The history of this specimen
is especially interesting because of the diagnosis
of tubal pregnancy, caused by the presence of a
cornual myoma and the occurrence of repeated
bleeding.

By far the most interesting specimen, in some
respects, of hydatiform degeneration among
those diagnosed as such upon gross examination,
is No. 1640. This abortus, received through
the courtesy of Dr. J. W. Williams, measured
40 by 20 by 15 mm. Upon examination, Dr.
G. L. Streeter found it to be composed of a
flattened decidual and chorionic mass which,
upon section, showed “pearl-like vesicular en-
largements which suggest hydatiform degen-
eration.” The exterior of this specimen is com-
posed of a thin, hemorrhagic decidua which
completely surrounds the villi. The hydatid
nature of this clearly is recognizable upon close
scrutiny with the unaided eye, and easily be-
comes evident upon magnification of 12 diam-
eters with the binocular microscope. Exami-
nation of the histologic preparations reveals it to
be a very fine specimen of relatively early
hydatiform degeneration.

No. 1914 (Dr. G. C. McCormick) is a fine,
very characteristic mass. It is like Nos. 749
and 1323, but very much larger, for in fluid it
completely fills a 2-liter jar. This specimen was
said to have accompanied a living 7-months’
fetus, having been expelled between the fetus and
the placenta. Only a small amount of clot, and
what seems to be a small portion of placenta and
membranes, accompanied it. Since the placenta
was not saved, it is impossible to say whether the
mass resulted from partial degeneration of the
placenta belonging to the living child or whether
it represented a degenerate twin placenta, which
is rather unlikely but not impossible, in view of

HYDATIFORM DEGENERATION

the well-authenticated cases found in the litera-
ture. This specimen is of interest not only for
the numerous large, clear cysts, one of which
measures 30 by 25 mm., which it contains, but
because it accompanied the birth of a living
child and because of the relative rareness of such
a coincidence. In regard to the latter, Dr.
McCormick added that in his experience of over
1,000 labors he had never before met this coin-
cidence. The rareness of the specimen is em-
phasized still further by the statement of Pro-
fessor Williams that such an instance has not
been observed in a series of over 17,930 osbtetri-
cal cases from the Department of Obstetrics of
the Johns Hopkins Medical School, as well as
by the small series of such cases recorded in the
literature.

No. 1926, a companion specimen to No. 1640,
is composed of material from curettage received
through the courtesy of Dr. Karl Wilson, of the
Department of Obstetrics of the Johns Hopkins
Medical School. It was removed from the same
patient about a year after specimen No. 1640.
Upon gross examination the hydropic nature of
some of the villi is plainly evident, and upon
microscopic examination the diagonosis of hyda-
tiform degeneration could be confirmed, al-
though the villi were extremely degenerate.
The menstrual history of this case fortunately
is known and is thoroughly reliable. The last
menstruation occurred January 24 and curettage
was done August 4. Bleeding occurred every
two or three weeks during March and April and
was repeated throughout May. Since the

uterus, which had reached the symphysis, had
not enlarged any for months, in view of the long
duration of pregnancy the operation was per-
formed. The major portion of the specimen is
very small. The chorio-decidual portion was
felt-like in consistency and extremely fibrous,

IN UTERINE PREGNANCY. 209

due largely no doubt to the long retention. Most
of the accompanying material looks like mucosa
rather than decidua, although some of the larger
pieces very evidently contained villi. Some of
these were relatively thick and fibrous, and
others were vesicular. All of the material was
extremely fibrous, making it difficult to get a
satisfactory teased preparation. Accompany-
ing this material was a small body 5 by 7.5 by
30mm. Both nodule and stalk contained some
remnants of the embryo. Although the appear-
ance of the stalk suggests the umbilical cord, it
contains fragments of the body of the embryo,
some of which evidently are composed of nerve-
tissue.

Microscopic examination of the pedunculated
mass further shows it to be composed of degen-
erate remnants of organs, tissues, and cells. It
is partly denuded and partly covered by a layer
of fibrous connective tissue which contains local
thickenings. In other areas this fibrous layer
gives place to a single or more-celled layer, or to
polygonal, epithelioid cells. The interior of this
specimen is composed of a degenerate jumble
including fragments of the central nervous sys-
tem, the heart, liver, and cartilages. The entire
body is chaotic in its structure, and small frag-
ments of the nervous system are scattered
throughout its entire extent. This would seem
to indicate that the disruption of the tissues
was mechanical. The material in which the
organic remnants are contained is composed of
coagulum, some mesenchyme, cellular detritus,
blood, and polymorphonuclear leucocytes, de-
generated cells, which appear to have been
phagocytic, but which are more likely fusion
products or ‘‘symplasma” (as Bonnet called
them). A few remnants of vessels are found
only in the fragments of cartilage.

This short review of the gross appearance of the cases of hydatiform degen-

eration recognized by the unaided eye with the customary criteria, originally
classed as such in the Carnegie Collection, shows that they vary decidedly in their
gross, naked-eye characteristics, both as to size and appearance. No. 1640 scarcely
is distinguishable as a case of hydatifo m degeneration from gross appearances
alone, unless one’s attention is directed especially to the matter, but all the rest
of the specimens, both small and large, not only are easily recognizable, but are
so characteristic that they could not possibly be overlooked. As was indicated
above, the incidence of these specimens of hydatiform degeneration among the
first 2,400 accessions in the Carnegie Collection was 1 in every 261 abortuses, or
more than 8 times the incidence given by Williamson, and 1.3 times that given
by Essen-Moller. Although this incidence is so much higher, it does not necessarily
contradict the statements of Williamson, for it represents the incidence of hydati-
form degeneration in abortuses belonging very largely below 7 months. Nor does
it tell the whole story for these months, for since the incidence of hydatiform

210 STUDIES ON PATHOLOGIC OVA.

degeneration given in the records of the Carnegie Collection is based upon deter-
minations made essentially in the usual way—that is, by unaided inspection of the
gross specimen alone—we must regard it also merely as an apparent, not as the
actual, incidence. For, as will appear later, the actual incidence can be revealed
only by a careful gross and microscopic study of all specimens, both normal and
pathologic. Such a study has not as yet been completed, but 348 uterine specimens
classed as pathologic, and 108 pathologic tubal specimens, contained in the first
1,200 accessions, were carefully examined.

The actual number of cases of hydatiform degeneration found among the
333 chorionic vesicles of uterine abortuses classed as pathologic in the first 1,200
accessions was 105, or 31.5 per cent of the whole. This includes some doubtful
cases, but a revision probably would add more than it would exclude. The inci-
dence of hydatiform degeneration in the pathologic tubal pregnancies was some-
what higher even, or 45 specimens of undoubted hydatiform degeneration out of
108, or 41.7 per cent. Since nearly all the tubal specimens are young, while the
uterine series contains many more relatively older ones, the effect of this fact upon
the determined relative incidence of hydatiform degeneration among the patho-
logic tubal and uterine specimens must be borne in mind. For a reliable conclusion
regarding the relative incidence in the uterine and tubal pregnancies it would be
necessary to select a series from each, composed of specimens of approximately
corresponding ages. What the incidence of hydatiform degeneration is among the
uterine and tubal specimens classed as normal I do not know, but it undoubtedly
is far below that in those classed as pathologic. It is well to remember, however,
that many, if not most, of the instances of beginning degeneration very likely will
be found among the specimens classed as normal. This is well illustrated by a
hysterectomy specimen, No. 836, represented in figures 96 and 97.

If we assume that the incidence of hydatiform degeneration among the patho-
logic specimens in the rest of the Carnegie Collection is the same as that among
those in the first 1,200 accessions, then we get over 375 estimated instances of
hydatiform degeneration in pathologic tubal and uterine cases alone. Since I have
found a number of chorionic vesicles accompanying embryos classed as normal
which also show hydatiform degeneration, this number would be increased still
further; but unfortunately too few of the specimens classed as normal were ex-
amined to justify an estimate. Yet these normal specimens form 60.4 per cent of
the first 1,000 and 40.7 per cent of the first 2,500 accessions. This supposed increase,
due to inclusion of specimens contained among the normal, would be offset some-
what, however, by the fact that the first 1,000 accessions contain a somewhat
larger proportion of young conceptuses, each succeeding 1,000 probably becoming
somewhat more representative of actual life conditions. The difference between
the composition of the first 1,000 accessions and that of the 1,000 between 1,500
and 2,500 is not very great, however, for the former contains only an excess of
17.6 per cent of cases falling in the first five groups of Mall’s classification, which
groups are composed largely of specimens below an embryonic length of 20 mm.
Then, the relative proportions of tubal and uterine specimens in the different thou-

HYDATIFORM DEGENERATION IN UTERINE PREGNANCY. 211

sands also must be taken into consideration. But in any case, the estimated
incidence of hydatiform degeneration in the Carnegie Collection, calculated
without regard to those contained among specimens classed as normal, is 8.7
per cent, and the actual incidence hence is probably more than 1 in every 10 acces-
sions.

Estimated on the basis of hydatiform degenerations found among the uterine
and tubal specimens classed as pathologie alone, the incidence would be 12.5
per cent of the first 3,000 accessions. Upon this basis the incidence among the
uterine specimens alone would be 9.9 per cent, and among the tubal alone 28.1
per cent. This difference of 200 per cent between the tubal and uterine specimens
may have some significance in connection with the cause of hydatiform degenera-
tion. That this estimate is not altogether too high is indicated also by the last
392 accessions, the first gross examination of which, made by others than myself,
revealed 21 hydatiform degenerations, or an incidence of 5.3 per cent. Since
these accessions contained a disproportionately large number of older, naked
fetuses unaccompanied by secundines, aborted during influenza, this incidence of
hydatiform degeneration undoubtedly is too low. Moreover, no histologic exam-
ination has as yet been made. Nevertheless, the incidence among those accom-
panied by secundines and classed as pathologie was about 14 per cent and among
those classed as normal about 4 per cent.

If, as alleged by various investigators, the great majority of abortions occur
in the first three months, it is highly probable that many of these early conceptuses
are lost and never come to the attention of anyone, and that therefore the propor-
tion of early specimens in this or any other collection is no doubt too small. More-
over, in quite a number of specimens of the first 1,000 accessions the chorionic
vesicles were too degenerate for examination and in others they were absent, but
we have reason to believe that this is not true to the same extent in the material
beyond the first 1,000 accessions. Then, too, since only a few relatively large
sections from a single portion of the chorionic vesicles were examined, it is evident
that some cases in which the degeneration may have been purely local were prob-
ably overlooked. Hence the actual as compared with the recorded incidence of
hydatiform degeneration in this collection is probably not merely 8 times but 240
times as great as that given by Williamson (1900), and 33.3 times as great as that
given by Essen-Moller.

Most persons will, I presume, be willing to regard an increase of 700 per cent
above that of Williamson as possible, but one of 24,000 per cent above Williamson,
or even 3,333 per cent above that of Essen-Méller, as wholly out of the question.
Yet, strange as it may seem at first sight, this is not a random guess, but an estimate
based upn the actual incidence of hydatiform degeneration as determined by a
careful gross and microscopic examination of mounted and unmounted material
from over 400 abortuses. However, I lay no special emphasis on these percentages,
and am using them merely to emphasize the great frequency of hydatiform degenera-
tion. It matters little whether we shall ultimately determine an incidence of 10
or 5 per cent, but it does matter considerably whether we regard the frequency as
5 or 0.05 per cent, for this is a difference in frequency of 10,000 per cent.

212 STUDIES ON PATHOLOGIC OVA.

In view of the prevailing opinion, I realize that these findings may seem
incomprehensible and perhaps incredible, unless it is distinctly borne in mind
that it is not stated that this incidence refers to the later months of pregnancy or to
term. What the incidence in the later months of pregnancy may be I do not know,
but I have called attention to an apparently well-founded belief that it is a rela-
tively rare condition, the estimates ranging from 1 in 2,000 to 1 in 728 or 300 cases.

In regard to the incidence of hydatiform degeneration in uterine specimens,
it should also be remembered that the life, in contrast to the laboratory, incidence
for the entire period of gestation is higher, not only because the chorionic vesicles
were not included in many of the aceessions and because others were too degenerate,
but because I have not as yet been able to recognize the very earliest stages with
entire certainty. Furthermore, many instances of hydatiform degeneration from
the early months of pregnancy, especially the first and second, are inevitably lost.
The increase due to these things would be offset somewhat, however, by the lower
incidence of hydatiform degeneration in specimens from the last months of preg-
nancy, relatively few abortuses from these months being contained in the Carnegie
Collection.

To what extent the material in this collection is truly representative of actual
life conditions is difficult, if not impossible, to determine. This question could
be answered only if all the abortuses and material from abortions actually reached
physicians, and if the latter sent all of them to the laboratory. My own impression
so far is that the material representative of a sufficiently large community probably
would have a somewhat lower incidence, notwithstanding the fact that many
specimens, not only of hydatiform degeneration, but of abortuses in general, espe-
cially from the first month of pregnancy, are lost. However, since the presence of
hydatiform degeneration is especially common among early specimens, the inclusion
of these might raise the incidence for the whole period of gestation more than the
inclusion of all specimens (not excepting those of the last 3 months) would lower it.
But the result obtained would represent the incidence of hydatiform degenera-
tion in abortuses alone, and not that in all pregnancies. The latter could be
obtained only by including all gestations which end normally. If we accept
Pearson’s (1897) estimate that approximately 40 per cent of all pregnancies end
prematurely, then the incidence of hydatiform degeneration among abortuses would
represent very nearly twice that in all pregnancies. Mall’s (1908, 1918) estimate
of 20 per cent prenatal mortality, on the other hand, would give us an incidence
only one-fifth as great as that among abortuses. Hence, the actual life incidence
of hydatiform degeneration in all gestations would then be 1 in 10, as based upon
Pearson’s, and 1 in 25, as based upon Mall’s estimated prenatal mortality. But
even if, as estimated upon this basis, 4 or 10 per cent of all conceptions end in
hydatiform degeneration, this does not necessarily contradict the current opinion
regarding its rareness at or near term.

A careful examination with the binocular microscope of all specimens has
shown that hydatiform degeneration as a rule is sufficiently general even in young
vesicles, so that sections of a single portion about 10 mm. square enable one to

HYDATIFORM DEGENERATION IN UTERINE PREGNANCY. 213

make a fairly reliable diagnosis. Now and then, however, the process seems to
be rather irregularly developed, especially in the larger specimens.

In order to determine accurately the question of distribution of hydatiform
degeneration over various portions of the chorionic vesicle, it is necessary to
examine a series of sections of portions of the chorionic vesicle for each small
specimen. This has not yet been done, but since the portions used for microscopic
examination had been taken at random without previous knowledge of the existence
of hydatiform degeneration in any but the 8 specimens so recorded and above
described, and since over 450 vesicles were examined, I can not believe that it can
often be limited to any particular small area on relatively young vesicles. In these
it usually is quite general even if not complete. It is of special interest in this con-
nection that Muggia (1915), after reviewing the small list of cases of alleged
hydatiform degeneration of the chorion leve in connection with a study of a case
of his own, came to the conclusion that these cases are not really degenerations
of the chorion leve, but merely partial degenerations of the placenta. Although I
have given no thorough attention to the normal changes in the chorion leve, I
am quite certain that they are not the cause of confusion in the series of hydatiform
degenerations from the Carnegie Collection. Cases in which whole chorionic
vesicles exquisitely hydatiform in character were contained in the tubes, and a
number of others which still were implanted within the uteri showed equally
exquisite hydatiform changes around the whole perimeter. Such cases as these
ultimately confirm the opinion that in young vesicles the condition is, as a rule,
general, except perhaps at its very inception. This is true particularly by the
time the degeneration has reached a stage which can be considered at all typical
in its gross development, as determined by careful examination of numerous
specimens with the binocular.

It is especially interesting that, just as soon as typical, hydatid, elliptical
villi or portions of the same begin to appear, the condition can be recognized with
some certainty under a magnification of 12 to 20 diameters with the binocular
microscope. It often was surprising how relatively early stages could thus be
detected and the diagnosis confirmed later by histologic examination. Indeed,
celloidin blocks of tissue from which sections had been cut gave splendid testi-
mony when examined in fluid with the binocular. One of the not very early
stages contained in utero and represented in figure 98 could be recognized with
the unaided eye; and when examined with the binocular, under a magnification
of about 12 diameters, the picture was unusually fine and wholly unmistakable,
as shown in figure 99.

That hydatiform degeneration is incomparably more common in the earlier
than in the later months of pregnancy, thus justifying the comparison made with
measles, is substantiated by statistics covering the material examined. From these
it is evident that, excepting cases of large hydatiform masses originally classed as
hydatiform degeneration from inspection of the gross specimens alone, practically
all of the specimens are relatively young. This is true especially of those from tubal
pregnancies, and we may hence regard it as established that hydatiform degenera-

214 STUDIES ON PATHOLOGIC OVA.

tion is a change which is exceedingly common in the earlier months of pregnancy,
just as measles is common in childhood, and that it becomes progressively less
common as the end of pregnancy is approached, just as does measles as senility
is approached. The obstetrician does not see most of the cases of hydatiform
degeneration, for they are merely reported as miscarriages and the specimens
often are destroyed or retained unrecognized by the general practitioner or the
midwife. They are often aborted spontaneously and completely with the decidua
and rarely are still contained in a closed decidual cast when they reach the lab-
oratory.

The spontaneity of the abortion, especially in early cases, was emphasized
also by Storch (see page 208). Cortiguera (1906) is reported by Pazzi (1908")
also to have declared that many moles disappear wholly without leaving a rem-
nant, even if occurring repeatedly in the same woman, and Donskoj (1911) also
stated that many of those aborted do not come to the attention of physicians
because of their harmlessness. This, however, does not imply that those which
persist and develop into large masses are equally harmless, and it must be remem-
bered that it is upon these that the current opinion regarding the tendencies to
malignancy of the hydatiform mole is based.

The conclusion regarding the greater incidence of hydatiform degeneration in
the early months of pregnancy is conclusively confirmed by its occurrence in 33
of the 45 tubal specimens, within the first two classes of the pathologie division of
Mall, and in 100 of the 105 uterine specimens in the first six classes of this division.
Most of the specimens in these classes are composed of villi, of empty chorionic
vesicles, or of vesicles with embryos most of which have a length of less than 20
to 30mm. That hydatiform degeneration is more common in the early months of
pregnancy is indicated also by the well-known reports of Kehrer (1894) on 50
cases, and of Dorland and Gerson (1896), who found that 63 per cent of 100 cases
had aborted in the fourth and fifth months of pregnancy. According to Seitz,
Hirtzman (1874) also found that 62.8 per cent of 35 cases had aborted between
the third and six months. Only 2 of Kehrer’s 50 cases, or 4 per cent, and only 3
per cent of the cases of Dorland and Gerson aborted at the tenth month. Donskoj
stated that 7 of the 10 cases reported by him aborted in the fourth month and
none after the sixth month. He stated further that 56 per cent of Bloch’s 50 cases
aborted before the sixth month, 44 per cent later than this, one being retained
until the fourteenth month. The latter case is especially interesting, because
retention not only beyond term but after the death of the mole,seems to be re-
garded as relatively rare. This, however, does not imply that retention beyond
the period of growth of the hydatid mole does not occur, although Sternberg (1910),
who also emphasized the great rarity of this condition, erroneously stated that the
German literature reveals only a single instance of missed abortion in case of
hydatiform mole, viz, that of Poten (1901). In this case a hydatiform mole of
the size of a duck egg was said to have been aborted approximately one month
beyond term. Hence growth must have ceased long before and the mole have
remained in utero as a ‘harmless body.” To this case of Poten, Sternberg added

HYDATIFORM DEGENERATION IN UTERINE PREGNANCY. 215

a case in which a hydatiform mole 14 by 9.6 by 4.3 mm. was aborted in the
twelfth month after the cessation of menstruation. Although Sternberg included
4 cases from other countries among these missed-abortion moles, viz, those o
Sheil (undated), Ferguson (also undated), Colorni (1908), and Gaifani (1908), one
can hardly doubt that more cases could be added. Since the case of Sheil was one
of twin pregnancy, in which one conceptus became hydatiform, it is not at all
unlikely that some other cases among this rather small series of twin pregnancies
accompanied by hydatiform degeneration may belong in this category.

Mayer (1911) also emphasized the fact that, although instances of retention
of fetuses are very common, instances of retention of hydatiform mole are very
rare, only a few cases having been recorded. Mayer referred to 2 cases by Kehrer,
3 of Dorland and Gerson, and 1 case of Lange, and reported 4 of his own. These
4 were found among 10 cases of hydatiform mole, an incidence of retention of
40 per cent. They are interesting, especially in connection with the observation
of Briggs (1912) that, contrary to current belief, uterine enlargement often is not
beyond the normal. Mayer reported that this enlargement was too great in but
1 of the 4 cases, and that retention lasted as long as 4 to 5 months.

At least 3 of the cases of hydatiform mole among those originally recorded
as such in the Carnegie Collection belong among retained specimens, as the illus-
trations alone suggest. But a fair percentage of detached chorionic vesicles
included in the list of cases here reported undoubtedly also was retained after the
cessation of growth, and it is for this reason that I further emphasize the fact that
the uterine volume in a considerable percentage of these cases also, instead of
having been too great for the duration of the pregnancy, unquestionably was too
small. This is well illustrated by the histories of specimens Nos. 70, 323, 1640,
and 1926, and by the specimens themselves.

The average menstrual age of 51 of 112 uterine specimens of hydatiform
degeneration—in which the data were available—was 66.6 days, or 214 months.
As will be seen, this is a far lower average age than heretofore reported, a difference
which explains itself from what has already been said. It is interesting that the
average menstrual age of 5 of the 8 specimens in the Carnegie Collection originally
classed as hydatiform degenerations is 168.2 days, or 214 times as great, thus
being in substantial agreement with the usual results. Three of these 5 are large
specimens, the fourth measures 40 by 20 by 15 mm., and the other is composed
of small fragments contained in material from curettage. From this alone it
follows that the menstrual age is a very uncertain guide, especially to the size
of a hydatiform mole.

It may seem superfluous to add anything to the good descriptions of the gross
appearance of the typical hydatiform mole found in the literature. Such cases are
so characteristic that even a novice can recognize them at sight. Yet if the findings
reported here are reliable, or even approximately so, it nevertheless must be evident
that, in the past, the great majority of specimens of true hydatiform mole have
remained unrecognized merely because they did not happen to present the cus-
tomary, well-known picture to the unaided eye. Small chorionic vesicles, such as No.

216 STUDIES ON PATHOLOGIC OVA.

2077 (shown in natural size in figure 100), which attract no attention upon cursory
inspection, may, and often do, present the most exquisite picture of hydatiform
degeneration when seen under a magnification of 3 to 20 diameters, as illustrated
in figure 101. This is true especially if the examination is made with the binocular
microscope. Since I have adopted this method of examination it has been possible
to recognize instances of decidedly general and typical hydatiform degeneration
in chorionic vesicles less than 2 em. in size, with later confirmation of the diagnosis
by a histologic examination. However, I have not been able to recognize very
early stages merely by examination of the gross specimens, for gross recognition
is possible only when portions of at least some of the villi have become sufficiently
elliptical or globular to attract attention. Histologic recognition is possible far
earlier than this, as shown in figure 102.

The general appearance of the whole chorionic vesicle is sometimes an aid in
gross identification, for the villi not infrequently are smooth, slightly branched,
and unusually long, so that the vesicle looks shaggy, as illustrated in figure 103.
Several hydatiform villi from this specimen are shown in figure 104. The typical
gross hydatid or watery, translucent nature of the villi can not be relied upon
in early stages, for normally shaped villi that have undergone considerable lysis
may be almost transparent and also somewhat more than normally bulbous.
However, save in the case of some specimens of tubal pregnancy, the swelling of the
villi, due to maceration or to luetic changes, is quite different in character from
that characteristic of hydatiform degeneration, and usually quite easily distinguish-
able from it. Judging from several specimens of villi which were macerated in
distilled water during a period of weeks, post-partum maceration never should
cause confusion, and the same thing undoubtedly is true of intrauterine macera-
tion. The differences in appearance between macerating villi with disintegrating
epithelium, stroma and blood-vessels, and others undergoing hydatiform degen-
eration, is well illustrated by villi from No. 640, shown in figures 105 and 106.
Though photographs can not register all the distinctions, the contrast is so marked
in this case that one can not fail to notice it.

Since numerous trophoblastic nodules are present also in other conditions,
notably in retained placente, as found by Aschoff and others, I have not been able
to regard their presence in unusual numbers, in some cases of hydatiform degenera-
tion, as of crucial value, but the absence of placental differentiation at a time when
it should be present, with a uniform and unusual development of the villi over the
whole exterior of relatively large chorionic vesicles, is decidedly significant and has
often been found to imply the presence of hydatiform degeneration. The same
thing is true of a very irregular distribution of the villi, or of uniformly distributed
fusiform enlargements on the villi and of the loss of the dull appearance of their
cut surfaces, as seen under the binocular. As soon as the stroma becomes hydati-
form, and even before liquefaction is present, the cut surfaces of hydatiform villi
look somewhat shiny and waxy or, perhaps better still, paraffine-like. This was
well shown in a previous paper (Meyer, 1920, fig. 21). A bluish tinge is always
present, and this appearance is very characteristic. However, how easily a speci-

HYDATIFORM DEGENERATION IN UTERINE PREGNANCY. 217

men of hydatiform mole can be recognized by examination with the binocular
alone necessarily will depend also upon the condition of the specimen. If the villi
are matted, glued, or macerated, not only the early hydatiform changes, but even
fairly advanced ones, are often masked so completely that recognition is difficult
or impossible without histologic examination.

In many early specimens the diagnosis could be made at sight from a histologic
preparation under low magnification, even when it was impossible to make a
diagnosis by examination with the binocular microscope alone. The field of sec-
tions of the villi also looks more scattered and the caliber of the villi shows greater
variations. What further makes this possible is not, as has been generally assumed
since Marchand’s epochal work on chorio-epithelioma, the appearance of the
syncytium or that of the Langhans layer or of the trophoblast, but the changes in
the stroma, which precede those in the epithelium. The evidence in regard to
this matter is overwhelming, and in the early stages, when the stroma already has
been altered, it often is impossible to tell whether the epithelial development is
normally or abnormally active. Moreover, in spite of Marchand’s conclusion,
extremely large hydatid vesicles often have but a single smooth layer of epithelium.
This has been asserted repeatedly by other investigators also. The two layers of
epithelium are not by any means always present, and, while there is no agreement
in the matter, the opinion nevertheless seems to be that the grade of epithelial pro-
liferation can not be used as a criterion for the determination of the presence of
hydatiform degeneration.

Langhans (1902) also stated that Marchand overemphasized the presence of
epithelial proliferation, and rightly declared that all sorts of gradations occur
between normal and hydatiform villi. Indeed, unless hydatiform villi invariably
arise as such when the earliest villi appear, or arise de novo later, all gradations
necessarily must exist between normal and hydatiform villi, thus contradicting
Marchand’s conclusion.

Menu said that the presence of marked epithelial proliferation was emphasized
early by Miiller (1847), Ercolani (1876), Franque (1896), and Owry (1897), and
according to Pazzi (1908°), Ercolani, and even Polano, denied the existence of
connective tissue in the hydatiform mole. The same thing was asserted by
Sfameni (1905), who claimed to have found further evidence of the exclusively
epithelial nature of the hydatiform mole. According to Sfameni, the hydat-
iform mole does not result from a modification of existing chorionic villi, but
from an entirely new growth which is wholly epithelial in character! But this
opinion, which was accepted also by Niosi (1905), seems to exist among Italian
writers only. According to Acconci (1914*), marked proliferation of the epithelium
occurs also in toxemia of pregnancy and in nephritis. A number of investigators
have found it common also in long retention.

I am unable to confirm the observation of Nattan-Larrier and Brindeau (1908)
that the syncytium of hydatiform villi breaks up into individual portions which
do not undergo degenerative changes, but penetrate deeper into the decidua.
These investigators thought that in normal villi the plasmodium always keeps its

218 STUDIES ON PATHOLOGIC OVA.

continuity with the proliferating Langhans layer, and that the syncytial masses
were more angular in form, of smaller size, and contained retracted nuclei. The
syncytial masses on the hydatiform villus, on the other hand, were said to be more
rounded in outline, elongated or polygonal in form, and to possess large nuclei
very rich in chromatin.

Although Durante (1898) represented extremely long syncytial buds, he never-
theless found (1909) epithelial proliferation present only where certain vascular
changes were present. Winter (1907) stated that the condition of the epithelium
varies greatly, and Falgowski (1911) emphasized that he could not demonstrate
the presence of an increased epithelial proliferation or of vacuolation of the syncy-
tium. Amann (1916) also found that epithelial proliferation may be wholly absent.

That the degree of epithelial proliferation varies greatly, and necessarily so,
not only in the villi of the different vesicles but in those of the same vesicle, is splen-
didly illustrated by the villi of No. 720b, shown in figures 107 and 108. In the
former epithelial proliferation has not extended beyond that required by the
increase in surface due to the increase in caliber of the villi, while in the latter a
very long, branching epithelial framework and smaller processes are present.
Likewise, in figure 109 (No. 540), the large villi show little epithelial proliferation,
while the small villus to the right shows very marked proliferation. Nor are the
variations in the degree of epithelial development limited to different villi of the
same specimen, for they may be present even in the same villus. Ballantyne
and Young (1913), on the contrary, found epithelial proliferation ‘‘so well developed
that it suggested that it is an essential process in the formation of the mole.”
They further likened hydatiform degeneration to edematous growths and empha-
sized that both really are epithelial new growths. This opinion is accepted also by
de Snoo (1914), who regarded the hydatiform mole as a neoplasm of the trophblast
with secondary changes in the stroma.

There is no agreement at present as to whether the epithelial changes are
primary or secondary. As is well known, Marchand (1895), and Miiller, Ercolani,
and Langhans long before that, regarded the epithelial changes as primary, but
most investigators seem to have come to an opposite conclusion. Some share the
opinion of Schroeder that hydatiform degeneration points to a stimulus resulting
in hyperplasia of the entire chorionic villus. Nor is there agreement as to what the:
initial changes are. Durante (1909) regarded the presence of vessels with an imper-
fect endothelial lining and with thick infiltrated walls as the initial lesion in hydati-
form degeneration. These changes were noted by him, especially in trunk villi,
and epithelial proliferation was most evident where the vascular lesions were most
pronounced. Durante further stated that the chain form of the hydatids is due to
the fact that the vascular lesions occur at intervals along the villus. Unfortunately,
the structure of long hydatiform villi does not confirm such an explanation nor
Durante’s conclusion that the hydatid cavities within the villi result from dilatation
of the capillaries. Many investigators report the early disappearance of the blood-
vessels, a phenomenon which some regard as secondary and others as primary to
the death of the embryo.

HYDATIFORM DEGENERATION IN UTERINE PREGNANCY. 219

In the course of this investigation a villus with a normal stroma and normal
vascularization never was found to have undergone true hydatiform degeneration,
but one with a normally active epithelium—both Langhans layer and syncytium—
often was truly hydatiform. That is, it not only was watery in appearance, but also
fusiform or globular, even in external form. In fact, Marchand (1895) himself found
that “Das Epithel welches die Zotten und ihre Anschwellungen bekleidet zeigt
ein sehr verschiedenes Verhalten.’’ Yet even today the feeling on the part of
many seems to be that unless a marked hyperplasia of the Langhans layer and of
the syncytium is present the condition is not one of hydatiform mole. This position
seems to me to be untenable, for, as Marchand himself said, the change in epithe-
lium usually is least in the young villi, and it must be added that it is unrecognizable
in the early stages and in young conceptuses. A perusal of the literature descrip-
tive of the actual cases leaves little doubt upon this point, and a careful study of
the advent of the earliest recognizable changes in hydatiform mole is absolutely
convincing. The earliest recognizable, even if not the incipient, changes occur in
the stroma and in the vessels and not in the epithelium. In passing, it may be
noted that although Marchand stated that the change in the epithelium is primary,
he nevertheless somewhat contradictorily added that the most important fact is
the degenerative change in the stroma of the villi.

Although not applicable to what I have come to regard as the incipent changes
in hydatiform degeneration, it nevertheless is true that the stroma often, if not
always, quite early becomes hydatiform—that is, glassy or clear, though not
necessarily watery. Moreover, the villous vessels often degenerate or disappear
completely at a very early stage.

Various grades of hydatiform degeneration with vitreous stroma and vessels
in various stages of disappearance are shown in figures 110 (No. 977), 111 (No.
516), 112 (No. 874b), and 113 (No. 396). The first and last of these specimens
are in a splendid state of preservation, so that maceration changes really can be
wholly eliminated. It is exceedingly difficult to make any definite statement
as to what is typical regarding the epithelium. This has been said by others
also. Indeed, this necessarily follows from the fact, agreed to by every one, that
histologically there is no true line of demarcation between the ordinary benign
hydatiform mole, the so-called destructive benign (?) hydatiform mole, what-
ever its status may be, and the malignant hydatiform mole or chorio-epithe-
lioma. Such a conclusion alone presupposes the existence of the widest differences
in the condition of the epithelium in these cases, and that such differences actually
exist is beyond question.

Marchand’s revolutionary investigation on chorio-epithelioma notwithstand-
ing, the epithelium is not always two-layered, nor is it always thickened, in hydati-
form mole. That the epithelium can not always be active beyond the normal
follows also from the fact that the proliferative changes in it are subsequent to,
even if not necessarily consequent upon, changes in the stroma. Furthermore,
like the latter, they are gradual in their evolution and may stop or be stopped at
any stage of their development. Then, too, the condition of the epithelium

220 STUDIES ON PATHOLOGIC OVA.

depends very largely upon the preservation of the abortus, and this, as is well
known, varies greatly. Finzi (1908) also found that the epithelium may be per-
fectly preserved or totally destroyed, and that central degeneration is the most
noticeable thing and due to the absence of vessels.

However, the most striking thing about the epithelium usually is not its
thickness, the presence of large masses of trophoblast, or of numerous syncytial
buds, but its splendid state of preservation, especially as contrasted with that of
the stroma. This is true of all except macerated or degenerate specimens, for the
life of the epithelium seems assured as long as there are periodic accessions of fresh
blood, which, as the clinical histories illustrate, is usually the case. The stroma,
on the other hand, probably not being wholly independent of the contained capil-
laries, is deprived very largely of its sustenance during, even if not in consequence
of, their degeneration. According to some, hydatiform degeneration of the stroma
is the result of an accumulation of nutritive products in consequence of the absence
of the vessels. Degeneration of stroma and vessels, however, may result from
malnutrition due to poor implantation. Daels (1908”) reported that the stroma
was densest where the syncytium was thickest, and most rarefied where it was
thinnest, but I could not determine such a relationship.

The epithelium of the villi often was found single-layered without any syncy-
tium whatever, or with at most a few syncytial buds. Nevertheless, both the
syncytium and trophoblast very often show evidences of a marked activity not
confined to implanted villi or to the epithelium of the villi as a whole, but which
extended to that of the chorionic membrane as well. Surprisingly long, complex,
syncytial buds, whorls, and festoons, as shown in figures 114 and 115, said to
have been observed by Fraenkel, often are present, especially on the villi, although
in a few instances fine buds and frameworks of syncytium also were seen arising
from the epithelium of the chorionic membrane. This feature (shown in fig. 115)
has, I believe, not been specially emphasized heretofore, though observed by
Clivio (1908).

Mounds formed by the Langhans layer were common, especially on the tips
of the villi where they frequently formed irregular masses of small nodules—the
“appendici durate’’ of Crosti (1895). These gave the villous tree the appearance
of a leafless orange loaded with fruit, only that the trophoblastic nodules are mainly
apical, as shown in figure 116. In several instances syncytial buds were found far
out on these trophoblastic masses, a fact which is of special if not of crucial sig-
nificance in connection with the old question of the origin of the syncytium, for
these buds undoubtedly had not been transported there. But, however one may
regard these things, such appearances as represented in figure 9 (plate 1, Chapter
IV) are unmistakable, for they show thickenings composed of Langhans cells and
garlands of considerable length, portions of which are composed of absolutely
distinet cells of the Langhans type, as well as other portions composed of syncy-
tium with every gradation between the two. Nor do I believe that the assumption
that syncytium can resolve itself into individual cells can be used to deny the
implication of these facts.

HYDATIFORM DEGENERATION IN UTERINE PREGNANCY. 221

Although hydatiform villi covered by a single layer of rather small cells of the
nature of Langhans cells, sometimes without visible cell boundaries, frequently
were seen, villi covered by typical syncytium only were never seen. The single
layer present, although syncytial in places, suggested Langhans cells rather than
the real syncytium. Moreover, since the cells of the Langhans layer usually were
smaller rather than larger than normal, it follows from this alone that their pro-
liferation nevertheless must have been marked, in order to completely cover the
enlarged villus, in spite of the fact that the layer remained single-celled. Were
this not the case the extraordinary increase in size which accompanies the formation
of large hydatid cysts could not possibly occur without rupture of the covering
layer.

Not infrequently proliferation of the epithelium without increase in thickness
may manifest itself in another way. The caliber of the villi in the earlier stages of
hydatiform degeneration sometimes does not increase much and no thickening of
the proliferating epithelium is noticeable, yet the latter shows marked proliferation.
Under these circumstances, the borders of the villi and of the chorionic epithelium
may appear extraordinarily sinuous, as illustrated in figure 117, and epithelial
invaginations from opposite sides may in rare instances meet in’ the center, as
indicated in figure 118, and, by fusion, completely isolate a portion of the stroma.
It is usually in these cases of very sinuous epithelium that the epithelial invagi-
nations sometimes become constricted, leaving a closed epithelial vesicle or a
nodule of epithelium attached to a stalk or wholly isolated within the stroma, as
shown in figures 119 and 120. All stages in this process of vesicle formation were
found, and rarely also extensions of epithelial sprouts, as described by Neumann
(1897) and others, were seen, portions of which had become isolated in the stroma
to appear later as typical syncytial giant cells. These facts, too, would seem to
throw a sidelight upon the origin of the syncytium for those to whom this ques-
tion is still an open one.

All these things abundantly testify to the activity on the part of the epithelium
in many hydatiform moles, even when thickening of it is absent, but they are of
diagnostic value only if present, and I wish to emphasize again that they may be
wholly absent and also unrecognizable in the early stages. Moreover, the degree
of epithelial proliferation varies greatly, as illustrated in figures 112, 121, and 122.

Until I am able to learn more about the structure of normal villi in various
stages of development, I am not willing to commit myself regarding the earliest
changes in hydatiform degeneration. These may be unrecognizable with present
methods. However, it is possible to say that in young conceptuses the disappear-
ance of the capillaries, which was regarded as a posisible cause for the development
of hydatiform mole by Hewitt (1860, 1861), and which was emphasized later
by Hahn (1864), Maslowsky (1882), and also by others, undoubtedly is a very
early and possibly the very earliest noticeable change in some cases. I do not imply
that death of the embryo is the cause of this disappearance, as Hewitt held, and
I am not ready to say that the vascular change is the very earliest one in all cases.
This would imply that hydatiform degeneration under no circumstances can

222 STUDIES ON PATHOLOGIC OVA.

begin before the capillaries have appeared in the villi. There is some evidence
which suggests that it possibly may appear before this time. If so, it would be
incorrect to speak of a disappearance of the vessels in such chorionic vesicles, for
if the advent of hydatiform degeneration can precede the appearance of the villous
capillaries, vascularization of the villi may never occur. In older conceptuses,
however, in which vascularization of the villi has supervened, the first recognizable
change is the disappearance of these capillaries. Manyspecimens in which the latter
were in various stages of degeneration were examined carefully, and the opinion
of Hewitt (1860) that hydatiform degeneration can not arise in villi which have
been vascularized can be regarded as of historical interest only. Different stages in
the process of vascular degeneration are represented in figures 123, 124, and 126,
and in figures 109 to 112, inclusive.

Coincident with the disappearance of the vessels, also noted by Veechi (1906)
in villi with vesicles only as large as a “millet” seed, changes in the stroma also are
noticeable. Usually it tends to become glassy, the individual nuclei becoming
separated farther. The stroma, though apparently solid, is uniformly slightly
bluish and vitreous, with well-defined, rather small, pyenotic, pointed nuclei, but
with not a vestige of a vessel, though the epithelium be splendidly preserved. The
latter may be one or two layered, and may -be accompanied by syncytial buds
and trophoblastic masses and nodules. In such specimens the entire picture
really is exquisite, and a mere glance through the compound microscope reveals
the lack of vessels in the vitreous stroma, its sparseness, and the marked differences
in size of the sections of the villi.

After these early changes, liquefaction of the stroma usually follows. As is
well known, it generally begins in the interior and first appears in the form of
vacuolation; but this vacuolation (which I can not regard merely as an edema)
is not intracellular but intercellular, and as it becomes more pronounced it really
takes on the nature of fenestration. Sections of the whole cross-section of the
villi, even though large, may be composed of a series of fenestrae (see fig. 125)
separated by exceedingly fine strands of the remaining stroma which may contain
remnants of the nuclei. But finally, even the fine trabecule separating the fenes-
tre disappear, and the stage of the watery, old, hydatid condition has been reached.
More generally, however, the vacuoles or small fenestr lying in the middle become
confluent at the center of the cross-section of the villus, which then is liquefied
completely. As is well known, this liquefaction gradually extends to the periphery
as the zone of the surrounding stroma is narrowed in the process. Not infrequently,
however, liquefaction of the stroma occurs quite generally throughout the cross-
section of the villus and is accompanied by the formation of numerous large cells—
the wandering or migrating cells of earlier writers. A few of these cells almost
always can be found, and rarely the whole section of the villus is studded with
or even formed by these large, erratic cells, which usually lie in fenestra in the
stroma (fig. 127.) In other instances a large portion of the sections of the villi
may be occupied by them, as shown in figure 128. The presence of these cells
in villi regarded as normal has long been known. Their presence in hydatiform

HYDATIFORM DEGENERATION IN UTERINE PREGNANCY. 223

moles was noted by Otto, Marchand (1898), Essen-Moéller, and many others.
Their occurrence in normal and pathological chorionic vesicles and their significance
are considered in Chapter XV. No matter what the condition of the epithelium
(or, more specifically, the Langhans layer), the syncytium, and trophoblast may
be, the above-noted changes in the stroma always are quite typical. They are
not the only changes noted, however, and may differ somewhat as to the time of
their advent.

Not infrequently, changes quite comparable to those in the villi occur also in
the stroma of the chorionic membrane itself, a fact which has not heretofore been
emphasized. It, too, frequently is decidedly glassy; liquefaction may occur
here and there and may become complete in the course of time. Hofbauer cells
also are not uncommonly present. Among the changes noted in this membrane, the
disappearance of the vessels is the most common and constant, although epithelial
proliferation is not rare, as already stated. Moreover, when (as in one of Storch’s
cases) a hydatiform villus is 15 em. long, one scarcely can doubt that the stroma
also must have proliferated—not merely degenerated. Some of the strings of hydatid
cysts in a specimen in the Carnegie Collection have a length of 10 to 12 cm.,
and in these cases also one can hardly assume that this increased length of the
villi was unaccompanied by proliferation of the stroma. From these things alone
it follows that the stroma can not remain passive always, although Gromadzki
(1913) concluded that it never proliferates. Vecchi (1906), however, reported an
increase in the stroma of the villi, and it will be recalled that Marchand also
implied the presence of proliferative changes in the connective tissue when he
wrote that they depend upon those in the epithelium.

I have never been able to find mitotic figures, a fact which may be accounted
for, however, by the presence of degenerative changes due to intrauterine separa-
tion and retention of most specimens. Indeed, the failure to find mitoses speaks
against proliferation in the stroma no more than in case of the epithelium, in which
the presence of karyokinetic figures has been reported by a few investigators only.
Yet pronounced proliferation of the epithelium is often present. The failure to
find mitotic figures very likely is due to the condition of the material.

Careful scrutiny of a large series of specimens has revealed the fact that the
disappearance of the vessels in the villi, in the chorionic membrane, and also in the
umbilical cord is centripetal as a rule. However, in many specimens the vessels
not only may be present in the chorionic membrane, although absent in the villi,
but may be very numerous and even engorged with blood. It is difficult to say
to what extent the engorged condition of these vessels and of those in the body of
the abnormal embryos sometimes contained in these hydatiform moles is due to
the propulsion of the contained embryonic blood before the advancing vascular
constriction and degeneration, but I am inclined to believe that the centripetal
movement of the process is not a negligible factor in this matter.

Although only a few instances of the birth of a living fetus or of a fetus which
has reached the later months of pregnancy are recorded in the literature, it is now
quite generally recognized that the fetus, though dead and too small for its men-

224 STUDIES ON PATHOLOGIC OVA.

strual age, usually is present. This stands in contradiction to the earlier belief
illustrated by the statement of Gierse (1847), that the fetus usually was reported
as absent, and that when present (as in the cases of Meckel, Gregorini, Otto,
Cruveilhier, and his own) it was usually less than an inch long, even when retained
for a period of from 3 to 10 months.

This apparent contradiction regarding the presence of the fetus in hydatiform
moles is explained easily by the fact that the cases in the earlier literature are old,
far advanced in degeneration, while the more recent literature contains many more
in the earlier stages of degeneration. Yet in spite of this fact the earlier opinion
survives to the present day, for Graves (1909-10) spoke of “‘the very unusual
presence of a normal fetus inside a mole,” and Vineberg (1911) still more strangely
held that the presence of a fetus excludes the specimen from the class of true hydati-
form moles!

Among the specimens concerned in this report many contained a fetus. This
was true of 24.5 per cent of 49 tubal and 64.4 per cent of 121 uterine specimens,
including some (9) doubtful cases. The fetal length ranges from 1 to 90 mm. in
the uterine and from 1 to 80 mm. in the tubal series. Although the average length
of the embryo in the tubal series is 12.3 mm., and that of the uterine only 10.1 mm.,
58 per cent of the tubal specimens nevertheless were below 7 mm. in length as con-
trasted with 52.5 per cent of the uterine. The presence of a fetus with a frequency
almost three times as great in the uterine series again indicates that the abnormal
conditions within the tubes lead to early death, digestion, and absorption, or at
least to dissolution, of the embryo. This fact again points directly to a faulty
nidus as causative agent, for if the absence of a fetus is to be laid to primary ovular
defects, then one must admit that relatively far more of such diseased ova become
implanted within the tube than within the uterus.

In some early specimens the fetus is in a state of excellent preservation. This
is what one might expect, for the onset of hydatiform degeneration is gradual and
may remain partial. The condition of the fetus alone in many of them also suggests
that its death was secondary to the degeneration.

This is exemplified splendidly by No. 2099, shown in figures 129 and 130.
This eyema shows the presence of undoubted maceration changes throughout,
but especially in the branchial region and on the umbilical cord, and the shaggy
chorionic vesicle shows the presence of a moderate degree of hydatiform degenera-
tion. A more advanced instance is that of No. 1260, shown in figures 131, 132, and
133, in which the form of the eyema is greatly modified and the hydatiform nature
of the villi much more obvious. That the death of the embryo is not the cause of
hydatiform degeneration would seem to be evident also from such instances as
No. 2250. In this case of twin pregnancy both fetuses are well preserved, as figure
134 shows, and yet the respective chorionic vesicles show the presence of well-
developed and quite general hydatiform degeneration as can be seen in figures 141
and 142 (plate 14, Chap. X). Indeed, in this instance the fetuses show less
maceration change than the vesicles, and it is particularly interesting that this

HYDATIFORM DEGENERATION IN UTERINE PREGNANCY. 225

abortion was attributed to influenza, although, in view of the presence of hydati-
form degeneration, it was inevitable. Influenza, to be sure, may have been the
immediate cause and may have precipitated the abortion, but uninterrupted
development of the hydatiform degeneration also would have done so. More-
over, the appearance of both fetuses suggests that they died shortly before the
abortion, and this is confirmed by a comparison of the menstrual and anatom-
ical ages, which differ by 6 and 10 days, if the larger or smaller fetus is used for
the determination of the latter age. However, if we can finally assume that the
menstrual age of all conceptuses exceeds their true age by about 10 days, then
they must have lived up to the time of abortion, or, strictly speaking, a few days
beyond it. That death of the cyema is not the cause of hydatiform degeneration
is indicated also by such specimens as No. 2411, represented in figures 143 and
144 (plate 14, Chap. X), a twin, double-ovum pregnancy, in which both the
cyemata and the chorionic vesicles show considerable and apparently the same
degree of maceration (figs. 145 to 147). Since both chorionic vesicles also show
the presence of quite general hydatiform degeneration, it is evident that if the
latter had arisen only after the death of the eyemata the vesicles should not
show anything like a corresponding degree of maceration, unless perhaps the
time of retention had been considerable.

Many other specimens of single pregnancy could be used to illustrate the
same thing, and since the development of hydatiform degeneration undoubtedly
is not a fulminating one, it might be expected that considerable development
of it might occur before the death of the cyema, which is due apparently to the
obliteration of the villous circulation. Since blood-vessels can and do arise in the
chorionic villi quite independently of those in the cyema, it also seems possible
that young chorionic vesicles showing hydatiform villi with disappearing blood-
vessels may be found, even if the intra-cyemic circulation never developed or never
united with the extra-cyemic or chorionic circulation. Such a surmise does not
imply, however, that hydatiform degeneration never begins before the blood-
vessels appear.

Of the many explanations which have been offered for the advent of hydati-
form degeneration, none seems to be better established than that of endometritis.
This was first emphasized by Virchow (1863). Lwow (1892) also reported 4
cases in patients under his care in whom lues could be excluded, and in whom he
held endometritis responsible. Emanuel (1895) was the first, it seems, to demon-
strate the presence of cocci in inflammatory foci of round cells in the decidua
accompanying a case of hydatiform mole. Veit (1899) also believed that disease
of the decidua is the cause of hydatiform degeneration. Veit further stated that
Waldeyer, Jarotzky, and Storch also believed that an irritative condition of the
decidua is responsible. Stoffel (1905) also found cocci other than gonococci present,
and says he can not avoid holding endometritis responsible in his case. The asso-
ciation of hydatiform degeneration and endometritis was noted also by Marchand
(1895), Oster (1904), and Sternberg; also by Essen-Moller, who reported the phe-

226 STUDIES ON PATHOLOGIC OVA.

nomenal case of a woman with endometritis, who had aborted a hydatiform mole
18 times in 9 years. Falgowski, on the contrary, concluded that the ova themselves
were diseased and argued that hydatiform degeneration should be much more com-
mon if it were due to endometritis. Taussig (1911) also stated that leucocytic
infiltration of the decidua is frequently present in hydatiform moles, but insisted
that “leucocytie infiltration in the placenta then should not be interpreted as
infection. . . . Inflammation and infection should be kept apart.’ I pre-
sume Taussig really meant infiltration and infection should be kept apart, and the
question then turns upon the structure of the normal decidua and the significance
of infiltration for the development of the ovum.

It may be recalled that Marchand (1904) reported the presence of isolated
groups of small cells in the normal decidua which looked like mononuclears under
low magnification, and which he believed have often been confused with them.
But even granting this, and the further facts that the exact histologic changes in
the decidua are not fully known, and that it is rather difficult to ascertain just what
decidual changes are regarded as evidence of the existence of an endometritis, any
one examining a large series of cases of hydatiform degeneration aborted with the
decidua can not doubt the presence of marked decidual changes in a very large
percentage of them. These changes are not limited to infiltration with scattered
round cells or erythrocytes, or to focal accumulation of the same, but often extend
to almost complete fibrosis, as shown in figure 135, plate 13 (see Chap. IX), so
that experienced investigators have mistaken the thin, fibrous decidua for a part
of the chorionic vesicle.

It is true that the existence of these changes in the decidua does not neces-
sarily imply that they were antecedent to the implanation of the ovum, but for-
tunately the clinical histories and material from curettage often supply crucial
evidence. From such cases and from the cumulative weight of evidence from the
large series of cases here reported, the great majority of which showed decidual
infiltration or other changes suggestive of endometritis, the frequent association
of abnormal deciduze with hydatiform degeneration is evident. The fact that the
incidence of hydatiform degeneration in the tubal was considerably higher than
that in the uterine series might be regarded as contradicting this relationship,
but such is not the case. The mucosa of the tubes at best is an unfavorable nidus
for implantation because of the absence of decidual formation alone. Hence, even
if salpingitis were somewhat less frequent than endometritis, difficult nidification
in the tube could easily more than account for the existing differences. Hence the
higher incidence of hydatiform degeneration in the tubal series in fact becomes
confirmatory of the conclusion that abnormal nidification really may be responsible
for the advent of hydatiform degeneration.

The only fact which might be interpreted as indicating that germinal defects
primarily are responsible for the development of hydatiform degeneration is the
relatively higher incidence of the condition in older women. Against this, however,
stands the other fact that such women also show the cumulative effects of endo-
metritis and pregnancy upon the endometrium. Furthermore, since hydatiform

HYDATIFORM DEGENERATION IN UTERINE PREGNANCY. 227

degeneration so often follows one or two normal births or abortions, it would be
impossible to find an adequate explanation for the release of the defective ova so
often after and not before these events.

I am reminded also in this connection of a case the detailed history of which
is fully known. It is that of a robust young woman who successively gave birth
to two moles and then to a normal full-term child and secundines. In this case
curettage was done in connection with each mole. Apparently the new endome-
trium, which had formed after the second abortion and curettage, permitted
normal implantation and normal development to progress to term. To ignore the
condition of the endometrium in this case and attribute the development of hydati-
form degeneration to the successive releases of abnormal ova would seem to dis-
regard important facts—especially so since no one has established the occurrence
of abnormal ova within the Graafian follicle, a possibility which I do not wish to
deny, although Donskoj’s report of a case of hereditary mole must surely be taken
cum grano salis.

That an abnormal nidus may be responsible for the advent of hydatiform
degeneration would seem to be indicated also by the fact that the process usually
was better developed and more general in the tubal than in the uterine cases. That
both endometrium and decidua show astonishing differences in structure under
pathologic conditions is well known. The entire tubal mucosa, on the other hand,
even when normal, forms an abnormal nidus which would affect all portions of early
chorionic vesicles somewhat alike, and since, as found by Mall, inflammatory con-
ditions in the tubes predispose to tubal implantation, the higher incidence of hydati-
form degeneration in the tubes is easily explained. Nor does the existence of partial
hydatiform degeneration argue against such an explanation.

Although Kehrer reported not a single fatality in 50 cases of hydatiform mole,
Hirtzman (according to von Winckel) gave the fatality as 13 per cent, Dorland and
Gerson as 18, and Williamson as 20 to 30 per cent. Von Winckel (1904) regarded
these percentages as entirely too high, however, although Oster (1904) reported 2
cases of malignancy out of 15 cases in which the late results were ascertain-
able. This is an incidence of 13.3 per cent. Since none of 15 patients who had
suffered from hydatiform mole had a recurrence, Oster concluded that the cause
of hydatiform degeneration is a fortuitous one. Schickele (1906) stated that only
3 cases of hydatiform mole with coincident chorio-epithelioma were found in the
literature; and Nattan-Larrier and Brindeau (1908) seem to avoid the implied
difficulty by premising the existence of a histological as contrasted with a clinical
malignancy, a distinction which recalls the conclusion of Schickele that it does not
follow that not all hydatiform moles are malignant merely because not all of them
cause the death of the patient. Kroemer (1907) found that chorio-epithelioma
developed in 5 out of 15 cases of hydatiform moles, or in 33.3 per cent, but only
twice in 3,841 “normal implantations.’’ Daels (1908) says La Torre claimed a
malignancy of 64 per cent, de Senarcleus one of 28.7 per cent, or 14 out of 49 cases.
L. Fraenkel (1910*) emphasized that the estimates of the number of cases in which
hydatiform degeneration is followed by malignant disease vary greatly, while

228 STUDIES ON PATHOLOGIC OVA.

Robertson (1915) quoted Findlay as finding that 16 per cent of 250 hydatiform
moles collected from the literature were followed by malignant disease. Briggs,
who reported 21 cases of hydatiform degeneration with 2 of chorio-epithelioma, or
an incidence of malignancy of 9.5 per cent, called attention to the “diminishing
ratio in the tendency to malignancy” shown by his series.

Findlay (1917) stated that chorio-epithelioma developed in 131 out of 500 cases
gathered by him from the literature, which is an incidence of 26.2 per cent, but,
as already stated, most of these cases from the literature are old, advanced degenera-
tions, many of which have been retained for a long time. The tendency to malig-
nancy in these probably can in no way be compared to that in smaller and younger
specimens, many of which are aborted entire with the surrounding decidua.
Consequently it need not surprise us that out of 19 cases of this series, in which
later reports were obtainable, none was reported as having developed chorio-
epithelioma.

Perhaps I may add a word of caution in regard to a possible change in atti-
tude toward the question of malignancy with a consequent relaxation of vigilance.
It is true that out of the 21 cases of Briggs only 2 developed chorio-epithelioma;
but it must not be forgotten that Briggs in part was, and I to a far larger extent am,
dealing with a different class of hydatiform moles than those upon a study of which
the prevailing conception of malignancy is based. Hydatiform moles which
continue to grow and which survive for months after the death of the embryo
evidently are more vigorous, and hence no doubt also more dangerous than those
which are aborted early and spontaneously. Since the latter formed the great
majority of all moles here considered, opinions regarding malignancy formed on
this basis probably would lead to disaster if applied in practice. Such conceptions
would be based upon a totally different incidence than the current one of 1 hydati-
form mole in every 2,000 cases. Instead of relaxing our vigilance, it would seem
wise to increase it, particularly in the cases of so-called spontaneous abortions—
the cases in which no ascertainable cause for the termination of pregnancy can
be found, especially if the chorionic vesicle is empty or if the embryo belongs in
one of the early groups of Mall’s classification.

The average age of 36 women aborting hydatiform moles was 31 years. Al-
though I do not regard the alleged ages as necessarily the actual ones, this average
age agrees very well with that of 6 cases reported by Poten, 10 by Donskoj, 23 by
Briggs, 6 by Gromadski, and 8 by Robertson. The average age of Poten’s cases
was 32 years, of Donskoj’s 25 years, of Brigg’s 28 years, of Gromadski’s 29.6
years, and of Robertson’s 28.4 years. Pazzi (1908”), on the other hand, stated that
Briquel placed the greatest frequency of hydatiform degeneration between 20 and
30 years. These averages are so far on the near side of the menopause that one can
make liberal allowances for the proverbial disinclination of women to state their
exact age, even to physicians, and nevertheless regard the prevailing opinion
regarding the greater frequency of hydatiform mole near the menopause undoubt-
edly as ill-founded. If, as Lewis and Lewis (1906) stated, it is necessary to add
only half a year to the average age of a large group of women in order to ascertain

HYDATIFORM DEGENERATION IN UTERINE PREGNANCY. 229

the actual average age when considering general social statistics, then everyone
will admit that still less allowance than this need be made in the ease of women who
are speaking to their physicians, knowing that whatever they may say will be
regarded as strictly confidential. That it is unnecessary to make large allowances
for understatement of their age on the part of these women is indicated also by
the average duration of their married life before aborting moles. This in the case
of 29 women was 7.1 years. Hence, if one bears in mind that the average age of
first marriages, according to Webb (1911), is 25.1 years, one easily can see that the
average age of the women aborting hydatiform moles, which was given as 29.6
years, probably is not too low at all, thus confirming the findings of Williamson,
who denied that hydatiform mole was especially common near the menopause.

The conclusion that the average age of 29.6 years undoubtedly is near the
actual is confirmed also by the fact that a hydatiform mole was the first abortion
in 19 out of 41 women, or almost half the number; 12, or almost one-third, had
aborted twice; and only 10 had aborted more than twice. But what is still more
confirmatory is the existence of a surprising parallelism between the data on abor-
tion and those on births; 9 of 33 women had given birth to but 1 child, and an equal
number had given birth to but 2. Hence over 50 per cent of the 33 women had
borne children twice, or less than twice, and only 15, or less than half, had borne
oftener than this.

This undoubted evidence of the youth of these women is confirmed still further
by the statement of Lewis and Lewis, who, from an analysis of 16,325 first births,
found that nearly one-half of them occur between the ages of 20 and 24, and
almost three-fourths between 20 and 29 years, although first births are more
frequent between 30 and 40 than between 15 and 19 years. I realize that social
statistics can not be translated from one country to another without modification,
but in such a mixed population as ours this modification probably need be less,
rather than greater, than in case of some countries.

The conclusion that the occurrence of but a single birth before the advent of
hydatiform degeneration probably implies that such women are relatively young
is emphasized still further by the statement of Lewis and Lewis that in one-third
of the marriages in Scotland ‘‘the bride had a child when unmarried or was preg-
nant at the time of marriage,’”’ and that 50 per cent of the first births in Scotland
occur within 9 to 24 months after marriage. Lewis and Lewis also give the
average interval between marriage and the first birth in 16,176 cases as 13.54
months, but little more than one year. Since Lewis and Lewis stated that the
interval between the birth of the first and that of the second child is but little longer
than that between marriage and the birth of the first child, being only 3.07 years, it
is evident that not even those women who had borne two children before the advent
of hydatiform degeneration could have been near the menopause. This conclusion
is emphasized still further by the fact that in 96.12 per cent of 16,176 fruitful
marriages fertility was demonstrated within three years after marriage.

Nevertheless, in spite of the clear implication of all these facts, I wish to
emphasize again that since what have been heretofore regarded as hydatiform

230 STUDIES ON PATHOLOGIC OVA.

degenerations were large specimens mainly, it well may be, and according to certain
authors it is true, that such cases occur later in the reproductive life of women. Yet
it certainly is significant that Findlay, in tabulating 500 such cases from the
literature, found that 275, or 55 per cent, occurred before the thirty-fifth year, and
of 36 specimens from the Carnegie Collection 23, or 63.6 per cent, came from
women below this age. It may also be recalled that 78 per cent of Kehrer’s
50 cases and 90 per cent of Bloch’s occurred before the fourth decade. That
hydatiform degeneration may occur very early in life is suggested by the remark-
able case of Stricker (1879) in a precocious child of 9 years.

Fourteen out of 23 cases, or 61.3 per cent of the uterine series, in which the age
was given, occurred at or before the thirtieth year, and 18, or approximately
80 per cent, at or before the thirty-fifth year. These things abundantly empha-
size the conclusion, reached by some investigators, that hydatiform mole is
not absolutely more common at or near the menopause; but it nevertheless may be
relatively more common. That is, the number of hydatiform moles aborted after
40, compared with the total number of pregnancies or births after 40, actually may
be greater than this ratio before 40 years.

From calculations based on data given by Lewis and Lewis, the average
number of births occurring after 40 years in Sweden, Norway, Denmark, Bruns-
wick, Berlin, Budapesth, France, and Scotland is 9.9 per cent. This agrees
remarkably well with Bloch’s estimate of 10 per cent. But if 77.2 per cent of
the cases of hydatiform mole occur below 40, and 22.8 per cent after that year,
then it is evident that hydatiform mole nevertheless is relatively more common
after than before 40 years, for approximately one-fourth of the cases of hydatiform
degeneration would be associated with one-tenth of the births. This would be an
increased frequency of 300 per cent after 40 years. A similar result would be
obtained by comparing Findlay’s or Williamson’s series. Hence, hydatiform
degeneration, though absolutely less, is relatively more frequent in later life. This
fact, however, does not necessarily imply that age in itself is responsible for the
increased incidence after 40. A comparison of the incidences of hydatiform degen-
eration in young and old primipare, of good health, might elucidate this question.

These statistics are not in agreement with the prevailing opinion that hydati-
form moles are more common in multipare than in primipare. Indeed, they
suggest rather that after the first conception, which was normal in a large per-
centage of these young women, something happened which interfered with the
normal development of succeeding conceptions. That, it seems to me, is extremely
significant and very suggestive. Here is a group of relatively young women, over
50 per cent of whom had borne but twice and some only once, and then gave birth
to a hydatiform mole. While I realize the necessity for cireumspection, especially
in these matters, these facts seem to me to suggest that something happened to
a normal endometrium. Other facts also point in the same direction.

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DESCRIPTIONS OF PLATES. 231

DESCRIPTIONS OF PLATES.

Puiate 8.

. Young chorionic vesicle in situ, showing hydatiform degeneration of the stroma and syncytial budding.

No. 836. X2.6.

. Same, under greater enlargement, with the cyema in view. 3.75.

. Hydatiform degeneration. A small portion of No. 1189 still in loco. 4.5.

. Another portion of the same specimen. 22.5.

. External appearance of an apparently normal conceptus, partly surrounded by decidua. No. 2077. 0.75.
. A portion of the same specimen, clearly showing hydatiform degeneration where in focus. The decidua

is reflected. 3.

. Portion of villi from No. 690, showing numerous syncytial buds, absence of vessels, and glassy stroma.

37.5.

. A chorionic vesicle showing shaggy appearance. No. 2258. 1.5.

. Hydatiform villi from same specimen. 4.5.

. Macerated normal villi in blood clot. No. 640. X71.

. Well preserved, early hydatiform villi from the same specimen. 33.25.
. Hydatiform villi without marked epithelial proliferation. No. 720b.

PLATE 9.

. Hydatiform villi with pronounced epithelial proliferation. No. 720b, also shown in figure 107. 50.
. Hydatiform villi without (at left) and with marked epithelial proliferation (at right). No. 540.

. Fairly late stage in the degeneration of the villous vessels in hydatiform villi. No. 977. 450.

. A slightly later stage in the degeneration of the villous vessels. No. 516.

. Almost complete disappearance of the vessels. No. 874b. X50.

. Non-vascular, early hydatiform implanted villi. No. 396. 450.

Puate 10.

. Portion of No. 435a, showing a small villus in the center with an extremely long syncytial bud. 450.
. Framework of syncytium arising from the chorionic membrane and from the villi. No. 962a. 450.
. Apical trophoblastic nodule. No. 516. x6.

. A portion of the chorionic membrane from No. 714, showing decidedly sinuous epithelium. 50.

. An early, non-vascular, hydatid villus from the same specimen, showing constrictions. 450.

. Epithelial vesicles within the stroma. No. 872. 180.

. Extremity of an epithelial vesicle within the stroma, same specimen. 300.

PuaTeE 11.

. Slight epithelial proliferation on markedly hydatiform villi. No. 134. X50.

. Extremely marked epithelial proliferation on a small hydatiform villus with glassy stroma. No. 415. X95.
. The disintegrating capillaries are represented merely by large, incomplete curved outlines. No. 749. 50.
. Collapsed capillaries in process of obliteration. No. 712. X95.

. Fenestrated, macerated, hydatiform villi among others which are quite fibrous. No. 651d. 50.

. Villi showing only a trace of the capillaries. No. 651g. 450.

Puate 12.

. Section of a villus from No. 510, showing scattered Hofbauer cells. 300.

. Section of a villus from No. 749, showing accumulation of Hofbauer cells, especially at the right. 50.

. A somewhat macerated normal embryo from a case of early hydatiform degeneration. No. 2099. X6.

. The chorionic vesicle of the same specimen, showing early hydatiform villi to left where in focus. X4.

. Basal area of No. 1260, showing pronounced hydatiform degeneration of the villi. 1.

. The same specimen, opened in the capsular region to show the presence of the cyema. X1.1.

. Marked macerated and deformed fetus from the same case. 4.

. Twin fetuses, No. 2250a and b, a case of hydatiform degeneration. 1. (See also figs. 141 and 142,

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CHAPTER IX.
HYDATIFORM DEGENERATION IN TUBAL PREGNANCY.

Strangely enough, the occurrence of chorio-epithelioma arising from tubal
pregnancy seems to be better known and also better established than the occurrence
of hydatiform mole within the tube. This is especially surprising in view of the
stress laid by Marchand (1895) upon epithelial proliferation in cases of hydatiform
mole and in view of the fact that trophoblast formation and epithelial prolifera-
ticn in general have been regarded as being greater in tubal than in uterine
implantation. This is illustrated well by such cases as that of Fellner (1907), in
which it was impossible to distinguish, by histologic examination, between the
epithelial proliferation present in a case of tubal pregnancy and chorio-epithe-
lioma. From these circumstances alone it seems to me that one might expect
hydatiform degeneration to be relatively more common in the tubes. Moreover,
when it is recalled that experts still regard it as impossible to decide upon the ques-
tion of malignancy or benignity in cases of suspected uterine chorio-epithelioma
from histologic preparations alone, this surmise gains more in probability. The
presence of hyperactivity in the trophoblast in many cases of tubal as compared
with that in uterine pregnancy was confirmed also by personal observation, and
if, as stated by Teacher (1903), chorio-epithelioma arose in hydatiform moles in
approximately 40 per cent of 287 cases, and according to Seitz (1904”) and Fraenkel
(1910) even in 50 per cent, the occurrence of hydatiform degeneration in tubal
pregnancy can hardly be doubted because of this fact alone.

Nevertheless, of the 7 cases of tubal hydatiform moles cited by him, Werth
(1904) regarded only the case reported separately by von Recklinghausen (1889)
and by W. A. Freund (1889) as well authenticated. Werth reserved judgment, how-
ever, on the case of Matwejew and Sykow (1901), a report upon which was acces-
sible to him, and to me, in a short review only. Seitz, however, accepted the short
review of this case as convincing, nor did he question the case of Otto (1871), or
that of Wenzel (1893),and he incorrectly credited Wenzel with two cases. Werth,
on the contrary, regarded these last two cases, and also that of Croom (1895),
which was accepted also by Veit (1899), as undoubted instances of “simple
hydropic degeneration of the connective tissue of the villi so common in aborted
chorionic vesicles, both from the tubes and from the uterus.”” Werth unfortunately
did not state just what he meant by “simple hydropic degeneration’’, but since
he spoke of it as common in aborted ova, one may conclude that he referred to
changes in the chorionic vesicle which followed its isolation within the uterus after
complete detachment from its implantation site. For want of a better term, such
changes may, I presume, be spoken of as maceration changes, although usually
they occur under non-putrefactive conditions. However, I do not thereby imply
that these changes are similar under sterile and under putrefactive conditions.

Since Werth spoke of simple hydropic degeneration in aborted ova, he did
not, I take it, refer to a dropsical condition of the villi, possibly due to an obstruc-

233

234 STUDIES ON PATHOLOGIC OVA.

tion of the venous return, for such a condition necessarily would be rare and not
common. Moreover, this condition of necessity would have to arise before and not
after the death of the embryo and detachment of the chorionic vesicle. As in one
of the cases of Hiess (1914), such a specimen also should contain blood-vessels;
for, as emphasized also by Ballantyne and Young (1913), the hydatiform villus
is not merely an edematous villus.

That any one at all familiar with hydatiform degeneration, in its earlier as
well as its later forms, could, upon gross and microscopic examination, confuse it
with maceration changes in a fairly well preserved specimen in any but its very
earliest stages does not seem possible to me. Normal villi contain capillaries, not
to mention other things characteristic of them. Hydatiform villi, on the contrary,
do not contain them, or only very rarely so, and only in the early stages. When a
villus becomes hydatiform—that is, when liquefaction of the stroma occurs—this
liquefaction appears in more or less restricted portions of the villus, thus giving rise
to the long fusiform and later spherical vesicles so characteristic of hydatiform
mole. But when a villus becomes macerated the change is general, and usually is
noticeable also in the embryo and chorionic membrane itself, or at least within the
epithelium. The latter usually is lifted from the stroma here and there, the caliber
of the entire villus is increased, and the capillaries and the stroma show maceration
changes as the villus becomes more translucent. This increase in caliber of the
entire villus is not due to local liquefaction of the stroma, but to the pseudo-edema
occurring in a villus of normal structure and form. In hydatiform moles, on the
contrary, the epithelium not only is firmly attached but usually hyperactive. The
changes characteristic of hydatiform degeneration may and often do appear in the
villi while they are still implanted, and not only after the chorionic vesicles are
detached. This does not imply, however, that the villi of a detached hydatiform
mole can not also undergo maceration changes. They frequently do so, and
it is in such cases as these that differentiation may be difficult or impossible, espe-
cially if it is to be made from an examination of ill-preserved fragments only. The
same thing is true also of the villi in the early stages of hydatiform degeneration
and maceration, especially when the latter masks the former. The difficulty would
be still greater in case of whole chorionic vesicles which are almost completely
dissolved, leaving only a shadow picture formed by a coagulum without nuclei,
which nevertheless may retain almost perfectly the form of the chorionic vesicle
and of the individual villi. It may long be impossible to differentiate such cases
as these, but they form only a relatively small proportion of the whole. The many
cases both of uterine and tubal chorionic vesicles which still were implanted and
show exceedingly fine instances of hydatiform degeneration, as well as the many
splendid examples of groups of villi which were still implanted in the tube or in the
decidua, and which were equally good examples of hydatiform degeneration, leave
no room for doubt as to the surprising frequency in the occurrence of this con-
dition, even after due allowance is made for the doubtful cases.

A careful examination of the few cases from the literature which have been
regarded as instances of pseudo-hydatiform degeneration leave one wholly uncon-

HYDATIFORM DEGENERATION IN TUBAL PREGNANCY. 235

vinced as to the occurrence of such a phenomenon. No one will deny that many
hydatiform chorionic vesicles are retained long after the death of the ecyema.
The material with which I dealt suggested very plainly that even isolated villi
can and do survive a surprisingly long time; but Herzog (1898), from an examina-
tion of 7 tubal pregnancies, came to the conclusion that ‘‘chorionic villi degenerate
with astonishing rapidity after the death of the embryo. This appears to be
especially true of villi of young placente.” Although the use of the word placente
suggests that Herzog really was not speaking of very young conceptuses, he never-
theless added that only the most intimate acquaintance enables one to recognize
villi after the embryo has been dead two or three weeks.

As stated in the preceding chapter, the cyema usually is absent in older, large
hydatiform masses, only remnants of the chorionic membrane and villi remaining.
Were these hydatiform vesicles not retained, the cyema would not be missing in
any but possibly some extremely young vesicles, and if retention per se were the
cause of hydatiform degeneration, then the latter should not only be best de-
veloped, but also most frequent among those longest retained. This, however, is
not the case. Furthermore, the high incidence of hydatiform degeneration in tubal
pregnancies, to which attention was called by Meyer (1919"), also shows that long
retention is not necessary for the development of splendidly typical and universal
hydatiform degeneration. Some of the finest specimens were found among tubal
pregnancies in small chorionic vesicles in which cyemata still were present. If
retention alone were the sine qua non, then hydatiform degeneration should not
be so common under conditions which preclude long retention. Even Marchand
(1895) found it well to emphasize that ‘Nicht jedes abortiv-Ei wird zur Blasen-
mole, nicht jede Blasenmole zeigt denselben Grad der Epithel Wucherung.”’

Werth further concluded that not one of the 7 cases of chorio-epithelioma
regarded as having arisen from tubal pregnancies recorded before 1904 was suffi-
ciently authenticated. Nevertheless, by 1910 Veit felt justified in saying that a
considerable number of cases of chorio-epithelioma arising from tubal pregnancies
had been described. He added that Risel (1895) gathered 11 cases from the litera-
ture and that a second case had been reoprted since Risel’s paper. Since my interest
in the subject is largely incidental, I have not taken the trouble to gather from
the literature cases of chorio-epithelioma alleged to have arisen from tubal preg-
nancies which may have been reported since Veit wrote. Moreover, I could not
presume to judge these cases critically. Hence I will accept the fact that chorio-
epithelioma arising from tubal pregnancy is regarded as established by a number
of investigators. If the conception regarding the relation of chorio-epithelioma to
hydatiform mole is justified, then the occurrence of hydatiform degeneration in
tubal pregnancy must follow on a priori grounds alone. Moreover, whatever the
causes of hydatiform degeneration may be, one is possibly safe in assuming that the
condition is not restricted to the uterus, and when I noticed that hydatiform
degeneration was so very common in young uterine abortuses the surmise that it
might be still more common in cases of tubal pregnancy seemed justified. Since
over 100 specimens of tubal pregnancies from the Carnegie Collection were included

236 STUDIES ON PATHOLOGIC OVA.

in the survey originally planned by Mall, a study of these specimens formed an
excellent opportunity for observations on this subject.

That the case of Otto, with its pathetic history, really was one of tubal hydati-
form mole, can not be doubted, in view of the careful description of the whole case—
its clinical history, necropsy, and the histologic examination. This case is interest-
ing also because the degeneration was in its early stages, the hydatids being only as
large as a pinhead and the embryo still being present. Moreover, from Otto’s
description it is very likely that the specimen contained Hofbauer cells, discussed
in a later chapter.

The history of the case observed by Wenzel in 1855 and reported in 1893 is
equally complete and equally pathetic, as could be surmised by all familiar with
the history of tubal pregnancy. In this case the mole was as large as a “hen egg,”
the hydatids varied in size from a dot to a “‘bird cherry” (wild? cherry), and the
degeneration was universal, although the menstrual age of this specimen was given
as only 51 days. It is significant that Wenzel expressed surprise that even excellent
handbooks of the day had nothing to say about hydatiform mole in cases of tubal
pregnancy, except perhaps to refer to the case of Otto. Nor does the case of Wenzel
seem to be the first one observed or that of Otto the first one reported, for Storch
(1878), in truly epochal, though largely ingored, observations on hydatiform mole,
cited Hennig (1876) as stating that two cases of moles in the tube were reported by
Blasius (very likely E. Blasius, 1802-75). Since Storch wrote on hydatiform mole,
it is implied that Blasius saw one of these and not one of another type of mole, and
since hydatiform mole is such a striking condition and has evoked much more
interest than the other forms, an observation regarding it in the tubes well might
travel down the decades, particularly since, until recently, the occurrence of
hydatiform degeneration in the tubes was regarded as extremely rare. This is
indicated also by the fact that Menu (1899) still referred to the case of Otto as a
curiosity.

Pazzi (1908”) stated that two cases of extrauterine moles have been described
each by Hennig (1872), Farell (1893), Donald (1902), and one case each by Otto,
Freund, Theileher, Maret, Matwjew (Matwejew?) and Sycow (Sykow?), and
Bland-Sutton, and one case of ovarian mole by Wenzel (1893). Wilkinson also is
said to have described a case of rupture of the tube with reduction of the mole to the
size of a cherry, and Lob (1902) a case of molar tubal pregnancy without cessation
of menstruation. Since I am quoting Pazzi essentially verbatim, it is evident that
he did not read the literature critically or discriminate between ordinary and
hydatiform moles, but was misled-by the old inclusive and confusing usage of the
terms mole and molar, still current at the present day.

Krueger (1909) also reported a case of hydatiform mole with a cyst as large as
a “walnut.” The pedicle was 4 cm. long and attached to the amnion near the
insertion of the cord. Krueger spoke of this as a placental cyst, but regarded it
as a hydatiform-mole-like structure which, microscopically, was limited to a single
villus. If this were the only evidence presented by Krueger, one might well ques-
tion the nature of the cyst, but he added that microscopically the beginnings of

HYDATIFORM DEGENERATION IN TUBAL PREGNANCY. 237

hydatiform formations could be recognized on other villi also. Hence it would seem
that Krueger’s case must be added to the authenticated cases of hydatiform degen-
eration in the tubes.

So far as I am able to learn, then, the literature contains reports of but 9 cases
of hydatiform mole occurring in the tube, and of these 2 or 3 cases are not well
authenticated. These 9 cases are formed by the 2 cases of Blasius or Hennig, that
of Otto, of von Recklinghausen and Freund, and of Wenzel, the 2 of Croom, that
of Matwejew and Sykow, and that of Krueger. A critical reading of Hennig’s
book on diseases of the tubes and tubal pregnancy makes it quite clear, however,
that Hennig merely said that Blasius discovered ‘“‘tubal moles” and that he ob-
served 2 and Behm 1 case of abortion of tubal moles. From the context it is alsa
very clear that Hennig was not discussing hydatiform moles, although it is not
possible to say whether he meant that he himself or Blasius observed 2 cases.
I should judge that the latter is the idea it was meant to convey. To these 7
authenticated cases I would add that of Maxwell (1910). In reading Maxwell’s
description one must feel that he himself regarded the case as one of hydatiform
mole, but deferred to the opinion of the ‘““committee.’’ This is suggested also by
the title of his article. The illustration which accompanies Maxwell’s article is so
very suggestive, and his description so characteristic of hydatiform mole, that it
seems very probable indeed that the specimen really was such. Maxwell stated,
for example, that “‘sections of the villi embedded in the wall of the tube have the
typical structureless, bloated appearance of such pathological villi; and though
there is no central cavitation in the villi, their structure, associated with the active
proliferation of the Langhans layer, suggests that one is looking at a stage just
short of vesicle formation.””? Moreover, as I am about to show, hydatiform mole is
so very common in tubal pregnancies as to increase still further the likelihood that
Maxwell’s case actually was one of hydatiform mole. However, this is merely
an opinion, and only a completer description or an examination of the specimen
itself could decide the matter.

In connection with what was said before, it was interesting that Maxwell also
emphasized that epiblastic activity is increased in all abnormal sites of implanta-
tion, but anyone interested in the problems of tubal pregnancy and acquainted
with Mall’s (1915) findings will be struck by Maxwell’s statement that microscopi-
cal examination of many cases of tubal gestation lends no weight to the view that
chronic inflammation of the tubes is at all a common causal factor of tubal preg-
nancy. Nor can I refrain, in this connection, from quoting the uncontradicted
ae of Doran, expressed in the discussion of Maxwell’s case, that tubal gesta-
tion ‘‘probably 22s some general deterioration in the generative power
among civilized women.’

To the 8 cases contained in the ineeranine I wish to add 48 found among the
first 1,200 accessions from the Carnegie Collection. Nor is it necessary to stop with
these, for this collection contains many more not here included. It is merely a
matter of recognizing the specimens by a routine examination, and since this paper
has been written a number of specimens have been recognized among the daily

238 STUDIES ON PATHOLOGIC OVA.

accessions of tubes received through the unselfish efforts and the scientific interest
of practitioners in all parts of the nation.

In addition to over 100 free specimens of uterine hydatiform degeneration,
I have also seen more than a dozen fine specimens in large sections of uterine
implantation sites, and some entire specimens still embedded in pregnant uteri and
tubes. Indeed, how many cases of hydatiform degeneration one can find in con-
ceptuses in tubal or hysterectomy specimens will depend very much upon the care
with which the examination is made, for the condition undoubtedly is extremely
common, and not rare, as heretofore supposed.

Although the alleged menstrual age of these conceptuses ranged approximately
from 6 to 218 days, most of them were young empty chorionic vesicles or mere
remnants of such. Portions of quite a number were still implanted within the tube,
however, and among these were two unusually fine ones in a rare specimen of twin
pregnancy in a tube donated by Dr. Cecil E. Vest, of Baltimore. Since the ques-
tion of superfetation has been raised also in connection with twin tubal pregnancies,
I hasten.to add that such a phenomenon, even if it ever occurs (which seems exceed-
ingly doubtful), can be excluded absolutely in this case. Both chorionic vesicles
were approximately of the same size and lay in practically the same cross-section
of the tube, the surfaces of contact being flattened.

There were 40 tubes containing villi only, and in 14 of these hydatiform
degeneration probably was present. In 10 specimens its presence was undoubted,
but in 4 it was probable only. I realize that this margin of probability is exceedingly
large, but this is easily understood if it is recalled that often only a few degenerate
villi embedded in clot were contained in the cross-sections of the tubes, and that
only a few sections were examined, not, of course, a complete series of each tube.
Had the entire tubes been examined, or if more villi had been present, and if
those present had been better preserved, the difficulty would have been almost
wholly obviated. However, it is idle to set forth these things, because such con-
ditions never will obtain, and the margin of probability becomes greatly reduced
if it is remembered that in a large series the specimens necessarily supplement each
other. Moreover, the changes in the villi often are so typical that they are unmis-
takable, even if only a few villi are present. Besides, examination in complete
series undoubtedly would increase, not decrease, the number found. In some of the
doubtful cases the existence of hydatiform degeneration became probable only
upon comparison with the many uterine specimens previously examined.

The evidence offered by the 36 tubal specimens in the second group, which is
composed of empty chorionic vesicles or parts thereof, was very conclusive, for the
cut portions of most of these tubes contained considerable portions or even sections
of whole chorionic vesicles, sometimes quite free from clot. Some of them were
implanted almost perfectly in the wall of the tube, and although many of them
were folded extremely and collapsed more or less, small areas of several were never-
theless implanted undisturbed within the tube. The villi in some of these implanted
specimens were so characteristic and the whole picture so exquisite that the spee-
imens rightly belong among the very finest instances of hydatiform degeneration
found anywhere so far. This is true in particular of the case of twin pregnancy re-

HYDATIFORM DEGENERATION IN TUBAL PREGNANCY. 239

ceived from Dr. Vest. In this specimen the two chorionic vesicles, the intervillous
spaces of which were devoid of blood, lay in almost the same transverse diameter of
the tube, and hence had distended the latter considerably. Both were implanted
quite well over the entire area of contact, which included the whole perimeter of the
tube. The chorionic vesicles were flattened at the region of mutual contact, which
divided the tube somewhat unequally (fig. 13, plate 2, Chap. IV). Although the
embryo and the amnion long had disintegrated completely, and although the
chorionic membrane itself is thin, covered by degenerate epithelium and also dis-
integrating, the epithelium of the villi not only is well preserved, but is accompanied
by large masses of trophoblast and considerable syncytium. Syncytial buds are
found on the chorionic membrane also. The tubal mucosa is largely and the
tubal wall partly destroyed by the invading trophoblast. Only a few small vestiges
of the walls of the villous vessels remain, and the stroma of all the villi has under-
gone changes characteristic of hydatiform degeneration, as represented in figure
136. One villus also contains an epithelial cyst resulting from epithelial invagi-
to nation with subsequent isolation of the distal extremity, a process to be referred
later in connection with uterine specimens. Since most of the villi of this and
similar specimens still are implanted in the tube, there can no longer be any ques-
tion as to the time in which hydatiform changes in the stroma of the villi may
be inaugurated. As illustrated in other instances in which isolated and small
groups of villi were still implanted, the advent of degeneration of the stroma occurs,
in part at least, before the villus is detached. Hence it is not merely a post-mortem
or maceration change.

Another very interesting specimen of tubal implantation is No. 1771, received
from Dr. H. M. N. Wynne, of the Johns Hopkins Hospital. The menstrual age of
this specimen is 49 days, but its anatomic age, as based upon length according
to Streeter’s (1921) curve, is 37 days, thus showing a discrepancy of 12 days
between the menstrual and anatomic ages. The embryonic length is only 12.5
mm., although with a menstrual age of 49 days it should be at least 18 mm.
Upon examination, Streeter found the chorionic vesicle to contain a good deal of
magma, some of which was still adherent to the embryo, as figure 148 (plate 14,
Chap. X) shows. As has been repeatedly emphasized in the literature, the presence
of this coagulum in itself probably indicates that the embryo died some time
previously.

The wall of the tube is quite thin, as figure 138 shows, but the implantation is
fairly well preserved around the whole perimeter of the specimen. The mucosa is
destroyed throughout the greater extent of the section and the trophoblast is
abundant, except in one rather degenerate and hemorrhagic area. The chorionic
membrane is thin, but contains some vessels distended with blood. The stroma of
many of the villi also contains vessels filled with blood, but the vessels in many
others are very evidently in degeneration. The syncytium is scanty, and many
of the villi are very plainly hydatiform, as seen in figures 137 and 139.

A third exceptionally fine specimen of tubal hydatiform mole is No. 2052,
donated by Dr. C. L. Davis, of Washington, District of Columbia. Figure 140
shows a portion of the tube containing a hydatiform mole, some hydatiform villi

240 STUDIES ON PATHOLOGIC OVA.

of which protrude through an incision in the wall of the tube. The whole opening
is filled with typical hydatiform villi which are noticeable with the unaided eye and
perfectly evident under an enlargement of 4 diameters. They present an extremely
fine picture when seen with the binocular under a magnification of 10 to 20 diam-
eters. Examination under a higher magnification shows that the preservation of
the specimen is unusually good and that all the villi are markedly hydatiform.
Trophoblastic proliferation is so marked that in some places it gives the appear-
ance of decidual formation. Relatively little syncytium is present, but the tro-
phoblast invades the muscularis in many places and a good deal of coagulum is
present, most of it apparently having arisen from degeneration changes in the
stroma of the mucosa and from similar changes in the trophoblast and the mus-
cularis. The latter is moderately invaded by round cells. No remnant of the
wall of the chorionic vesicle or of the amnion or embryo could be detected in
the sections examined, both evidently having been absorbed completely, only some
of the villi remaining behind; or, the chorionic vesicle may have been aborted and
these villi left implanted within the tube.

Some exceedingly fine hydatiform villous trees were found among the speci-
mens in this group. Scaffoldings or frameworks formed by proliferating syncytium
arising from the epithelium of the chorionic membrane also were seen. Since the
syncytial buds were found far out on proliferations of trophoblast which capped the
villi, and also in the center of trophoblastic nodules, the origin of the syncytium
from the Langhans layer again would seem to be exceptionally well confirmed.
In some cases a detached hydatiform villus was fastened by opposite extremities
to two portions of the tube wall. It is well to remember, however, that one of these
attachments probably was gained before the separation of the particular villus
from the chorionic vesicle.

Of the 36 cases remaining in this group of chorionic vesicles without amnion,
after deducting 8 (7 of which belong in group 1 and 1 which belongs in group 2),
50 per cent showed the presence of undoubted hydatiform degeneration, and in
1 additional case its existence was doubtful.

Since only a few specimens are contained in each of the last five groups, I shall
treat them as one. Among 28 specimens remaining in these groups, 12, or 43
per cent, showed the presence of hydatiform degeneration, and 4 others were doubt-
ful. From this percentage it is evident that the incidence of hydatiform degenera-
tion among tubal specimens seems to increase rather than decrease with advancing
age of the conceptus, as was emphasized in connection with the uterine specimens.
This probably can be attributed to the fact that the specimens in the first group
are composed of villi only, and that many of the empty chorionic vesicles in group
2 were detached from the wall of the tube by hemorrhage before hydatiform degen-
eration had developed sufficiently to enable me to recognize it. Moreover, it must
be remembered that all tubal specimens, no matter in what group they are clas-
sified, are in fact young specimens, and since those falling in the latter groups
succeeded in maintaining a foothold in spite of repeated hemorrhages, a large num-
ber of them might rightly be expected to show the presence of a hydatiform change.

HYDATIFORM DEGENERATION IN TUBAL PREGNANCY. 241

The incidence of hydatiform degeneration in the 108 tubal pregnancies classed
as pathologic is 45, or 41.7 per cent of the whole. This is a somewhat higher
incidence than was obtained in the uterine abortuses classed as pathologic, and
may be accounted for partly, or even wholly, by the greater incidence of young
specimens in the tubal series. That the tubal specimens undoubtedly were y ounger
follows from common knowledge regarding tubal pregnancies alone, but it also
is shown by the average menstrual age, which was 43.4 days in 25 tubal as com-
pared with 66.6 days in 51 uterine specimens. Moreover, 32 of the 48 tubal speci-
mens of hydatiform degeneration, or 66.6 per cent, fall into the first two groups,
thus again showing that the majority are small, young specimens. However,
by comparing the percentage of hydatiform degeneration in the first five groups
of the pathologic tubal and uterine cases composed of conceptuses of approximately
the same age, the same difference in incidence is noticeable, it being almost twice
as great in the tubal as in the uterine series.

Although the incidence of hydatiform degeneration among the pathologic
tubal specimens is but slightly higher than that among the pathologic uterine
specimens, the incidence of hydatiform degeneration in all tubal specimens con-
tained among both the normal and pathologic is twice as high as that among the
same classes of uterine specimens. This can be explained only partly by the fact
that a larger proportion of the tubal specimens are young and pathologic. The
pathologic tubal specimens form 70.5 per cent of 153 normal and pathologic tubal
specimens found among the first 1,200 accessions, but the pathologie uterine
specimens form only 33.6 per cent of the normal and pathologic uterine groups
among the same accessions. But the real question remains, for the incidence of
hydatiform degeneration among the specimens classed as pathologic was essentially
the same in tube and uterus. Hence an increased incidence of 200 per cent in hy-
datiform degeneration in the tubes may be due to the less favorable nidus found
there. If so, it throws a very significant light upon the probable cause of hydati-
form degeneration, which would seem to lie in the conditions surrounding the
implantation and early development rather than in the ova or spermatozoa them-
selves.

The conclusion, reached in a study of uterine specimens, that hydatiform
degeneration is absolutely less, not more, frequent near the menopause is confirmed
also by the study of the tubal specimens. The average age of 20 women in the
tubal series was 33.9 years, as opposed to an average of 31 years obtained from 36
women in the uterine group. This age difference offers a tempting opportunity
for generalization, and did the statistics include thousands of cases one might be
willing to say that it points to a progressive change as cause, which begins in the
uterus and finally reaches the tubes. But strangely enough, the average number of
years of married life of 15 women in the tubal series is exactly the same as that of
29 women in the uterine series, or 7.1 years. This fact at once guards against a
venturesome hypothesis, for it allows a no longer period for the supposed ascending
change to reach the tubes than the uterus.

242 STUDIES ON PATHOLOGIC OVA.

Eight of 20 women from the tubal series had borne one child, 4 had borne two,
and 3 more than two, thus again more than confirming the statistical findings in
the uterine series, which show that 9 of 33 women had borne once and 18 but twice.
The parallelism between these statistics is striking indeed, especially if the small
numbers be considered; 14 of 23 women, or 60.8 per cent, in the tubal series had
aborted but once, as compared to 19 out of 44, or 46.3 per cent, in the uterine series,
a fact which again points to the middle rather than to the end of the reproductive
life of these women.

I do not know whether or not hydatiform degeneration in the tube also is
relatively more common near the menopause, for I have not been able to obtain
data on the relative frequency of tubal pregnancy in the different decades in the
reproductive life of women. However, since by far the greater number of pregnan-
cies usually occur early in this period, it probably would be safe to assume that most
of the tubal pregnancies occur also at this time. Consequently, it might well
follow that the ratio of tubal hydatiform degeneration to the number of pregnancies
occurring in the later actually might be greater than that in the earlier decades.

DESCRIPTION OF PLATE.

Puiate 13.

Fic. 135. A portion of a rather fibrous decidua. No. 874a. 300. (See Chap. VIII.)

Fig. 136. Hydatiform villi in section. No. 825. X45.

Fig. 137. Cross-section of tube and vesicle. No. 1771. 4.

Fic. 138. Cross-section of same, showing hydatiform villi. x2.

Fic. 139. Hydatiform villi from same, in section. X45.

Fig. 140. Hydatiform villi protruding through an incision in the tube wall. No. 2052. x2.

MALL AND MEYER

—.t

CHAPTER xX.
ALLEGED OCCURRENCE OF SUPERFETATION.

From time to time reports of alleged and apparent instances of human super-
fetation appear in current medical literature. Reports of similar instances in other
mammals occur also, although more rarely, in the nonmedical literature. As recent
instances of the former may be cited the cases reported by Logan (1917) and
Gustetter (1918). Of instances of the latter may be mentioned the cases of King
(1913), Sumner (1916), and Harmann (1917, 1918). The latter group of cases
were found in the rat, the mouse, the cat, and the cow, respectively.

Without accepting the alleged or apparent cases in mammals with bicornuate
uteri as unequivocal, it is easy to see that, aside from ectopic implantations, the
conditions under which superfetation necessarily would have to occur in the human
uterus may be totally different from those that may obtain in bicornuate uteri.
Since the usual intermenstrual period in women is 28 days, it would also seem,
as often asserted, that the older of two fetuses in a case of human superfetation
certainly would occlude the uterine cavity rather effectively, and alone make fertil-
ization of any ovum, liberated at a subsequent ovulation, difficult. It would seem
to do this, entirely aside from the possible effect of the cervical mucous plug so
frequently referred to in the literature.

These things are true especially in such instances as that of Gustetter, in which
the time interval between the ages cf two fetuses is estimated to have been as great
as 65 days. Moreover, it would seem that the development of the first fetus and
that of the corpus luteum in such a case as this would have inhibited the occur-
rence of subsequent ovulations. An obstacle to the implantation might also be
found in the condition of the decidua, even if later ovulation actually occurred.
Since Loeb (1912) found that in the pregnant guinea-pig the endometrium can not
be stimulated to form a new decidua, it is evident that the fertilized ovum might
encounter insuperable difficulties if similar conditions obtain in the human being.
However, if a young blastocyst really can become implanted on the bare surface
of an ovary, or on the peritoneum even, then it may well be doubted whether a
new decidual reaction is essential for implantation of the ovum in the human being.
Furthermore, when implantation in the Graafian follicle occurs, there is no de-
cidual reaction, at least nothing comparable to what occurs in the uterus, although
the proliferating luteal cells may possibly act vicariously to some extent. How-
ever, there are other obstacles to superfetation, such as those mentioned above
and the possible occlusion of the uterine tubal orifices in consequence of hyper-
plasia of the uterine musculature and mucosa.

Although it is being established that ovulation and menstruation apparently
are not contemporaneous phenomena, succeeding ovulations nevertheless prob-
ably are periodic and separated by a considerable interval of time from each
other. Such a conclusion seems to be fully warranted, although it is, of course,
well known that ovulation may occur without menstruation in normal nonpreg-

243

244 STUDIES ON PATHOLOGIC OVA.

nant women. This, however, does not establish the occurrence of ovulation during
pregnancy. According to Fraenkel (1910°) and Miller (1910), ovulation normally
precedes menstruation by about 9 days; but from a study of 100 cases in which the
time of occurrence of the menstrual period and the approximate time of coitus were
known, Siegel (1915) concluded that ovulation usually occurs between the seventh
and fourteenth day post menstruum. Cosentino (1897) and also a few others
have reported cases of ovulation during pregnancy in women, but we unfortunately
know little as to the exact conditions which obtain, so that the entire matter
remains as yet rather undecided.

Franco (1910), while reporting a case of spurious superfetation, gave a long
list of Italian writers who were said to believe in the occurrence of superfetation.
Unfortunately, this literature at present is largely inaccessible to me in the original,
and such as is accessible remains unconvincing, as all of it apparently seemed to
Cuzzi, who isreported by Franco as regarding superfetation only as a theoretical pos-
sibility. Nor does there seem to be good evidence that ovulation occurs during
pregnancy in other higher mammals. The only case cited is the questionable one
in a cat reported by Christopher (1886). At present it has not even been established
that superfetation occurs in the rare cases of double ovarian or of combined ovarian
and uterine pregnancies, although these cases would seem to furnish far more
favorable conditions. Did thealleged occurrenceof superfetation not involvea series
of assumptions each one of which remains unproved, belief in it would seem easier.
Consequently, in view of all these things, the conclusion of Gustetter that super-
fetation is “a frequent though often overlooked cause” of abortion in women
seems rather venturesome, and anyone who critically examines Herzog’s (1898)
article will see that the evidence he presents really does not justify the claim that
it “demonstrates fairly well that there is very little if any reasonable doubt left as
to the occurrence of superfetation in the human race.’”’ Indeed, although the
cases here presented would seem to offer far more conclusive evidence of the
occurrence of superfetation than any presented heretofore, there is no doubt that
such an interpretation of them would be a mistaken one.

The possibility of superfecundation, however, is not necessarily excluded by
these considerations, for ova from the same ovulation still might be fertilized at
somewhat different periods by some spermatozoa from the same or from subsequent
coituses. But even while theoretically possible, it is evident that the relatively
limited period of vitality of the unfertilized ovum, as contrasted with the duration
of pregnancy, would make it extremely difficult, if not impossible, to recognize
such cases. This would be true even if they occurred in the earlier stages of devel-
opment, for normal growth differences are too great when contrasted with the
greatest differences that could possibly exist under these circumstances. This
would seem to be true even if we grant that the spermatozoa have a somewhat
more tenacious life than ova. Mall (1918) considered evidence which seems to
indicate that the life of the fertilizing power, even if not the life of the spermato-
zoon, is a decidedly limited one. Hence, if this be true, superfecundation is limited
still further as a factor in the problem of superfetation.

ALLEGED OCCURRENCE OF SUPERFETATION. 245

In all instances in which the discrepancy in size or development between two
fetuses is such as to suggest that one of them arose from an ovulation so far removed
from the other as to produce unusual differences in size in the later months of
prenatal development, the assumption of independent action of the ovaries, con-
sidered by King in the case of the rat, would not avoid the foregoing difficulties.
Nor could the occurrence of deferred fertilization, which is‘advanced by Sumner
as an explanation for the occurrence of supernumerary broods in mice, be used
as an explanation in human cases, for the period of vitality of both the ovum and
the spermatozoon would seem to be entirely too short to become responsible for
marked development differences.

Sumner found supernumerary litters to occur in 3 per cent of 250 broods in
young mice. Such litters were particularly frequent in young deer mice. The
frequency of supernumerary broods would seem to vary greatly in closely allied
mammals, however, for King observed only 2 cases, and these she regarded only
as “seemingly” instances of superfetation, among 700 normal broods of rats. This
is an incidence of 0.28, or a frequency only one-eleventh as great as that found by
Sumner in mice. Sumner also stated that more than 80 per cent of the super-
numerary broods survived nearly or quite nearly to maturity, and King added
that all of those broods in rats were raised to maturity and that some were used for
breeding purposes later.

Although both King and Sumner regarded the occurrence of superfetation
with considerable reserve, neither seems to have considered the possibility of
delayed parturition in one horn of the uterus as worthy of consideration in connec-
tion with supernumerary broods between which the time interval was short.
Whenever this interval was relatively long as contrasted with the gestation period,
such a suggestion is untenable, unless corresponding developmental differences
were present. It might be helpful as well as interesting to make a careful gross and
microscopic examination of the broods concerned in order to contrast the respec-
tive states of development.

Since L. Fraenkel (1910°) found that some rabbits copulate while pregnant,
it would be of especial interest to know if supernumerary broods are particularly
common in such rabbits, and whether supernumerary broods can be produced
in mice should comparable conditions obtain. A particularly interesting question
would seem to be raised by the occurrence of such cases as reported by Guerra
(1909), in which a second implantation is said to have occurred while a dead
fetus still was retained in utero. Under these circumstances the smaller, younger
fetus should always be best preserved. Although ovulation, and perhaps also
menstruation, could occur under such circumstances because of the occasional regen-
eration of the endometrium, even before abortion, one scarcely can regard such a
sequence of events as established at present. However, Franco (1910) stated that
there is no lack of cases in which a second pregnancy occurred under such circum-
stances. But that does not establish the occurrence of superfetation, for in a
physiological sense death of a conceptus really terminates a pregnancy. Since at
least partial regeneration of the endometrium may occur in the presence of a dead

246 STUDIES ON PATHOLOGIC OVA.

conceptus, it is conceivable that a new implantation might occur in spite of the pres-
ence of a dead conceptus. This, however, would be a case of pseudo-superfetation
only, for if the term has any real significance it can only mean the superposition
of a second pregnancy upon one that is still living.

Sumner quite rightly called attention to the fact that in the great majority
of cases of superfetation recorded in man, one or both fetuses were macerated
before born, and King concluded that ‘many cases that have been reported as
due to superfetation unquestionably are instances of superfecundation or of
blighted ova.”’ Nevertheless, King regarded the case in a sheep reported by
Arrowsmith (1834) as probably genuine, and added that “although Christopher
found that ovulation might occur during pregnancy in the cat, superfetation is
not known to occur in this animal.’”’ However, Jepson, in 1883, reported such a
case, and Harman (1917) another. Neither report, however, would seem to bear
critical scrutiny, although both are quite as trustworthy as other reports of alleged
superfetation. In the case of Harman it would seem more probable that intra-
uterine death of one fetus with survival of the other was responsible for the miscon-
ception. It should be recalled that such instances are relatively common in the
rat, guinea-pig, rabbit, ferret, marmot, pig, and some other mammals. These
phenomena have been discussed by Strahl and Henneberg (1902), Henneberg
(1903), L. Fraenkel (1903), Koebner (1910), Huber (1915), Mall (1915), and
Meyer (1917’).

As is evident from figure 149, in which the so-called younger superfetus,
reported by Harman in a cat, is contrasted with a normal cat fetus (fig. 210, plate
8, Chap. XIII) of approximately the same length, the latter has a totally
different form. The same thing is evident also, although to a lesser degree, on
comparing the illustration accompanying Harman’s article with one from Kunz
(1916), shown in figure 150. Since the latter, the larger of two macerated ap-
parent superfetuses, in the report of Kunz, was deformed by retention, it may
have measured a little more or less—probably more—than 10 mm. at the time
of its death. However, even were it a trifle older than the fetus in figure 210, as
its form would seem to suggest, the difference is slight and may be ignored for
purposes of comparison. Kunz spoke of the larger fetus, shown in figure 150, as
entirely normal, which it apparently was, for the deviations from the normal
form (figure 210), which the illustration so clearly shows, undoubtedly are due
to post-mortem, ante-partum changes so common in human abortuses. Junz’s
conclusion that all three fetuses in his case in the eat resulted from ova which were
fertilized approximately at the same time heartily commends itself. Kunz further
concluded that these specimens furnish no evidence for the occurrence of super-
fetation, in spite of the fact that two smaller macerated distorted fetuses, which
were only 9 and 10 mm. long, accompanied a nearly full-term fetus.

Harman (1918) also reported a case in the cow which, however, she regarded
merely as one of ‘“‘probable superfetation.”” Unfortunately this report rests very
largely on the statement of a veterinarian, who made no further examination of
the specimen. Hence it would seem that we have no unequivocal evidence regard-

ALLEGED OCCURRENCE OF SUPERFETATION. 247

ing the occurrence of superfetation, even in mammals other than man. More-
over, as far as man is concerned, the large amount of literature on the subject
furnishes no cases more convincing than that of Calderini (1909). Most of them
can be easily recognized, from the reports alone, as probable instances of twin
pregnancy, in which one fetus died and then was retained until the birth of the
other. Confusion is due largely to the fact that dead fetuses often are retained
for a considerable period without showing very evident changes in form or gross
structure. This seems to be due, in part at least, to retardation in the lytic proc-
esses in embryonic as compared with adult tissues, a phenomenon which has
been referred to the slow post-mortem development of acidity in embryonic tissue.

Since external form is mainly relied on as a criterion by the general practi-
tioner, it is easy to see how misinterpretation of the facts arises, and it is significant
that it is only the specialist who has come to doubt that superfetation ever occurs
in human kind. This assumes, however, that by superfetation is meant the partly
simultaneous intrauterine development of two or more fetuses derived from ova
liberated by independent ovulations separated from each other by a considerable
period of time; or, in brief, the superposition of one pregnancy upon another.

Since most reports on superfetation concern fetuses in the later months of
pregnancy, it occurred to me that a representation of certain instances of twin
pregnancy from the earlier months of pregnancy might be of special interest,
because such specimens could more easily and rightly be taken for examples
of true superfetation. In the cases under consideration, one fetus evidently
died some time before the abortion of both, a circumstance that resulted in con-
siderable differences in age and form between the two. An examination of the
accompanying cases will make it clear that all the instances here reported easily
could be included among the alleged instances of superfetation found in the litera-
ture without doing the least violence to that literature. More than that, the in-
stances here reported would form fine examples among such cases.

The youngest specimen contained in the Carnegie Collection which came
to my attention, and which might be regarded as one of superfetation, is No. 587,
donated by Dr. F. A. Conradi of Baltimore. The cavity of the larger chorionic
vesicle in the fresh specimen measured 32 by 23 by 23 mm., and that of the smaller
about 6by6by9mm. The latter was empty, but the former contained a cylindrical
embryo 7 mm. long which Mall found greatly dissociated with a practically solid
brain and only a remnant of the intestine. The amnion was present, and as shown
in figure 31 (plate 4, Chap. IV), both vesicles formed a single mass which was
covered by infiltrated decidua. That these chorionic vesicles both once contained
an embryo, no embryologist will doubt. It is evident also that both were retained
for some time after life and growth had ceased. The gross and histologic appear-
ance of the entire specimen alone is sufficient proof of this. Although the smaller
chorionic vesicle was incorporated in the margin of the larger, its death did not
lead to its abortion or to that of the surviving twin. Yet the smaller of these
twins undoubtedly died a considerable period before the larger. This is indicated
also by an examination of the specimens and by the presence of decidua between

248 STUDIES ON PATHOLOGIC OVA.

the villi belonging to the respective vesicles at a point where they come in closest
contact. An examination of this area shows that the ovum giving rise to the smaller
conceptus was embedded independently, although undoubtedly also contempo-
raneously with the larger. Hence this specimen can not be rightly regarded as
one of superfetation.

The next specimens of twin pregnancy which might be regarded as a case of
superfetation are Nos. 788 a and 6, donated to the Carnegie Collection by Dr.
Anfin Egdahl. These twin chorionic vesicles, which were almost of the same
size, measured 60 by 45 by 40 and 60 by 55 by 40 mm., respectively. Although
of approximately the same size, the former contained a stunted embryo 17 mm.
long, the latter a nodular one only 3 mm. long. The differences in size and in
the character of the two embryos are so marked that they prompted Mall to
make special inquiry of the donor as to whether these chorionic vesicles were
really obtained from the same patient, as reported. This inquiry Dr. Egdahl
was able to answer promptly and positively in the affirmative. Here we are again
dealing with a case of twin pregnancy, in spite of the fact that the size of the em-
bryos might seem to indicate that we really have a case of superfetation under
consideration. But that the case is not such is shown also by the fact that the
chorionic vesicles practically are of the same size. The smaller abortus with a
partially inverted chorionic vesicle containing the better preserved of the twins is
shown in figure 21 (plate 3, Chap. IV). Figure 19 (plate 2, Chap. IV) shows the
appearance of the larger abortus, which contained the smaller nodular embryo
only 3 mm. long. The latter is seen at a midpoint near the upper third of the
illustration. Both illustrations are practically of natural size. The larger fetus,
the external form of which was fairly preserved, had an approximate age of about
48 days, as estimated by the Streeter (1921) curve. Mall noted that the organs
could all be outlined, but that they were dissociated, and that the mandibular
region had fused with the skin of the thorax. The small nodule, which represents
the only remnant of the embryo belonging to the larger chorionic vesicle, contains
a large cavity, with thick, fibrous walls, but nothing save epidermis and a remnant
of the nervous system could be recognized.

A far more convincing instance of apparent superfetation was found in a
specimen of twins donated by Dr. Jane Ross of Binghamton, New York. The
fetuses, Nos. 1840 a and b, contained in this abortus are shown in figures 151
and 152. The larger measured 31 mm., but the smaller only 15 mm., indicating
respective ages of 63 and 45 days. The chorionic vesicles belonging to these twins,
which formed a single mass, are shown in figures 153 and 154. The incised vesicle
containing the smaller fetus is shown in figure 154, and the larger vesicle, which
is somewhat inverted, in figure 153. Since the latter had been opened and the
larger fetus exposed, I at first overlooked the smaller fetus and found it only at a
subsequent examination made for the purpose of determining the cause for the
peculiar consistency and appearance of this portion of the abortus. The condition
of the smaller fetus, which is well revealed in figure 152 under a magnification of

ALLEGED OCCURRENCE OF SUPERFETATION. 249

4 diameters, is abundant evidence of the fact that it died a considerable period of
time before the abortion occurred. This interval must have been several weeks.
This specimen also nicely illustrates the fact that the death of one fetus does not
necessarily result in the immediate abortion of it and its vesicle or of the other
chorionic vesicle, as is sometimes still assumed.

Through the generosity of Dr. Gustetter, I am also enabled to present repro-
ductions of the fetuses spoken of in his article. They are shown in figures 155 and
156 and from these illustrations it is clear that the smaller of the 2 fetuses
probably stopped growth at about the sixth week. After this it became macerated
and finally disintegrated, while the larger continued to grow, as in case of the speci-
men from Dr. Ross. The larger of these fetuses is practically normal in appearance
except for the post-partum shriveling. It is approximately 100 days old.

Other specimens in the Carnegie Collection, such as No. 2036 a and 6, well
might be included here, for one fetus was grouped as normal and the other as
macerated. Indeed, it is a not very rare occurrence to find that the fetuses in a
twin pregnancy had to be placed in different groups by Mall and his associates at
the Carnegie Laboratory. However, this was not done because such specimens
were regarded as instances of superfetation, but because the fetuses, although of
the same age, differed in form and appearance. It is interesting that Saniter (1903)
also reported a case of two unequally developed tubal conceptuses, one of which
was implanted in the isthmus and the other near the fimbria. The former was
said to be only of the third to the fourth week, while the latter contained a
fetus 4 em. long. Both chorionic vesicles were said to have ruptured freshly. In
commenting on this ease of Saniter’s, Werth (1904) said that he regarded the
question as to whether it was a case of superfetation or merely one of twin preg-
nancy an open one.

It may be recalled that the occurrence of fetus papyraceus in cases of twin
pregnancy also has been attributed in the past to superfetation. Moreover, as
stated above, intrauterine death of one or more fetuses belonging to the same
litter is relatively common in some mammals. However, since Jenkinson (1913)
stated that the allantois and its blood-vessels and also the syncytium are regu-
larly retained at birth in some marsupials, to be absorbed later through the
activity of maternal leucocytes, it is evident that one must use caution in judging
on the basis of experience in other mammals, especially the lower ones. In some of
these the conditions are apparently quite different from those encountered in man.
Strahl and Henneberg (1902) also pointed out that in the mole the entire placenta
and membranes, as Hubrecht stated, are often retained for a month after parturi-
tion. No one would assert that the human uterus shows the same tolerance
or the same resorptive power, yet the daily experience of physicians, as well as
the literature in obstetrics and gynecology, is replete with instances of retention
of the membranes or the entire conceptus long after the death of the fetus. Al-
though the presence of a surviving conceptus in multiple pregnancy materially
alters the intrauterine conditions, it also would seem to predispose to retention

250 STUDIES ON PATHOLOGIC OVA.

rather than to hasten the expulsion of the dead mate. That is, the survival of one
twin, especially in the earlier stages of development, may depress rather than
enhance the factors that lead to abortion.

The impulses arising from the presence of the dead fetus may be counter-
balanced or offset, for a time at least, by the presence of the living fetus, and thus
tend to prolong the status quo. This would be the case particularly whenever, as
in the specimen donated by Dr. Ross, the two chorionic vesicles are fused into a
single mass; for then the portion belonging to the dead fetus, even if it forms one-
half of the combined mass at first, soon is outstripped in size by the surviving
vesicle, which, in the absence of infection, may continue to grow quite undisturbed,
for some time at least; and even in the case of infection of the dead vesicle, prompt
invasion of the living does not necessarily occur. Aside from clinical experience,
this was indicated also by the experiments of Maffuci (1894) on incubating eggs
and on pregnant rabbits and guinea-pigs. The apparent resistance of the young
fetus to syphilis, the characteristic lesions of which have not as yet been success-
fully demonstrated in fetuses much before the second half of pregnancy, would
also seem to point in the same direction.

From these considerations it would seem to follow that especially favorable
conditions for the production of gross differences would exist in some cases of
twin pregnancy. Hence it need not surprise us that these differences have been
largely responsible for the quite general belief in the occurrence of superfetation
in women. But at present it remains merely a possibility, for the evidence on
which this belief rests is wholly inadequate. It is interesting to recall that, in
the past, fetus papyracei have also been regarded as examples of superfetation,
as illustrated by the specimens reported by Fasola (1887).

DESCRIPTION OF PLATE.

Puate 14.

Figs. 141-142. Hydatiform villi from No. 2250a and b, shown in fig. 134, plate 12, Chapter VIII. 4.
Fics. 143-144. Twin conceptuses, both with hydatiform chorions. No. 24l1la and b. (See Chap. VIII.) 1.35.
Fic. 145. Enlarged fetus from same, showing maceration effects. 2.

Fics. 146-147. Macerated hydatiform villi from the same case. X6.

Fic. 148. Cyema covered with magma. No. 1771. (See Chapter IX.) 2.67.

Fic. 149. Apparent superfetus from a cat. (After Harman.)

Fic. 150. Macerated, distorted normal cat fetus 10 mm. long. (After Kunz.)

Fic. 151. Slightly macerated twin fetus. No. 1840a. 11.35.

Fic. 152. Pseudosuperfetus. No. 18406. 2.67.

Fic. 153. Opened, everted vesicle of No. 1840a and incised vesicle of 1840b. 0.66.

Fic. 154. Opened chorionic vesicle of 1840b and placental area of 1840a. 0.66.

Fic. 155. Twin fetus. No. 2036b. 0.66.

Fic. 156. Pseudosuperfetus, No. 2036a, disarticulated by maceration. X2.

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CHAPTER XI.
OVARIAN PREGNANCY.

Although the Carnegie Collection contains almost 3,000 specimens of abor-
tuses and others from operations upon the tubes and uteri, it includes only 2
cases of ovarian pregnancy. The first of these (No. 550) was described by Mall
and Cullen (1913) and the second (No. 1522) by Meyer and Wynne (1919). This
is an incidence of only 1 in 1,500 miscellaneous accessions composed mainly of
abortuses, but it is not at all unlikely that the near future will experience an in-
creased frequency, if not among the accessions to the Carnegie Collection, at
least in the cases reported. For, although the first case of ovarian pregnancy
under that heading in the Index Medicus is that of Kouwer (1897 [van Tussen-
broek, 1899]), careful scrutiny of the titles listed for the last decade reveals the
fact that 5 cases of ovarian pregnancy were reported in 1908, 4 each in 1909 and
1910, 7 in 1911, 13 in 1912, 9 in 1913, 7 in 1914, 3 in 1915, 1 in 1916, and 5 in 1917.
This makes a total of 58 apparent cases reported within this decade. Since the
reports on some of the cases were published in three different journals, these were,
of course, counted merely as one, and although the authenticity of 4 of the cases
must be questioned on the basis of the titles alone, the series, nevertheless, is a
large one in spite of these facts and of a marked decline in the number reported
during the war. Since Norris (1909) stated that only 19 certain cases, approxi-
mately only one-third as many as all cases listed in the last decade, were reported
in the decade between 1899 and 1909, it would seem that ovarian pregnancy is not
only receiving increasing attention, but that a change in attitude as to what
constitutes ovarian pregnancy is probably in progress. This conclusion would
seem to be justified, even though a careful examination of the descriptions of
the cases reported in the decade between 1908 and 1917 would reduce somewhat
the number listed.

Lockyer (1917) accepted as authentic only 22 cases of those reported between
1910 and 1917, but his review is only a partial one. Even so, it shows that there
is a decided increase in the number of cases which have been regarded as genuine
from decade to decade. The marked increase in the number of genuine cases
reported in recent decades becomes still more evident if one recalls that Williams
(1910) found only 13 positive cases up to 1906, whereas Norris found 19 positive
cases in the single decade between 1899 and 1909. That is, Norris found more
positive cases reported in that decade than had been reported in all previous medi-
cal history up to 1906. This surely is striking.

The opinion that many, even if not all, cases of so-called hematocele, hema-
toma, apoplexy, blood-cysts, and rupture of the ovaries are probably nothing but
cases of ovarian pregnancy in disguise has been held by various investigators for
some time. Hence, if hematocele of the ovaries repeats the history of hematosal-
pinx, it is not unlikely that the near future will see a marked increase in the reported
frequency of ‘‘a fact so curious and important in itself,” as Granville aptly put it

251

252 STUDIES ON PATHOLOGIC OVA.

a century ago. This would seem to be true in spite of the fact reported by Norris
and Mitchell (1908) that only a single case of ovarian pregnancy was found among
44 extrauterine specimens and 58 hemorrhagic cysts contained in the collection
of 1,700 gynecological specimens at the hospital of the University of Pennsylvania.
At any rate, a careful microscopic examination of all such cases would seem to
be indicated in the future in order to determine, if possible, which cases are and
which are not conceptual in origin.

Werth (1887) is said to have collected 12 cases, among which he regarded
only that of Leopold (1882) as authentic. Leopold (1899) reported 14. Gilford
(1901), in a splendid, succinct review of the literature, gave 28 cases, 16 of
which he regarded as undoubted and 12 as probable. Roche (1902) accepted
only 12 cases, Fiith (1902) accepted 21. Kantorowicz (1904), using the criteria
of Leopold (1899), together with a microscopic examination, as a basis, grouped
the cases recorded in the literature as certain, probable, and uncertain. He
considered 17 as certain, 10 as probable, and 13 as uncertain. And to the 17
cases regarded as certain by him, Kantorowicz then added 2 of his own, basing
his decision, however, mainly upon the presence of decidua in the ovaries, thus
making 19 cases regarded as authentic by him. Freund and Thomé (1906) re-
garded 23 of all the cases reported up to that time as certain. Norris and Mitchell
(1908) considered 16 as positive, 15 as probable, and 9 as fairly probable. Warba-
noff (1909) collected 34 cases and Norris (1909) regarded 19 of those contained in
the literature of the previous decade as positive; but Williams (1910), from a
critical review of the literature up to 1906, and upon the basis of the criteria of
Spiegelberg, regarded only 13 as positive, 17 as highly probable, and 5 as probable.
Mapes (1914) collected 30 cases, but wholly from secondary sources, and Lockyer
(1917) 42, from the years 1910 to 1917. Of these cases Lockyer accepted 22 as
authentic and 20 as questionable and undecided from the evidence available to him.

This short summary suffices to show that there is as yet no consensus of opin-
ion as to what constitutes an ovarian pregnancy. Although this fact finds its
explanation partly in our lack of sufficient knowledge, it is due also to the meager-
ness of some of the reports. However, if complete disintegration and lysis of intra-
ovarian conceptuses can occur, then it must always remain a question of opinion
in the future whether some of the cases so reported really were or were not true
ovarian pregnancies. This must remain true, no matter how thorough the micro-
scopic examination, unless the clinical history or changes in the maternal organism
can afford us crucial tests in such cases.

Anyone who reads far into the literature of ovarian pregnancy must also
become aware of the fact that even very recently skepticism has been carried too
far. Jacobson (1908), for example, placed the case of Kouwer-van Tussenbroek
(a case which finally convinced Bland-Sutton) and that of Webster (1904) in the
doubtful class! Furthermore, he also insisted upon the presence of an embryo
or fetus as absolutely essential.

It must be emphasized, however, that even a liberal attitude on the part of
a reviewer would not justify him in accepting all cases reported as genuine upon

OVARIAN PREGNANCY. 253

the basis of the reports themselves, for they—especially the older ones—are often
too meager to enable one to form a reliable opinion. This is illustrated also by
such recent reports as those of Garrard (1916), Martin (1917), Sweeney (1917),
and Mills (1917). Although it must be remembered that from the very nature
of things it is sometimes impossible to make a report which in itself carries con-
viction, it is regrettable that in a number of relatively recent cases, in which such
a report apparently could have been made, this was not done. Mills’s case seems
to have been an instance of ovarian implantation in a region other than the Graaf-
ian follicle, and hence recalls the first case of Granville and the cases of Franz
(1902), Norris (1909), Paucot and Debeyre (1913), and perhaps also that of Kouwer
(1897 [van Tussenbroek, 1899]).

Today it is no longer true, as stated by Freund and Thomé (1906) and by
Sencert and Aron as late as 1914, that authentic cases of ovarian pregnancy
belong to the great rarities. Yet the fact that many of our States, as well as many
large clinics, have not a single case on their records seems to suggest that the
condition is still seldom recognized, a century after Granville observed his first
case. Moreover, a number of continental gynecologists and obstetricians, for a
quarter of a century, have regarded the occurrence of ovarian pregnancy as un-
doubted. Anderson (1917) stated that German writers began to report cases of
ovarian pregnancy with some frequency after 1901, and Gilford (1901) also called
attention to the fact that continental opinion had long accepted ovarian implan-
tation not only as possible, but as proved. Gilford further referred to the often-
quoted opinion of Tait that ovarian pregnancy is as rare as “‘a blue lion or a swan
with two necks,” and in his article in 1899 also called attention to the opinion of
Bland-Sutton that ovarian pregnancy not only has no existence, but that it is
impossible. These opinions are particularly interesting in view of the careful
reports made by Granville (1820 and 1834) in connection with the two cases
which he then and which others since have regarded as cases of undoubted ovarian
pregnancy, in spite of the absence of microscopic examination. In view of this
lack, it is particularly fortunate that both of these reports of Granville are accom-
panied by splendid illustrations by Bauer, which also won him praise and admira-
tion and which greatly strengthened his cases. It may be recalled in this connec-
tion that Werth (1901) accepted Granville’s case recorded in 1820, but said nothing
about his second more convincing instance reported in 1834.

Although there is as yet no agreement as to what constitutes an authentic
case, a review of the literature justifies the growing and apparently well-founded
belief that in the past too much emphasis has been laid on certain criteria which
later experience has shown to be partly inapplicable. It is becoming clear that
some cases, formerly excluded for reasons regarded as sufficient, with our present
knowledge could no longer be rejected. Moreover, it does not seem at all im-
probable that some cases listed as tubal really were ovarian in origin. Nor must
it be forgotten that not even the entire absence of remnants of the conceptus
can positively exclude a case from the category of true ovarian pregnancy. Ina
number of cases in the literature, and also in our own cases, the clinical history

254 STUDIES ON PATHOLOGIC OVA.

and gross anatomic findings suggest the conclusion drawn by Scott (1901), on
a priori grounds alone, that the conceptus may be completely resorbed. It may,
of course, also be aborted or disintegrate completely. That such an assumption
is justified is indicated by the lysis of the embryo or fetus in a large number of
cases of ovarian pregnancy, and also by the very degenerated condition of some
of the vesicles and of the surrounding ovarian stroma. The possibility of such
an occurrence in the ovary is established also by similar events in uterine and tubal
pregnancies discussed elsewhere (Meyer, 1919°). It probably is illustrated also
by such cases as those of Anning and Littlewood (1901), in which no mention is
made of an embryonic disk in a translucent conceptus the size of a “‘pea.”’ Then,
to be sure, there are the cases of unruptured ovarian pregnancies containing villi
only, as well as the rare case, probably of double ovarian pregnancy, of Holland
(1911). Although one can not be certain that embryonic tissue was removed
from the left ovary with the blood-clot which was forcibly expelled at the time
of operation in this case, it is not at all improbable that the small plasmodial
masses found in the left ovary were the only remnants of the conceptus. We realize
fully that the conclusion that young conceptuses may be wholly dissolved is fraught
with great uncertainty, but it nevertheless appears to be justified by the facts, and
that it therefore is in the direction of truth. It could only fail to be so if every
ovum that becomes implanted within the ovaries were aborted or were removed
by operation before lysis was possible.

One can not rightly refuse to recognize the possibility of the spontaneous
disappearance of an ovarian pregnancy. Since implantation in the ovary occurs
under such abnormal conditions, it would seem that for this reason alone the great
majority of such implantations inevitably must succumb. This would seem
probable, wholly aside from considerations regarding the development of the corpus
luteum, although lack of, or interference with, the development of the latter
also would seem to condition early death of the conceptus if the results of the
long series of experiments on rabbits by L. Fraenkel (1903, 1910”) are indicative
of the réle played by the corpus luteum in early implantations in man also. It
surely is difficult, if not impossible, to see how implantation within the Graafian
follicle, and especially the later development of the conceptus, can fail to inter-
fere with the development of a normal corpus luteum. Cases in the literature,
and also our case No. 1522, did not reveal the presence of any well-preserved
or even true luteal cells at the time the pregnancy was terminated. Although
this fact does not presuppose an entire lack of development of these cells in the
earliest stages of the implantation, it undoubtedly does imply a defective devel-
opment, which in itself may have become responsible for the death of the con-
ceptus. Nor should the possible toxic effect of luteal cells upon the conceptus be
forgotten in this connection.

It is not assumed that the clinical symptoms and signs alone should suffice
finally to group a specimen as truly ovarian, but when these are indicative of the
presence of an ectopic gestation, and when undoubted intrauterine decidual
changes are present, in the absence of abdominal pregnancy or tubal involvement

OVARIAN PREGNANCY. 255

and a normal corpus luteum, and the presence of a blood-clot within the ovary,
there would seem to be little reason for doubting the authenticity of the ovarian
implantation, even in the absence of embryonic remnants. Since changes suggest-
ing decidual reaction in the ovary have been reported so seldom, it is doubtful
whether much emphasis can be laid on them. One seems justified in saying this in
spite of the fact that the presence of decidua in the ovary formed the only ana-
tomie evidence upon which Kantorowicz (1904) confidently classed his two rather
advanced cases of ectopic, among authentic ovarian pregnancies. Moreover, if it
be true, as stated by Webster (1904), that changes which can not be distinguished
from true decidual changes not infrequently occur in the ovary in connection
with normal uterine pregnancies, then the presence of islands of pseudo-decidual
cells in an ovary surely can not be regarded as indicative of ovarian pregnancy.
Perhaps, however, with modern histochemical methods, it would be possible
to distinguish genuine decidual cells. In making this observation, we are fully
aware that various criteria have been advanced from time to time by means of
which to judge ovarian pregnancies, and that many of these have met with objec-
tion and have hence been modified. Such modifications would seem to be inevi-
table as long as there is progress in the solution of an unsettled question.

The absence of the fetus in many of the recorded cases in itself demonstrates
the entire inapplicability of the criterion added by Jacobson (1908). Moreover,
the histologic appearance of the ovarian tissue around certain portions of the
blood-clot in the present, and also in some of the cases in the literature, would
seem to suggest that it may be very difficult to find remnants of ovarian tissue at
several points in a case of pregnancy which has advanced far. Hence this criterion
of Spiegelberg (1878) can not be regarded as necessarily crucial. Whenever the
implantation is developed at the outer instead of at the inner margin of a follicle,
as in the case of Banks (1912), early destruction, even if not early rupture, of the
overlying ovarian stroma and capsule would seem to be inevitable. Indeed,
whenever the layer of ovarian stroma overlying the placenta is thin, very early
death of the fetus would seem to be inevitable from defective nutrition alone.
On the other hand, when placental development occurs in the region of the follicle
directed toward the body of the ovary, great destruction of the ovarian stroma
would seem to be unavoidable, even if something akin to normal decidual forma-
tion actually took place. In the case of Engelking (1913), for example, not a trace
of an ovary was found in an ovarian pregnancy which had become interstitial.
Even without assuming the complete authenticity of this rather equivocal case,
it would seem highly probable that the presence of ovarian tissue later in the preg-
nancy probably is determined very largely by the location of the fertilized follicle
within or by the exact location of the implantation upon the ovary.

From evidence contained in the literature, it is clear that further reports of
single cases are not needed for the purpose of emphasizing the occurrence of ovarian
pregnancy, yet such reports nevertheless may help in the determination of the
relative frequency of this novel and sinister condition, and also throw further
light upon its genesis and the finer relations of the implantations, as well as upon

256 STUDIES ON PATHOLOGIC OVA.

other matters. Moreover, the cases which are accompanied by a careful histologic
examination, and which for this reason alone are wholly unequivocal from an
anatomic standpoint, are still relatively few.

Specimen No. 550 of the Carnegie Collection is of interest to both the surgeon
and the embryologist. It is also of great scientific value, for it shows conclusively
that the ovum had lodged itself in the Graafian follicle, undoubtedly in the one
from which it came, indicating that the sperm must have entered the follicle
after it had ruptured. The fertilized ovum then found lodgment in the follicle,
around which the corpus luteum developed. As in other cases which have been
reported, no decidua was formed, showing that the decidua is not of embryonic
origin.

This case illustrates well the advantage of cooperation in research. Under a
special organization, with a properly equipped laboratory attached to a surgical
clinic, specimens of great scientific value may be recognized and properly reported;
and it is not necessary to have an entire medical faculty attached to each clinical
laboratory in order to make progress in medico-biological science.

The specimen was sent to the Gynecological-Pathological Laboratory to be ex-
amined and the following record was made:

“‘The specimen consists of a tube and ovary from the right side. The tube at its
outer extremity has been considerably mutilated. The portion received measures 6 cm.
in length and is somewhat tortuous. It shows a few adhesions on the surface. Section
through the middle portion of the tube shows the mucosa to be somewhat thickened
and blood-tinged. Section through the distal portion gives a similar picture. There is
no gross evidence of an extrauterine pregnancy. There is a portion of the fimbria present,
but the port:on of the tube between this and the middle is missing. There is nothing
to suggest placental tissue. The mucosa appears normal in the sections.

“The ovary measures 5 by 4 by 3.5 em. The surface shows a few old adhesions.
On section the ovary shows a cyst 3 cm. in diameter. Clinging to the wall and bulging
into the cavity is a blood-clot 2 em. in width and 8 mm. in thickness. This on section
appears to be corpus luteum. It is intimately connected with the walls of the cystic
space. Further sections show villi in the clot attached to the inner surface of the space
in the ovary.”

The appearance of the specimen, with a section through the ovary, is shown
well in figures 157 and 158. When received there came with it several sections
from the Gynecological-Pathological Laboratory and these two drawings by
Professor Brédel. These sections included the chorion, ovary, and uterine tube.
The sections of the uterine tube appear normal, with a very extensive infolding
of mucous membrane and occasional lymph-nodules in its walls. Doubtless the
sections are from the distal or fimbriated end of the tube. The sections from the
chorion are apparently at right angles to its main wall, as shown in the figure.

The villi, which are irregular in arrangement, show attachment to the main
wall of the chorion, while at their distal ends they invariably abut against the
blood-clot (figure 162). In no instance is there any sign of the decidua, nor do the
sections through the villi contain any of the adjacent ovarian tissue. The blood-
clot is well organized, with strands of fibrin extending in all directions and without

OVARIAN PREGNANCY. 257

distinct red blood-corpuscles. Most of the villi have a fibrous mesenchyme; in
some it is mucoid. Scattered through the mesenchyme of the chorion there are
blood-islands, or rather groups of blood-cells, within the blood-vessels from the
embryo. These are especially numerous where the villi are attached to the main
wall of the chorion, showing that in its development the embryo must have been
present at an earlier stage. The distal ends of the villi are apparently covered
with a double layer of epithelial cells, which is as should be in normal development.
However, a rich peripheral trophoblast is missing. In the trophoblast are nu-
merous small masses of disintegrating cells. These appear to be pretty well inter-
mingled with mesenchyme cells at the tips of the villi, as shown in the figure.
Many polymorphonuclear leucocytes are present where the trophoblast comes in
contact with the blood-clot. Among the leucocytes there are isolated cells of the
trophoblast. At points the isolated cells are also embedded in the mesenchyme
of the villi. Altogether, these processes are quite identical with those found in
the villi of the uterine moles, where there is also every indication of degeneration
of the villi and their trophoblast, due to either faulty implantation or to infection.
In none of the sections is there any indication of the embryonic mass, nor do the
sections which were sent show the character of the ovarian tissue adjacent to the
clot containing the villi, although in a number of sections the chorionic wall is
shown to be composed of two layers, which doubtless represent both the chorion
and the amnion (figure 162, Am and Ch). In one section these two layers are
blended for a short distance, and at this point there are numerous embryonic
blood-vessels. The fact that the amnion, which is quite characteristic, is in close
apposition with the chorion, and the presence of numerous blood-islands show
quite conclusively that they are identical with an ovum which is sufficiently well
advanced in development to contain an embryo about 15 mm. long.

When the specimen came to us it was composed of two pieces which were
formed by cutting directly into it on the side of the rupture, as shown in figures
157 and 158. These are drawn natural size, and therefore give the dimensions of
the ovary. A loose piece of clot was taken out and cut into serial sections, but
upon close examination with a microscope no trace of the chorion could be found
in any of them, so it appears as though we received only the clot and a small
remnant of the chorion attached to it, which had possibly invaded the ovarian
tissue and lodged itself freely within it. The ovary was then cut into slabs about
5 mm. thick, and at a distance from the cavity containing the villi a large corpus
luteum, 10 mm. in diameter and entirely filled with blood, came into view (figure
159). New sections of the wall of the cavity were then made. These show that
the cavity as a whole is lined with a smooth, grayish membrane barely 0.5 mm. in
thickness. In the tissue between the corpus luteum and the main wall of the cavity
there is an extravasation of blood which enters a few of the adjacent Graafian
follicles. The arrangement of these follicles is well shown in figure 158, but the
corpus luteum, which is filled with blood, is much nearer the proximate pole of
the ovary, and is therefore not shown in this section. It is close to the point
marked Adh (figure 157). Sections were then cut through the whole ovary, and

258 STUDIES ON PATHOLOGIC OVA.

give the entire wall of the cavity containing the ovum. The sections, showing
most of the structures, are at right angles to the ovary (directly through the letter
O in the word ovary, figure 157). They were stained in a great variety of ways:
hematoxylin, acid fuchsin, iron hematoxylin, orange G, and a number of connective-
tissue stains. In general, they show that the ovary is active and not fibrous,
apparently normal, containing numerous blood-vessels and a ring of large Graa-
fian vesicles (figures 158 and 159), with an outside zone of small vesicles containing
small ova. To all appearances this is as it should be in a young ovary.

The wall of the cavity, containing the blood-clot and villi, is lined almost
throughout with a layer of lutein cells (figure 161). This layer is quite uniform,
ranging from 0.5 to 1 mm. in thickness. Between the lutein cells are numerous
strands of blood-vessels, but on their inner side is a layer of fibrin before the blood-
clot begins. On the outside the lutein cells form small islands of more compact
cells which stain more intensely in hematoxylin (figure 161, Cl’). The section
reminds one very much of a section of the adrenal. We have here a layer of lutein
cells well spread out, possibly due to the distention of its cavity by the ovum
and representing the corpus luteum, which, according to our conventions, is about
as old as this ovum appears to be. In other words, it is clear that the ovum devel-
oped within the cavity of the Graafian vesicle to which it belongs. The corpus
luteum, filled with blood, near the proximate pole of the ovary (figure 160), which
at first appears to represent the one from which the ovum came, is considerably
more advanced in development than the one containing the ovum; therefore it
belongs, in all probability, to a previous ovulation. Had it not been for the addi-
tional sets of sections we made, it would have been necessary to interpret this
specimen as Teacher, Bryce, and Kerr (1908) did theirs. The hemorrhage in the
ovary between the older corpus luteum and the cavity containing the ovum could
easily be viewed to indicate that the ovum invaded the ovarian tissue, as shown
by the illustrations of the authors mentioned.

The older corpus luteum demonstrates once more very clearly that it is
imperative to standardize anew the development of the corpus luteum. It is
encircled by a very marked corpus fibrosum, which is wavy and forms a uniform
sheet about 0.5 mm. in thickness beyond the clot (figures 159 and 160). There
are few lutein cells within it. On the inner side of the corpus fibrosum there is a
thick layer of degenerated blood, and in the center a large mass of well-defined
red blood-corpuscles. Within the very center of the clot is a cleft which is curiously
lined and filled with red corpuscles, staining somewhat differently from those of
the rest of the clot. Also, at the periphery of this clot there is a curious vesicle
lying immediately under the outer fibrous layer, which may indicate a more
recent hemorrhage. At any rate, the lutein cells encircling the cavity containing
the clot and ovum prove quite conclusively that the ovum did not wander from
a distant Graafian vesicle and become implanted freely within the tissue of the
ovary. This conclusion has also been reached by Serebrenikowa (1912) in a report
of a case of ovarian pregnancy, which confirms fully that of van Tussenbroek.

OVARIAN PREGNANCY. 259

Bryce, Teacher, and Kerr have given an excellent review of the literature on
ovarian pregnancy and Serebrenikowa has presented it from another standpoint.
Both of the papers demonstrate that in ovarian pregnancy no decidua is formed,
showing that a true decidua can not arise from the tissues of the ovary.

Since the cavity containing the ovum in ovarian pregnancy does not always
seem to be encircled by a layer of lutein cells, it is concluded that the ovum either
invaded the ovary from its surface or that it burrowed from the Graafian vesicle
after fertilization. Undoubtedly the latter is the case in the specimen recorded
by Bryce, Teacher, and Kerr. In it the growing ovum broke through the layer
of lutein cells and made for itself a cavity in the vascular stroma of the ovary.
This conclusion could also have been drawn from our specimen had not a second
set of sections been made which shows that a beautiful and characteristic layer of
lutein cells is present. In the first set of sections the wall of the cavity was faulty,
while the second was perfect. We do not wish to question the accuracy of other
observers in this respect; we want only to record our own experience. At any
rate, the possibility of a secondary attachment of the ovum to the ovary through
its direct wandering from the Graafian vesicle into the adjacent tissue, or indirectly
through a reinvasion from the surface of the ovary, can not be denied until it
is shown that the ovum is invariably lodged in a Graafian vesicle and surrounded
by a layer of lutein cells of the same age as that of the ovum. Before this is pos-
sible it will be necessary to standardize the corpus luteum in relation to the ovum
and embryo, and also to present as evidence only well-preserved specimens of
ovarian pregnancy.

Specimen No. 1522, which was donated to the Department by Dr. H. M. N.
Wynne, is a firm, nodular, dark-colored mass, 26 by 16 by 11 cm., shown in figures
163 and 164. In the gross, it especially recalls the specimens of Freund and Thomé
(1906), Giles (1914-1915), and Jaschke (1915), and Lockyer’s (1917) second case.
The exterior is smooth though bosselated and formed by a rather injected layer which
is extremely thin, showing the blood-clot beneath, around the greater extent of
the specimen. The surface layer is eroded over several small elevated areas in
which the blood-clot underneath is exposed. Hence, the capsule may have been
ruptured in several or only in one of the areas as noted at the time of the operation.
Near the region of amputation through the mesovarium shown to the right in
the figure and marked by the corrugations of the hemostat, the tissue overlying
the clot becomes more opaque, thicker, and also more yellowish. Here it is studded
with small cysts, the character of which in itself suggests ovarian tissue. The
color of the area to the right is also suggestive, and the cysts later were found to
contain a clear, viscid fluid, so characteristic of cysts of the ovary. The location
of the main portion of the ovarian stroma shows that implantation occurred near
the mid-point of the free convex or posterior border of the ovary, and that the
stroma forming the sides gradually was forced apart, not by the growing con-
ceptus, except perhaps at the beginning, but mainly by the hemorrhage itself.

The major portion of the surface of the divided specimen shown in figure 165
is composed of blood-clot, the presence of which confirms the ‘“‘blood-clot crepitus”

260 STUDIES ON PATHOLOGIC OVA.

spoken of in the history. This clot contains an empty vesicle, the wall of which is
formed for the greater part of its extent by a thin fibrous layer, except near the
proximal or lower portion in the figure, where a thicker portion of ovarian tissue
hoods the clot. Approximately only about one-third of the ovarian stroma seems
to be preserved.

Near the exterior of the thicker portions of the latter, a small cyst with clear
content is found directly beneath the surface, as indicated in figure 166. The
distal or upper portion in the figure shows the clot to contain an empty, smooth-
walled, degenerate chorionic vesicle, such as is frequently seen in tubal clots.

Examination of the cut surface with the binocular microscope shows the pres-
ence of only a few isolated, degenerated, and some hydropie villi scattered through
the clot. Examination of the chorionic vesicle shows the presence of only a few
attached villi and that the amnion is fused to the chorion. Since the entire speci-
men obtained at operation is covered still by a layer of ovarian tissue which is
unbroken save in a few very small areas, it is evident that we are dealing with a
very good example of an undoubted ovarian pregnancy in spite of the absence of
an embryo. The latter undoubtedly did not escape through the small rupture
in the capsule, for the chorionic vesicle seems entirely intact. Although the ab-
sence of a corpus luteum in the opposite or left ovary was not especially mentioned,
lack of comment would seem to suggest that none was present, for the ovary very
evidently was examined. Hence, this implantation probably took place within the
Graafian follicle itself, and not in some other area of the ovary.

Celloidin sections of the excised portion show that the blood-clot contains
no fibrin and that it is composed of relatively fresh and fairly well-preserved cells
in the region near the main body of the ovarian stroma. The latter is quite normal,
although decidedly vascular, and contains ova. The layer of the ovarian stroma
which surrounds the clot becomes thinner and thinner the nearer the free border
is approached. It also becomes more trabeculated, hemorrhagic, and degenerate.
No overlying layer of smooth muscle, as mentioned by Young and Rhea (1911)
and also by Kantorowicz, was seen. Some infiltration with polymorphonuclear
leucocytes is noticeable. Degenerate villi are scattered about in the blood and a
few others are apparently still attached to the equally degenerate ovarian stroma.
Trophoblast is absent on these, although some of the villi that lie isolated in the
clot possess a very evident epithelium and also are associated with a few small
masses of very degenerate syncytium. Only a few degenerate, nonvascular villi
are still seen on the chorion. Very little evidence of epithelial proliferation is
present on these, despite the fact that the blood in which the vesicle is embedded
is not very degenerate. This seems to suggest that the hemorrhage which caused
the rupture of the ovary was comparatively recent, although the conceptus had
been dead for some time. Some of the villi scattered about in the blood-clot are
outlined by degenerate syncytium only, and nothing but small degenerate masses
of the latter are seen on the chorionic membrane or lying about isolated in the
degenerate blood found in other places. Nevertheless, the epithelium of the cho-
rionic vesicle is thickened at several points. The amnion is fused with the chorion

OVARIAN PREGNANCY. 261

and both membranes are very degenerate and destroyed amost completely in
several places. The surrounding ovarian tissue, which is markedly vascular and
degenerate, shows infiltration in places, especially where it is stretched over the
large clot. No fibrous layer bounds the implantation cavity, as in the case re-
ported by Seedorff. The ovarian stroma merely is slightly condensed here and
there, and in places contains areas of hyaline degeneration, the exact origin of
which could not be definitely determined. A few of these are found near the thin
bounding layer of the ovarian stroma, but no lutein layer or even luteal cells could
be recognized. The only objects seen which might be regarded as possibly luteal
in origin are two microscopic rhomboidal areas which lie near a small depression
upon the surface, indicated in figure 167. These areas, which were covered by a
very thin layer of ovarian stroma only, were made up of parallel, degenerate,
slightly separated cords consisting of a syncytium containing numerous rather
pycnotic, unequal-sized nuclei. No pigment was seen in these areas, and were it
not for the arrangement of the syncytial cords, one would not be reminded, even
remotely, of a possible luteal origin. Although the germinal epithelium was wholly
absent in the areas examined, these questionable areas nevertheless may have
had such an origin. In the absence of lutein cells the present case corresponds to
those of Freund and Thomé and others, and stands in marked contrast to the cases
of van Tussenbroek, Franz, Anning and Littlewood (1901), and Thompson (1902).
As in the case of Seedorff and others, no decidua was present, and nothing sug-
gestive of an attempt at decidual formation, as reported by Franz, Webster (1904,
1907), Kantorowicz (1904), and Caturani (1914), was seen in the portions examined.

In describing his case, Seedorff declared that in some places of contact be-
tween the fetal and maternal tissues he could not discriminate between tropho-
blast and connective-tissue cells which looked like decidual cells and lutein cells.
It is interesting that Seedorff also spoke of villi which were almost filled with Lang-
hans cells, an observation which naturally makes one wonder whether by any
possibility these could have been Hofbauer cells.

The preserved ovarian tissue which was found near the amputation stump
contained hemorrhagic follicles, as observed also by Mall and Cullen (1913). A
Graafian follicle 3 mm. in section, shown in figure 166, protruded above the rest
of the stroma and was quite mature. The presence of this follicle might be taken
as an evidence of the occurrence of ovulation during pregnancy, were it not for
the fact that the presence of so degenerate a conceptus shows that as far as any
effect upon the maternal organism was concerned, the pregnancy virtually had
been terminated long before. That both ovulation and menstruation can and do
return after the death of an ovarian conceptus, but before its removal from the
ovary, is illustrated also by cases in the literature, especially by that of Norris
(1909). One must assume, however, that few, if any, surviving fetal elements
can be present under these circumstances. This conclusion also would seem to be
confirmed by the remarkable case of Sencert and Aron (1919). These authors
reported a case of ovarian pregnancy in which nothing but a portion of an umbilical
cord 5 mm. long, containing Wharton’s jelly, two arteries and a vein, and what was

262 STUDIES ON PATHOLOGIC OVA.

regarded as a placenta, remained. The latter was said to be composed of a narrow
layer of plasmodium and a much thicker layer of trabeculated syncytial tropho-
blast containing blood between the trabecule.

Because of the singular structure of this placenta and also because of the
failure to find villi or any remnant of the membranes, the authors concluded that
the chorionic vesicle therefore could not have reached the villous stage. How such
a supposition can be reconciled with the survival of a portion of an umbilical
cord entirely normal in structure it is difficult to see. The ovary concerned was
brown, of the size of a “large fresh walnut,’”’ and contained a tumor, apparently
the so-called placenta, which was 2 cm. in diameter. Although these fetal rem-
nants had brought about not only almost complete amenorrhea for two years and
also atrophy of the ovary and uterus, ablation of the affected ovary was followed
not only by a return of the menses, but by a normal pregnancy within 7 months.

A second instance of ovarian pregnancy of special interest was that of Giles.
No fetus was found, although the pregnancy was unruptured, and Giles estimated
that the conceptus had died in the third or fourth week. The operation was not
done until 5 months after the onset of the pregnancy. What is particularly inter-
esting in this case is that Giles speaks of the mucoid degeneration of the connective
tissue of the villi. The latter were found to be large, much branched, and had
ramified in the clot. Since Giles also spoke of one of the illustrations as showing
a vesicular state of some of the villi, it seems possible that this was a case of hydati-
form degeneration, even though there were no signs of activity of the syncytium.
Since the fetal membranes were isolated in a blood-clot, very much degenerated,
and the villi were without a Langhans layer, one scarcely could expect to find much
evidence of epithelial proliferation so common (but not essential) in hydatiform
degeneration. Giles estimated that 4 months had elapsed since death of the con-
ceptus, and if this specimen really was a hydatiform degeneration, it is the first
one observed in ovarian pregnancy and hence of particular interest for this reason
alone.

Several features in the clinical history of our second case deserve comment.
First among these is the menstrual age as compared with the size of the chorionic
vesicle. Since the cross-sections of the latter measure 15 by 18 mm. and since it
and the amnion are degenerated and devoid of an embryo, it is evident that the
latter must have died a good while before the time of operation. Hence, the
menstrual period reported for June 25, 1916, very evidently was not the last
period before pregnancy supervened, but the first period which recurred after
the death of the conceptus. Consequently, this pregnancy undoubtedly dates
from near April 13, the time of the first omitted period. Moreover, the conceptus
must have died long enough before June 25 to have made inhibition of the suc-
ceeding period impossible. It should be noted, however, that the original menstrual
cycle apparently was broken, for with the customary intermenstrual period of
28 days, menstruation normally would have fallen due on June 7instead of June
25. Hence the maintenance of the original cycle would have brought rupture
of this ovarian pregnancy, as indicated by the symptoms, on July 7, in direct

OVARIAN PREGNANCY. 263

relation with the onset of menstruation. Nor does it seem unlikely that the hy-
peremia accompanying the return of menstruation on June 25, if such it really
was, may have been partly responsible for the onset of a sufficiently large and per-
sistent hemorrhage to cause the slight rupture indicated by the symptoms on
July 7. It must also be remembered in this connection that cases of ovarian
pregnancy have been reported in which menstruation was uninterrupted. But
in the case of Chiene (1913), for example, the death of the conceptus may have
occurred so early that the succeeding period was not inhibited, and the same thing
may have been true in the case of Lea (1910).

Since the material from the curettage, done at the time of operation, showed
the presence of a normal endometrium, the uterine decidua associated with this
pregnancy must have been shed some time previously. Such a conclusion also
would seem justified by the condition of the conceptus, which apparently was
unable to prevent a return to the normal menstrual cycle. The absence of decidua
at the time of operation also suggests that what was reported as a return of normal
menstruation on June 25 may have been hemorrhage accompanying the expulsion
of the decidua.

Since, in the present case, the chorionic vesicle was so degenerated and so
completely isolated in a large clot, and especially since no well-implanted villi
were found in the sections and gross portions examined, it is not at all probable
that the hemorrhage that caused the rupture was due to a contemporaneous
invasion of the vessels by the fetal trophoblast, such as occurs in uterine and tubal
implantations, and as has been actually described also in ovarian implantations
by Franz (1902) and by others. In the present and in similar cases in the litera-
ture it would seem that hemorrhage was made possible also by degenerative
changes in the highly vascular stroma of the ovary, which had been greatly com-
pressed and stretched by the proportionately large blood-clot, the organization
of which would seem to have been precluded by its size alone.

The fact that relatively few unruptured ovarian pregnancies are recorded
suggests that the old tenet that rupture is less likely the more advanced the preg-
nancy becomes, probably is open to serious doubt, as suggested by Banks (1912),
who believed that the tubes can accommodate themselves more readily than the
ovary. Banks stated that in the majority of cases of ovarian pregnancy rupture
occurred in the first two or three weeks, and Caturani (1914) also expressed
doubts regarding the dictum that rupture of the ovary is less likely the more
advanced the pregnancy. No one will deny, I presume, that the symptoms of
rupture may have been totally absent, as reported in the cases of Norris (1909)
and Grimsdale (1913), but this does not necessarily imply that the ovarian stroma
or the germinal epithelium still surrounded the full-term conceptus. Such an
occurrence would be possible only if the ovarian stroma and the overlying ger-
minal epithelium underwent an astonishing hyperplasia. Although such a thing
is conceivable, it is decidedly significant that no one has reported any such finding
or observed the presence of mitotic figures.

264 STUDIES ON PATHOLOGIC OVA.

Instead of undergoing hyperplasia, the ovarian stroma in this case is found
invaded, stretched, compressed, and degenerate, and the germinal epithelium is
entirely absent. The fact that several observers have seen what they took for the
fibrin layer of Nitabuch also shows that degenerative changes in the ovarian im-
plantations may be extensive. Hence, it would seem to follow that the absence
of symptoms of rupture merely may mean that the ovarian stroma and epithelium
which happened to overlie the fetal membranes have gradually died and degenerated
before being forced apart by the expanding conceptus or the increasing hemorrhage.
That such a sequence of events is possible would seem to be undoubted, and mere
distention of the ovarian stroma until it completely surrounded a full-term preg-
nancy is hardly conceivable; whereas, the absence of pain upon the yielding of an
exceedingly thin degenerate layer of ovarian stroma is quite conceivable.

That rupture may occur very early is exemplified also by the cases of Chiene
(1913), Seedorff (1915), and especially by that of Anning and Littlewood (1901)
and of Holland (1911). In such curious instances as that of Grimsdale (1913)
one can hardly assume that the ovarian tissue was preserved about the entire
conceptus, and it is not at all unlikely that full-term ovarian pregnancies, which,
according to Warbanoff, supplied a surprisingly large percentage of all cases
collected by him, will form a far smaller percentage in the statistics of the near
future. Indeed, they already form a far smaller percentage of those reported up
to the present, and the advances in diagnosis alone make it very unlikely that in
the future many cases of ovarian pregnancy will advance far before being detected.

A feature noticeable in both of these cases, and not heretofore described, we
believe, is the presence of clubbing of some fibrous villi, as shown in figure 168.
This is marked in the villi from case No. 550. It is less pronounced in case No.
1522. The villi and vesicles of both these specimens are so degenerate that one
is almost led to surmise that these vesicles never became properly implanted, but
depended very largely upon the surrounding blood for nutriment. As long as the
fetal circulation was not established these conditions would seem to offer no special
obstacles, for up to that time the conceptus necessarily is dependent upon other
means of nutrition in uterine implantation also. Moreover, it may be doubted
whether anything akin to true implantation can occur in the ovary or tube in the
absence of decidual formation, and hence also of a capsularis. For even if the
ovum buried itself in the ovarian stroma, the continued hemorrhage and the
failure of a similar and proper response on the part of the ovarian stroma never-
theless would furnish decidedly abnormal conditions.

OVARIAN

PREGNANCY.

CLINICAL HISTORIES.

No. 550.

The patient, who was 24 years old, came to the
Johns Hopkins Hospital June 1 with a diagnosis
of appendicitis, which later was changed to
ovarian pregnancy. The diagnosis was made
unusually difficult by the patient’s misleading
statements.

When admitted to the ward the patient was
not complaining of acute pain, but only of
general soreness in the abdomen. There were
paroxysms of pain, general throughout the
abdomen, with intermissions in which she was
somewhat more comfortable. With difficulty
the pain was localized in both left and right
sides of the abdomen.

When examined, general soreness of abdomen
was found, the pain being more acute along the
left side, shooting up to the right shoulder.
The pain had not changed in character or
intensity. There were sharp attacks of pain,
especially in the left side, when the patient tried
tomove. There was also difficulty in breathing.

During the afternoon the condition of the
patient was very uncomfortable, with repetition
of the symptoms just given. The pains became
more acute after taking ice. A renewed onset
occurred at 11 p. m., and this continued with
some nausea and occasional vomiting.

The pain had been sharp (not crampy), and
had apparently gone up under the right C. M.
inthe morning. There had been pain also under
the shoulder. The patient said she had never
had any similar attacks, and was not constipated
previous to this one.

On June 3 patient said she had a similar attack
of abdominal pain three years before. This was
general at first and finally became more pro-
nounced on the right side, accompanied by
nausea and vomiting. From this attack she
did not recover entirely for 10 days. She had
a similar but milder attack several months later.
Dr. Finney writes:

“When I saw the patient I did not think it
was appendicitis, but the history of similar
attacks, which I had reason to believe afterwards
were fictitious, and the patient’s misstatements
as to the subjective signs, together with the fact
that the patient was unmarried, misled us as to
the true diagnosis. Upon opening the abdomen,
however, it was found to be filled with blood.
At once the diagnosis was clear. I looked for the
tubes, but found both intact. The right ovary
was the point of bleeding; it was swollen and
appeared as you found it in the specimen. The
whole process was so definitely confined to the
ovary that it seemed, clinically, to be a definite
case of ovarian pregnancy.”

No, 1552.

The patient, an Italian woman of 37 years,
was admitted to the Gynecological Service of
the Johns Hopkins Hospital July 12, 1916, com-
plaining of a pain in the lower abdomen, nausea,
and vomiting.

Family history.—Negative.

Past history—General health good. She has
never had any serious illness. For the past 5
years following a labor she has had recurring
mild attacks of pain in the abdomen without
nausea or vomiting.

Menstrual historya—Always regular every
month, except when pregnant or lactating.
Duration 4 to 5 days; painless, moderate flow.
Last period June 25, 1916. Last preceding
period, March 16, 1916. No intermenstrual
bleeding before present illness.

Marital—Married 18 years; seven children,
oldest 16, youngest born 114 years ago (died,
1915). Hashad three miscarriages. History of
labors and puerperia vague.

Present illness—Began 5 days ago (July 7,
1916) with sudden pain in lower abdomen,
nausea, and vomiting. She has had marked
dysuria and painful defecation. For 12 hours
after onset there was rather profuse bleeding
from the vagina and there has been a bloody
vaginal discharge since.

(The patient does not understand English and
her husband acted as interpreter.)

Physical examination.—T. 101.6 degrees F.
P. 96. W. B.C. 8400. Hbg. 46 per cent.

The patient lies in bed grunting with pain.
The skin is pale. The lips and mucous mem-
branes are quite pale. There is a systolic blow
heard at the apex and increasing toward the
base, being loudest over the pulmonic area.

A drop of clear fluid was expressed from the
right breast.

The abdominal respiratory movements are
limited, although she does not complain of pain
on deep inspiration. The flanks bulge some-
what. There is no demonstrable movable dul-
ness. There is tenderness all over the abdomen,
most marked over the lower left quadrant.
There is increased resistance over the lower
abdomen, but no muscle spasm. No masses can
be made out.

There is a profuse bloody vaginal discharge.
The cervix is pushed up behind the symphysis
by a soft, exquisitely tender mass, filling the
cul-de-sac. No crepitus is made out. Rectal
examination confirms the vaginal. The fundus
of the uterus is not felt.

July 13, 1916.—Ether examination.

There is a dark, bloody discharge from the
vagina. There is no vaginal cyanosis. The
cervix is lacerated, firm, and normal in size.

266 STUDIES ON

The fundus of the uterus is about normal in
size and is in anteposition. A boggy mass fills
the cul-de-sac and to the right of the uterus a
fairly firm mass, the size of a small orange, which
is somewhat movable, can be felt. Definite
blood-clot crepitus can be felt on rectal examina-
tion.

Pre-operative diagnosis.—Extra-uterine preg-
nancy, ruptured.

Operation.—A free midline incision was made
below the umbilicus. The peritoneum was
blood-stained. The abdomen contained 200 to
300 c.c. of dark fluid blood and clots, and a large
clot filled the cul-de-sac. Active bleeding had
ceased. The left tube and ovary were normal
and free of adhesions. The right tube, which
was quite normal in appearance, lay over a mass
which had replaced the right ovary. This mass
was roughly spherical, 5 to 6 cm. in diameter and
semi-solid in consistency. Over the surface
there were six or eight nodular projections, about
1 cm. in diameter. At the top of one of these
projections there was a very small opening,
from which bloody fluid could be squeezed.
The surface of this mass was white, with spots of
bluish-black discoloration.

PATHOLOGIC OVA.

The appendix was normal, except at the tip,
where it was adherent to a blood-clot.

The tumor was removed by clamping, tying,
and cutting into the right infundibulo-pelvic
ligament and the right utero-ovarian ligament.
The right tube was not removed. The appendix
was also removed and all blood and clots were
cleaned out of the abdomen. The incision was
closed without drainage. At the close of the
operation the uterus was curetted. The uterine
cavity measured 7.5 cm. in length.

A subcutaneous salt solution infusion was
started on the table and continued on the ward
until 2,000 ¢.c. had been absorbed.

The patient was in good condition at the end
of the operation and made an uneventful
recovery.

The urine on admission contained red blood-
cells, white blood-cells, no casts, acetone, a
trace of albumin, and no sugar. Several days
after the operation it was negative, except for
a faint trace of albumin.

August 2, 1916.—Discharged in good condi-
tion.

Gyn. Path., No. 22346.—Normal endometrium
from curettage.

DESCRIPTIONS OF PLATES.

Puate 15.

Fia.
Fia.
Fia.

. Drawing of posterior view of pregnant ovary with tube.

. Transverse section of pregnant ovary cut at point of rupture.

. Outline of transverse section of ovary taken in the region of the letter o in “Ovary’’ (fig. 157).
lutein cells; Bel, Blood clot; Cf, corpus fibrosum; G, Graafian follicle.

No. 550.

cl
X2.

Fic.
Fic.

Fic.

Fia.
Fic.
Fia.
Fia.

Fia.

Fic.
Fia.
Fic.
Fia.
lia.

Fia.
Fic.

. External appearance of intact specimen.
. External appearance of same specimen, showing where block was removed. 0.75.
. Appearance of cross section of pregnant ovary and tube, same specimen.
. Photograph of a section taken from the thick portion of the ovarian stroma near the mesovarium, showing

. Marked clubbing of villi of No. 550.
. Cross section of decidua and conceptus.
. Section of conceptus, decidua, and muscularis.
. Section of decidua and conceptus.
. Section of a part of the conceptus, showing chorionic membrane, cyemic (?) rudiment (x) and yolk-sac.

. External view of No. 2047, showing the distended amnion.
. Section of the tube and the conceptus.

. Drawing of portion of the corpus luteum, indicated by small square to the left in fig. 159 (marked fig. 4

in drawing). Ot, tissue of ovary. 70.

. Drawing of a portion of the ovary, indicated by small square to the right in fig. 159 (marked fig. 5 in draw-

ing). X70.

2. Drawing of a section through free surface of clot, illustrated in section in fig. 158, showing wall of chorion

and a villus surrounded by clot. Tr, trophoblast; L, leucocytes; Ch, chorion; V, villus; Coe,

celom. X50.
PLATE 16.

No. 1522. 0.75.

0.75.
X2.25.

a well-developed Graafian follicle. Same specimen.

. Section of part of the same specimen, showing the clot which contains the empty vesicle largely surrounded

by ovarian stroma. 1.9.

X2.25.

No. 698. (See Chapter XII.) 4.5.
No. 970. (See Chapter XII.)

(See Chapter XII.) 4.5.

X4.5.
No. 962.
No. 1843. (See Chapter XII.) 51.5.

(See Chapter XII.)

(See Chapter XII.) 3.3.

X2.25.
No. 977.

159

MALL AND MEYER
158 157

Free fimbr. end

-
Clot containing

chorionic villi

Site of rupture

Posterior view

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MALL AND MEYER

CHAPTER XII.
LYSIS AND RESORPTION OF CONCEPTUSES.

It has long been known that considerable intrauterine retrogression of a con-
ceptus can occur in multiparous mammals. D’Outrepont, for example, on page
192 of the catalogue of his collection, is said (Miiller, 1847) to represent the uterus
of a rabbit, in which an apparently full-term fetus is found near the distal end of
one horn, although the approximate portions of both horns contained but rem-
nants of fetuses, one in each. According to Miiller, the enlargement in the right
horn contained a “cyst filled with rabbit hair embedded in a soft mass and that
on the left side a similar convolute of hairs without a cyst.’ This, as far as I
know, is the earliest reference to, even if not the earliest observation upon, a fetal
retrogression, But since rabbits are born naked, one is left to speculate upon the
validity of this observation. However, that the idea holds is indicated also by
some experimental work.

Giacomini (1889) stated that he could effect absorption of the embryo in
rabbits within a few days by killing the embryo upon the seventh or eighth day
of gestation. Since this is just about the time that implantation of the ovum
occurs in the rabbit, I presume Giacomini really meant on the seventh or eighth
day after zmplaniation. Giacomini added that these things show a close relation
between nodular and atrophic forms and the entire absence of embryos. Strangely
enough, Giacomini (1893) reported that puncture of or slight pressure upon the
implantation cavity on the ninth day of gestation was followed by complete
absorption of the conceptus by the thirteenth day, but he did not think that the
human blastodermie vesicle can undergo simple degeneration.

Sokoloff’s (1896) meager report also seems to indicate that in dogs bilateral
ovariotomy leads to the death of the embryo and to abortion of it and of the entire
conceptus. Strahl and Henneberg (1902) also found that conceptuses in different
stages of retrogression occur quite commonly among normally developed ones
in the ferret, marmot, and mole. They also found that the entire placenta and
probably also the fetal membranes, as stated by Hubrecht, are normally retained
for some time, even up to a month after parturition in the mole. Similarly, L.
Fraenkel (1903) was able to cause the death and also the uterine absorption of
conceptuses in rabbits up to the twentieth day of pregnancy, through destruction
of the corpora lutea. Fraenkel found that after 14 days all that remained in the
way of evidence of some pregnancies was an anemic ring which disappeared com-
pletely within three weeks. Henneberg (1903) also found that intrauterine death
and retrogression of the guinea-pig fetus can be effected experimentally through
various means, and, according to Koebner (1910), not merely ova or young fetuses
are absorbed, but even the bones of older ones disappear completely under experi-
mental conditions in the rabbit. It would seem unlikely, however, that such could
be the case in any but the very earliest stages in the development of the skeleton,
for a considerable degree of acidity would have to develop in order to make this

267

268 STUDIES ON PATHOLOGIC OVA.

possible. Since it is believed that the development of acidity not only is slow but
also slight in embryonic tissues, Koebner’s conclusion regarding the bones seems
to be open to some doubt. Wiener (1905) also found that autolysis is very slight
in tissues with an alkaline reaction and that a slight increase in acidity greatly
accelerates it.

Fraenkel (1910”) extended and confirmed his work done in 1903 by a very
large series of experiments touching various phases of the corpus luteum problem,
and among other things concluded that one corpus luteum can protect at least
three ova sufficiently to insure continued development.

Although the degenerating ova found by Huber (1915) in the rat were very
young, the significance of the facts would seem to be similar. Likewise Mall
(1915), while writing “On the fate of the human embryo in tubal pregnancy,”
stated that ‘‘we have no data on the number of ova which disintegrate early, but
the study of comparative embryology warrants the conclusion that many young
ova degenerate and disintegrate. I am informed by Dr. Huber, who has studied
with great care much material among rats, that some of the fertilized ova break
down before implantation. The same seems to be true regarding the pig. We
usually find more corpora lutea in the ovaries than embryos in the uterus, indi-
cating that all of the ova do not produce normal embryos.” Similar phenomena
also were reported by Meyer (1917*), in regard to young conceptuses in the guinea-
pig. Curtis (1915) also reported the absorption of ova in guinea-pigs in con-
sequence of the injection of extracts of the human placenta, but unfortunately
Curtis did not give convincing evidence regarding his knowledge of the presence
of pregnancy in the animals concerned, nor did he make a microscopic examination.
Since Curtis stated that injections of defibrinated human blood had the same effect
as the injection of extracts of the human placenta, and that the injection of extracts
of guinea-pig placenta and of guinea-pig blood had no effect whatever, one can
not help but feel decidedly skeptical regarding the trustworthiness of his experi-
mental proof.

It is well to remember in this connection that phenomena which occur in
other mammals, or conclusions drawn from these phenomena, must be used with
caution when referred to man. The uteri of other mammals may well show a
greater tolerance to the presence of dead fetal tissue and also greater resorptive
power. Robinson (1904) stated that Vernhout showed that maternal tissues are
not shed at the time of birth in the mole, and that some of the fetal tissues are
retained to be absorbed later. Hill, it seems, found the same thing to be true in
Perameles and Dasyurus. Jenkinson (1913) also stated that in Perameles the
allantois and its blood-vessels are regularly absorbed through the agency of ma-
ternal leucocytes by the parturient uterus and that fetal tissues are absorbed some-
what similarly in Dasyurus. However, since the young of some marsupials are in
a very immature state during the first months of gestation and are then transferred
to the marsupium as naked little fetuses, said to be only about an inch long in the
kangaroo, it is clear that absorption of the secundines at this stage of development

LYSIS AND RESORPTION OF CONCEPTUSES. 269

would be something quite different from their resorption at the end of the gesta-
tion period in higher mammals, especially man.

Although we have considerable evidence regarding retrogression and the
partial or even the total intrauterine absorption of conceptuses in various mammals,
I have not been able to find any conclusive evidence in the literature regarding
the occurrence of this phenomenon in man. It is true that cases of E. Fraenkel
(1903), Rosenkranz (1903), Polano (1904), and cases reported by others also are
referred to as such examples, but a careful examination of the reports shows that
those cases can hardly be regarded as falling under the head of intrauterine
absorption of ovum, embryo, or fetus. It is true that in the cases of Polano and
Rosenkranz, the skeletal elements only were seen to have been discharged, but
in the case of Polano the amniotic fluid nevertheless may have carried a great
many fragments of embryonic tissue away with it beforehand. Furthermore,
Polano did not claim his case as one of complete intrauterine absorption, but
merely as one of remarkable intrauterine maceration under aseptic conditions.

The history of the case of Rosenkranz, on the other hand, shows quite clearly
that the fetus was destroyed by putrefactive changes. Rosenkranz himself em-
phasized this, but strangely enough ruled out entirely the occurrence of macera-
tion. He further stated that the patient herself noticed the discharge of some
bones with the “menstrual” flow. However, under the above conditions the
recurrence of true menstruation is exceedingly unlikely unless the fetus was dead
a considerable period before the rupture of the membranes occurred, and the
placenta had been detached at least partly, for only under such circumstances
could some regeneration of the mucosa occur and thus make a return to true
menstruation possible. It is nevertheless possible, however, that the time of
abortion was coincident with the date on which menstruation might have recurred.
A small number of cases in the Carnegie Collection have a history which makes
such a suggestion probable. Just why the expulsion of a dead, retained conceptus
should occur at the time when menstruation would have recurred normally had
pregnancy not supervened it is difficult to say, but since the inhibitory effect
upon the menstrual cycle exercised, directly or indirectly, by the living fetus is
absent in cases of premature death and retention, it is possible that the abortion
might occur at a time when the impulses of a return to the normal non-pregnant
status of the maternal organism becomes more evident; that is, at the time of the
recurrence of the normal menstrual cycle.

One can not but recall in this connection another group of cases which give a
history of uninterrupted menstruation throughout the entire period of pregnancy.
In some of these cases it is evident that it is a question of more or less regular
hemorrhage rather than of true menstruation, and it may be possible that in the
others these hemorrhages happened to fall at intervals of the same length as the
normal intermenstrual periods. In the last group the exact status of the cases
can not be discerned from the histories alone. However, since there is no en-
dometrium, or at most a partial one, to shed, genuine menstruation manifestly
can not occur throughout pregnancy. Indeed, it seems more probable that the

270 STUDIES ON PATHOLOGIC OVA.

cases of supposed uninterrupted menstruation fall into the last group, although it
is not impossible that rarely hemorrhage may occur only at the dates of normal
recurrence. This would seem possible because of the defective inhibition of the
returning normal impulses exercised by the dead or dying conceptus and the
retrogressing corpus luteum. This conclusion harmonizes with the tendency to
abortion which seems to be present at the time of periodic hyperemia and hyper-
irritability in some of these cases.

Although dissolution of the embryo or fetus alone has long been known to
occur, there seems to be no convincing evidence in the literature of the occurrence
of intrauterine autolysis and absorption of entire conceptuses. Moreover, as
already stated, it is to be doubted very seriously whether complete intrauterine
absorption is possible after the formation of the skeleton has been well begun.
The fetal parts at this time are so resistant that the uterus is stimulated to expel
the macerated remnants long before absorption of them can occur. Furthermore,
complete absorption would also seem to be hindered by the physical conditions
which obtain in the human female. Only so long as the decidua capsularis
is relatively thick, and hence effectively prevents the escape of the products of
autolysized embryonic tissue, does complete absorption of a young uterine
conceptus seem to be possible. The same thing is probably true in some cases
of tubal pregnancy, although the occurrence of early and repeated, or even
prolonged, hemorrhage in them makes complete intratubal absorption much
less likely. However, that complete intrauterine absorption actually seems to
occur in the human female, it is my purpose to establish.

The occurrence of missed abortion and also of missed labor have long been
matters of common knowledge among physicians. But these are phenomena
usually connected with the later months of pregnancy. In the overwhelming
majority of these cases the fetus was retained for a considerable period after its
death and then aborted in a more or less macerated condition. Under these cir-
cumstances it may, to be sure, undergo absorption in part, but expulsion of macer-
ated or even calcified remnants of the fetus nevertheless eventually occurs. That
this is so, even after an exceedingly long period of retention in utero, is shown
splendidly by the case of Schaeffer (1898). In view of the exceedingly common
occurrence of retention of conceptuses in utero, it is surprising that as late as 1896
Graefe succeeded in collecting only 58 cases of missed abortion from the literature.
Graefe stated, however, that he himself met with 11 cases in 7 years, to which
number he added 12 observed by a friend. Nevertheless, from these facts one
might assume that retention of conceptuses after death is a rare rather than a
very common thing. The explanation probably lies in the fact that the term
“missed abortion” is understood as referring to advanced rather than to early
cases of pregnancy. Retention of the latter for varying periods of time is exceed-
ingly common, however, and one might say that retention is the rule, for it is
exceedingly rare that a fresh, wholly unmacerated conceptus is obtained through
abortion unprovoked by mechanical means or acute disease. Hence post-mortem

LYSIS AND RESORPTION OF CONCEPTUSES. 271

prepartum changes must be expected in practically all other specimens which
form the great majority of all abortuses.

Among the large series of over 2,000 abortuses in the Carnegie Collection, I
have so far found only a few specimens of almost complete intrauterine absorption.
In one of these, No. 698, only a few vestiges of syncytium and trophoblast remain.
Not a single fragment of the chorionic or amnionic vesicle or of the embryo could
be found upon microscopic examination. Were it not for the presence of decidua
and the above microscopic remnants, one might doubt whether pregnancy really
had supervened in this case. However, since the specimen shown in figure 8
(plate I, Chapter IV) was aborted with the entire intact decidua which still sur-
rounded the remnants of the conceptus completely, as shown in figure 169 (plate
16, Chap. XI), there manifestly could have been no loss of embryonic tissue either
before or during abortion. This abortus, which measured 50 by 20 by 13 mm., was
donated by Dr. N. E. B. Iglehart, of Baltimore. It had a menstrual age of 56
days, but the condition of the few remnants and the size of the implantation cavity
show that development did not proceed very far before growth was inhibited.
Aside from the absorption of almost the entire conceptus, the decidua not only is
infiltrated, but also shows degenerative changes. As illustrated by figure 169,
which shows the intact capsularis separated by a narrow space from the parietalis,
the former is filled completely by blood-clot. It is at the periphery of this clot
that the isolated microscopic remnants of the syncytium and trophoblast, together
with a few gossamer or shadow villi, are found. Since there is no blood between
the capsularis and the parietalis, it would seem to follow that the hemorrhage was
limited entirely by the capsularis, a conclusion which is indicated also by the
absence of a history of bleeding. Since the last menstruation began on April 11
and the abortion occurred on June 6, it is seen that the latter occurred on the first
day of the beginning of the second lapsed menstrual period. Although the appear-
ance and the condition of the decidua seem to suggest that considerable regeneration
of the endometrium had occurred, it is possible, though unlikely, that the bleeding
accompanying the abortion was menstrual and that hence the abortion should be
regarded as a mere incident accompanying the return of normal menstruation
rather than as the predominating event.

That considerable restoration of the endometrium may occur while the con-
ceptus still is within the uterus was shown by the case of Orloff (1895). In this
case the endometrium was composed of a cylindrical epithelium and the uterine
musculature showed no evidences of the presence of gestation changes. Iwanoff
(1898) also found the decidua absent in a case of long retention and its place taken
by a low cylindrical epithelium, although the placenta was still partly attached to
the uterus. E. Fraenkel (1903) also emphasized the fact that regeneration of the
endometrium may begin before abortion occurs, and these things make it possible
that hemorrhage, which may occur at time of abortion, may largely be true men-
strual hemorrhage.

The absence of blood between the capsularis and the parietalis and the absence
of a history of bleeding do not imply that the development of this conceptus

272 STUDIES ON PATHOLOGIC OVA.

progressed uninterruptedly until birth. The histologic picture alone is conclusive
proof to the contrary. In the absence of any larger portion of the conceptus it is
impossible to say about how far development had proceeded, but it is unlikely
that it proceeded much beyond the first month. In any case, disintegration,
solution, and resorption of almost the entire conceptus surely must have consumed
several weeks at least. Indeed, it is possible that the ovum never became firmly
attached, though embedded in the decidua.

In other cases it also seems likely that the fertilized ovum became embedded
quite normally, but that it was strangulated by severe hemorrhage which loosened
the attaching villi, thus interrupting the intervillous circulation. Since the
resulting stagnation of the blood must make impossible the indispensable chemical
interchanges upon which the life of the embryo depends, the latter probably dies
first. It is decidedly interesting that considerable hemorrhage, sufficient, in fact,
to result in the death of both the embryo and the chorionic vesicle, can occur
while the whole conceptus still is surrounded by the decidua capsularis, without
rupture of the latter. The failure of absolute or complete absorption of the last
few small remnants of this conceptus probably may be attributed to the fact that
the small remnants of degenerate trophoblast and syncytium which remain, or the
influence of the corpus luteum, no longer were able to inhibit menstruation. Hence
the decidua, together with these few small remnants of the conceptus, were expelled
in toto, and it may be extremely significant that this occurred exactly two menstrual
months after the beginning of the last period. Since 3 other specimens of a series
of 17 composed of villi only were aborted at the time of recurrence of the regular
period, the idea that abortion occurs oftener at this than at any other time would
seem to receive some confirmation. Moreover, it would seem quite natural that a
detached decidua which has subserved its functions would be more likely to be
shed at this time and that an unabsorbed conceptus, which had been converted
essentially into a foreign body, should then also be expelled. Since detachment
of the decidua also permits regeneration of the mucosa and isolates the conceptus,
it removes the inhibitory effects of the conceptus upon the maternal organism and
clears the way for a return to the normal non-pregnant status.

It is impossible to decide how far the development of this conceptus had pro-
gressed before its death, but the marked extent of the absorption shows beyond
doubt that the latter would have been completed long before the advent of the
next or third menstrual period had the second period also been inhibited. Under
these circumstances the empty decidual cast would then have been expelled alone
and might well have directed attention to the possibility of the existence of a tubal
rather than a uterine pregnancy.

A second ease is No. 970, donated by Dr. R. W. Hammack, of Manila. This
specimen is interesting not only because it is a case of marked intrauterine absorp-
tion, but also because it was obtained with the entire uterus at necropsy. The
chorionic vesicle, which measured only 3 by 5 mm., together with the entire thick-
ness of the decidua and the musculature, is shown in section in figure 170 (plate
16, Chap. XI). The uterine cavity contains some blood and the entire decidua

LYSIS AND RESORPTION OF CONCEPTUSES. 273

was covered with hemorrhagic nodules, the largest of which were about 10 mm.
in diameter. One of these, which was a trifle larger than the rest, contained the
conceptus. The cavity of the chorionic vesicle was filled with a homogeneous
substance containing degenerate cells and portions of disintegrated chorionic mem-
brane. The villi are about 0.5 mm. in length and are covered with trophoblast
and syncytial buds. No trace of the embryo or of the amnion was found, although
the whole conceptus is still covered by the capsularis, which, like the rest of the
decidua, is infiltrated. Although lysis and absorption did not progress so far in
this as in the previous specimen, the process nevertheless is far advanced. It pro-
ceeded no farther because the mother committed suicide, although the multiple
hemorrhages in the decidua would seem to suggest that abortion nevertheless was
seriously threatened, if not inevitable, before she took her life. That the focal
hemorrhages in the decidua could be attributed to the hydrochloric acid swallowed
with suicidal intent is extremely doubtful, for the histologic condition of the con-
ceptus shows conclusively that the changes in it could not possibly have been
produced in the short interval of 4 days which elapsed between the suicidal attempt
and death. Since the menstrual history of the case remains unknown, it is im-
possible to determine the menstrual age of the specimen, but the degenerate
chorionic vesicle would seem to imply an age of only about 10 or 12 days. How-
ever, as this young woman was but 16 years old and apparently illegitimately preg-
nant, itis more than likely that the suicidal attempt occurred, as so often is the
case, during the time of the first lapsed period. Hence the surmise that the mul-
tiple hemorrhages in the decidua may have been provoked by the returning men-
strual cycle gains somewhat in probability, especially so since the size and the
condition of the conceptus both suggested that it must have died some weeks
previous to the necropsy.

A third early specimen illustrating the progress of intrauterine absorption
is No. 962, donated by Dr. Joseph M. Jackson, of Pittsburgh. In contrast to the
preceding two, this chorionic vesicle contained a macerated embryo 4 mm. long.
The menstrual age is unknown, but the chorionic vesicle measured 34 by 28 by 24
mm. and was covered almost entirely by villi. The latter, which contained degen-
erating vessels, are matted together with necrotic trophoblast and show other
evidences of retention. As shown in figure 171 (plate 16, Chap. XI), which repre-
sents a section of the entire conceptus with the surrounding decidua, the amnion
was preserved and contained some coagulum. Mall found the embryo greatly
macerated and the organs and cavities partially obliterated. The slight break
in the decidua capsularis may be the result of handling or of technical procedures.
Since the specimen was aborted with the entire decidua, there can be no question
of escape of a portion of the conceptus.

That it is not alone very young conceptuses which may undergo almost com-
plete lysis is illustrated by No. 606, a chorionic vesicle measuring 18 by 13 by 18
mm. This specimen, which was donated by Dr. Charles 8. Parker, of Baltimore,
is covered with villi 2.35 mm. long. Yet Mall found no trace of an embryo and
stated that, in spite of the outwardly normal appearance of the chorionic vesicle,

274 STUDIES ON PATHOLOGIC OVA.

the villi and the chorionic membrane are structureless. In the absence of the
clinical history one must needs be cautious, but I think it can be safely assumed
that in this case neither embryo nor amnion disappeared solely as a result of post-
partum maceration. That this assumption probably is correct is shown also by
other specimens, the histories of which fortunately are known. Nevertheless,
maceration, although not necessarily putrefactive maceration, undoubtedly was
an important factor in the production of the state in which this specimen is found.
This conclusion is confirmed by the occurrence of all manner of transitions between
the almost perfectly preserved structure and the pure shadow or gossamer pictures
such as are presented in the photograph of the cross-sections of the villi of this
specimen shown in figure 11 (plate 1, Chap. IV). All that remains of the villi are
spiderweb-like outlines, the fibers of which are exceedingly fine, but which never-
theless preserve the form of the villi and of the chorionic membrane so perfectly
that Mall especially recorded that the external appearance of the chorionic vesicle
was normal.

Since chorionic vesicles devoid of an embryo when examined form about 32
per cent of those classed as pathologic in the Carnegie Collection, it is evident that
absence of the embryo itself is relatively common in early abortuses. It would
be incorrect, however, to assume that they had undergone absorption in all these
cases. A fine example of one of these empty chorionic vesicles is No. 1224, a
portion of which is shown in figure 10 (plate 1, Chapter IV).

This specimen was found in an unopened uterus removed at hysterectomy
for cervical myoma. The chorionic vesicle, which measured 36 by 25 by 13 mm.,
was collapsed, free from the uterus, and embedded in coagulum. The only con-
tent of this chorionic vesicle was a dark grayish coagulum which contained no
remnant of the embryo or of the amnion. This almost amorphous so-called magma
included only a few isolated cells. In spite of this fact, the trophoblast, which had
markedly proliferated, is well preserved over large areas, and many of the
vessels in the chorionic membrane are filled completely with erythroblasts. A
few degenerate masses of trophoblasts and fused degenerate villi are also present.
Some villi show evidences of maceration, others of ‘mucoid’ degeneration, al-
though they still may contain vessels. Some, however, are represented by a
hyaline outline only. The stroma and the epithelium of many of the villi are well
preserved, however, and the same thing holds for the chorionic membrane. The
decidua shows slight general and very marked local infiltration. Some remark-
ably dense periglandular and perivascular zones of infiltration are also present.
The mucosa, too, is infiltrated and contains islands composed exclusively of round
cells. Besides maceration effects, many of the villi show marked changes, un-
doubtedly hydatiform in character. In this case it is possible that we are dealing
not so much with absorption as with dissolution of the embryo, for the digestion
products of embryo, yolk-sae, and amnion, instead of having been wholly absorbed,
may still be contained in the fluid within the chorionic vesicle.

Before briefly considering the evidence regarding absorption offered by tubal
and ovarian specimens, I wish to refer to No. 1843. This unique specimen, which

LYSIS AND RESORPTION OF CONCEPTUSES. 275

was donated to Stanford University by Dr. Eugene V. Falk, of Modesto, Cali-
fornia, had the villi rather sparsely and irregularly distributed, as shown in figure
7 (plate 1, Chap. IV). However, the entire specimen was so splendidly preserved
that investigators of unique opportunity and experience were uncertain as to its
normality. Even after careful inspection under low magnification, the writer,
too, felt uncertain, but on receipt of the specimen he informed Dr. Falk that it
probably was pathologic. This opinion was based almost wholly on the irregular
distribution of villi, their complete absence on part of the surface, the large size
of the yolk-sac, the unusual translucence of the entire specimen, and upon the
apparent absence of the embryonic disk. About one-third of the entire surface
of the chorionic vesicle was devoid of villi, and where they were present they seemed
to be in widely different stages of development. They differ markedly not only
in length and in diameter, but also in the complexity of their branching. Some
which were represented by fine threads were found to be represented by stroma
only, the epithelium having been stripped, probably during the removal of the
blood from which the specimen was freed before it was received at the laboratory.
Other villi are torn, those which are preserved are clubbed but slightly, and some
are so short that they look like little droplets on the surface of the chorionic mem-
brane. Those near the bare areas are almost transparent, but nearer the other
pole they become more opaque. The caliber varies from 0.16 to 1 mm. and the
greatest length is 2.25 mm. The chorionic vesicle measured 6 by 4 by 5 mm.
and the partially invaginated yolk-sac 2 by 2.6 by 1.8mm. A smaller, less trans-
parent vesicle, which was thought to represent the amnion, was seen between the
yolk-sac and the chorionic membrane, but no embryonic disk could be recognized.

An examination of the microscopic sections of this vesicle showed that it was
macerated. The epithelium is missing in many places and the histologic details
are wanting. Hence this chorionic vesicle very evidently ceased to live some
time before it was aborted, and this conclusion is corroborated also by the clinical
history. The menstrual age of the specimen is 39 days, but the chorionic vesicle,
which was approximately spherical, measured only 6.5 mm. instead of 35 to 40
mm. as implied by the menstrual history. That growth ceased long before the
occurrence of the abortion is implied also by the fact that Dr. Falk stated that the
patient had a slight uterine hemorrhage about 10 or 12 days before. It is interest-
ing, and probably also significant, that the date of this hemorrhage also coin-
cides with the time when the first lapsed period was due. This is possible because
this conceptus apparently had been dead sufficiently long to fail to inhibit the
return of menstrual bleeding. Since the size of the chorionic vesicle suggests an
age of 10 to 12 days, this assumption seems warranted, especially since it may
be assumed that development probably never proceeds undisturbed to the time
of abortion whenever the pregnancy is terminated spontaneously, or perhaps
better, without the intervention of external or internal mechanical forces or fac-
tors. It may be largely because of this fact that conceptuses from abortions
resulting from intrauterine causes are always macerated.

276 STUDIES ON PATHOLOGIC OVA.

Careful examination of the serial sections, generously made in the Carnegie
Laboratory of Embryology, fails to reveal any remnant of the body of the embryo
except, perhaps, a small nodule shown above the X in figure 172 (plate 16, Chap.
XI). Yet, according to the menstrual age, the embryo should be 10 to 12 mm.
long. The appearance of this nodule suggests that it may be a remnant of the
primitive streak in spite of its deep location, although it may also be a rudiment
of the allantois. The yolk-sac is large and invaginated and its size out of all
proportion to that of the rest of the embryonic rudiment. In the latter there is
a rather large mass of cells containing a space which, I take it, represents the
amniotic cavity. An examination of this cavity and of the surrounding cells
suggests that it resulted from splitting or cavitation, as is the case in bats and as
is assumed also for man by Eternod and others. This cavity may have resulted
from dissolution of the cells in situ, and if in fact it represents the early amniotic
cavity, then, whatever its genesis, it is probable that it was not formed in conse-
quence of folding.

It would seem, then, that we have here a conceptus in which the process of
development of the embryo itself was inhibited very early but that the yolk-sac
and the chorion continued to grow for some time.

Aside from showing a probable and hitherto unobserved stage in the forma-
tion of the amniotic cavity, this pathologic chorionic vesicle is of special interest
also in the absence of coagulum or so-called magma. The chorionic vesicle and
the space taken for the amniotic cavity were filled with perfectly clear fluid. Al-
though this small conceptus is markedly macerated, it is only in the early stages
of disintegration. Nevertheless, much longer retention might have resulted in its
complete dissolution, even if not its complete absorption. Since this small vesicle
was aborted in its entirety with blood-clot, it is highly probable that most of these
degenerative changes occurred after it was loosened from the implantation site,
probably by rupture of the decidua capsularis in consequence of hemorrhage.

In other older conceptuses in earlier stages of disintegration, as No. 2047,
the amnion is preserved and distended, as shown in figure 173 (plate 16, Chap.
XJ). Both chorion and amnion are macerated and distended with clear fluid,
and it seems strange indeed that the embryo and the yolk-sac may disappear
completely without even a final clouding of the amniotic fluid. There may have
been temporary clouding, but every now and then a specimen is received in which
both the vesicles are distended with absolutely clear fluid, a fact which also implies
that autolysis of the embryo occurred without digestion of the enveloping amnion.

Since only a pseudo-decidua forms, and then but rarely and very early, in
cases of tubal pregnancy, the sequence of events leading to dissolution of the
conceptus must be rather different. There can be no accumulation of blood in a
capsularis. Hence the conceptus usually becomes isolated in blood or blood-clot
within the tube, and undergoes degeneration as the hemorrhage continues and the
tube becomes distended. If detachment of the conceptus occurs very early, it
is conceivable that it may undergo complete disintegration also within the tube,
that the latter may heal and the symptoms subside completely. While the occur-

LYSIS AND RESORPTION OF CONCEPTUSES. PAE

rences of such instances of spontaneous cure of tubal pregnancy undoubtedly are
exceedingly rare, evidence at hand seems to show that they can not be wholly
excluded. This, I am told, agrees also with contemporary clinical opinion.

The possibility of tubal abortion with subsequent intraperitoneal disintegra-
tion, lysis, and absorption must also be borne in mind. The occurrence of nothing
but fragments of villi in a tubal clot, as shown in the case of No. 977, represented
in figure 174 (plate 16, Chapter XI), however, can not be accepted as positive
proof that all the rest of the conceptus was absorbed intratubally. A portion may
have been aborted, yet specimens such as Nos. 2035 and 1938 speak eloquently for
the possibility of absorption. The embryo and yolk-sac in the latter specimen are
disintegrated almost completely and the scarcely recognizable remnants lie isolated
in the chorionic cavity, which is moderately filled with an amorphous coagulum.
The stroma of the chorionic membrane is edematous and degenerate, but never-
theless contains some well-preserved vessels, a few of which contain some blood-
cells. The same thing is true of the stroma and of the vessels of the villi, which
also are in process of dissolution. A moderate amount of trophoblast is present,
but there is very little syncytium. The epithelium of some of the villi has under-
gone hyaline degeneration. The blood-cells in the large clot in which this chorionic
vesicle, which measured 8 by 5 mm. in section, was embedded, are preserved fairly
well, especially near the vesicle. Nevertheless, the old conceptus very apparently
is in a state of disintegration and lysis, the tube-wall is very thin, and the mucosa
congested, hemorrhagic, and atrophic.

No. 2035, also a tubal specimen, likewise is an empty chorionic vesicle in
process of disintegration, and many other specimens might be listed, but these
examples suffice to indicate that intratubal as well as intrauterine lysis and, in
part at least, of resorption of conceptuses undoubtedly occurs in the human being.
It is of course exceedingly unlikely that in case of the uterus this can occur before
the impregnated ovum is embedded, for, failing to embed, it undoubtedly would
escape relatively promptly, although the observations of Kirkham (1916) show
that the fertilized ova in mice suckling their young may lie unimplanted within
the uterus for over a week.

A free fertilized or unfertilized ovum which disintegrated within the tube
might be absorbed completely. The same thing holds for early conceptuses
within the implantation cavity, for a relatively small amount of hemorrhage could
detach them completely without rupturing the capsularis. Death, disintegration,
and absorption, as illustrated in the cases above, might then occur. In case of
older specimens, the hemorrhage responsible for the loosening of the conceptus
would have to be proportionately much greater, for the attachment of the placenta
is firmer, though rupture of the capsularis is probably easier. That this assumption
is correct is shown also by the almost universal history of bleeding in these cases,
and it is only in the early stages of development that the conceptus can be expelled
intact while still contained in the implantation cavity and aborted, completely
wrapped in the decidua, as in case of No. 698.

278 STUDIES ON PATHOLOGIC OVA.

Since 12.8 per cent of all abortions and 32.3 per cent of all those classed as
pathologie in the first 1,000 accessions in the Carnegie Collection are composed
of villi only, of empty chorionic vesicles, and essentially of chorion and amnion
alone, one might assume that all these specimens represent stages in the process
of intrauterine disintegration and absorption. Most of them undoubtedly do
belong in this category, but in many cases in which villi only are found the rest
of the conceptus, and in others the embryo as well, has been lost. Since 46.4 per
cent of all tubal specimens and 71 per cent of all those classed as pathologic are
composed of villi only, of empty chorionic vesicles, and of chorion and amnion
only, it might be assumed that digestion and absorption are more active within
the tube than within the uterus. Such a conclusion is not justified, however, for
almost all tubal specimens are isolated while young, and only exceptionally does
one reach the later months of pregnancy. Hence, those falling in the above-
named three groups of tubal specimens form a relatively larger percentage.

Cases of partial dissolution of the embryo are of course common, as almost
every one knows. As far as I can learn, however, the two cases reported here are
the only ones offering unequivocal proof that dissolution of the entire conceptus
may be absolutely complete and that the intact empty decidua then may be
aborted. Such an event could, for various reasons, probably occur only in the early
stages of pregnancy and must undoubtedly be relatively rare. Nevertheless, I
am convinced that careful examination of all material aborted will multiply the
evidence. From these things it would also seem possible that rarely pregnancy
might supervene and be terminated without having attracted any attention what-
soever.

The phenomenon of intrauterine lysis is interesting also from a chemical
standpoint. What the anatomist would like to know is not merely in what respects
the composition of the intra-amniotic and peri-amniotic fluids has been changed,
but just what the enzymes are that have caused a complete lysis of the embryo,
where these first arise and act, and how and why they become active. These and
many other questions the chemist only can answer. For this answer fresh ma-
terial is indispensable, but this the neighboring practitioners or a closely associated
clinic can supply. That the lysis of these early embryos, and undoubtedly also of
the chorionic vesicles, is not due primarily or even very materially to phagocytic
activity is very evident, even upon cursory examination. In the presence of the
intact chorionic and amnionic vesicles in some specimens, such a process is wholly
excluded. Besides, one never sees any evidence of phagocytosis of the preserved
fetal by the maternal tissue in human conceptuses. Evidences of the contrary
process, however, are not wanting.

That the embryo or fetus usually is the first member of the conceptus to dis-
appear has already been implied by stating that in 32 per cent of the abortuses
grouped as pathological in the Carnegie Collection the embryo is missing. Al-
though the absence of the embryo does not necessarily mean, in every case, that
it underwent complete autolysis, this no doubt is true in by far the great majority
of these cases. The fact that the embryo disappears first may be due to a lower

LYSIS AND RESORPTION OF CONCEPTUSES. 279

resistance on its part than that possessed by either amnion or chorion, or to a
preponderance of enzymes within it. Autolysis of the body of the embryo before
that of the membranes may also be due to the fact that the adnexa, especially the
chorion, or at least parts of it, often preserve vitality long after the death of the
embryo because of its direct relation to the uterus. Nevertheless, it often is
surprising how long the form of a small retained fetus, or even of the amnion, has
apparently been preserved, although it should be remembered that in some cases
the preservation of external form gives little indication of the true state of the
constituent tissues. If the advent of proteolytic fat- and carbohydrate-splitting
enzymes in fetal tissues is gradual, the surprisingly long time during which some
of the small embryos are preserved may be due to a considerable degree to this fact.
Jones and Austrian (1907) found, for example, that the liver of a young pig embryo
contains no nuclein enzymes, but that these increase as fetal development pro-
ceeds. The latter finding seems to be confirmed also by data given by Mendel
and Leavenworth (1908), although these investigators found enzymes present at
allages. Schlesinger (1903), who was, I believe, the first to establish the occurrence
of autolysis in retained human fetuses, also found that the rate of autolysis varied
with age and other conditions.

Since the chorionic villi do not undergo autolysis first, the conclusion that
heterolysis is not an important factor in lysis of the conceptus also seems justified.
If enzymes of decidual origin played any large part in the process of lysis of the
conceptus, one might, I presume, expect to find instances in which at least portions
of the chorionic vesicle underwent lysis, although the embryo itself remained quite
unaffected. This, however, never seems to be the case, and the same thing holds
for the placenta and the chorionic vesicle and also for the decidua. That heterolysis
probably plays only a very subsidiary réle is indicated also by the fact that autol-
ysis takes place in tubal implantations as well, and still more convincingly by its
occurrence in ovarian implantations, as illustrated especially by the case of Holland
(1911) and by other cases referred to by Meyer and Wynne (1919), in which the
escape of portions of the conceptus from the ovarian implantation cavity could be
wholly excluded.. One reason for prolonged preservation of the decidua no doubt
lies in the fact that it as a whole, or at least in large part, retains vitality because
it remains quite undisturbed in its vascular relations.

CHAPTER XiIil.
POST-MORTEM INTRAUTERINE CHANGES.

In discussing post-mortem changes, it is necessary to distinguish between the
death of and changes in the cyema and the vesicles, that is, between intracyemic
and extracyemic changes. Such a distinction would be unnecessary if the death
of the one were impossible without that of the other. It has been assumed in the
past not only that the latter is not the case, but that the fetal vesicles may sur-
vive the cyema for some time. Under such circumstances, then, considerable
post-mortem changes might take place within the cyema and perhaps within the
amnion also, while the chorion might remain largely, even if not wholly, unaffected.
Since such an assumption involves the implication that the fetal circulation is
not indispensable for the life of the chorionic vesicle even after the usual time of
the advent of the former, an assumption of independent survival of the entire
vesicle would seem somewhat venturesome, although it is highly probable that
certain constituents of the chorion nevertheless might survive death of the cyema.

That the amnion, which usually is non-vascular, and which fuses with the
chorion quite early in development, may survive death of the embryo is entirely
possible, not only because it is nutritionally more independent, especially in its
early stages, but also because survival of the chorion would condition survival of
the amnion after the latter fuses with the former. The belief, not only in the
survival, but also in the growth of the fetal vesicles after death of the cyema, is
relatively old and rests largely upon the disproportion in size between the embryo
and the chorionic vesicles so frequently seen, and upon the existence of a similar
disproportion between the placenta and the fetus in cases of retained abortions.
According to Panum, von Baer, describing a rather firm, brownish-red, bean-
shaped lump, unlike an embryo of either bird or mammal, which was surrounded
by an envelope and in relation to a vascular area, was said to have regarded it as
a liver which had continued to grow after the death of the embryo. It seems that
von Baer came to this conclusion, largely because of the color of the gross specimen
and because he thought it possible that in poorly regulated incubators the ‘‘vege-
tative” portions of the body of the embryo very often continue to live, although
the “animal” parts die. It must be added, however, that Panum (1860), from
whose monograph this statement is taken, added that he thought von Baer only
regarded these questions as propositions for investigation and proof, and not as
established facts. However, Giacomini (1893) adduced experimental evidence in
favor of such a belief, for he stated that the membranes also continued to grow in
rabbits in which the cyema had been killed experimentally. He further stated
that, although the embryo may be inhibited in growth or even be destroyed com-
pletely, the chorion and amnion not only may show. no degenerative change,
but actually may continue to grow. His (1891) spoke of evidence of an interrupted
growth, and Giacomini (1894) also believed in the occurrence of an inhibition of
growth before the death of the embryo oceurred. According to Waldstein (1913),

281

282 STUDIES ON PATHOLOGIC OVA.

von Winckel also spoke of a slowing in development before the death of the embryo
occurred. Taussig (1903) stated that both Breus and Gottschalk concluded that
retained “ova’’ grow, and Graefe (1896) called attention to the opinion of Veit that
“ova”? may continue to grow after the death of the embryo, but added that the
existence of bare areas and the bunching of villi in some of the retained specimens
argue against the conception of His that ‘ova’ with these characteristics have
continued to grow for some time.

No one seems to have suggested that the entire embryo may continue to grow
after cessation of the fetal circulation, but Wallenstein (1897), who made a careful
microscopic examination of some early abortuses, not only believed that cellular
proliferation can oecur in the embryo after its death, but that either the lateral
or the dorsal or ventral halves may continue to grow independently of each other
after the death of the eyema. Wallenstein believed, even, that the cyema can
become diseased after its death, and concluded that intravascular cells not only
outlive the rest of the cyema, but that they proliferate and invade the dead or
dying tissues of the latter.

Schaeffer (1898) also stated that the chorionic and amniotic vesicles continue
to grow, provided death of the embryo occurs before the fourth month, and Mall
(1900, 1903) also spoke in favor of growth in them after death of the embryo.
Engel (1900) believed that the caudal half of the body of an embryo may continue
to grow after the cephalic half has died. However, Engel’s conclusion regarding
the proliferation of cells was based largely upon the observation that the volume
of the disintegrating central nervous system was too great to be accounted for
merely by the cells which normally compose it.

Giacomini (1894) believed that even the isolated amnion may continue to
grow and that the chorion may continue to live after all else has died. That the
individual portions of very young conceptuses undoubtedly have considerable
power of independent, though not necessarily post-mortem, growth is shown by
such specimens as No. 1848 (fig. 7, plate 1, Chap. IV), a conceptus in which the
chorion and yolk-sac have reached a considerable size, although the embryo and
amnion both are absent, except perhaps in the merest rudiments, as shown in figure
172 (plate 16, Chap. XI). However, it is highly probable that this power of
independent growth is far greater before than after the time when the fetal cireu-
lation has become established in the cyema and chorion. Soon after this time cessa-
tion of the embryonic circulation necessarily would seem to interfere effectively with
growth of the cyema and increasingly with the nutrition of the chorion and more
indirectly also with that of the amnion. However, before the fetal circulation
has been established, it is highly probable that even fhe embryonic disk may be
much more resistant to inhospitable surroundings, and one could pronounce these
very young conceptuses dead only after correlated cellular proliferation had ceased
entirely.

Although the chorions of older specimens may die a more gradual death than
the cyema, one scarcely would expect any villi to be formed anew after the
death of the latter. The syneytium and trophoblast, however, both might con-

POST-MORTEM INTRAUTERINE CHANGES. 283

tinue to grow for some time and apparently often do so, for, as is well illustrated
by many things, they are much more independent, not only of the fetal circulation,
but also of the conceptus, than the other components. Strahl and Henneberg
(1902) also found the ectodermic elements of the placenta in guinea-pigs more
resistant than the mesodermic. Some investigators (His, for example) expressed
the opinion that, although survival of tissues, within both the cyema and the
vesicles, is possible after death of the embryo, one really can not regard such
tissues as truly living, although cell proliferation nevertheless may be present.
Giacomini and His both spoke of cell proliferation, and Mall later used the term
dissociation as including both migration and proliferation of cells. It may be
recalled in this connection that Miiller (1847) also spoke of proliferation of the
epithelium of the villi as being common in aborted ova, and that Giacomini (1888)
stated that the cells of the central nervous system tend to become uniform and
also seem to multiply because they no longer can be accommodated in the space
provided for them. His, Giacomini, Grawitz, Mall, and Engel all believed that at
least a proliferation of ‘‘round cells” occurs and that they are wandering or migra-
tory in nature. Marchand (1895) also spoke of an infiltration of the conceptus by
leucocytes, but did not believe, as did Grawitz, that they were autochthonous in
origin. Although Daels (1908) stated that maternal leucocytes can penetrate
normal syncytium in order to reach a necrotic area beyond, Nattan-Larrier and
Brindeau (1905*, 1908) concluded that leucocytes never invade the stroma of the
villi as long as the epithelium is intact. The conclusion of the latter investigators
is wholly in accord with my own observations, and it would seem extremely diffi-
cult to determine whether leucocytes seen somewhere in the stroma of the villi or
of the chorionic membrane really are fetal or maternal in origin. According to
Windle (1893), the so-called round cells arise in the stroma of the villi, but Wallen-
stein believed that such an infiltration can occur only into dead or dying embryonic
tissue. Berlin (1907) also spoke of the presence of extensive leucocytic infiltration
in one of her cases, and Engel (1900) concluded that in one of the cases described
by him the liver was completely destroyed by proliferating round cells which he
apparently assumed to be phagocytic.

Microscopie evidence for the survival and growth of the ecyema or certain
parts thereof does not rest solely upon the transformation of various tissues and
organs into “round cells,” however. Giacomini and Wallenstein both stated that
mitotic figures were observed by Chiarugi, but the latter seems to stand alone in
regard to this observation. But, even if confirmed, the occurrence of mitoses
locally would not establish the occurrence of a correlated proliferation which could
rightly be designated as growth. Nor could the well-known independent survival
or even growth of still-implanted villi or, more properly speaking, of the syn-
cytium and stroma, in cases of hydatiform degeneration and chorio-epitheliomata,
be regarded as establishing the occurrence of normal growth in the vesicles or the
cyemata of conceptuses.

Post-mortem obliteration of the vessels would seem to fall more in this cate-
gory, but the post-mortem occurrence of this phenomenon even is as yet unproved.

284 STUDIES ON PATHOLOGIC OVA.

Besides, upon a priori grounds alone it would seem that the adverse conditions which
cause the death of the embryo, and eventually also that of the entire conceptus,
alone would make conditions of post-mortem growth rather unfavorable even for
the most resistant of the dependent tissues. Other factors also would tend to make
these conditions unfavorable for the occurrence of post-mortem proliferation, even
for such growth as we have in recent years come to know as growth in vitro. I have
rarely found appearances identical with those seen in certain artificial cultures, as
figure 175 so well illustrates; but these appearances involved connective tissue
only and always occurred in the interior of the chorionic membrane, or between the
latter and the amnion when the two were separated somewhat. Nevertheless, the
rareness of these appearances in itself throws much doubt on the occurrence of
genuine growth after death, and in view of the fact that I have been unable to
find any thickening of the chorionic and amniotic membranes at these places, I
am more inclined to regard such appearances as these as due to a migration rather
than to an actual proliferation of cells. Nor have I seen much evidence in favor of
a post-mortem migration other than that of cells intravascular in origin. What has
been termed lymphoid infiltration or transformation seems to be due rather to a
degeneration of cells zn loco, the degenerate forms simulating round cells and thus
giving rise to misinterpretations. Indeed, the idea that a complete transformation
of the entire body of the embryo into round cells can occur without the phagocy-
tosis of the cells composing the various organs seems to imply that this so-called
lymphoid infiltration really is a transformation in loco. That an apparent tem-
porary increase in volume of the central nervous system has been noted is not
surprising. But this does not postulate an actual increase in the number of cells
any more than the old observation of maintenance in weight and volume of the
central nervous system under conditions of inanition implied that the nerve-cells
remained unchanged. That the latter is not the case was shown by Meyer (1917’).

It may be recalled that Merttens (1894) also reported finding obliteration of
the blood-vessels due to proliferation of the intima. However, since Merttens
found these obliterative vascular changes only in the chorion leve, his conclusion
that these changes undoubtedly were post-mortem is open to very serious doubt.
This doubt is greatly increased by the facts that Merttens suspected the existence
of lues in a case in which these obliterative changes were present and that almost
complete obliteration of the vessels was present in a specimen which was regarded
as having been retained only 11 days. Since calcium deposits were present in this
specimen, the latter estimate is open to grave doubt, however.

Berlin (1907), although aware of the fact that an ante-mortem obliterative
endarteritis had been shown to occur in conceptuses, nevertheless concluded that
the degree of obliteration found in the placental vessels roughly parallels the dura-
tion of the retention. She added that the processes found by her recall those
observed in portions of a blood-vessel isolated by ligature and represented appear-
ances within the placental vessels almost identical with those represented in figure
175. In spite of the similarity of these figures, it would seem unwarranted, how-
ever, to assume that phenomena identical with those observed in the chorionic

POST-MORTEM INTRAUTERINE CHANGES. 285

vesicles could lead to obliteration of vessels. In the chorionic vesicle the picture
presented is that of migration rather than that of proliferation, and it is indeed a
long step from these things to complete obliteration of blood-vessels, especially
when it is recalled that the latter involves the growth of new capillaries, as was
reported by Merttens and as is the case in the normal postnatal obliteration of the
umbilical vessels. Schickele (1907) also observed obliteration by endothelial
proliferation in the various vessels, but insisted that they do not occur with the fre-
quency reported by Merttens. Schickele further stated that obliteration occurs
rapidly and that it is not necessarily post-mortem.

Waldstein, who made a very careful histologic examination of some abortuses,
stated that, although the regressive changes had not yet been sufficiently studied,
he did not believe in a continued growth of the embryo, but merely in a further
differentiation of some of the constituent tissues, and also in a round-cell infiltra-
tion. Waldstein claimed that in some specimens examined by him the striations
in the central musculature were maturer than they should have been, and hence
concluded that post-mortem differentiation had taken place inthem. He believed
that the round cells had an intravascular origin. Boerma (1912), who described
a young macerated embryo, also stated that the amniotic cavity contained cell-
masses from the embryo which he believed had survived the parent mass.

His (1891), Giacomini (1894), Schaeffer (1898), Mall, and the writer occasion-
ally found local thickenings of and adhesions between certain epidermal surfaces.
These adhesions and thickenings, referred to in Chapter IV, group 7, were present
in the lower extremities of the fetus shown in figures 64 and 65 (plate 5, Chap. IV).
In this case, as in those of Lomer and Schaeffer, the extremities are glued together
by epidermis. The appearance of the lower extremities at this point also suggests
that there has been an accumulation of sloughed epidermis in the region of contact.
To what extent this gluing is due to fusion of dying tissues and cells, rather than
to growth, it is difficult tosay. In other cases, as stated by His (1891), the extremi-
ties may be glued to the trunk, or the head to the chest, as observed also by Mall
and as illustrated in figure 176. The mandibular region may adhere to the chest
and the lips coalesce so completely that the epidermis is absolutely continuous
from the chest to the chin and also across the lips, as represented in section in
figure 180.

Giacomini (1889) further described invaginations of the epidermis into the
mesoderm on the dorsum, lateral to the spine in an atrophic embryo 5 mm. long.
Although not regularly symmetrical, these epidermal invaginations nevertheless
were said to have a metameric arrangement, there being 6 on the right and 10 on
the left side. Giacomini stated that these epidermal growths reminded him of the
lateral-line organs of elasmobranchs, and added that he saw them at the caudal
extremity of another specimen. Epidermal accumulations in various places were
noticed also by Mall in long-retained cyemata, but nothing justifying Giacomini’s
interpretation was encountered either by Mall or myself. The accumulations
noticed by us were small, irregular, and rather poorly preserved mounds of epider-
mis, as illustrated in figures 76 and 77.

286 STUDIES ON PATHOLOGIC OVA.

That the placenta may continue to grow during retention after death of the
cyema was once firmly believed. This idea had its origin in the disproportion
frequently present between the size of the placenta and that of the cyema. At
present, belief in the growth of the placenta after death of the cyema seems to have
been abandoned, however. It was in connection with the placental changes, and
especially with changes in the vessels of the villi, that the question of the survival
and growth of cyemic tissues attracted attention. Among the placental changes
which suggested the presence of growth was the proliferation of the ectoderm of the
villi, indicated in so many specimens. It is interesting that Schickele (1907) re-
garded this apparent post-mortem proliferation as a direct cause of cyemic death.
Schickele believed that proliferation of the ectoderm of the villi results in encroach-
ment upon the placental circulation and ultimately in death of the cyema. It
seems strange, however, that Schickele (1905) stated that proliferation of the syn-
cytium usually does not occur, except in cases of long-standing retention. Litt-
hauer (1887) also had believed in the continued growth of the placenta as a result
of retention, and had concluded that the death of the eyema was attributable to
interference with its nutritive supply through proliferation of the endometrium.

Taussig (1903) stated that the vessels in the villi of retained ‘‘ova’’ may be
preserved for a long time, as reported also by Davidson, and Berlin believed that
obliteration of the villous vessels is a purely post-mortem phenomenon. As
previously stated, Berlin affirmed the belief of Merttens (1894) that the degree of
vascular obliteration somewhat parallels the duration of the retention. If this
obliteration actually occurs post-mortem, this conclusion of Merttens may be
correct, for it is well known that the degree of obliteration of the umbilical vessels
is dependent upon the duration since birth. However, the occurrence of ante-
mortem vascular changes established by numerous investigators can not be ex-
cluded. Nor is it necessarily an easy matter to differentiate the ante-mortem
from the post-mortem proliferative vascular changes. If the villi can continue
to grow after death of the fetus the rate of obliteration will be very much affected,
no doubt, by this fact. It is interesting that Graefe, although granting the possi-
bility of independent growth of the villi in retained uterine conceptuses, stated
that he saw hypertrophy of the villi only once. Schaeffer also believed that the
villi are preserved for a long time after death of the cyema, and Mall (1915) stated
that in cases of tubal pregnancy the villi may continue to grow independently
after death of the embryo.

Crosti (1896) stated that if the ovum is not aborted immediately after death
of the embryo the villous capillaries gradually disappear. Crosti also believed
that the villi are preserved longer than the rest of the conceptus, and that even the
“appendici durate’’ may become hydropic. It must be borne in mind, however,
that the disappearance of the villous capillaries in consequence of maceration is
one thing, and the obliteration of the vascular lumen by proliferative processes
is quite another. Obliteration such as that represented in figure 177 illustrates
the former process, which is a purely post-mortem phenomenon as far as the partic-
ular villus is concerned, while that represented by No. 317, shown in figure 178,

POST-MORTEM INTRAUTERINE CHANGES. 287

illustrates proliferative obliteration of the vascular lumen which undoubtedly was
ante-mortem. However, it must be recalled that not all of a chorionic vesicle
necessarily dies at the same time, and that implanted villi, or those in very young
conceptuses which are not yet dependent upon the fetal circulation, may well con-
tinue to live and perhaps even continue to grow for some time. But such villi
hardly can justly be designated as dead, and since death of the cyema does not
necessarily result in simultaneous death of the entire conceptus, this distinction
is not an unimportant one.

There seems to be no agreement among writers, however, as to which of the
tissues of the cyema are most resistant to post-mortem changes. Litthauer (1887)
found the muscles of certain fetuses well preserved, although the cartilages had
lost all their normal structure. Virchow, Wyder, and Baumgarten, according to
Litthauer, also found that the muscles are among the most resistant of structures.
Giacomini (1888) thought the central nervous system very resistant, but Engel
came to a contrary conclusion. Phisalix (1890) thought the epithelium the most
easily affected by pathological processes, and while there is great difference of
opinion, all investigators seem to be agreed that the cyema is affected before the
vesicles.

Von Winckel (1904) spoke of three grades of maceration in the cyema, the
first being that of bleb formation, the second that in which the epidermis is broken
and shed in fragments, thus exposing the chorion, and the third stage that in which
the joint capsules and ligaments are loosened, the joints consequently relaxed,
and the extremities contorted. Von Winckel also set an approximate time-limit
for the occurrence of these stages, the last stage being reached in three weeks.
Nevertheless, von Winckel concluded that the degree of maceration could not be
used as a criterion for the determination of the duration of intrauterine retention.
Miiller also was impressed by the post-mortem changes, and rightly stated that
many embryos are deformed beyond recognition by maceration, bleb formation,
and mummification.

Although it is incorrect to regard the changes which many conceptuses undergo
after death and before abortion as maceration in the customary sense, no other
word seems to be available. These changes undoubtedly are accompanied by
softening, collapse, deformation, and no doubt also by autolysis. Whether im-
bibition and swelling are invariably present I do not know, but if they occur they
usually are slight and their effects minor in character. Most of the changes
enumerated here may occur under sterile conditions, and since maceration, even in
this restricted sense, must effect changes, not only in the chemical composition, but
also in the microscopic structure of cells, long before changes in external form of
embryo or chorionic vesicle become apparent, a discussion of maceration changes
really should begin with these. But the earliest modifications in microscopic
structure remain very largely, and those in chemical composition almost wholly,
unknown to us at present.

Although it undoubtedly is true, as stated by Miiller (1847), that very young
embryos may retain their form surprisingly long after death if retained in sterile

288 STUDIES ON PATHOLOGIC OVA.

amniotic fluid, it does not therefore follow that they really remain structurally
unchanged. However, I can not confirm the opinion of Herzog (1898) that chori-
onic villi degenerate with astonishing rapidity after the death of the embryo, which
Herzog claimed was true especially in young placentz. According to Herzog, only
the most intimate acquaintance enables one to recognize the villi after the embryo
has been dead two or three weeks. Since the villi are usually the last thing to dis-
appear and may survive the death of the embryo by months, even in the case of
early conceptuses, it is difficult to understand what may have been responsible for
Herzog’s opinion. Leopold (1882) stated that it has been shown that a bare fetus
in the peritoneal cavity will macerate and become disarticulated, but that a fetus
surrounded by the intact membranes will become dry and leathery. Just what
the basis for this statement is I do not know, but it would seem that compar-
atively prompt disarticulation of any except perhaps very young cyemata must
imply the presence of putrefactive conditions, for the length of time which dead
tissues can survive depends very largely upon the advent of putrefaction.

Microscopic changes no doubt appear quite promptly after death in all con-
ceptuses, but, strange as it may seem, the most pronounced internal changes
may sometimes fail to manifest themselves externally. In one instance (No. 962),
for example, Mall had noted that the shape of the embryo had been preserved so
perfectly that the specimen seemed normal in form. Yet the slightest jar on the
containing vessel resulted in its complete disintegration. Apparently this speci-
men was somewhat farther advanced than embryo No. 2197 (figure 29, plate 4,
Chap. IV). The same thing may be true of the villi, the shape of which may be
preserved perfectly, although structurally they may have become mere gossamers,
as illustrated by the villi of No. 606, shown in figure 11 (plate 1, Chap. IV).

Since very few abortuses are expelled promptly, practically all are macerated
to a greater or lesser degree. This applies to specimens classed as normal, as well
as to those classed as pathologic. Nor can the mere fact that a specimen was
obtained in utero at operation assure one that it is not macerated. No. 1224, for
example, although obtained at operation, is a very greatly macerated, empty
chorionic vesicle which was isolated completely in the uterine cavity. In another
specimen (No. 1767), also obtained at hysterectomy, an abscess is found within
the implantation site. No. 782, a third specimen of the same kind, and also other
hysterectomy specimens, as previously stated, contain young hydatiform vesicles.
Although the uterus and conceptus of No. 872 were placed in 10 per cent formalin
after operation and kept in a thermostat for two days, the villi nevertheless are
markedly macerated. They are also almost wholly non-vascular, remnants of the
vessels being present in some of the villi only. The amnion is absent, the fibrous
chorion also shows maceration changes, and the decidua is decidedly infiltrated.
Hence it is important to remember that unless one is dealing with a normal im-
plantation and a wholly normal uterus, the fact that the specimen was obtained
at operation and preserved immediately with the best of care is not an absolute
guarantee against the presence of early maceration changes. This is illustrated
especially well by tubal specimens, which so frequently are embedded or isolated

POST-MORTEM INTRAUTERINE CHANGES. 289

in blood-clot, as was the case with Nos. 1938 and 2035, shown in figures 179 and
181. The embryo and yolk-sac of the former are almost completely disintegrated,
for nothing but scarcely recognizable remnants lie isolated in the chorionic cavity,
which is moderately filled with an amorphous coagulum. The stroma of the
chorionic membrane is edematous and degenerate, but contains some well-
preserved vessels, a few of which contain some blood-cells. The same thing is true
of the stroma and of the vessels of the villi, which also are in process of dissolution.
A moderate amount of trophoblast is present, but there is very little syncytium.
The epithelium of some of the villi has undergone hyaline degeneration. The
blood-cells in the large clot in which this chorionic vesicle, measuring 8 by 5
mm. in section, was embedded, are preserved fairly well, especially near the vesicle.
Nevertheless, the whole conceptus is very apparently in a state of rapid disin-
tegration and lysis. The tube-wall is very thin and the mucosa congested, hemor-
rhagic, and atrophic.

It is not difficult, as a rule, to identify maceration changes in the villi, for the
appearances are rather characteristic, as figures 182 and 183 illustrate. But when
other changes, such as the obliterative process shown in figure 184, are present at
the same time, it is sometimes impossible to decide whether such changes as these
were ante-mortem or post-mortem. In this case the lumina of the capillaries are
plugged by what reminded Mall of “epithelial pearls,” though he recognized that
the cells were endothelial in origin. That such an obstruction of the lumina of
blood-vessels can occur through a shedding, swelling, and clumping of the endothe-
lial cells there can be little doubt, although proliferation of the endothelium can
perhaps not be wholly excluded.

The earliest noticeable external post-mortem change in the color of the embryo
is due to the oecurrence of a greater opacity. The tissues lose their normal trans-
lucence, so that they look whiter and denser, and the surface also becomes less
glistening. Later they also become yellowish and occasionally hemorrhagic, and~
the cutaneous surface becomes less smooth. Coincident with these changes,
softening and some swelling also take place, as illustrated by No. 2146, shown in
figure 187, and bleb formation occurs, especially on the abdominal extremity of
the umbilical cord and elsewhere, as previously shown in figures 54, 70, 71, and 72
(plate 5, Chap. IV).

In consequence of the softening of the tissues, the upper extremities, if suffi-
ciently developed, tend to gradually droop, as shown in figures 58 and 66 (plate 5,
Chap. IV). Later, the caudal extremities also sag, and both pairs may gradually
develop unusual curvatures. Changes occur also in the face, for the ocular mar-
gins become irregular and everted, or, if the lids have fused, they may prematurely
open. But all these are relatively slight gross changes and merely herald the more
profound modifications in form if retention continues under favorable conditions.
What is now needed is a correlation between these early changes in external form
and appearance and the histologic and cytologic changes. Although the advent
of changes in color is quite prompt, it can safely be assumed from other evidence

290 STUDIES ON PATHOLOGIC OVA.

that the incipient structural changes are microscopic and can be detected long
before changes in external form and color occur.

Since the chorionic vesicle almost invariably is surrounded by more or less
blood and decidua in eases of abortion, it is naturally difficult to detect early gross
post-mortem changes in it by inspection alone. However, the earliest noticeable
external change in the villi is a decrease in translucency and a dulling of their
surface. The villi of very young specimens also seem to become somewhat larger
in caliber and look stiffer and slightly bulbous in places. They also frequently
are somewhat matted, as was the case in No. 1878, a very young specimen, a
portion of which is shown in figure 188, the chorionic vesicle of which measured
but 10 by 12 mm. However, in No. 18438, which is a still younger specimen,
measuring 5 by 6.5 mm. (figure 7, plate 1, Chap. IV) and shows more marked
maceration changes upon microscopic examination, these changes, nevertheless,
were not evident to the unaided eye, for the vesicle was unusually translucent.
The chorionic and villous epithelium has sloughed over most of this vesicle and
the remaining tissues stain but weakly. The cell-boundaries also are rather in-
distinct and the yolk-sac shows marked changes.

The first noticeable change in histologic structure seen in routine prepara-
tions seems to be a blurring of the structural detail in the tissues and a haziness in
appearance of the cytoplasm. This early state is followed, if not preceded, by auto-
lytic changes. As has so frequently been emphasized, evidences of disintegration,
noticeable particularly in the central nervous system, supervene very early and
the brain and cord become swollen and the folds become effaced, as shown in
figure 185. These changes are accompanied and may be followed by complete
dissociation of the constituent elements, with some shifting if not migration of
cells. All the constitutent cells become rounded, the cytoplasm may disappear
entirely, and the nuclei become more pycnotic. When this stage is reached the
structure of the brain and cord is quite uniform and cells of various origins may
all be quite properly designated as round cells, for all look alike, the changed
nuclei only remaining. The entire central nervous system, for example, may be
composed of these densely packed round cells and be characterized quite properly
upon superficial appearances alone as lymphoid, as suggested by Giacomini.
Finally, however, the nuclei also disintegrate and form a fine, granular material,
spoken of by Mall as nuclear dust. Morever, not only the nervous system, but all
the organs of small fetuses, may be so transformed, as illustrated in figure 186.

These things, however, do not necessarily or materially change the form of the
eyema, and the effects produced by retention in utero after death will depend not
so much upon the exact duration of the retention as upon the age of the cyema.
A few weeks may suffice not only to change greatly the external form or the inter-
nal structure of young eyemata, but to effect complete absorption. In case of an
approximately mature fetus, on the other hand, such a short period of retention
after death might modify the form inappreciably and result merely in maceration
of the epidermis.

POST-MORTEM INTRAUTERINE CHANGES. 291

One might expect that maceration, even under sterile conditions, especially
in case of young specimens, would result in general distention, but this does not
always seem to be the case. Edematous areas do, indeed, frequently form locally,
as previously illustrated and as generally observed; but swelling due to imbibition,
such as occurs when fresh young specimens are placed in formaldehyde, was
observed only in a minor degree, as illustrated by No. 2146, shown in figure 187.
Sometimes this swelling is local, as represented by the cephalic region of No.
1750. A subsequent reduction in size is much more common and may be due to
absorption of salts from the amniotic fluid, with resultant concentration of it and
of extraction of tissue fluid from the cyema itself. In very young specimens, such
as No. 786 (fig. 189), an embryo 4 mm. long, the first noticeable shrinkage change
in form seems to occur in the cephalic extremity, the frontal prominence of
which recedes and the outline of the vertex of which becomes more and more
rounded and also is reduced in size.

In consequence of these changes, the cephalic extremity becomes relatively
too small, as is well illustrated by comparing this specimen with No. 1380, shown
in figure 190, a cyema of the same development but 5.5 mm. long and in an excel-
lent condition of preservation. This reduction in size of the cephalic region would,
to be sure, result in a reduction in length were the measurement taken from tip
to tip, and were it not for the fact that during this process the cephalic extremity,
if indeed not the entire embryo, usually unbends and in becoming straighter com-
pensates for, or even more than compensates for, the loss in length due to reduc-
tion in size of the cephalic extremity. This does not always occur, however, as Nos.
1299 and 2216 so well illustrate (see figs. 191 and 192). These changes make the
trunk look disproportionately large and the features somewhat stunted. Previous
to these changes, or coincident with them, the tissues lose their elasticity and also
become softer, and the surface of the specimen becomes duller, more opaque, and
finally more yellowish. Other changes noticeable in the specimen just referred to
are the loss in detail of the surface relief, evident particularly in the branchial
region, and in the effacement of the myotomes. In other instances, such as No.
2035 (a portion of a tubal specimen), a marked change is very evident in the caudal
extremity, which has become shorter, blunter, and straighter, although upon close
inspection other changes also are noticeable. Because of these things the actual
soon may become less than the original length and only roughly indicate the true
age of the cyema.

The change in the cephalic extremity, the decrease in the natural curve
which accompanies erection of the specimen, and the loss in detail just spoken of
are illustrated still better by No. 187a, which is a somewhat older embryo, 7 mm.
in length. Young embryos which illustrate the early changes in form are Nos.
208 and 1296, shown in figures 193 and 194—embryos which are respectively 7
and 4 mm. long in their present state.

A somewhat similar, though slighter, effect of maceration upon relatively
young specimens is illustrated by Nos. 1697 and 1477, shown in figures 195 and
196, cyemata 15 and 18.5 mm. long respectively. In the first of these two speci-

292 STUDIES ON PATHOLOGIC OVA.

mens the gaping mouth and blunted and rounded upper extremities are especially
noticeable. That sagging of the upper extremities does not always occur, even in
the presence of a more marked degree of maceration than present in the above
specimen, is illustrated by No. 705, shown in figure 197, a somewhat older cyema
with more marked maceration, and to a less degree also by No. 1477, both of which
also show a rounding and shortening of the extremities.

A still more striking series of transformations is illustrated by the somewhat
older specimens, Nos. 2244, 1891, 1655, 1260, 1333, 1926, and 1379, shown in
figures 198 to 204 inclusive. Inspection of this series will show that the transition
from one to the succeeding specimen is not very marked, although the difference
in form between the first and last specimens is very great indeed, and could have
been made more striking by accompanying each figure by a normal one of the
same (or approximately the same) stage of development.

Such oddly shaped bodies as those shown in figures 203 and 204 scarcely can
be identified positively as cyemic remnants by the unaided eye, and even under
some magnification give little indication of their internal structure. The same
thing is true, though to a lesser degree, of Nos. 885 and 1333, shown in figure 202,
and also in figure 22 (plate 3, Chap. IV). In these specimens the limbs are still
present in such an abbreviated form that the latter suggests amelia. Hence the
question at once arises whether these specimens show mere post-mortem deforma-
tions or true developmental anomalies. This question is presented still more
forcibly by smaller, younger specimens such as Nos. 1226 and 2361, shown in
figures 205 and 206. These cyemata may be truly anomalous, but they also may
be macerated young normal embryos, and in case of young specimens the question
can be decided only by a microscopic study of the sections, as was illustrated while
considering the nodular group in Chapter IV. It must be borne in mind, however,
that minor external deformities may be obliterated completely by post-mortem
deformations, and that in such cases no positive conclusion can then be reached.

An unbending or erection of the eyema does not always occur, as is illustrated
by No. 208 (fig. 191), which also is a 7-mm. specimen. Although this cyema
is markedly macerated, there has been but little change in the total outline, save
as a result of pitting, increase in flexure, and shrinkage. Whether or not failure
to unbend on the part of this specimen is due to an early coagulation of the am-
niotic fluid, and the tissues of the embryo itself, I do not know, but that this might
be an important factor does not seem improbable. Similarly, early coagulation
of the cyema itself might postpone other changes in form, similar to those shown
in No. 589 (fig. 207), a cyema of 10 mm. This cyema very apparently was not
surrounded by a coagulum. In such soft specimens the whole surface may be
wrinkled, the hand plates may look excavated, and the head may be sunken
deeply upon the chest. Since this particular specimen remained extremely soft
and pliable, the extremities also were rotated somewhat and the body became
rather collapsed, as if compressed. Just why some cyemata remain relatively
stiff, firm, and opaque, and others become extremely soft, swollen, and more

POST-MORTEM INTRAUTERINE CHANGES. 293

translucent, remains unknown to me, but it is not impossible that the reaction of
the amniotic fluid is the controlling factor.

In slightly older specimens the first marked changes in external form resulting
from maceration sometimes are seen near the abdominal attachment of the um-
bilical cord, as illustrated in No 1523 (fig. 70, plate 5, Chap. IV), an embryo of
19 mm. Several blebs are sometimes located on opposite sides of the cord or
surround it, as in the case of No. 1475, shown in figure 54 (plate 5, Chap IV).
It is interesting that large blebs not infrequently are present in this location, even
if the body of the cyema has suffered relatively little change. The size of these
blebs, to be sure, may be considerable and, instead of local edema, the entire
epidermis may be lifted and the entire cord may be swollen, but such a condition
usually arises only later, during longer periods of retention. Sometimes the whole
nuchal region is edematous, forming a marked prominence far above that nor-
mally present, or is occupied by a single large bleb. For some reason these blebs
are common, especially on the head, the dorsum, and on the umbilical cord.

Sometimes a prominence on the dorsum is due to the swollen, macerated, and
completely disintegrated central nervous system, which may form a marked ridge,
as illustrated by No. 521f, shown in figure 208, a specimen in which lumbar spina
bifida was present. Not infrequently, however, a marked prominence in the
upper dorsal region is due to collapse of the brain and drooping of the head, as
illustrated in No. 175, a ecyema of 13 mm. This collapse of the central nervous
system occurs most frequently in the brain of older specimens and is not infre-
quently followed by collapse of the calvarium in younger specimens. It may
result in marked cutaneous depressions or sulci, as illustrated in No. 1250, a speci-
men 13 mm. in length (fig. 209). Rarely, these sulci or ridges may extend entirely
down the dorsum of young specimens.

It is decidedly significant that some intrauterine changes in external form
can be simulated by post-mortem extrauterine changes. This is splendidly illus-
trated by figures 210 and 211, which are photographs of a fresh and well-preserved
and a poorly preserved cat embryo respectively. Similar changes have also been
produced experimentally by incubation in sterile solutions, and are further illus-
trated by No. 1358f, shown in figures 212 and 213. The former shows the appear-
ance of the somewhat macerated specimen before staining and preservation in
alcohol, which very materially shrunk the tissues, as shown in the latter. Were
the history of this case unknown, one would have been justified in calling it a
rather decidedly soft, macerated specimen. Nor do two specimens of identical
age, which existed under identical conditions, necessarily present exactly the same
appearance. This is well illustrated by Nos. 2258a and 22580, single-ovum twins,
shown in figure 214.

The relatively early loss in detail in the normal relief of the cyema is illus-
trated extremely well by No. 2014 (fig. 215), an embryo 17 mm. long. The normal
relief of this specimen is replaced by a molding due to maceration. These changes,
which are noticeable over the entire body, show particularly in the eyes and ears
and in the gaping mouth. The effacement of the normal features in young speci-

294 STUDIES ON PATHOLOGIC OVA.

mens is sometimes very complete, but this is true also of older ones, so that the
external form may suggest the amorphous group. An intermediate form between
the latter and No. 2014 is represented by No. 1495d (fig. 216), a eyema 12.3 mm.
long, but of approximately the same stage of development as the other two. A
still more advanced change of this type is illustrated by No. 921, shown in figure
39 (plate 4, Chap. IV). The difference in length between some of these specimens
of corresponding development is not infrequently due mainly to shrinkage accom-
panying maceration and retention. No. 1495d is interesting also because the
placental site was marked internally by numerous subchorial hematomata (fig.
217). I do not wish to enter into a discussion of these so-called ‘‘Breus hema-
tomatous moles” of which so much seems to have been made, but all the speci-
mens which have come to my attention had been retained for a long time. It
would seem that when, for some reason, the placental margins and also certain
intermediate placental areas are more firmly adherent than the rest, the looser
portions may be detached and forced inward by hemorrhage, thus producing a
series of hummocks on the internal surface of the placenta. If the chorion and
amnion over these areas rupture, blood may enter the amniotic fluid, and just
in proportion as the latter is reduced in quantity the process of eversion of the
placental site must be facilitated. It is, of course, entirely possible that a mix-
ture of blood with the amniotic fluid, so common in these specimens, may help
to preserve the cyema, but the abortuses with subchorial hematomata which I
have seen did not give me the impression that their preservation was any better
than that of the non-hematomatous type.

Blunting and rounding of the extremities of the cyema, with consequent
shortening and loss of detail, are present in still more decided form than previously
illustrated. Beginning sagging of the extremities is shown well in No. 1358,
which is 18.3 mm. long, and in still older specimens, such as No. 1710 (fig. 66, plate
5, Chap. IV). The abnormal curvatures, and especially the blunting of the ex-
tremities, are exemplified still better, and the drooping mandible, gaping mouth,
and locally edematous cord are also well shown in No. 797, a fetus 35 mm. long,
represented in figure 218. Changes in curvature of the extremities are splendidly
illustrated in No. 1860 (fig. 219), and become more pronounced the older the
specimen, up to the period when skeletal development makes them extremely
difficult or even impossible.

The changes in the extremities do not stop, however, with the production of
abnormal curvatures, for not infrequently the hands and feet undergo an outward
clubbing, shown in pronounced form in No. 1958 (fig. 220), a decidedly macerated
specimen 41.5 mm. long. Separate views of the extremities of this specimen are
given in figures 221 and 222. Earlier stages in this process are illustrated by No.
1751 (fig. 223), with separate views of the extremities in figure 69 (plate 5, Chap. IV).

Since the extremities in earlier stages of development are less resistant, they
become soft and are more easily contorted; but at a somewhat later stage of develop-
ment, when they are more resistant, it is not uncommon to find the arms especially
assuming more extended positions of gesture. Hence grotesque figures occur, such

POST-MORTEM INTRAUTERINE CHANGES. 295

as exemplified in Nos. 1462 and 1309 (figures 224 and 225), which are purely acci-
dental forms. As maceration becomes extreme, even without the presence of
putrefaction, marked softening and distortion take place and the face may be
drawn into grimaces, as illustrated by No. 1775 (fig. 226) and by other specimens
previously represented. In these older specimens the epidermis, instead of falling
off in flakes or hanging in streamers, especially from the extremities of the digits,
may become rolled up and accumulate in welts, especially at points of contact of
the extremities, as illustrated in No. 1859 (fig. 64, plate 5, Chap. IV).

If dehydration occurs under sterile conditions, the transition from such a
specimen as No. 1859 to 1474a, shown in figure 61 (plate 5, Chap. IV.), is an easy
one, and if continued beyond this stage it may eventually lead to typical mummi-
fication. If the amniotic fluid is finally completely or almost completely absorbed
and the uterus then contracts upon the specimen, such rolled-up forms as Nos.
1525, 1976 (figures 227 and 228) and No. 1041 (figure 40, plate 4, Chap. IV.) may
result. Sometimes the placenta and membranes of these long-retained, leathery
specimens are found in the form of a firm covering with a small opening through
which the fetus has escaped, as illustrated by No. 1850, a fetus of 17 mm., shown
in figure 229.

In other instances the fetal tissues, instead of becoming dehydrated, as in
case of the above and No. 1295a, shown in figure 230, remain soft, as represented
in a comparatively early stage by No. 1350, 66 mm. long, shown in figure 61 (plate
5, Chap. IV).

A more advanced stage of this process is represented by Nos. 2034 and 1925,
fetuses 96.5 and 147 mm. long respectively, shown in figure 234 and figure 48 (plate
5, Chap. IX). If this process of maceration becomes extreme, or if putrefac-
tion supervenes, such disintegrated forms as No. 1515 (fig. 50, plate 5, Chap. IV)
are finally produced, and the stage of disarticulation is at last reached.

That the advent of rigor mortis does not necessarily change the attitude of
young embryos is suggested from occurrences observed personally under experi-
mental conditions. As long as the amnion closely invests a mammalian embryo,
‘the extremities of the latter can not become extended during rigor, and hence may
retain the intrauterine position. The same thing holds, to a considerable extent
at least, for the trunk also, for neither is it so free to extend as when the amnion
has been opened or been removed. In the human conceptus the amnion soon
becomes sufficiently large, however, but coagulum could have a similar influence.

Although little is known regarding intrauterine rigor mortis, Wolff (1903)
stated that it is not rare, and held that an accumulation of waste products pro-
duced in consequence of circulating disturbances in the mother may be responsible
for its early advent. In any case it probably is quite transitory, and the later
rigidity of aborted cyemata undoubtedly must be due to something else.

At present we are not in position to accurately evaluate slight changes in
bodily form of cyemata, for as long as the exact form of normal cyemata remains
undetermined, it is inevitable that macerated specimens will be mistaken for and
represented as normal in form, even in contemporary embryologies. Abnormal

296 STUDIES ON PATHOLOGIC OVA.

forms likewise have been described as normal, and macerated normal specimens
also as pathologic, although no one would, I presume, defend the opinion that a
dead conceptus may become pathologic.

Although His emphasized that the softness of aborted forms easily results in
unusual folds and flexures, he, it seems, greatly reinforced, even if he did not intro-
duce, the idea that embryos that are abnormal in form are pathologic. He
apparently came to this conclusion because he did not believe that post-mortem
changes could be responsible for modifications in form present in the specimens
which came to his attention. Giacomini (1888) also believed that many of the
deformities so common in embryos of the first months are due purely to regression
after death, but added that he did not care to stress the idea that post-mortem
changes can account for many of the deformities seen. Later Giacomini evidently
became skeptical, however, and decided that it remained to be determined whether
the changes in the embryo are primary or secondary. Furthermore, in 1894, he
declared that one never meets with changes in abortive forms which one can
attribute solely to softening, and concluded that embryos that die soften and dis-
integrate quickly, only those which merely are inhibited in growth being preserved
for months. Waldstein (1913) also stated that von Winckel spoke of a slowing of
development before death of the embryo occurred. While it is conceivable, and
even probable, that inhibition in growth may occur, experiments now under way
show that dead mammalian fetuses nevertheless may be preserved in sterile nutrient
and non-nutrient solutions at body temperature for extended periods of time—for
months—without indication of growth and with very little change in external form.

Although one must frankly recognize that it is extremely difficult to simulate
intrauterine conditions closely, these experiments nevertheless very seriously
question the conclusion of Giacomini. His (1891) also emphasized that dead
embryos may be preserved in utero for months, and there is abundant evidence in
the Carnegie Collection corroborating this conclusion. But it is conecivable that
slight modifications in body-form might arise from gradual inhibition in growth,
as well as from post-mortem changes of secondary origin. Panum (1860), in dis-
cussing what he termed monstruositates totales amorphoides occurring among chicks,
also expressed the opinion that the changes in embryonic form noticed by him arose
during life. He claimed that these changes could not have resulted from macera-
tion, because adhesions of the membranes were present, because the specimens
showed a total divergence from the normal form, and also because of the differences
in size and consistency found to exist among them. Panum was led to the conclu-
sion that all the deformities noticed by him in chicks were the result of the condi-
tions under which development occurred and through the absence of evidence
supporting the opinion of Bischoff that the cause of monsters was germinal. But
Panum nevertheless believed that gases formed from putrefaction might com-
press the embryo and produce a fetus papyraceous.

When considering these greatly modified or even bizarre forms of human
embryos, one also is reminded of the fact that Panum believed that monstrous
chicks resulted directly from a lowering of the temperature during incubation.

POST-MORTEM INTRAUTERINE CHANGES. 297

However, since Panum found deformations especially common in the cephalic
extremity, and further stated that many of his so-called ““monstruositates totales
cylindrice’’ were mummy-like, with features effaced, it seems more likely that he
was dealing with maceration forms the death of which was due to the chilling.
Just why some chick embryos, the heart-beat of which has been temporarily sus-
pended by chilling, die quite promptly, and others only late in development,
near the end of the normal incubation period, I do not know, but personal observa-
tions leave no doubt regarding this matter, and variation in vitality is all that
I can suggest as an explanation at present.

It is only just to state that Panum considered the possibility that the anoma-
lous forms were secondary in origin, and concluded that some were germinal in
origin. His (1891), too, at first regarded certain abnormal forms of human embryos,
such as the nodular, cylindrical, and flexed (geknickte), as germinal, but later
inclined to the belief that they nevertheless arose from changes occurring after
the death of the embryo, saying:

“‘Seitdem ich mir aber Rechenschaft gegeben habe von den histologischen Ver-
anderungen welche eine Folge des Absterbens sind, von der Quellung des Gehirns und
den Verinderungen der urspriinglichen Gewebe durch eine Zellenbrut, bin ich weit
mehr geneigt, die abortiven Formen von Embryonen als secundir enstanden anzusehen.
So werden speciell auch die so auffilligen Cylinderformen verstindlich, sowie man sich
davon Rechenschaft giebt, dass von dem friiheren Embryo neben einem auffalligen Skelett
fast nur noch die Haut iibrig geblieben ist. Als ausdehnbarer Sack kann sich dieselbe
mit fremdem Material, mit Wanderzellen und zum Theil mit Fliissigkeit ausfiillen und
nun giebt sie die alten Kérperformen nur noch in den allergrobsten Ziigen wieder.”

In spite of these words, His insisted that poorly preserved normal forms never
show changes seen in so-called abortive forms, and emphasized that, although the
cells in abortuses may not all be dead, we nevertheless can not speak of these
abortive forms as living.

The mere fact that post-mortem changes may produce misleading modifica-
tions in form makes the identification of post-mortem deformations extremely
important. If all conceptuses were aborted immediately after their death, the
problem would be a far simpler one, for such an event would at once dispose of
such difficult questions as, not only those of survival, but also of the independent
growth of one or more members of the cyema, or of the whole of the vesicles, after
the death of the cyema. That outward apparent stunting is a fairly common
occurrence in young embryos is fully attested by the many specimens in the
Carnegie Collection which illustrate this phenomenon, but I have not been able
to find convincing proof indicating that it is also physiological. In the case of
older fetuses with apparent brachydactyly, osseous development seems to have
been normal and the modifications attributable to changes in the soft parts. Hence
I am prompted to conclude that, although growth may be retarded in consequence
of circulatory disturbances, it continues wholly normally, unless influenced by other
things, until the heart stops.

It also may be difficult to tell whether a given condition arose before or after
death of the embryo, merely because of the presence of maceration changes, even

298 STUDIES ON PATHOLOGIC OVA.

when these changes may have occurred in a sterile medium. The difficulty of
distinguishing between ante-mortem and post-mortem changes, which impressed
Phisalix and also others, is very great, if not insurmountable in some cases. This
is true especially if it be assumed that an irregular or uncorrelated growth can occur
under post-mortem, ante-partum conditions, for such growth could easily produce
anomalous forms. But it must be admitted that the existence of a genuine post-
mortem growth is merely an inference at present.

In considering some of the strange forms to which attention has been called
one can not disregard such instances in the newborn as that reported by Cowie
(1914). The posture of this infant reminds one very strikingly of some of the
fetuses in the accompanying illustrations. This seems very disconcerting at first
thought, but there is, of course, no reason why a condition responsible for the
occurrence of multiple intrauterine fractures, such as are present in this infant,
should not result in very abnormal postures. Moreover, if fetal bone disease may
begin very early, it is also probable that some of these strange, relatively early
fetal forms well may be genuine fetal anomalies and pathologic in addition.

The cases reported by de Lima (1915), especially cases 2 and 3, also belong
among those which simulate some early fetal forms. Nevertheless, in these, and
also in the other 2 cases reported by him, de Lima found bony defects. The same
thing was true of the outwardly similar cases in infants and children reported by
McKenzie (1897).

However, in view of the occurrence of these outward resemblances, it is not
always possible to distinguish normal specimens which have suffered post-mortem
deformations or changes in posture of the extremities from true developmental
anomalies by outward inspection alone. This difficulty is particularly great in
connection with changes in form and position of the hands, the feet, and the head
and neck, and greatest of all, in connection with the knees. Even a cursory ex-
amination of some of the accompanying figures must also show that we at present
are unable to decide whether any of these young specimens with pronounced
deflections of the head and neck are cases of genuine torticollis and others are
genuine cases of club-hand or club-foot, or genu varus, or valgum, for example.
Indeed, this difficulty could be avoided only if these conditions arose only late
in pregnancy, or if the cyemata showing them never were aborted before term.
Waiving the exact definition of club-hand and club-foot, it must strike the attention
of anyone that caput obstipum and apparent club-hands and club-feet so often are
associated in these relatively early specimens, most of which are decidedly macer-
ated. In 10 out of 21 cases of club-hand and club-foot listed as such among 3,000
accessions, excluding 2 cases with an embryonic length of 2.5 and 16 mm., respec-
tively, clubbing was present in all the extremities. This is a wholly different
relationship from that which obtains between these anomalies at the time of birth,
when they seem to be associated but very rarely. However, in practically all of
these cases of universal clubbing of macerated specimens the anomaly is associated
with other developmental defects, as is not infrequently the case in the congenital
condition.

POST-MORTEM INTRAUTERINE CHANGES. 299

Three of these 21 cases of clubbing were classed among the normal and 18
among the pathologic. With the exception of 3 fetuses which had a length of 100,
130, and 220 mm., respectively, all were less than 100 mm., the average length being
48.9mm. While it may be possible to recognize genuine clubbing, due to the absence
of the bones or to defects in them so early in fetal life, by microscopic examination
or by other special methods, this certainly can not be done by inspection alone.
Hence it is clear that the term club-foot, as used in the classification of this col-
lection, is without special implication, except that it tells something about the
shape of the periphery of the extremities.

It would also seem that if all these cases of deformed extremities in fetuses
were true developmental anomalies, they should be encountered in well-preserved
specimens, and more frequently in the older ones. That other anomalies should
be found associated more frequently also seems to follow from our knowledge of
congenital club-hand and club-foot. Among these genuine cases defective develop-
ment of the bones seems to be more frequently noted, for congenital club-hand
nearly always is accompanied by absence of either radius or ulna, while in the
cases under consideration here such an absence has not been established. Nor is
it without significance that the most pronounced forms of club-hand and club-
foot found in these fetuses always occurred in those longest retained and most
macerated. Many of them also show quite general evidences of the presence of
pressure defects, and unless it can be shown that a tendency to progressive elimina-
tion of specimens with double club-foot and hand exists, with survival of those
suffering from club-foot alone, one can not harmonize the frequent association of
these defects in fetuses with the conditions as known to exist at the time of birth.
However, since certain forms of congenital club-foot are probably also the result
of intrauterine pressure, the types found in fetuses if the latter survived would be
quite similar or even identical, in a morphologic sense, with the condition in the
newborn; yet in one case growth would have ceased before the pressure became
effective, while in the other it continued. The fact that congenital clubfoot is
relatively seldom due to bony defects would also seem to point to external factors
as causes, but I have no final opinion on this matter and am calling attention
to it merely to emphasize the fact that post-mortem intrauterine changes resulting
from maceration and pressure, or from both, may easily cause confusion in young
cyemata.

300 DESCRIPTIONS OF PLATES.

DESCRIPTIONS OF PLATES.

Pate 17.

Fig. 175. A portion of a chorionic vesicle, showing appearances identical with tissue cultures. No. 545. 135.
Fic. 176. Fetus showing gluing of hand to face. No. 316.

Fic. 177. Villi showing obliteration of vessels by maceration and disintegration. No. 640.

Fra. 178. Villi showing obliteration of vessels by proliferation. No. 317. 97.5.

Fic. 179. Macerated tubal specimen imbedded in clot and undergoing lysis. No. 1938. 0.75.

Fic. 180. Fetus showing continuity of epidermis across the mouth, with obliteration of the labial slit. No. 885. 4.5.
Fre. 181. Macerated tubal specimen, only the chorionic vesicle remaining. No. 2035. 0.75.

Fia. 182. Slightly macerated villi. No. 275. 37.5.

Fic. 183. Greatly macerated villi. No. 7236.

Fic. 184. Macerated, long-retained villi, with lumina of capillaries plugged with coagulum. No. 286. 37.5.
Fig. 185. Fetus in sagittal section showing maceration, especially of the nervous system. No. 285. 4.5.
Fra. 186. Cross section of cyema showing homogeneous structure produced by maceration. No. 205. 11.25.

Piate 18.

Fig. 187. Slight swelling of fetus from brief maceration. No. 2146. 2.

Fic. 188. Matted, slightly macerated villi. No. 1878. 4.

Fie. 189. A macerated, disproportional cyema 4 mm. long, showing a development of 5.5mm. No. 786. 4.

Fig. 190. A well-preserved cyema 5.5 mm., of the same development as the preceding. No. 1380. X4.

Fies. 191-192. Cyemata illustrating failure of extension of the body upon maceration. Nos. 1299 (<2) and 2216 (4).

Fics. 193-196. Cyemata illustrating changes in form due to maceration. Nos. 208 (2), 1296 (2.67), 1697 (X2),
and 1477 (X2).

Fig. 197. Illustrating beginning changes in form due to maceration. No. 705. 1.35.

Fies. 198-204. Similar specimens, showing more pronounced changes. In figure 203 the structure of the specimen
is chaotic. Nos. 2244 (X2.67), 1891 (X2), 1655 (X2.67), 1260 (2.67), 1333 (X2.67), 1379
(X 2.67).

Fias. 205-206. Doubtful normally developed eyemata. Nos. 1226 (2.67) and 2361 (x4).

Fic. 207. A cyema illustrating post-partum changes. No. 589. 2.67.

Fic. 208. Cyema showing maceration sulci and ridges, and drooping of the limbs. No. 521f. 1.66.

Fic. 209. Cyema showing maceration sulci and ridges, and swelling of the cord. X2.

Fig. 210. Normal, well-preserved cat fetus.

Fic. 211. Normal, poorly preserved cat fetus of approximately the same length.

Fic. 212. Appearance of fetus before fixation. No. 1358. X2.

Fic. 213. The same specimen, showing wrinkling due to fixation and staining. X2.

Fic. 214. Macerated, distorted single-ovum twins. No. 2258. 2.67.

Fic. 215. Minor changes in relief, due to maceration. Swelling and constriction of cord. No. 2014. X2.

Fig. 216. An intermediate maceration form. No. 1495d. 2.67.

PuaTeE 19.

Fic. 217. Interior of the chorionic vesicle showing subchorial hematomata. No. 1495d. 0.77.

Fig. 218. A fetus and cord showing marked maceration changes. No. 797. 1.35.

Fia. 219. An older fetus, showing bleb-formation and curvature in extremities, due to maceration and retention.
No. 1860. 1.35.

Fig. 220. A fetus showing marked clubbing of the extremities and obliteration of the features. No. 1958. 0.87.

Fias. 221-222. Extremities of same specimen. 2.67.

Fig. 223. External appearance of fetus in situ. No. 1751. 0.57.

Fia. 224. An older, macerated fetus, with extremities extended instead of folded. No. 1462. 0.77.

Fia. 225. A similar specimen. No. 1309. 0.23.

Fic. 226. A long-retained, soft, rolled-up form, photographed in extension. No. 1775. 0.47.

Fic. 227. A similar specimen with markedly flexed head. No. 1525. 0.66.

Fig. 228. A similar specimen. No. 1976. 0.47.

Fia. 229. A similar specimen with mummified chorionic vesicle. No. 1850. X6.

Fia. 230. A decidedly mummified fetus. No. 1295a. 0.77.

Fic. 231. Unilateral development of villi in a vesicle classed as normal (?). No. 2092. (See Chapter XV.) X1.35.

Fic. 232. A somewhat macerated young vesicle with quite uniformly distributed villi which are slightly abnormal in
form and structure. No. 1878. (See Chapter XV.) x4.

Fia. 233. A ne same specimen, showing the somewhat more than normally bulbous and rather matted
villi. 2.67.

Fig. 234. A very softened, macerated fetus. 0.5.

PLATE 17

MALL AND MEYER

MALL AND MEYER

a”

e

MALL AND MEYER

S

CHAPTER XIV.
HOFBAUER CELLS IN NORMAL AND PATHOLOGIC CONCEPTUSES.

The history of these cells illustrates very well how a rediscovery, when accom-
panied by a fuller description, succeeds in domiciling itself in anatomical literature
as an original discovery. As we shall presently see, Hofbauer (1905) was impressed
especially by a conspicuous phase in the life-history of a particular cell. He
noted its reaction, in the fresh state, to certain stains, described it more fully, and
speculated with some freedom on its functional rédle; but he did not discover this
cell, as he supposed, in 1903. Although Hofbauer, in his book published in 1905,
referred to his address given in 1903, he did not refer to or list the paper based on
this address, published in 1903, in the title of which these cells are referred to as
“hitherto unknown” and as “constantly occurring.’”’ Hofbauer’s failure, in 1905,
to recognize earlier workers was, I presume, an oversight, which apparently led
Essick (1915) and others to assume that “‘Hofbauer first called attention to specific
round cells appearing in the human placenta toward the end of the fourth week of
pregnancy.”

The type of cell which in recent years has been designated with Hofbauer’s
name was known previously, especially as Wanderzelle, and had been represented
by various investigators. Minot (1911), in a footnote, referred to the latter fact
and rightly added: “It has long been known that strikingly large free cells appear
in the mesenchyme of the chorion. They are pictured in my Human Embryology.”
Reference to the illustration in this work shows a large, rather granular cell, with
a somewhat eccentrically placed, vesicular nucleus, but without vacuoles. More-
over, previous to the publication of this Embryology, Minot (1889) not only spoke
of large, granular, wandering cells in the stroma of the chorion, but also repre-
sented them. From Minot’s familiarity with the work of Langhans (1877) and of
Kastschenko (1885), it does not seem unlikely that, among others, he had these
investigators particularly in mind when he referred to earlier descriptions.

In the absence of a more discriminating term for these erratic and largely
ephemeral elements, the original designation of wandering cell would seem far
preferable to the designation “‘lipoid interstitial cells,” used by certain Italian writers.
The former is a non-committal term and, although too inclusive, is for this reason
no more objectionable than the expression giant cell. Although these cells may
not—indeed, probably do not—wander in the sense of the ameeba or the leucocyte,
they nevertheless may change their location decidedly. The qualification “‘inter-
stitial” is objectionable for the very reason for which it was chosen—the alleged
analogy to the interstitial cells of the testis and ovary—and since they may con-
tain lipoid substances merely because they are degenerate, the adjective lipoid
is equally objectionable. For reasons to appear later, the designation “‘plasma cell’’
used by certain Italian writers since 1905, would not seem to be justified.

Virchow (1871) stated that isolated cells with clear vesicular spaces in their
protoplasm are found in the stroma of the villi in cases of hydatiform degeneration,

301

302 STUDIES ON PATHOLOGIC OVA.

and identified them with certain other cells (physaliphores) previously described
by him. He found these bubble-like cells, as he called them, also in the thymus
of the new-born, in cancer, ete., and, according to Virchow, they were not merely
vacuolated cells. He seems to have regarded them as identical also with the vacuo-
lated syncytial masses, for he stated that Miiller described them as occurring in
the chorionic epithelium. Since syncytial elements are not uncommon in the
stroma, instances of confusion of these two cell types can be found in contemporary
literature also.

Langhans (1877), in describing the stroma of the villi, said that it contained
“Sharply delimited large cells with many granules in the protoplasm. Their form
is variable—circular, spindle, and star-shaped.” These cells were said to lie mainly
near the periphery. However, Langhans, who was interested mainly in other
problems, did not represent them nor discuss their probable significance. But
Kastschenko (1885) represented them and described them as being about 9 yu
large, and as corresponding exactly in form and size to the white blood-cells of the
same embryo. According to Kastschenko, the cytoplasm is reduced in quantity
after the first month, so that the nucleus no longer is surrounded by it. The nuclei
also are said to undergo a change and to appear later as solid structures. The
latter observation can not fail to remind one of pyenosis and of one of its well-
known significances. Kastschenko found these cells mainly near the epithelium
of the villi and stated that they vary greatly in size, number, and occurrence in the
same placenta. The fact that Kastschenko identified the cells found in the mesen-
chyme of the embryonic villi as leucocytes might seem to indicate that what he
saw and described were other than Hofbauer cells. However, his illustrations,
especially when considered in connection with those of earlier investigators and
those of Minot, leave little doubt that all these investigators saw the same type
of cell. Moreover, it is not improbable that Kastschenko was influenced in his
interpretation of these cells by the origin and current use of the term ‘‘Wander-
zelle.”” It will be recalled that von Recklinghausen (1863) showed that the leu-
cocyte preeminently belonged in this class of cells, but even at the time that
Kastschenko was writing, and far later, all cells which were regarded as foreign
to the tissue in which they lay were still included in the designation ‘‘Wander-
zelle.”” Reference to the literature of that period will make this fully evident.

The presence of these cells in conceptuses classed as pathologie was noticed
repeatedly by Mall (1908), who also designated them as wandering or migrating
cells in his earlier protocols. Chaletzky (1891) also saw and described these cells,
but perhaps the best description from an earlier date is that given by Kossman
(1892), who also referred to the Hofbauer cells as ““Wanderzellen,”’ and gave excellent
representations of them. Indeed, from an inspection of the latter alone there can
be no question as to the identity of these ‘‘Wanderzellen”’ and the Hofbauer cell.
In speaking of them, Kossman said:

. Auffallend sind zahlreiche grosse Zellen, die eine sehr wechselnde, oft
amoboide, niemals sternférmige Gestalt haben. Die Filarmasse ihres Protoplasma’s ist
durchaus fein, netzartig angeordnet und firbt sich stark in Hiimatoxylin. Die Zellen

HOFBAUER CELLS. 303

enthalten einen oder mehrere grosse blasenartige Hohlriiume, von denen ich leider nicht
sicher sagen kann, ob sie Fett fiihrten, da sie mir erst nach Behandlung des Priparats
mit Xylol auffielen. Der Kern dieser Zellen enthielt stets Nucleoli. Die Zellen sind
also jedenfalls nicht in lebhafter Vermehrung; wahrscheinlich sind es Wanderzellen, und
da sie auf einem wenig dlteren Stadium wieder fehlen, mag ihr Vorkommen in einigem
Zusammenhange mit der um diese Zeit beginnenden Vascularisation des Stroma’s
stehen.”’

Merttens (1894) found the same cells in abortuses, and, in describing the
stroma of the villi of his first case, said:

“An den Ernihrungszotten ist es kernreich, vielfach aufgelockert, mit stern- und
spindelférmigen Zellen, in den Maschen jene oben fiir die normalen ersten Stadien
beschriebenen grossen, runden oder polyedrischen Zellen mit kérnigem oder auch
vacuolirem Protoplasma mit grossem, blischenférmigem, rundem Kern.”

Merttens seems also to have suggested that these cells are swollen stroma
cells, but since he made this observation somewhat disconnectedly I am not quite
certain of his meaning; yet the mere suggestion is particularly interesting, in view
of Minot’s special emphasis upon the degenerate character of the Hofbauer cells.
Marchand (1898) also wrote:

“Die durchsichtigen hellen Zellen im Stroma normaler oder pathologischer Zotten
sind mir wohlbekannt, sie konnen denen der Zellschicht sehr ahnlich sein; ich halte sie
jedoch fiir gequollene, rundlich gewordene Bindegewebszellen, da man Ubergiinge zu
solchen findet, ebenso wie in andern Schleimgeweben.”’

Ulesco-Stranganowa (1896), who also saw these cells, says that if one com-
pares the Langhans cells with reund nuclei with these cells scattered about the
stroma of the villi, and which have been named ‘‘Wanderzellen”’ by Kastschenko,
one becomes convinced of the identity of these two types of cells. According to
Ulesco-Stranganowa, then, the Hofbauer and Langhans cells are identical. Mall
(1915) also called attention to this possibility, for, when speaking of the invasion
of the mesoderm of the villi by trophoblast, he called attention to the presence
of numerous Hofbauer cells, and added: “It would seem possible that these Hof-
bauer cells are free trophoblast cells within the mesoderm of the villus, an opinion
already expressed in my paper on monsters.’”’ Neumann (1897) also noticed these
cells and referred to Virchow’s opinion regarding them, and von Lenhossék (1902)
is credited by the reviewer of his paper in 1904 with having examined a large series
of young human embryos, and having suggested that what Kastschenko regarded
as ‘““Wanderzellen” were mesenchyme cells. It should be noted, however, that
von Lenhossék apparently came to this conclusion largely because of the absence of
blood-forming organs or lymphatic centers in embryos, in the villi of the chorionic
vesicles of which he found these cells. Strangely enough, Kworostansky (1903)
also recorded the presence of these cells, and after describing the stroma of the
villi wrote:

“Zwischen den genannten Bindegewebszellen giebt es in der wolkigen Grundsubstanz
Liicken, und am Rande oder im Winkel derselben sitzen freie andere Bindegewebs-
zellen, die sehr gross sind, lappige, runde Form, wabenartiges Protoplasma und gleiche
Kerne wie andere Bindegewebszellen haben; ihre Kerne werden auch, hie und da stern-

304 STUDIES ON PATHOLOGIC OVA.

férmig getheilt. Da sie stets nur in Gewebsliicken gefunden werden, so glaube ich, sie
als Lymphgefiissendothelien, oder vielleicht als Lymphocyten bezeichnen zu diirfen.
Man findet sie in spiteren Stadien der Placenta nur sind dann natiirlich die Zellen nicht
mehr gross.”

The illustration which accompanies Kworostansky’s article, as well as his
description, leaves no doubt that the cells seen by him are the same as those which
we are considering, although his surmise that they are lymphocytes and that they
arise from the endothelium of the lymphatics may, upon first thought, seem rather
irreconcilable with such an assumption.

From these references alone it is evident that Minot’s statement that the
so-called Hofbauer cells were repeatedly mentioned in the earlier literature is well
founded. Muggia (1915) stated that these cells were described also by Guicciardi
(1899), Clivio (1903), Stoffel (1905), Veechi (1906), and Pazzi (1904). Indeed,
many other names could be added, for surely any one of the many who studied
even a small series of chorionic vesicles must have seen some of them in some villi,
especially in unrecognized cases of hydatiform degeneration, but since they have
been referred to as Hofbauer cells, it is his description that especially interests us.
In describing the chorionic villi, Hofbauer (1905) spoke of certain gaps or spaces
between the meshes of the mesenchyme of the villi which he thought might belong
to the lymphatics or contain tissue fluid. In these spaces he found certain granu-
lar, round cells arranged longitudinally. He thought they were often spherical,
with a diameter of 10.5 u to 12.5 u, but more commonly star-shaped or branched.
By means of these branches they come into direct relation with other similar cells
or with connective-tissue cells. However, Happe (1906) stated that he could not
with certainty find cells united by their processes, as described by Hofbauer, in
preparations stained after Hiinsen. According to Hofbauer, the cell processes
are delicate, and the cells contain one or two nuclei from 4.7 u to 5.7 u in diameter,
oval or circular in form, eccentric in position, with a definite membrane and a
dense chromatin network. Mitoses were common, and fragmentation of nuclei
and indications of pluripolar mitoses also were seen. Hofbauer emphasized that
the most characteristic thing in these cells which he regarded as being specific
was the presence of vacuolation in the ‘‘plasma” and the existence of a perinuclear
clear zone, which was said to be the result of fusion of “small light spots.’’ As the
cytoplasm becomes vacuolated the nucleus is said to become pyenotic, which
stage is followed by failure to stain and finally by its complete disappearance.
Hofbauer also noticed the presence of granules and fat droplets, and regarded the
life-history of these cells as a circumscribed one. He did not find them present in
real young villi. They were said to appear at the end of the fourth week, and were
more common in young than in old placente. They reacted to vital stains like
plasma cells, and Hofbauer regarded the vacuoles as having an assimilative and
digestive function. A reference to the plates accompanying Hofbauer’s mono-
graph, however, suggests that vacuolation was not always present, and that the
largest of the cells were almost twice the size of the smallest.

+A re-reading of Stoffel's article shows quite conclusively that he did not describe the plasma cells of Hofbauer.

HOFBAUER CELLS. 305

In his earlier paper Hofbauer (1903) also said that his preparations, taken
from material from the fourth to the ninth week of pregnancy and obtained at
operation, showed these cells in all stages of mitotic division. Hofbauer further
wondered whether the spaces surrounding these cells are lumina of capillaries,
added that the cells discovered by him undoubtedly are found in capillaries, and
made some rather unguarded surmises concerning them.

Berlin (1907), in writing on the changes in retained placente, also spoke of
large, swollen, hydropic cells which lie in spaces. These cells she regarded as un-
doubted mesenchyme cells. However, Berlin did not believe that they are de-
generation products, although her description certainly would lead one to suppose
that they were such. Even when she stated that they bear no sign of degeneration,
emphasizing that the chromatin network is fine, she nevertheless spoke of swollen
nuclei which have gathered a larger amount of protoplasm about them, phenomena
which she regarded as signs of luxurious nutrition. Moreover, Berlin never ob-
served mitoses and never found the nuclei increased, in villi containing many of
these cells, an observation wholly in harmony with that of others and directly
opposed to the idea of proliferation.

Grosser (1910), who was plainly aware of the fact that Hofbauer was not the
discoverer of these cells, also represented a cell, which, however, is non-vacuolated
and binucleated, and added that their significance is still unknown.

I have given Hofbauer’s description, partly to emphasize the vacuolation,
for it was this which also impressed Minot (1911), who rightfully stated:

“We frequently find in the literature mention of wandering cells with vacuolated
protoplasm, but they seem not to have been recognized as degenerating cells. . . .
The disintegration by vacuolation has, so far as known to me, not been described hereto-
fore, and consequently may be treated somewhat more fully. . . . . Renewed in-
vestigation has led me to the conclusion that we have to do with erythrocytes which have
gotten into the mesenchyma and, remaining there, have swollen by imbibition and are

undergoing degeneration by vacuolization of their protoplasm. . ... . We can
explain the appearance of these cells by the assumption of imbibition, in which the
nucleus has participated. . . . . Since I have found similar cells in a considerable

number of placentas, I draw the conclusion that they are constant and normal. I regard
the interpretation of the pictures unattackable as proof of progressive degeneration.”

In association with these remarks, Minot represented a series of cells showing
progressive degeneration, beginning with the nucleated red cells and ending with
a highly degenerated, but nevertheless nucleated, Hofbauer cell which apparently
is in process of disintegration. These cells were seen by Minot especially in a
human embryo of 15 mm. length, from the Carnegie Collection.

As shown in the references to the literature above, it is not quite correct to
say that the degenerate character of vacuolation has not before been recognized, for
the surmises that Hofbauer cells contain fat granules may, and that they are
swollen mesenchyme cells must, carry this implication. Moreover, those familiar
with the effects of inanition know that investigators of this subject long ago called
attention to vacuolation as one of the evidences of degeneration, although, cer-
tainly, no one contends that it always is such.

306 STUDIES ON PATHOLOGIC OVA.

Instead of regarding these cells as degeneration products, certain Italian
writers (notably Acconci, 1914”) regarded cells which they found, especially in the
first half of pregnancy, as morphologically and functionally comparable to the
interstitial cells of the ovary and testis. Acconci believed that certain cells which
he and other Italian writers after him designated lipoid-interstitial cells, probably
produce a special internal secretion. He, like Hofbauer, found these cells to con-
tain lipoid granules, and regarded them also as equivalent to certain cells ‘‘described
by Ciaccio in various parts of the organism, or by Brugnatelli in the interstitial
tissue of the mammary gland.’”’ Acconci further emphasized certain similarities
between the syncytium and the interstitial cells, both of which he conceived as
exercising a protective rdéle. Muggia (1915), too, instead of regarding the lipoid
interstitial cells of Acconci as degenerate, emphasized his belief that they are
particularly resistant to degeneration, being found perfectly preserved in the
midst of detritus. Since the young connective-tissue cell loses, or rather retracts,
its processes as it becomes converted into a Hofbauer cell, it need not surprise us
that the latter survives the former. Retraction of the processes contributes to
the apparent increase of cytoplasm of the rounded swollen cell and also is involved
in the formation of the spaces in which these cells usually lie. Muggia, who con-
sidered the cells found by him in great numbers in a case of partial hydatiform
degeneration as identical with those described by Acconci, gave a fine detailed
description absolutely typical of the cells previously described in greatest detail
by Hofbauer. Moreover, the excellent illustrations which accompany Muggia’s
article leave no doubt as to the identity of the cells or of their degenerate character.
Muggia stated that these cells in normal villi increase until the end of the fifth
month, when, according to Savare, they are most numerous. Muggia further found
numerous cells very similar to the interstitial cells of Acconci, or ‘‘the plasma-like
cells of Hofbauer,” which he says are regaredd by some as early stages of inter-
stitial cells and by others as mast-cells, concluding that he regarded the latter as
partially differentiated interstitial cells.

Until I had seen sections of the chorion of No. 1531 I was largely at a loss to
know why Hofbauer cells were so frequently described as lying in gaps or spaces
in the mesenchyme. However, in this specimen cross-sections of a number of
villi showed splendid examples of this condition, which alone made the cells very
conspicuous. The cells often were very numerous, in fact more numerous than the
mesenchyme cells which remained, although some well-preserved villi contained
no Hofbauer cells whatever. Some of the younger specimens also contained none.
This was true of a chorionic vesicle with an embryo 1 mm. in length. They were
found most commonly in the villi, but not infrequently some of them lay in areas
of the chorionic membrane which had undergone degeneration. They were not so
common here, but sometimes were exceedingly numerous in small areas. They
were found in the amnion also, in the umbilical cord, and in the tentorium cere-
belli, and as isolated specimens in embryonic mesenchyme elsewhere. As em-
phasized by other investigators, there seemed to be nothing particularly character-
istic about their distribution, except that they were more common in places where

HOFBAUER CELLS. 307

the mesenchyme was degenerating. Sometimes a considerable number were con-
tained in one villus and none in an adjacent one. As many as 12 might lie in one
field and none in the next. In rare instances there was a solid mass of them,
as shown at one side of the villus in figure 128 (plate 12, Chap. VIII), but
usually they were scattered about at random, although groups were also seen.
The better-preserved cells were small, the poorer-preserved larger, the size varying
from 8.5 1 to 30u. The smaller cells were usually quite circular in outline, stained
evenly, and possessed a non-granular cytoplasm with a nucleus quite centrally
located. Binucleate cells, as described by Grosser, were not uncommon, and
multinucleated cells—fusion products—were also found. The nuclei of the latter
were frequently more unequal in size, and usually also more oval in outline, than
the single nucleus of the typical Hofbauer cell. Measurements of some of the
largest cells, made with a micrometer caliper, gave the following results: 25.5
by 20.4, 30.4 by 27.5, 18.0 by 12.0, 21.5 by 25.5, 18.0 by 14.04. These figures
are considerably above those given by Hofbauer, whose estimation of a size of
10.5 » to 12.5 uw applies to the average-sized cell.

However, the size of the cells varied from specimen to specimen of chorionic
vesicle, but not nearly so much as their state of preservation. This, no doubt, is
partly due to the varying state of preservation of the villi themselves.

In outline they varied from irregular to circular, as stated by Hofbauer, and
as represented by Minot (1911) in his series showing progressive degeneration.
Although it was easy to distinguish the vacuolated Hofbauer cell from the well-
preserved mesenchyme cell with cylindrical nucleus and many processes, speci-
mens which represent transition forms, as stated by Marchand, and as shown in
figures 235 to 237, were quite common. The latter generally were oval or slightly
irregularly formed cells with a number of short processes, which latter, as well as
the character of the nuclei and the form of the cell itself, certainly suggested a
mesenchymal origin. They were also most numerous in villi, the stroma of which
had become glassy, vacuolated, or fenestrated. In these the reciprocal numerical
relationship between the Hofbauer and the mesenchyme cells was often especially
evident. In certain areas in which almost no mesenchyme cells remained intact,
numerous Hofbauer cells occurred in all stages of degeneration. In other portions
of the chorionic membrane or of the villi, mesenchyme cells with processes in all
stages of retraction were also clearly outlined in the homogeneous ground sub-
stance. Such evidences naturally remind one of Hofbauer’s statement that Mar-
chand called his attention to the fact that these cells were mesenchyme cells, a
conclusion which Hofbauer accepted. My implication, however, is not that
degeneration of the mesenchyme or of individual mesenchyme cells can proceed
only through a Hofbauer stage, but that, especially in the chorionic villi, a form
of degeneration of the mesenchyme seems to occur which gives rise to this peculiar
cell-form, the degenerate character of which rightly impressed Minot. This rela-
tionship also attracted the attention of Mall (1915), who represented degenerating
villi and stated:

308 STUDIES ON PATHOLOGIC OVA.

“The core of the villus gradually breaks down and disintegrates. While this process
is taking place we often see scattered through the stroma of the villus large protoplasmic
cells. . . . . These cells, which I have repeatedly seen in the villi of pathological ova,
may be a type of wandering cells; at any rate, when the villus is being invaded by the
leucocytes and trophoblast it might be thought that they arise from the latter, but this
is improbable.”

It is of particular interest in this connection that Virchow (1863) stated that
Schroeder van der Kolk (1851) had concluded that large, clear cells in the stroma
of the villi, later classed among the “physaliphores’” by Virchow, occurred too
frequently to be correlated with hydatiform degeneration. This suggests that the
so-called Hofbauer cells were known since the early days of cytology, and that
some one must have noticed, even at that early date, that they were very common
in some hydatiform moles. Whether or not this was van der Kolk himself
I am unable to say, but that Hofbauer cells are especially numerous in some
cases of hydatiform degeneration is undoubted. But it does not therefore follow
that they are constantly present in this condition. Large numbers of Hofbauer
cells were present in 17 out of the 61 cases of normal and pathological chorionic
vesicles in which they were especially studied. Of these 17 cases, 14 were later
independently identified as showing hydatiform degeneration, and the other 3 were
considered as possibly such. In other words, every case of this series in which the
Hofbauer cells were numerous was one showing hydatiform degeneration of the
villi. It also is true, however, that 34 cases containing but a few or some Hofbauer
cells were not identified as being hydatiform moles, although 3 cases containing
small numbers of these cells were so recognized. Moreover, not a single case of
this series of 61 specimens which contained no Hofbauer cells whatever was later
identified as showing hydatiform degeneration.

Somewhat similar evidence was afforded by the study of 22 cases in the
protocols of which Mall had previously noted that Hofbauer cells were present.
Of these 22 cases, 13 were later identified as showing this degeneration. However,
since a total of 153 cases of hydatiform degeneration were identified among 315
of those classed as pathologic among the first 1,200 accessions in the Carnegie Col-
lection, it is evident that the presence of Hofbauer cells was especially noted in
but a relatively small percentage of this series. Of 30 cases containing Hofbauer
cells in sufficient numbers to attract especial attention in the course of a routine
examination made for other purposes, 17, or 56.6 per cent, were later identified
as instances of hydatiform degeneration. Since the 61 cases in the first series were
examined especially for the purpose of study of Hofbauer cells, the higher per-
centage of correlation observed in this series may be due partly to this fact. At
any rate, that such a correlation exists seems to be quite clear, although I do not
conclude that the two conditions necessarily or invariably are associated.

It is interesting that Pazzi (1908") considered a distrophy of the connective
tissue with the development of cellular elements “not very well differentiated, but
like the plasma cell of Hofbauer,” as the initial and pathognomonic change in
hydatiform degeneration. Pazzi further stated that the plasma cell of Hofbauer

HOFBAUER CELLS. 309

may be in a state of hyperactivity or of degeneration, and questioned the state-
ments that Hofbauer cells appear only at the end of the fourth week and that they
have a short life. Pazzi regarded the Hofbauer cell as fundamentally a constit-
uent of the villi, as the decidual cell is of the decidua. He, like Essick, attributed
their origin to the endothelium of the vessels, and further suggested that the Hof-
bauer cell may have a special internal secretion intended to preserve the stroma
of the young villus against degeneration. Pazzi also considered the question
whether a Hofbauer cell can transform itself into an epithelial cell and finally into
a syncytial cell, and added that the invasion of the stroma of the villus by epithe-
lial growths, such as represented in figure 119 (plate 10, Chap. VIII), is only a
special development of Hofbauer cells!

As already stated, Muggia also found these cells very abundant in a case of
partial hydatiform degeneration,and held that their appearance and condition are
correlated with proliferation and vacuolation of the syncytium, maintaining that,
as the latter becomes vacuolated, the lipoid interstitial cells of Acconci appear,
the changes in the two being wholly parallel.

Since 32 of the 51 chorionic vesicles in this series of 61 containing a few, some,
or many Hofbauer cells had been classed among the pathologic, it follows that
these cells were noticed more frequently in the pathologic than in specimens
classed as normal. This becomes especially evident if we exclude from this series
of 51 cases all those containing some or many Hofbauer cells, for of 27 of these,
19, or 70.4 per cent, had been classed among the pathologic. Moreover, since the
great majority of the conceptuses classed as normal are abortuses, one would be
entirely justified in questioning the strictly histologically normal nature of the
chorionic vesicles which accompany some embryos classed as normal. At any rate,
it is evident that the plasma cell of Hofbauer is associated with degenerative
changes in the mesenchyme of the villi. Since such changes are more common in
abortuses classed as pathologic, it is not surprising that Hofbauer cells are more
common in the latter than in normal specimens, and, since degenerative changes in
the stroma are especially pronounced in advanced cases of hydatiform degeneration,
it is still less surprising that Hofbauer cells are particularly common in this con-
dition. But they are not necessarily pathognomonic of hydatiform degeneration,
although it is true that when at all numerous they are associated with hydatiform
degeneration in about 75 per cent of the cases.

It also should be recalled that the great majority of the specimens classed as
pathologic microscopically show the presence of both degeneration and macera-
tion. However, it never was the most macerated but the most degenerate speci-
mens in which Hofbauer cells were most numerous. Hence, whatever the cause
of this transformation of the mesenchyme into Hofbauer cells, it may also be
the cause of hydatiform degeneration.

After a careful survey of a considerable number of specimens, both normal
and pathologic, ectopic and uterine, of human abortuses of widely different ages,
I am led to concur entirely in the opinion of Minot that the typical vacuolated
cell, as described by Hofbauer, is a degeneration product, though usually not a

310 STUDIES ON PATHOLOGIC OVA.

degenerate erythroblast, as Minot concluded. However, in rare instances I have
seen a chorionic vesicle in which the rather small, clear, isolated Hofbauer cells
scattered throughout the stroma of a villus undoubtedly were erythroblastic in
origin. In these villi capillaries in various stages of disintegration were present,
and the erythroblasts could be traced directly to these degenerate capillaries.
In the earlier stages of this degeneration these degenerating erythroblasts are not
surrounded by spaces, however, and this is true also of early stages in the degen-
eration of the fixed or already detached mesenchyme cell, which later forms the
typical degenerating wandering cell. However, it represents but one stage in this
degeneration.

It is significant that, although Hofbauer suggested that these cells might have
a digestive or assimilative function, he, too, frequently found fragmentation of the
nuclei and complete disappearance of the cytoplasm and even of the cell itself.
All stages of degeneration, as manifested by crenation of both cytoplasm and nu-
cleus, even to complete disappearance of the cell, can easily be found. Signet-ring
forms are common, and the nuclei are found in all stages of extrusion and
degeneration. The cell boundaries are often ragged, the nuclei crenated and
pycnotic, the cytoplasm granular, vacuolated, webbed, or fenestrated, until finally
nothing but a faint ring or shadow form without a trace of a nucleus remains.
However, in these transparent or shadow forms the nuclei, if not previously ex-
truded or dissolved, are frequently represented by a mere outline or only by a
faint trace of one. Since all stages between the latter and the well-preserved cells,
without vacuoles and with well-preserved nuclei and cytoplasm, and also with
processes, occur in well-preserved material, one can scarcely doubt their origin.

Undoubted instances of mitoses were never seen in any Hofbauer cells, no
matter how well preserved. This no doubt can be accounted for by the fact that
from the time the mesenchyme cells retract their processes and become isolated
in the villus, they are in a stage of degeneration. Under such circumstances one
would hardly expect to see instances of cell division, although it possibly may be
simulated by necrobiotic phenomena.

Hofbauer (1905), as also in his first publication, stated that the cells deseribed
by him increase by mitoses which are frequent. He also found examples of what
seemed to be instances of pluripolar mitoses, and also noted fragmentation of the
nuclei. Acconci (1914”) also found mitotic figures in cells designated lipoid inter-
stitial cells by him, but most investigators say nothing about this. On the
contrary, a number of them specifically state that they could not find an actual
increase in the number of nuclei present in the stroma of villi containing large
numbers of these cells. Furthermore, every one except Muggia (and he also in
his description and illustrations, as also Acconci) has noted characteristics and
described the cells in such a way as to suggest the presence of degeneration changes.
When at all distinct, the cells are of various shapes and sizes and are surrounded by
a relatively large clear zone. Their occurrence is erratic, they contain lipoid granules
or vacuoles, and have nuclei varying considerably in size, position, and staining
reaction, as does also the cytoplasm. They are most frequent in degenerate villi

HOFBAUER CELLS. 311

and not infrequently lie in detritus. The better preserved the stroma the fewer
cells one finds, and in these observations on this rather large series of chorionic
vesicles, some of which were obtained fresh—one living—in hysterectomy speci-
mens, I have found only a few instances of what possibly could be regarded as
mitotic figures. Since almost all are agreed that these cells are of mesenchymal
or connective-tissue origin, it is easy to see that considerable difficulty must be
encountered in deciding just when to regard a mesenchyme cell, which is its pre-
cursor, as a Hofbauer cell. Since I have not made this aspect of the question a
particular subject of investigation, I have no evidence to offer on this point.

Since some of these cells, during the early period of degeneration, after they
have become quite circular in outline and the nucleus has taken an eccentric
position, have a decidedly granular or even a lumped cytoplasm, the confusion
with plasma cells, or their earlier designation as granular wandering cells, need not
surprise us. Nevertheless, the term plasma cells is hardly applicable, as many of
them are not granular. Moreover, no one has shown that in fixed preparations
these cells take the stains specific for plasma cells. Indeed, although he stained
material with borax methylene-blue after Jadassohn, Happe (1906) did not find
any of the Hofbauer cells impregnated. It must be remembered, however, that
failure to stain may be dependent very largely upon the degree of degeneration
which the particular cells have undergone, for, as already stated, Hofbauer found
that in fresh material they reacted as plasma cells to vital stains.

The opinion of Minot that Hofbauer cells are degenerating erythrocytes can
probably be accounted for by the fact that in the chorionic vesicle from which
Minot’s series, showing a progressive degeneration of the latter into the former,
was obtained, it was impossible to distinguish between the two. This difficulty was
due partly to the poor state of preservation of the particular specimen. A larger
survey, especially of better preserved material, would have revealed the fact that
Hofbauer cells are found in villi, the blood-vessels of which contain no erythro-
blasts. Moreover, as will appear later, the distribution of Hofbauer cells in the villi
is not such as one rightfully would expect if they have their source in the vessels.
However, since the final form of the typical Hofbauer cell is a mere shadow cell,
it necessarily may be impossible to determine the kind of cell from which this
shadow form arose, for, as is well known, the end-forms in the process of degenera-
tion of many different types of cells are indistinguishable. Consequently, a group
of swollen, highly vacuolated Hofbauer cells may also contain among them degen-
erated, nucleated red blood-cells, as Minot held. Indeed, degenerating erythroblasts
which are indistinguishable from some Hofbauer cells can be seen occasionally
not only in the vessels, but in the heart itself, and also within the cavity of
the chorionic vesicle; but such findings do not prove that the Hofbauer cells
of the villi arise from erythroblasts. That this is usually not the case follows
also from the fact that well-preserved, non-vacuolated Hofbauer cells occur in
villi which have not become vascularized or which, as stated above, no longer
contain vessels. It is true that it is often impossible to distinguish between de-
generate erythroblasts within the vessels and Hofbauer cells lying outside of, even

312 STUDIES ON PATHOLOGIC OVA.

if near to them, in the stroma of the villus. However, this difficulty is entirely
avoided by examining the older specimens without nucleated reds, for, since
Hofbauer cells are always nucleated, except in their very last stages, confusion
with nucleated cells is thus avoided.

Although the elimination of the erythroblast as the source of the Hofbauer
cell was thus very easy, some difficulty was encountered, strangely enough, with
regard to polymorphonuclear leucocytes. This is largely due to the fact that the
nucleus of the latter often ceases to be polymorphous as these cells degenerate.
Instances of this kind are quite common, especially in the membranes of hemor-
rhagic or infected abortuses. They are, however, also met with in the decidua.
Since the polymorphous character of the nuclei of these leucocytes can usually
be recognized without difficulty in degenerate accumulations of pus, I was at first
predisposed against regarding a circular nucleus as possibly polymorphous in
origin, but careful scrutiny of numerous specimens in which these misleading
degeneration forms occurred soon left no doubt as to the facts.

As stated above, Hofbauer cells were found in the cavity of the chorionic
vesicle in abortuses which contained blood or had become infected. In these
specimens the degenerated polymorphonuclear leucocytes usually lie in groups,
or more commonly in rows along the inner borders of the chorionic membrane,
or in long narrow clefts or folds of the same. Some also were scattered about
among the degenerating erythrocytes, but an examination of the contained blood
usually surprises one by the entire absence, not only of well-preserved polymorpho-
nuclear leucocytes, but of all leucocytes whatsoever. This is in marked contrast to
what is found in the case of ordinary hemorrhages and is a fact full of signifi-
cance for the question under discussion. Most of the degenerated polymorpho-
nuclear leucocytes, many of which contained undoubted evidence of phago-
cytosis, possessed a relatively small, circular, vesicular nucleus which often was
eccentric in position. Others were filled with a granular cytoplasm, or even with
very discrete golden granules, while still others were filled with dark, black pig-
ment granules corresponding in size to the golden ones. Here and there the field
of degenerating erythrocytes may also be studded with masses of pigment which
clearly declare their origin by the presence of all manner of transition forms be-
tween the well-preserved, easily recognizable polymorphonuclear leucocytes and
the disintegrated pigmented detritus. The phagocytic nature of these cells is
especially noticeable in the specimens of .young chorionic vesicles, with nucleated
reds, stained with iron hematoxylin, for in these the leucocytes are often seen
filled with a mass of nuclei only.

Similar appearances can also be seen occasionally in the decidue from cases
of endometritis, as well as in portions of a decidua in which the glands have under-
gone considerable maceration and degeneration. In the former the polymorpho-
nuclear leucocyte is the misleading form, while in the latter the degenerating, cast-
off glandular epithelial cells simulate Hofbauer cells in almost every morphologic
detail. I have also seen similar specimens of degenerated polymorphonuclear
leucocytes in ill-preserved hemorrhagic lymph-nodes, especially from cases of

HOFBAUER CELLS. 313

septicemia, and, until the true nature of such degenerate leucocytes became
evident, it was very puzzling to see why the Hofbauer cell, which never was found
to contain evidences of phagocytosis when lying in the stroma of a villus, should
become phagocytic when contained in a degenerated amniotic or chorionic mem-
brane or when lying in a hemorrhagic area. Undoubted instances of phagocytic
Hofbauer cells were never seen, although, in addition to those already mentioned,
certain misleading forms, as shown in figure 238, were encountered also in pregnant
tubes and in an ovarian pregnancy. Among these misleading forms were speci-
mens of binucleate cells in which one nucleus had undergone almost complete
chromatolysis, leaving only a nuclear membrane. These nuclear remnants or
so-called nuclear shadows can easily simulate a phagocytosed erythrocyte. The
same is true of small areas of cytoplasm which stain but faintly, and hence look
more translucent, and particularly of vacuoles themselves.

Essick (1915) found what he regarded as morphologically similar cells in
transitory cavities in the corpus striatum, and believed them to be macrophages.
Consequently, he concluded that Hofbauer cells also are phagocytic and regarded
them as having an endothelial origin. I have not been able to find any evidence
for the latter origin, however, for in specimens in which the capillaries are plugged
with degenerate endothelial cells, or in which they are composed of a layer of
greatly enlarged edematous endothelial cells, so as to make the cross-section of the
vessels look not unlike that of a duct, Hofbauer cells were never found in close
proximity to capillaries or other vessels or in unusual numbers elsewhere in the
stroma of such villi. Nor did I see any evidence for such an origin in villi taken
from hemorrhagic or inflammatory cases, and although Hofbauer cells often lay
near to, or even in extravasations in the villi, they were never found engorged with
erythrocytes or pigmented. Nevertheless, if Hofbauer cells arise from mesen-
chyme cells, it stands to reason that they at least may be potentially phagocytic,
and failure to find them so may be accounted for by the fact that they possess a
lowered vitality in consequence of degenerative changes.

I am prompted to suggest, in connection with the question of phagocytosis,
that, unless we regard the process as other than an actively vital movement on
the part of the cell for the purpose of engulfing things, we have undoubtedly
misused the term. That the mere incorporation of parts of cells, or even of whole
cells, within the cytoplasm is not sufficient evidence for the possession of phago-
cytic activity on the part of a particular cell, seems to me beyond question. In
some instances, for example, degenerating phagocytic leucocytes fuse with each
other in groups of twos, threes, or even in greater numbers, thus forming large,
multinucleated, and not infrequently vacoulated complexes. Similar phenomena
can be seen also among degenerated erythroblasts and trophoblasts and in Hof-
bauer cells, as shown in figures 239 and 240. Although it would be incorrect to
regard these degenerate fusion products as true, living giant-cells, they neverthe-
less simulate such very closely indeed. Moreover, when these larger fusion prod-
ucts fuse with an individual cell of the kind that gave rise to them, it would be
quite natural to regard them as being phagocytic, while, as a matter of fact, the

314 STUDIES ON PATHOLOGIC OVA.

process is merely one of degeneration. Another example of what we may call pseu-
do-phagocytosis is that represented by the isolated erythroblasts rarely seen in the
stroma of a villus. In some instances two or three cells, whose boundaries for the
most part still are clearly outlined, can be seen to have partly fused, forming a
so-called giant cell. All transition forms and stages can be found, and were it
not for this fact, the resultant large multinucleated fusion product, if seen to join
with an isolated trophoblast cell, might be regarded as being phagocytic. Other
instances of a similar nature were discussed briefly elsewhere (Meyer, 1918), and
I am inclined to believe that the non-vital character of this kind of cell formation,
which occurs under conditions of cell degeneration, needs further emphasis. It
certainly would seem to be a non-vital rather than a vital phenomenon. It is
indicative of degeneration and death rather than of regeneration and life.

Cells which are morphologically identical with certain stages in the degenera-
tion of the Hofbauer cell can also be found in entirely different locations than
those mentioned, as in the Graafian follicle, for example. In some of these, germinal
epithelial cells which have become detached and displaced in the liquor folliculi
become swollen and transparent and the nucleus takes an eccentric position. In
all details of structure and ordinary staining reactions, as shown by hematoxylin
and eosin, by iron hematoxylin, by van Gieson, and by Mallory, these cells are
identical with phases in the typical Hofbauer cells, as illustrated in figure 241.
This, however, does not justify us in designating them as such, unless we wish to
extend the use of this name to degenerating and disintegrating forms of cells of
very many different types and origins.

DESCRIPTION OF PLATE.

Fics. 235-237. Transition forms between mesenchyme and Hofbauer cells. No. 645, slide 3; No. 592, slide 1;
No. 645, slide 3b. 330.

Fic. 238. A phagocytic pseudo-Hofbauer cell. No. 645, slide 2. 650.

Fics. 23Q-240. Fusing Hofbauer cells forming a giant cell. No. 645, slide 2. No. 985, slide l. 300.

Fig. 241. Pseudo-Hofbauer cells in the ovary. No. 970. 650.

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CHAPTER XV.
THE VILLI IN ABORTUSES.

As long ago as 1832 Seiler stated that, although he could not be certain from
a magnification of 40 diameters, he did not think that chorionic villi were hollow.
Although Seiler concluded even at this time that villi are filled with cellular tissue,
the idea that they are hollow nevertheless persisted up to 1889. Seiler thought
that the first vessels invaded the villi as late as the third month. He represented
individual villi from chorionic vesicles from the fourth, fifth, and twelfth week as
clubbed in form, and also pictured several good villous trees. It is of particular
interest that he also represented a branching villus ending in a spherical termina-
tion, which suggests the ‘‘Zellknoten”’ of Kastschenko.

Miiller (1847) claimed that villi may grow until they are 2 inches long by the
fifth month, at which time he thought they still might cover two-thirds of the
entire surface of the chorionic vesicle. However, Miiller’s statement that the
villi are often cystic indicates quite clearly that he was not dealing with wholly
normal material, and that he probably saw degenerate or even hydatiform speci-
mens.

Robin (1854) apparently assumed that normal villi are hollow, for he stated
that fibrous, fibrinous, scirrhous, tubercular, fatty, and calcareous changes of the
placenta are made possible by fibrous obliteration of the cavities present in normal
villi. Robin believed that such changes as these normally occur in the non-pla-
cental portion of the chorionic vesicle, and stated that unbranched and degenerate
villi are found in placentz of all ages. From his descriptions one may conclude
that Robin noticed both the fibrinoid and the decidual layers of the eee and

possibly also the presence of so-called infarcts.

According to Winckler (1872), Bidder, Jr., showed that the villi are especially
densely set and particularly thick in caliber at fee margin of the placenta. Winck-
ler himself distinguished three kinds of villi. He stated that atrophic villi are
found everywhere, and that they never penetrate the maternal tissues beyond
the closing plate (Schlussplatte) described by him. These villi, which were said to
reach the cavernous spaces of the decidua, he declared to be uncovered by epithe-
lium. Indeed, Winckler believed this to be true also of all other villi as long as
they had not penetrated the closing plate of maternal tissue, into which his second
class of villi were said to continue considerable distances without branching.
He believed that the villi obtain a covering of epithelium only after they reach
the cavernous spaces or blood-sinuses. His third class of villi, which also were
said to be devoid of epithelium as long as they lay in the maternal tissue, differed
from the second class only through their greater development.

Langhans (1877) emphasized the irregularities in the villi which had been men-
tioned by Miiller, and concluded that villi always are vascularized.

Kolliker (1884) was especially impressed by the fact that the form of the villi
varies so greatly that one can hardly make any generalizations. He found that

315

316 STUDIES ON PATHOLOGIC OVA.

branching might occur even at right angles, and that terminal branches which do
not reach the placenta remain free. These free endings were said to be present
in placente of all ages, and to be filiform, cylindrical, pear-shaped, or club-shaped.
Branching was said to be so frequent and the interlacing of these branches so
common that only narrow intervillous spaces could be preserved in the placental
area. KOlliker particularly distinguished branches which he called fastening
rootlets (Haftwurzeln), which, according to him, were described by Ercolani and
also by Langhans. These were said to always enter the placenta and to become
attached to it so firmly that only considerable tension can separate the chorionic
vesicle from the placenta. Kdlliker stated that these fastening rootlets are com-
monest near the septa of the maternal tissues which separate the cotyledons, but
that they nevertheless are found also in the center of the latter.

Kastschenko (1885), in a careful study of the epithelial covering of the villi,
stated that they become more numerous in the region of the serotina by the end
of the second month, and believed that villi grow only by means of terminal and
never by lateral buds.

Minot (1889) accepted the opinion that villi are hollow during the earliest
stages of development only, and stated that the villous nodules are especially
common in older placentz. In speaking of the collaginous tissue (Gallertschicht)
composing the inner portion of the villi, Minot stated that it usually contains a
considerable number of large, uninucleated, granular wandering cells, now fre-
quently spoken of as Hofbauer cells and discussed more fully in the previous
chapter.

Giacomini (1892), in describing a young tubal conceptus, the villi of which
were not evident macroscopically, apparently regarded some of the syncytial
buds as representing young villi, and later (Giacomini, 1893°), when considering
chorionic vesicles devoid of an embryo, which had evidently undergone hydatiform
degeneration, again spoke of the presence of many syncytial buds, some of which
he again interpreted as being young villi.

De Loos (1897), who had no material from the first 6 months, believed that all
early conceptuses are covered completely by villi which are solid epithelial buds in
the earliest stages. He further believed that they become hollow later and
are invaded by mesenchyme after vacuolation of the syncytial buds has prepared
the way for this invasion. According to de Loos, all villi in contact with the
decidua basalis become vascularized, and he distinguished between stem, or original,
and fastening or nutritional villi. From a study of cross-sections of villi, he
concluded that the number of villi with small caliber increases from the third to
the fifth month, and that the caliber is greatest at the fourth month. De Loos
also thought that the caliber of the villi decreases with the branching, and that
there are relatively more villi of small caliber in full-term placente, which he
regarded as evidence that new villi are constantly arising. Since Wiskott (1882)
had found only syneytium present on villi at the sixth month, de Loos concluded
that villi in older placente which still are uncovered by epithelium necessarily
are hollow.

THE VILLI IN ABORTUSES. 317

J. Kollmann (1898) found villi 1 mm. long and well developed in a chorionic
vesicle of 6 mm. and stated that they might either be universally distributed or
merely equatorial. This writer, who limited the term ectoderm to the Langhans
layer, apparently referred the syncytium to a maternal origin. He also spoke
of nonvascular villous branches about 1 mm. thick, which played the rdle of
fastening villi, and distinguished two kinds, viz, ectodermic villi without a stroma
and mesodermice villi with it. In 1907 Kollmann used the term villi terminales
for villi which had traversed trophoblastic nodules, and villi adherentes for those
the terminations of which ended in or were joined to each other by the trophoblast
or a decidual plate.

Paladino (1899), although studying mainly the epithelium, stated that one of
the vesicles, the age of which he estimated as 13 or 14 days, was covered com-
pletely by villi. Webster (1901), who devoted considerable attention to villi,
recognized the presence of floating villi and found that villi, as a rule, are much
more numerous and are branched by the sixth week. According to Webster, the
mesoblast in the youngest villi is finely granular, vacuolated, and stains but faintly.
He also found villi which were attached to the chorionic vesicle by syncytial
stalks only, an occurrence which he attributed to failure of the mesoblast to pene-
trate the early plasmodial bud. He found many more small villi present by
the fourth month, and stated that the mesenchyme around the vessels is usually
condensed at this time. By the sixth month the villi were said to be slender and
more branched, and lateral budding was said to be much less frequent. Aside from
changes in the epithelium, Webster found the connective tissue of the small villi
to be loose or mucoid as term was approached, and stated that the villi are more
simple, possess fewer buds and branches, and are in part nonvascular in the region
of the chorion leve by the sixth week.

Marchand (1903) found that villi 1 mm. long uniformly covered a chorionic
vesicle 14 to 15 mm. in size, except at its mid-portion, in which a fold was located.
None of the villi were said to reach the capsularis at this time and all were non-
vascular. Marchand stated, however, that the mesenchyme cells frequently were
arranged in rows so as to simulate young capillaries. In a second specimen, 14
mm. in size, the villi, on the contrary, were largely restricted to the region of the
decidua basalis. Only isolated villi were found at the opposite poles, and but very
few on the lateral surfaces. These were branched but slightly, but some of them
were vascularized.

Bonnet (1903) described early lymphatics in the villi and represented a
ciliated border and also a membrana limitans. It seems that Kupffer (1888) was
the first to describe the ciliated border, reported later also by Marchand (1903),
and even more recently by Friolet (1905), Stoffel (1905), Daels (1908*) and Herzog
(1909), in all thin sections of the villi. Rossi Doria (1905) explained the so-called
ciliated border by the manner in which the erythrocytes become embedded in the
margin of the syncytium; and although a reticulum also has been described in the
stroma of the villus, later histologic studies do not confirm the presence of it, of a
membrana limitans, or of a ciliated border. These things, however, do not deny

318 STUDIES ON PATHOLOGIC OVA.

the faet, confirmed also by Fossati (1906), that a network can be revealed in
the stroma by the use of the Apathy, Golgi, Van Gieson, Mallory, and Cajal
methods of staining. This, however, does not necessarily demonstrate the
existence of a true reticulum.

Rossi Doria (1905) found young villi which had not yet been invaded by
mesenchyme and emphasized that the two layers of chorionic epithelium had
not yet differentiated in Peters’s ovum. Nevertheless, a reference to the illustra-
tion accompanying Peters’s monograph shows very clearly the presence of short
villi containing stroma, even in this specimen. According to Rossi Doria, the
mesenchyme begins to appear first in the villi during the second week, at which
time they also begin to branch and become vascular.

Friolet (1905), who examined a chorionic vesicle 11 by 12 by 9 mm., the age
of which he estimated as 3 to 4 weeks, concluded that villi arise by the extension
of the fetal mesoblast into the trabecule of trophoblast, and regarded a brush
border as a natural attribute of the syncytium. Friolet found the villi developed
better in the region of the basalis and especially around the whole periphery of
the mid-zone of the chorion. They were sparser in the capsularis, though without
degenerative changes.

Kworostansky (1903) discussed the mesodermic structure of the villi, includ-
ing the Hofbauer cells, finding the stroma much as we know it now; but Michaelis
(1903) claimed to have found a granular line between the stroma of the villus and
the Langhans layer, which he regarded as indicating the existence of a definite
limiting membrane. Michaelis concluded that the existence of this membrane
finally disposed of the idea that the Langhans layer may arise from the stroma, but
anyone familiar with the appearances produced by Bielchowsky’s stains between
the epithelium and the stroma of the villi will question Michaelis’ conclusions.

Von Lenhossék (1902) also recognized the existence of a basement membrane,
and Frassi (1906), upon the basis of material stained with silver nitrate, stated
that the villi in the greater number of moles have a limiting membrane, fibrous
in nature, which he regarded as “‘identical in form and structure with that demon-
strated and described in the villi of young placente.’’ However, Daels (1908°),
from the use of Weigert preparations, concluded that a layer of fibrin, the product
of degenerative changes, forms between the exochorion and endochorion, and
Friolet, who at first could not find a membrana limitans, said to have been described
first by Langhans, found a definite hyaline zone in an abortus from the third
month.

Happe (1906) found the villi of chorionic vesicles of the fourth to the sixth
week branched and about 2 to 7 mm. long, but nevertheless nonvascular. The
form of the youngest villi, which were about 2 mm. long, was said to be polyp-
like, the ends being swollen. Most of the villi of the three conceptuses from
the fourth to the sixth week showed an increase in caliber at the point of
branching, the swellings being especially marked at the origin of the terminal
branches of some of the villi. Happe stated that Hofbauer cells were not present
in the youngest villi, and that those of the older conceptuses contained only a few.

=

THE VILLI IN ABORTUSES. 319

Eternod (1909) divided the development of the villi into five phases: (1) a
primordial, avillous syncytial phase; (2) an avillous trophodermic phase; (3) a
trophodermic, transitory, zonal villous phase; (4) a diffuse, placental villous phase;
and (5) a diffuse, chorionic, and chorion-frondosum phase. Eternod placed the
conceptuses of Peters and Leopold in the second or avillous phase, in spite of
the fact that both these vesicles had short villi containing mesenchyme. His
third phase was illustrated by the specimens of Reichert and Ahlfeld and one of
his own in which the villi had an annular or equatorial distribution. According
to Eternod, the portions of the chorionic vesicle which later are in contact with
the basalis and capsularis are devoid of villi during this phase, which he regarded
as a transitory, but nevertheless necessary, phase. He believed that the bare
areas upon the chorionic vesicles resulted from inequalities in the expansion of
the chorion, and stated that in the specimen of Reichert and in one of his own, the
ventral or capsular bare area is less evident than the basal or dorsal, as he called it.
He believed that the ventral bare area disappeared earlier than the dorsal, only
to reappear again, however, when the chorion leve developed. Although he was
not absolutely decided in this matter, Eternod believed it improbable that young
villi are interpolated between the older, concluding that the chorion frondosum is
enlarged through the addition of villi at its periphery with far greater regularity
than heretofore suspected.

The fourth phase in the development of the villi, according to Eternod, occurs
in vesicles with a length of approximately 9 to 16 mm. In such the villi are
branched and their terminations fused by trophoderm. The fifth phase follows
the fourth very quickly, for it is said to be present in chorionic vesicles 17 mm. in
size, and to be characterized by great inequalities of growth and by far greater
complexity in the basal area than in that of the capsularis.

Dandy (1910), in describing a chorionic vesicle 16 by 14 by 12 mm., found the
villi branched and about 0.1 mm. thick and 1.25 mm. long. He stated that they
“are more numerous at the point of attachment of the Bauchstiel and gradually
fade away on all sides until, finally, a clear zone results from their absence on
the opposite pole. . . . From the epithelial layer of the chorionic membrane
and villi numerous buds develop, some from the syncytial layer alone, others from
both layers of the epithelium. These represent proliferating and new forms of
villi.”

Miller (1913), in describing a conceptus 0.83 mm. in greatest diameter, stated
that the mesodermic villi were as yet absent, and that the Langhans and syncytial
layers were structurally identical, although already distinct. Lazitch (1913)
called attention to the fact that the conceptuses described by Peters, Leopold,
Strahl and Beneke, and Fetzer showed the earliest villi to be mesodermal buds, and
that the specimen reported by Jung already showed the presence of dichotomy.
Lazitch stated that the villi are less irregular and more cylindrical in form in the
fifth month, and that curious forms, such as “‘little-horns,” are rare. She stated
further that the villi became long at term and possessed fewer buds, some of which
looked as though they were branches arrested in development. Lazitch also found

320 STUDIES ON PATHOLOGIC OVA.

many ectodermic nodules or proliferating islands. In a conceptus measuring 26.5
by 22.0 by 14.5 mm., she found the villi 3 or 4 mm. long, with branches and
trunks so oblique that they were almost parallel to the chorionic surface. Accord-
ing to her, the villi converge towards the poles of the chorionic vesicle, as stated by
Eternod, but possess so variable a form that it is difficult to describe them, the
caliber changing from thick to thin, from wide to narrow, from cylindrical to folded
so quickly that a single branch sometimes possesses all these characteristics. She
found anastomoses fairly numerous, but free villi ending in epithelial prolongations
were rare. Most of the anastomoses seen resulted from ectodermic fusion, but
villi separated by some distance and united by true villous bridges containing
mesoderm were also seen. According to Lazitch, dichotomy occurred in 65 to
70 per cent of the villi, trichotomy in 20 to 25 per cent, and a more complex form
in 10 per cent. The branching usually was at an acute angle, but branches which
diverged 180° also were found. Since buds were present on the chorionic mem-
brane, Lazitch concluded that a moderate amount of interpolation of new villi
among the old undoubtedly occurs.

Johnson (1917) found the villi on a chorionic vesicle, containing an embryo
with 24 somites, variable in size and 1.1 to 1.3 mm. long in the region of the chorion
frondosum. Johnson stated that the villi were usually smaller at the bases, and
that smaller villi, although few in number, were found among the larger.

Ingalls (1918) also found the villi on a chorionic vesicle 9.1 by 8.2 by 6 mm.
to vary greatly in size and shape, but stated that the chorionic vesicle seemed to
be covered by them over all of its surface. This finding of Ingalls seems to be in
accord with observations upon the best-preserved and youngest specimens in the
Carnegie Collection. Small chorionic vesicles, with one or two opposite bare areas,
and others with sparsely set villi, are not rare, but at present we possess no evidence
establishing the strictly normal nature of these specimens. Among these speci-
mens is the vesicle represented in figure 7 (plate 1, Chap. IV). Isolated and
sectioned villi from this specimen show the presence of but slight branching and
rather cylindrical villi. The absence of some of the villi in this specimen is due
to the mechanical means used in the removal of the blood-clot before the specimen
was received.

A vesicle which, though macerated, deviates only very slightly from the nor-
mal, is No. 1878, the exterior of which is represented in figure 232 (plate 19, Chap-
ter XIII), and the portion bearing the embryo in figure 233. As seen in the
latter figure, these young villi look unusually matted and bulbous, though it
must be remembered that young villi necessarily are united and covered by
trophoblast in which they are implanted. Some isolated specimens of these
villi are represented in figure 242, and what especially strikes one’s attention is the
presence of an exceedingly fine basal portion in the villus to the left. Although
the caliber of normal young villi varies considerably, I do not believe that such
forms as this can be regarded as strictly normal, and this belief is confirmed by an
examination of sections of the villi, shown in figures 243 and 244. It is possible
that maceration alone is responsible for some deviation from the normal form of

THE VILLI IN ABORTUSES. 321

these villi, but it is not improbable that one of the specimens, shown in figure 244,
illustrates incipient hydatiform changes.

In contrast with this specimen stands the vesicle, No. 2053, shown in figure
245. This is a somewhat older, but perfectly normal, chorionic vesicle, some of the
villi from which are shown in section in figure 246. All of the villi of this specimen
are of approximately the same development, and although trichotomy is present
and simpler forms of branching are common, no marked diminution of the parent
stem seems to occur at the point of branching. Moreover, the branches are approx-
imately as large in caliber and sometimes even larger than the main trunk.

Somewhat older vesicles are Nos. 866, 2108, and 1892, represented in figures
247, 248, and 249. The first of these possesses decidedly fibrous, filiform villi,
partly covered by decidua, such as are not uncommon in cases of retention. No.
2108 shows the characteristic towsled appearance of the villi in many chorionic
vesicles with early hydatiform changes. The villi in these vesicles are usually
longer than they ordinarily should be, and this fact alone shows that the stroma
must have grown, unless one assumes, as did Daels (1908*), that it is mere y pulled
along by the proliferating exochorion. In view of this belief, it is especially inter-
esting that Daels thought that the stroma nevertheless might be increased instead
of rarefied.

The villi in No. 1892 show early maceration changes, and that growth of this
vesicle ceased some time before abortion is indicated also by a menstrual age of
54 days, although the size of the vesicle suggests an age of only 42 days. Some
villi from this specimen, represented in figure 250, show the presence of maceration
and also establish the fact that the villous trees have reached considerable com-
plexity at this time. When maceration changes are more prolonged and lysis of
the villi advances so far that they are structureless or almost so, one gets such
shadow forms as those represented in No. 2197 (fig. 251). In these villi nothing
remains but a mere gossamer, and the exterior of the entire chorion often has an
eiderdown appearance, as suggested in a minor degree by this specimen (fig. 252)
and to a far greater degree by No. 993, shown in figure 259. The villi of the former
vesicle, the exterior of which measured 23 by 20 by 16 mm. and the interior 16
by 13 by 10 mm., although only 2 to 4 mm. long, nevertheless have reached con-
siderable complexity in form, for a dozen or more branches sometimes leave the
main stem at about the same place. Villi from other vesicles of approximately
the same age may, however, be much longer, as illustrated by No. 1287, represented
in figure 253, a specimen which also shows early hydatiform degeneration. In this
ease the relatively small size of the chorionic vesicle is evident at once upon
inspection of the cross-section of the entire vesicle. The presence of matting
and maceration is equally evident, and anyone at all familiar with these vesicles
would not expect to find many traces of an embryo.

The presence of hydatiform degeneration is very common in abortuses of the
fifth to sixth week. This is well illustrated by the villi shown in figure 255. A
fairly normal villus and, for a specimen of this age, the largest found, is repre-
sented in figure 254. Many small knobs are seen along the branches of this villous

322 STUDIES ON PATHOLOGIC OVA.

tree, to the right of which there also are some macerated villi and to the left others
fused by trophoblast. The contrast in form, surface, and appearance between
the hydatiform and the normal villous tree is very striking indeed, and it would
seem that the hydatiform villus largely loses its power of branching, and, except
for local increases in caliber, grows mainly in length.

A somewhat older, apparently normal chorionic vesicle with normal villi is
No. 2361, shown in figure 256. In this vesicle, which measures 35 by 35 mm. and
which has an age of about 41% weeks, some of the villi in the basal area are very
plainly hydatiform, although also macerated. Both of these changes are notice-
able also in some degenerated villi shown in figure 257, but inspection of the cap-
sular area of this chorion shows that no hydatiform change is evident here, nor
is it evident on the external surface of the abortus represented in figure 258. This
is due to the fact that the process is in its early stages, and because the conceptus
is surrounded by decidua. Although the specimen has a menstrual age of 124
days, the abnormal embryo (shown in figure 206, plate 18, Chap. XIII) is but
3 mm. long and the chorionic vesicle only 35 mm. in diameter, measurements which
indicate anatomic ages of 414 and 61% weeks, respectively. Hence, if the menstrual
age can be relied upon, this specimen must have been retained 80 days. This does
not imply, however, that the chorionic vesicle necessarily had been dead during
all this time. Judged by the menstrual age, the fetus should be 150 mm. long, and
as judged by the chorionic diameter it should be 13 to 14 mm. long instead of 3
mm., its actual length.

A second good example of the development of hydatiform degeneration,
especially in the area of the basalis, in vesicles of this size is found in No. 2077
(represented in fig. 101, plate 8, Chap. IX). This vesicle, which measured 40.5
by 28.5 by 18.5 mm., was reflected from the underlying decidua, but was never-
theless left attached to it so as to expose a large field of exquisite hydatids, a portion
of which is shown in focus in the center of the figure.

The eiderdown appearance due to maceration changes, which was referred to
above and which is produced especially by post-partum maceration, is shown par-
ticularly well in No. 993, a portion of which is represented in figure 259. The only
possibility of confusion of these changes with other conditions is that one might
take an instance like this for intrauterine lysis, but usually other criteria will
enable one to differentiate the two conditions. However, when the two conditions
are associated such differentiation may become impossible. How very complicated
the branching of the villi has already become in these vesicles of the sixth week,
of a measurement of about 48 by 41 by 15 mm., is shown by the bush-like villus
represented in figure 260. The thick main stem of this villus stands out in marked
contrast to some of the branches, many of which are exceedingly fine and others
matted and fused. Fine, thread-like villi are common, especially in the area of
the chorion lave, as early as the sixth to seventh week. This is exemplified well
by the specimens shown in figure 261. However, these fine villi, which usually
have a fibrous, non-vascular stroma, occur also in long retention and elsewhere
on the vesicle than in the area of the chorion leve. They are present in the macer-

THE VILLI IN ABORTUSES. 323

ated but otherwise normal villous tree in figure 262, the branches of which bear
decidual masses and trophoblastic nodules. Nothing could stand in more marked
contrast to this and other normal villous trees than the excellent hydatiform villi
in figure 263, which were taken from a vesicle 40 by 36 by 18 mm., of approximately
the seventh week. This contrast is emphasized further by such normal specimens
as the villi from No. 837, shown in figure 264, transition forms between which and
the former are typified in the villi represented in figures 265 and 266, taken from
vesicles 45 by 35 by 30 mm. and 80 by 60 by 50 mm., respectively, the former of
which also shows maceration changes.

Other types of normal villi from vesicles of the eighth week are shown in figure
267. In these villi from a vesicle 54 by 50 by 48 mm., as in some older specimens
to be referred to later, the most striking thing is the presence of many small knobs
on all sides of the branches. This is illustrated splendidly by the villous tree
shown in figure 268, which was taken from a placenta of the thirty-sixth week.
There seems to be a great variation in the occurrence of this knobbing which
probably does not signify beginning branching. The knobs are too numerous for
this when they are at all well developed, and, since they are so uniform in size, one
would have to think of a perfect shower of branches arising at the same time.
Since the placente in which knobbing of the villi was especially evident look abso-
lutely normal, I have come to regard its presence as typical for villi beyond a certain
age, without, however, regarding those in which it is present only in a minor degree
as necessarily pathologic. A villous tree in which sparse knobbing is evident only
upon magnification is that shown in figure 269, in which rather miscellaneous
branching is present. Other filiform villi, and a group of them from this placenta
of the eighth to ninth week, are shown in figure 270.

What a contrast in external appearance villi from different placentze may show
is illustrated in figures 271 to 278, villi of the eleventh, twelfth, fourteenth, fifteenth,
thirteenth, nineteenth, twenty-fourth, and twenty-fifth week, respectively. Nor
are these variations in the‘external appearance of the villi to be attributed to age
alone or necessarily to pathologic changes. The villi shown in figures 271, 272,
and 274 look hydropic because of maceration, and those in figure 272 are decidedly
fibrous and largely non-vascular. The chorionic membrane of this vesicle was
decidedly infiltrated. The villus shown in figure 277 is also macerated, and the
chorion likewise was infected, but the stroma in this case was edematous and had
disappeared completely in places.. Not infrequently the blood-vessels can be
seen as fine white lines on the exterior of these macerated specimens. The villi
shown in figure 273 came from a vesicle which had also been retained a consider-
able period of time, and those shown in figure 275, though filiform and fibrous, with
nodules at the extremities, are also macerated.

Villi of small caliber are encountered quite frequently in apparently normal
older placentz, but are especially common in the capsular region, at a time when
retrogression of the chorion lwve is taking place. The contrast in form of the
villi shown here is remarkable. Those in figure 278 appear like the leafless branches
of an oak hung with streamers of lichen. These strange appearances are due to

324 STUDIES ON PATHOLOGIC OVA.

the presence of many exceedingly fine branches and perhaps even of early villi, almost
all of which, nevertheless, are highly vascular. Those in figure 276 are practically
unmacerated, for they came from a fresh, normal abortus, and in spite of their
extreme delicacy and curliness, I know of no reason to regard them as pathologic.
That shown in figure 277 came from a retained infected conceptus, but to w
extent its form can be attributed to these facts is difficult to decide. It scarcely
seems to me that such a marked diversity in form could exist in strictly normal villi,
and it is possible that local conditions may to a large extent influence, even if
they do not determine, the type of a particular villus.

I regret that it has not been possible to compare villi from placentz of the
same age, but from different pregnancies, in the same women, in order to determine
the possible occurrence of variations in the type of villi in succeeding pregnancies.
There seems to be no doubt that the diversity in form of villi increases rather than
decreases with advancing age of the conceptus, and that the differentiation extends
even to the last months of pregnancy. At this time, however, the more prevailing
type of normal villus appears to be such as that from the thirty-first week, shown
in figure 279.

Normal villi apparently vary greatly, not only in length and caliber, but also
in complexity and manner of branching, and in the appearance of their surfaces,
which change from smooth to extremely knobbed. It is not uncommon to find
that exclusion of the villi reduces the measurement of a chorionic vesicle from one-
third to one-half. This is illustrated by the specimens in figures 231 (plate 19,
Chap. XIII) and 253, both of which are relatively small vesicles. Nor are these
long villi always slender and unbranched, for frequently, as illustrated in figure
281, in which a more branched, bushy villus from a vesicle 70 by 50 by 40 mm. is
represented, they are decidedly umbelliferous. However, as is usually the case,
the villi of this specimen were somewhat unequally developed.

Extreme grades of fibrosis, as represented in figure 283 (plate 24, Chap. XVI),
with vessels in varying degrees of disappearance, have been found to occur in
cases of long retention in lues and also under conditions of infection. These
particular villi were taken from a vesicle measuring only 55 by 35 by 20 mm.
Rather unusually formed, clubbed, decidedly macerated villi from an ovarian
pregnancy are shown in figure 168 (plate 16, Chap. XI). Anomalous development
of villi seems to be more common in tubal, and perhaps also in ovarian, than in
uterine pregnancy. In tubal specimens the villi not infrequently are but sparsely
developed and bare areas seem to be much more frequent. Moreover, the chori-
onic vesicles are often too small in proportion to the contained fetus. This is
illustrated well by No. 1151, shown in figure 280. To what extent this dispro-
portion is the result of reduction in the size of the vesicles after death of the fetus
or to retardation in growth because of an abnormal location, or to both, I am
unable to say. Some of the villi of this small vesicle also show hydatiform
degeneration, while others merely are macerated, as shown in figure 282.

Careful examination of young chorionic vesicles has failed to reveal villi which
are purely epithelial or ectodermic, nor have I seen any formed by the extension

THE VILLI IN ABORTUSES. 325

of mesoderm into the trophodermic trabecule. As soon as an area of the syncy-
tium and the Langhans layer becomes elevated at a given point, the mesoderm
accompanies them if this elevation represents a beginning villus. No matter how
marked the syncytial development, I have never noticed the presence of a normal
structure in the distal portion of a villus and a purely syncytial structure in the
basilar portion. No matter how long or how complicated the syncytial buds
became, they never were invaded by mesenchyme or became vascularized. How-
ever, this fact does not preclude the inclusion of blood within syncytial skeins or
trophoblastic nodules, or within invaginations of epithelium in the mesoderm of the
villi. All these appearances not infrequently are seen in specimens in which there
has been considerable growth of syncytium or of the Langhans layer, but I have
never seen evagination of these two layers without a mesodermal core. No matter
how long vascularization of a villus is delayed, and in some cases this seems never
to occur, such villi otherwise have the same structure as the rest, just as tropho-
blastic development on the early villi seems to be universal and not visibly influenced
in its first stages by the location of the embryonic disk or the shape of the early
conceptus. These facts undoubtedly are not without significance for the nutrition
of the early conceptus. The universal presence of villi establishes conditions much
more favorable to circulation of the surrounding fluids, besides very materially
increasing the area of absorption. Hence I do not believe that bare areas in the
basal and capsular regions of a young conceptus can be regarded as normal.

Branching of the villi oceurs exceedingly early and does not seem to develop
any special plan or be limited to any particular plane. The angle generally is an
acute one, probably because of the fact that the branches aim to reach the
trophoderm or the decidua. It is not at all uncommon to find several branches
arising at the same level, or they may leave the parent trunk in quick succession.

Although considerable variation in size and complexity of the villi seems to
exist even in normal chorionic vesicles, these differences are not necessarily so
pronounced in the same as in different specimens. However, one not infrequently
meets with simple, unbranched villi among others of great complexity, but I did
not get the impression that, except in the first few months, much interpolation of
villi occurs later in development. It is quite surprising how large a placental
area can be formed by a single villous tree, and placental differentiation occasion-
ally seems to be present in chorionic vesicles with embryos of a length of only
17 mm., which implies an age of only about 7 weeks. Indeed, it does not seem
improbable to me that close observation will show that some placental diffentia-
tion exists as early as the sixth week.

326

Fic. 242. Isolated villi from No. 1878, shown in figures 232 and 233, plate 19, Chapter XIII. 4.5.
Fios. 243-244. Appearance of villi in section, same specimen. 7.5.

Fig.
Fic.

245.
246.
. 247.
. 248.
. 249.
. 250.
. 251.
. 252.
. 253.
. 254.
. 255.
. 256.

. External appearance of abortus, same case. 0.75.

. Changes in external appearance of villi, due to maceration alone. No. 993. 3.
. Isolated villous tree from same vesicle. X3.

. Isolated filiform villi. No. 1639. <3.

. Isolated villous tree. No. 2336. 6.75.

. Fine hydatiform villi. No. 1797. x3.

. Normal villi. No. 837. 2.25.

. Transitional villi between normal and hydatid. No. 432. 2.25.

. Transitional hydatiform villi. No. 437. 2.25.

. Normal, knobbed or budded villi. .No. 1063. 2.25.

. Villous tree from a normal specimen, illustrating many small knobs. No. 2335. 6.75.
. Villous tree showing few buds or knobs. No. 1840a. 2.25.

. Filiform villi and a portion of the vesicle from the same specimen. 3.

. Villi showing maceration changes. No. 2348. 6.75.

. Villi showing maceration changes. No. 2339. 6.75.
. Villous tree with smooth villi. No. 2253. 6.75.

. Villous tree with knobbed villi. No. 2372. 6.75.

. Filiform villus. No. 2326. 6.75.

. Fine, frowsy villus. No. 2414. 6.75.

. Massive villous tree. No. 2283. 6.75.

STUDIES ON PATHOLOGIC OVA.

DESCRIPTIONS OF PLATES.
Pate 21.

Cross-section view of an entire normal vesicle with cyema and adnexa. No. 2053. 3.
Section of villifrom same. X36.

External appearance of conceptus, showing filiform villi. No. 866. 1.5.

External appearance of conceptus, showing presence of hydatiform villi. No. 2108. 2.25.
Sparsely villous area from No. 1892. 1.5.

Isolated villi from same specimen, showing maceration changes. X3.

Isolated shadow or gossamer villi. No. 2197. x9.

External appearance of same specimen. 1.5.

Cross section of No. 1287. 1.5.

Villi from No. 1466. 2.25.

Hydatiform villi from No. 2233. x4.

Section of chorionic vesicle with hydatiform villi in basal area. No. 2361. 1.5.

PLATE 22.

. Isolated villi from No. 2361, showing both maceration and hydatiform degeneration. 6.75.

Pate 23.

. Knobbed, curly villi. No. 2384. 6.75.

. Mossy villi. No. 2249. 4.5.

- Tubal conceptus (No. 1151), showing disproportion between the chorionic vesicle and the fetus, sparse
development of the villi, and some hydatiform degeneration. 1.5.

. Villous tree from No. 651k. 2.25.

. Villi from No. 1151, shown in figure 280. x3.

MALL AND MEYER
PLATE

MALL AND MEYER

MALL AND MEYER

CHAPTER XVI.
VILLOUS NODULES.

That the occurrence of numerous small nodules on the villi of young concep-
tuses must have attracted the attention and aroused the curiosity of early embry-
ologists, one can not doubt. They often are so conspicuous, so spherical, and, when
located on the tips of the villi, also so striking in appearance, that they could not
be easily overlooked. Hence it does not surprise one that Miiller (1847), in his
interesting monograph on moles, described them, and that Sommering (1799) had
represented them, as figure 284, reproduced from the latter, shows. Miiller re-
marked that he did not always find them, and that they sometimes were absent
in normal specimens. As will appear later, this is a very interesting and probably
also a significant observation. Langhans (1877), in connection with a thorough-
going microscopic examination of the placenta, spoke of these appendages as
“insular nodules of maternal tissue,” and also represented one. Langhans spoke
of them as being 1 mm. in diameter, and said that their white color and turbid
nature distinguished them from the more transparent swellings of the villi them-
selves. Their form was said to vary, and some were found to be located on the
curved, enlarged processes of the villi, while others capped these processes. Micro-
scopically, they were said to be composed of large, oval, round, polyhedral, spindle-
and star-shaped cells, usually a little flattened, which could easily be distinguished
from the fetal cells by their size alone. Langhans stated that the cells composing
these islands were decidual in origin, but that their nuclei were the size of the
nuclei of the epithelium which separated them from the stroma of the villus.
Langhans regarded them as decidual prolongations which penetrated the fetal
placenta, and which hence might appear on the surface of the chorionic membrane
itself.

As long as the exact origin of the placenta had not been decided at this time, it
need not surprise one that Langhans should speak of these nodulesas being composed
of maternal tissue. Moreover, everyone who has examined conceptuses still
implanted in or aborted with the decidua will admit that often it is impossible to
draw a definite line of separation between the cells composing these nodules and
the adjacent decidua. But it is not unlikely that exact differentiation between
the two tissues is possible by the use of histochemical methods.

Kastschenko (1885) referred to the insular nodules of Langhans merely as
cell nodules (Zellknoten), and stated that they are always composed of chorionic
epithelium. It is not clear to me, however, whether Kastschenko did not, after
all, confuse these nodules with syncytial buds. Besides, he stated that, although
these cell nodules develop from the epithelium of the chorion, they later become
serotina cells.

Heinz (1888) stated that the “‘insulze of maternal tissue’’ are especially common
in placentz from the third to the sixth month, and that he never found them at
term. He concluded that they are always composed of maternal tissue, that

327

328 STUDIES ON PATHOLOGIC OVA.

they are firm, and are located halfway between the serotina and the tips of the
villi. In figures 3 to 5 accompanying his article, good representations of sec-
tions of villi with nodules partly embedded in the stroma of the villi are found.
Heinz believed that they became separated from the rest of the maternal tissues
by the growth of the villi, and thus became isolated and related to the latter. He
thought that as the villi develop they begin to devour the maternal tissue with
which the implanting conceptus is in contact, and that these nodules represented
the only remnants of these maternal tissues. While Langhans thought that these
nodules are formed merely by the invasion of the maternal by the fetal tissues,
Heinz believed that they resulted from an invasion of the maternal tissues
by villi, with accompanying destruction of the former. In support of his opinion,
he referred to the well-known destructive power of the villi first revealed by
Virchow, who called attention to the invasion of the maternal blood-vessels by
fetal villi.

Minot (1889), contrary to Heinz, declared that the nodules within the villi are
commoner in old placentz, a conclusion which prompts the inference that Minot
may have regarded them and the so-called decidual islands of contemporary litera-
ture as identical.

Hofmaier (1890), in describing his Case V,a conceptus 20 by 5 mm., containing
an embryo of 4 mm., stated that small nodules the size of the head of a pin were
present everywhere on the villi. These nodules the author regarded as composed
of decidual cells.

Kossman (1892) also spoke of insular nodules of maternal tissue and made
fine drawings of sections cut 3 to 4 4 thick. He declared that it was plain that
these nodules were composed of decidual tissue in which some of the villi be-
came embedded, his idea being that portions of decidua became isolated from
the rest and then were retracted by villi which lost their attachment to the
decidua. Kossman stated that he never found nodules covered entirely by
syncytium, as reported by Kastschenko, and doubted the occurrence of such.
He further concluded that the cells composing these nodules do not simulate
those composing the Langhans layer nearly as closely as Kastschenko had stated.

Crosti (1896) also spoke of these nodules and referred to them as appendici
durate, saying that they become hydropic in retained conceptuses.

In discussing conceptuses of the sixth week, Webster (1901) stated that he
could distinguish three kinds of ‘‘Zellknoten.’’ One was said to be composed of
“undoubted decidual cells, along with a mass of cells which evidently belong to the
proliferated Zellschicht at the end of an attached villus.” These were said to be
surrounded more or less by syncytium and might contain portions of it and also of
the villi. Webster regarded this form of nodule as due to decidual elevations upon
which the villi were implanted. A second form of Zellknoten was said to be com-
posed solely of closely placed villi, along with several processes or strands of the
syncytial layer. The third variety was said to be composed of villi surrounded by
fibrin.

VILLOUS NODULES. 329

Pfannenstiel (1903) thought that the villous nodules are composed partly of
decidua, but Rossi-Doria (1905) frankly stated that they are nothing but prolifera-
tions of the Langhans layer, especially common on the tips of the villi. Rossi-
Doria nevertheless believed that the syncytium also may take part in their forma-
tion through proliferation by amitosis. This investigator, who made a careful
examination of a conceptus 9 by 8 mm., stated that the trophoblastic nodules which
form on the ends of the branches of the villi begin to appear after the second week
of pregnancy. He concluded that they form not only on the free, but also on the
fastening villi (Haftzotten), and doubted whether syncytium really can invade
these nodules, as held by some investigators. J. Kollman (1907) also reported
them in a conceptus 8 weeks old, and showed villi joining after passing through the
nodules, forming what he called ‘“‘villi adherentes.”’

If these nodules, found in such number on villi of many abortuses, and repre-
sented so well in the conceptus from S6mmering, shown in figure 284, are decidual
in origin, then it is clear that their substance is in fact preformed, and if they
antedate the formation of the villi it would seem that they might appear very soon
after the formation of the latter. If, on the other hand, they are products of the
epithelium of the villi, then a short interval after the formation of the latter is
necessary to enable such accumulations to form. No one has held that they are
direct products of the ovular ectoderm, which secondarily become related to the
villi, and, from what has been described in the earliest known implantation stages,
_it would seem that this is not the case. Although the ectoderm of the implanting
ovum apparently is extremely active, probably especially so during the invasive
stage of the implantation, these nodules apparently do not arise directly from it.

In the description of some of the cases, and also in publications, I have some-
times used the term trophoblastic nodule. The cells composing these nodules,
however, undoubtedly arise from the Langhans layer, the syncytium usually
being absent; and since the nodules really are not remnants of the early tropho-
blast, it would perhaps be better to relinquish this term altogether and to refer
to them merely as villous nodules. However, I have been greatly puzzled to find
a good name for these special masses of cells arising from the Langhans layer.
The term insular nodule, introduced by Langhans, would be entirely acceptable
did it not carry with it the possibility of confusion with decidual islands, for
if they really were islands, confusion would be particularly likely, because
Langhans thought that they were maternal in origin. The term cell-nodule (Zell-
knoten), introduced by Kastschenko, also is not without objection for the same
reason. The designation ‘“‘appendici durate’’ used by Crosti does not recommend
itself either, because one scarcely can speak of most of them as appendages, for the
simple reason that they are almost wholly embedded in the stroma of the villi.
Then, too, they are so small that one scarcely feels justified in speaking of them
as hard. In very young villi the designation trophoblastic or trophodermic nodules
would seem quite appropriate, especially since they frequently contain syncytial
masses among the Langhans cells; but later on, long after the trophoderm or tro-
phoblast has ceased to exist as such, this designation seems far less appropriate.

330 STUDIES ON PATHOLOGIC OVA.

Nor is the term villous nodules wholly unobjectionable, for they are not, as a
rule, composed to any appreciable extent of villi, though a group of 6 or more
villi not infrequently pass through or are united by them. But since it seemed
the least objectionable term, I have adopted it.

That these nodules really have the origin attributed to them by Rossi-Doria
seems undoubted, although it is not impossible that rarely they may contain
some adhesions or inclusions of decidual cells. These would be entirely accidental,
however, and would result from portions of the decidua adhering to or being
surrounded by the proliferating Langhans cells, and thus becoming included
in the nodules. If, as Rossi-Doria stated, and as I believe, they arise from the
Langhans layer of the villi, then the fact that they frequently contain masses of
syncytium within their interior or at their margins offers no difficulties to those who
believe that the syncytium arises from this layer. Nor would it be difficult to
explain the presence of included syncytial masses within the nodules upon the
assumption that the syncytial layer has an origin independent of the Langhans
layer. But in any case, an origin from either of these layers would imply that they
might be expected to be especially numerous in any condition in which unusual
activity occurs in these layers. Hydatiform degeneration is such a condition,
and that these nodules are especially numerous in many of ‘the specimens of
hydatiform degeneration can easily be demonstrated. Whenever the epithelial
proliferation is very pronounced, however, it does not manifest itself in the for-
mation of nodules, but in the production of irregular trabecule, garlands and
even trellis-works of cell-cords, such as represented in figure 9 (plate 1, Chap. IV).
It also is conceivable that these spherules might form during the stage of spon-
taneous regression of hyperactivity of the epithelium or in the earlier stages of
hyperactivity; for a more or less spherical nodule manifestly could result only
from proliferation in many instead of predominatingly in one or two directions only.

I have also found these nodules common upon the ends of the villi, as is shown
so well to the left in figure 285 and still better in figure 116 (plate 10, Chap. VIII).
But, as noticed by previous investigators, and as shown in figures 285 and 286,
they are not limited to these locations. I have never found them stalked, but
always sessile, and embedded in the stroma of the villi even, as shown in figure 287.
Indeed, not infrequently the epithelial proliferation, instead of resulting in an ele-
vation upon the surface of the villi, extends largely into the stroma, so that sections
of nodules were completely surrounded by it. All manner of transition stages
between extravillous and intravillous locations were seen, and more or less hemi-
spherical accumulations also were found directly upon the chorionic membrane.

It is not at all uncommon to find these nodules located nearer the base of a
villous tree, as shown in figures 288 and 289. This does not, however, imply that
those so located were not apical once, for they may have formed on a short side-
branch which they completely surrounded. Not infrequently several villi, even
up to half a dozen or more, may be united by and terminate in a single nodule,
as shown in figure 291; or they may penetrate it, as represented by Kollman.
Not infrequently considerable groups of nodules are found in a single small region,

VILLOUS NODULES. 331

as illustrated by the teased preparation shown in figure 290. It is not uncommon
to find half a dozen or more nodules in section in a single field of the microscope
under low magnification of cross-sections of villi, and when they are so numerous
as this the villi in these areas may look matted in consequence.

They never seem to attain any considerable size, seldom becoming larger
than 1 to2 mm. This would seem toimply that, whatever the cause of their for-
mation, the process is self-limited. I have never seen a chorionic vesicle in which
large areas were capped or united by these proliferations, as are the early villi
by trophoderm, for example; but they are decidedly resistant and persist long
after the villi have degenerated. Nor have I ever seen them detached, for they
seem to retain their hold even after the villi become decidedly macerated, as illus-
trated in figure 292. I, too, have found them most common in relatively small
chorionic vesicles, and never have seen one on mature, normal villi.

Since I used no special microchemical methods, I can add but little to what
is recorded in the literature regarding their structure. I do not believe, however,
that the syncytial inclusions are syncytial in origin, or that they are ordinarily
degeneration products. They seem to arise directly from the cells composing the
nodules. Hence,as stated elsewhere (Meyer,1918), this conclusion, if correct, offers
further confirmatory evidence of the origin of the syncytium from the Langhans
layer. It can easily be demonstrated that the villous syncytium is penetrated rapidly,
as a rule, by proliferation of the underlying Langhans layer, and all stages in this
process of protrusion of the cellular accumulations, through the underlying syn-
cytium, can be found. Since marked proliferation of the Langhans layer can occur
without hyperactivity on the part of the syncytium, it also is clear that the syn-
cytium may for this reason alone fail to take part in the formation of these nodules.
No matter how numerous the syncytial buds in eases of exquisite early hydatiform
degeneration, for example, I have never seen appearances suggesting in the slight-
est the origin of these nodules from syncytium. It is difficult to form an opinion
of their functional significance, but it does not seem improbable to me that they
may result from an attempt on the part of the younger branches of the villi to gain
contact with the decidua and so restore better nutritional conditions.

DESCRIPTION OF PLATE.
PLaTE 24.

Fig. 283. Cross section of intensely fibrous villi from No. 765b. (See Chapter XV.)

Fia. 284. Conceptus showing numerous trophoblastic nodules. (After Sommering.)

Fig. 285. Portion of chorionic vesicle showing an apical villous nodule to the right and others elsewhere.
No. 1495a. 2.4.

Fic. 286. Chorionic vesicle showing numerous small villous nodules. No. 2197. X1.6.

Fic. 287. A villous nodule completely surrounded by stroma, except at its free surface not shown in the figure.
No. 556.

Fic. 288. A villous nodule near the base of a villous tree. No. 2365. 7.2.

Fic. 289. Villous nodules and lichen-like streamers on a villous tree. No. 2204. 7.2.

Fic. 290. A group of teased villi bearing numerous trophoblastic nodules. No. 2225. 4.8.

Fia. 291. Several villi ending in a single trophoblastic nodule. No. 308. 4.8.

Fria. 292. A macerated villous tree, one branch of which bears a noduleon its extremity. No. 2472. x

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MALL AND MEYER

CHAPTER XVII.
CHANGES SUGGESTIVE OF LUES.

Since Schaudin’s discovery, attention naturally has been directed very largely
from placental lesions of syphilis to the presence of spirochetz. But unfortunately
the hope that the presence of this organism would form not only a crucial but also
an infallible criterion for the determination of fetal lues does not seem to have
been realized. The search for spirochetz seems to have been attended by such
uncertain results that a routine examination of the placenta has not even been
recommended by prominent obstetricians. Slemons (1917”), for example, stated
that the presence of spirochztz in the placenta can be demonstrated in only
about one-third of the cases of lues, and Mracek (1903) found no histologic evi-
dence of lues in 82 out of 160 placentse from syphilitic women. Slemons found
the examination of stained sections more satisfactory than a gross examination of
the villi, and stated that a proliferative inflammation of the vessels in the terminal
villi constitutes the beginning change in lues. The lumina are said to become
obliterated, the connective tissue of the villi increased, and the villous epithelium
not only proliferates, but also invades the stroma.

Some uncertainty still seems to attach to the use of the Wassermann test, for
Williams (1917) emphasized that lues may develop in an infant even when this
test applied to the mother was found negative at the time of its birth. As stated
by Williams, others also have observed the contrary condition of a positive Was-
sermann in the newborn, later becoming negative spontaneously. Slemons, how-
ever, found the Wassermann reaction and the placental histology to coincide in
95 per cent of 345 cases, and in 99 per cent even, if misleading cases of toxemia of
pregnancy were first excluded. Lues was present in 10 of the 345 cases examined
by Slemons, who emphasized the fact that areas in which the structure of the
placenta is normal may be present. From these things it seems that, regarding
the existence of lues in early specimens, one is thrown back again upon the old ques-
tion whether fetal lues in its early stages is characterized by any lesion or by any
group of lesions which can be regarded as pathognomonic. Since it is recognized
that the existence of maternal lues does not necessarily imply its existence in the
fetus, the importance of independent criteria regarding its existence in the fetus
becomes much greater. This is true in spite of the fact that belief in the trans-
mission of paternal lues direct to the offspring without infection of the mother
now seems to be quite generally abandoned. This was inevitable as soon as the
cause of lues became known.

Even in this day there seems to be no agreement upon what constitutes valid
histologic evidence of the existence of fetal lues, but the opinion that recurring
abortion of a macerated fetus, in the absence of other causes, is strongly indicative
of lues seems to be held quite generally. It was the belief of obstetricians and
gynecologists that abortion or premature labor occurred in a large percentage of
cases in which maternal lues antedated conception by several years. Seitz (1904*)

333

334 STUDIES ON PATHOLOGIC OVA.

credited Lutowski as finding that such a result inevitably followed, and himself
found gestation interrupted in 91.6 per cent of such cases. Seitz classified 50
per cent of these interruptions of gestation as premature, 16.6 per cent as immature,
and 21 per cent as abortions. Fuoss (1888) also quoted Ruge as saying that the
fetus is still-born in 80 per cent of the cases of lues. The number of cases in which
children which were born prematurely, but living, died soon after birth, is also
surprisingly large in the series of Thomsen (1905), in spite of recourse to anti-luetic
treatment, and Slemons (1916) reported that all luetic children among 17 which
were prematurely born died.

Thomsen found that lues could be excluded with considerable certainty in
only 11 out of 27 controlled cases which had given birth to macerated fetuses.
But more important still is the fact revealed by examination of Thomsen’s pro-
tocols, that 24 out of 27 still-born fetuses of luetic mothers were macerated. It
should be added, however, that no evidence of the existence of lues was present
in 8 of these 24 macerated fetuses. Premature labor occurred in only 62 per cent
of Thomsen’s series of luetic mothers, as compared with 91 per cent in that of
Seitz, and 100 per cent in the series of Lutowski. However, Urfey (1901) cautioned
against the assumption that repeated abortion in the later months of pregnancy
always is due to lues, and held that a non-specific chronic endometritis is not
infrequently the cause. This indeed seems highly probable when considering the
marked changes which may be produced in the decidua by chronic inflammation.
Unfortunately, Thomsen’s protocols do not state whether the evidence of lues
was based on gross or upon microscopic examination or upon both. This is espe-
cially regrettable, because this series included cases which bore no gross but only
microscopic evidence of the existence of lues.

The foregoing statement abundantly emphasizes the lack of correlation existing
between the effects of lues upon the life of the conceptuses and the continuation of
the gestation and the histologic and bacteriologic evidences contained in the con-
ceptus. If neither spirochete nor characteristic histologic changes can be found
in many of these prematurely born and macerated, luetic conceptuses, then one
would seem to be compelled to assume not only that death of the conceptus is due
to the influence of toxins, but that toxins may cause its death without producing
any recognizable structural change in either placenta or fetus. The use of anti-
luetic treatment may be responsible for the differences in the varying frequency
with which luetic mothers give birth to luetic babies, and it is possible that the
use of antiluetic treatment may affect the time of appearance of fetal lesions.
Surely, a chronic systemic disease, which is believed almost invariably to cause
the death of the conceptus and premature birth, especially after the sixth month
of gestation, can scarcely be presumed to produce no structural fetal changes
whatsoever before this time. This would seem to be possible only if the maturing
fetus showed a decidedly diminishing resistance, both to the luetic disturbances
and to infection.

How early luetic lesions may appear in the fetus has been especially considered
by Engman (1912), who thinks that many placental lesions which have been

CHANGES SUGGESTIVE OF LUES. 335

referred to lues probably may not be such. This opinion was expressed also by
Williams (1917), and Thomsen called attention to the fact that luetic changes in
the fetal organs, so common in the seventh to the tenth month, are exceptional
in the first 6 months of gestation. But it is well to remember in this connection the
caution of Mracéek (1903) that cases of abortion occurring in the third and fourth,
and especially in still earlier months, usually do not come to hospitals for treat-
ment, and that observations on the placental lesions in lues hence have been made
very largely upon material from the seventh and eighth months. Mraéek found
luetic placental lesions as early as the fifth month, and Slemons (1916) slightly
earlier than this. Since 10 of the placentz in a series of 78 examined by Mracek
weighed from 200 to 300 grams, it is evident from this fact alone that he dealt
with some rather early cases of gestation. In a routine examination of 400 pla-
centz, Slemons found luetic lesions present in 6 out of 17 premature deliveries
in which the fetus had a length of 30 to 40 em. and a weight of 1,000 to 2,000
grams. Since fetuses in the Carnegie Collection with a length of 30 to 40 em.
have an age of approximately 34 weeks, and those weighing 1,000 to 2,000 grams
an age of 28 to 3514 weeks, it is evident that the weight of these luetic fetuses ex-
amined by Slemons was relatively low, as might be expected.

The appearance of fetal luetic lesions may depend upon many factors, and
Thomsen’s observation, that luetic inflammatory changes in the extra-abdominal
portions of the umbilical vessels never were present before the fifth and sixth
month, can not be regarded as final, in view of the differences of opinion concern-
ing the specific nature of these changes. Thomsen also implied that the vascular
were accompanied by other changes in the fetal organs.

That changes which are entirely comparable to what has been called “granu-
lation cell proliferation’ by E. Fraenkel (1873), or “granular hyperplasia” by Erco-
lani (1871, 1873) occur in very young villi, is abundantly evident from an exam-
ination of specimens in the Carnegie Collection. However, it does not therefore
follow that such specimens are necessarily luetic. Thomsen, too, recognized that
these changes in the villi, to which, and edema, he attributed the disproportion in
weight between fetus and placenta, possibly occur in other conditions, but it is
significant that he never found them present in controls. Thomsen further em-
phasized that this hyperplasia of the stroma of the villi is never so pronounced
in other conditions as in lues, and that the degree of hyperplasia of the stroma and
of infiltration of the extra-abdominal portions of the umbilical vessels run parallel
with the severity of the infection. Thomsen also concluded that, although other
diseases can cause similar changes in the umbilical vessels, such occurrences are
extremely rare. Mratek found changes in the cord present in only 10 out of 78
cases of lues, and Simmonds (1912) in 20 out of 40 full-term labors in which the
presence of maternal lues had been established. Moreover, Simmonds found
inflammatory changes in the cord present in 32 cases in which lues was excluded,
and the fact that vascular changes have been found to be uncommon near
the placental, and spirochetz near the abdominal end of the cord still waits for
explanation.

336 STUDIES ON PATHOLOGIC OVA.

If such changes as these alone could be regarded as pathognomonic of lues,
it would be a relatively easy matter to determine its presence. Thomsen also laid
great stress on the presence of abscesses in the placenta, accompanied by hyper-
plasia of the stroma, and stated that he had never observed such a coincidence in
any condition except lues, adding that although he found placental abscesses
only 8 times in 100 cases in which maternal or fetal lues had been established, he
never found them present in 1,250 placente in which lues could be excluded with
considerable certainty. Thomsen further stated that infiltration of the mem-
branes, although not specific, nevertheless is quite characteristic of lues, and is
most marked when the syphilitic infection is severe.

If Thomsen’s conclusion were justified, one would be compelled to believe
that fetal lesions which are pathognomonic of lues nevertheless exist. It may be
recalled in this connection that Schwab (1905) also emphasized the necessity for
considering the “tout ensemble” and claimed that a fairly reliable diagnosis of lues
can be made from an examination of the placenta alone. According to Schwab,
the lesion complex consists of (1) a disproportion in weight between the fetus and
the placenta, with an excess in weight of the latter; (2) hypertrophy of the villi;
(3) perivascular cirrhoses; (4) inconstant proliferation of the syncytium; and (5)
arteritis of the decidual vessels. Schwab recognized that any of these lesions may
be present in other conditions, and laid special emphasis on the total picture.
Solowij (1902) had gone much farther than this, however, for he held that lues is
the cause of most placental lesions, even in the cases in which neither parent
shows evidence of the presence of the disease in active form. Solowij even regarded
this as established clinically, and held that lues alone produced the changes in the
arteries described by him.

Slemons believed that the most trustworthy evidence of the existence of fetal
lues is found in the chorionic villi, which are clubbed and the vessels of which
are not apparent in luetic cases. Slemons asserted that “‘when delivery occurs
prematurely, the placental findings are significant; for in that case the question
of syphilis may always be fairly raised.”” Since Slemons found placental evidences
of lues in 10 per cent of 400 placentae accompanying a living child of the fifth
or later months, it would seem that a higher percentage of cases from the earlier
months would contain evidences of lues, unless it can be assumed that early
conceptuses are more resistant to infection. The failure to find spirochetze in
conceptuses before the fifth month would seem to suggest that no lesions can be
expected before this time unless they can result from the influence of toxins. Should
this be considered as impossible and the failure to find spirochet be accepted
as conclusive evidence of their absence, then lues apparently must be excluded
as a cause of abortion before the fifth month, except in so far as the disease may
affect the health of the mother adversely, or cause changes at the implantation site.

While considering the probable factors in the termination of gestation in the
case of abortuses in the Carnegie Collection, it became evident that mechanical
interference—therapeutie or otherwise—and hydatiform degeneration seemed to
be the predominating causes. These can be recognized with some certainty, but

CHANGES SUGGESTIVE OF LUES. 337

the customary difficulty was encountered regarding lues. Consequently, a series
of abortuses from the group of fetus compressus, in which lues was present in
mother or offspring, were selected for special study. From the findings in these
cases, and taking the entire specimen as well as the clinical history into considera-
tion, an attempt was made to isolate a group of specimens which might be regarded
as probably luetic.

Even if it be incorrect, as variously stated, that a large percentage—even
up to 95 per cent—of all long-retained macerated abortuses are luetic, the mere
fact that a very large percentage of luetic fetuses are retained for some time before
being aborted introduces a special difficulty into the examination of them. It is
relatively rare that a satisfactory teased preparation of the villi can be obtained
even in early conceptuses. Hence, for this reason alone, the existence of clubbing
of the villi, even if present in early cases, is much more difficult to determine.
This is true of all specimens which have been retained sufficiently long so that
the villi have become macerated, glued, and more or less compressed. Such glue-
ing, or matting, apparently can arise in a relatively short time, for it is present in
placentz which accompany fetuses which are not markedly macerated. Although
often not due to lues, this glueing makes a gross examination of the villi very
difficult and unsatisfactory.

So-called typical, granular hyperplasia of the stroma of the villi can be found
present in very small chorionic vesicles and probably can be caused by other
things than lues. But obliterative arteritis was not seen in any very young chori-
onic vesicles, although present much earlier than the fifth month. In some of
these cases the obliterative changes were present not only in the vessels of the
villi, but in those of the chorionic membrane as well. It was noticed but rarely
in the umbilical vessels, but since the entire cord was included in relatively few
specimens, no thorough examination could be made regarding this matter. Con-
siderable thickening of the chorionic and amnionic membranes as a result of fibro-
sis was quite common, however. When present in a marked degree, the fibrous
change in the stroma of the villi and the obliterative changes in the vessels, both
of those in the membranes and of the larger villous stems, often were so typical
that on the basis of these alone, especially when they were accompanied by some
infiltration with mononuclear leucocytes, one is justified, I believe, in regarding
these specimens as very probably luetic. The placente of such of these specimens
as had been retained for some time after fetal death showed the presence of coagu-
lation necroses—so-called infarction—with the presence of considerable masses of
degenerate trophoblast, and usually also of some calcification. The accompanying
decidua also not infrequently showed the presence of fibrosis and later also of
endarteritic changes in the decidual vessels.

If spirochetz are absent in the conceptus before the fifth month, then it
would be unjustifiable to assume that the cases showing these changes were defi-
nitely leutic, unless fetal lesions can arise in the absence of the specific organism
within the conceptus. Nevertheless, I feel justified in emphasizing that these
morphologic changes seem to be characteristic even if not pathognomonic of lues.

338 STUDIES ON PATHOLOGIC OVA.

Whether they could be produced before the advent of the organism itself I am not
in a position to say. But if lues can lead to the premature birth of a living child
and also to retention of conceptuses which died because of the existence of
maternal infection, it would seem that the presence of this serious disease in the
mother could be expected to affect the life of the conceptus more profoundly in
other ways than through the direct effect of the characteristic lesions themselves.
Moreover, it would seem that when other causes can be excluded clinically, one
would be justified in suspecting the existence of maternal lues. I am aware
of the fact that retention alone, wholly regardless of the cause of death of the con-
ceptus, has been suggested as responsible for changes similar to those attributed
to lues, but I am quite certain that the changes in some of the cases here concerned
undoubtedly are not due to retention.

The gross appearance of these specimens is so well known that a full description
is unnecessary. The fresh decidua is frequently markedly macerated, the placental
area of the chorion, when differentiated, is pale and firm and its maternal surface
furrowed, the ridges being formed by fibrinoid masses and badly preserved decidua
and the sulci by pink, better-preserved decidua. The membranes are degenerate
or necrotic even, and thickened, especially in the placental area. The amniotic
fluid usually is reduced considerably in quantity and the fetus greatly macerated.
The cut surface of the fixed placenta shows the presence of some intervillous
blood, in spite of the existence of large waxy areas, which, upon microscopic exami-
nation, are found to be composed of degenerate decidua, trophoblast, so-called
infarcts, and apparently fibrous areas constituted by large villous stems and
coalesced villi.

As is well known, a history of repeated abortion is common in these cases and
the presence of lues frequently unsuspected. In one such ease, in which attention
was directed to the probable nature of the specimen, further inquiry and examina-
tion revealed the existence of relatively recent maternal lesions, including mucous
patches. Although this may be a mere coincidence, I am quite certain that the
subject deserves further attention.

The placental changes in most of these specimens remind one somewhat of
the placenta accompanying a fetus 12 cm. long, reported by Welch (1888) under
the caption, ““Hyaline metamorphosis of the placenta,” and it is interesting that
Welch stated that the changes in the stroma of the villi in this case reminded him
of those attributed to lues by Fraenkel. Although the few cases in the Carnegie
Collection in which the infant was known to be definitely leutic were of considerable
value in this matter, those in which lues was suspected or even reported, or in
which the Wassermann test was negative or positive, were of little value, because of
the well-known disagreements between the clinical findings and the occurrence
of luetic lesions in the fetus.

CHAPTER XVIII.
SOME ASPECTS OF ABORTION. '

In considering the possible reasons for the interruption of gestation, one must
not only distinguish between the alleged and the real causes, but must also bear
in mind the fact that we still speak of the occurrence of spontaneous and habitual
abortion. It is scarcely necessary to emphasize that there can, of course, be no
such thing as spontaneous abortion, for no gestation can be presumed to be inter-
rupted without a cause, whatever its nature. This is self-evident, and I gladly
would let the matter pass without comment were it not for the fact that the con-
clusion that a certain abortion was spontaneous often ends further inquiry.

Hegar (1904) directed especial attention to the presence of pathologic changes
in the conceptus as a cause of abortion, thus clearly recognizing that the difficulty
may not lie in the maternal organism, although it must not be forgotten that
many of the so-called pathologic changes present in conceptuses nevertheless
may be due to adverse influences, somatic and maternal rather than germinal in
origin. However, since the presence of anomalies in the fetus usually is determined
by inspection of the gross specimen, it is evident that only the presence of external
deformities generally is noted. But from dissecting-room experience alone we
know that pronounced anomalies commonly are present internally without having
become evident externally. This may be true of such extreme anomalies as situs
viscerum inversus even, and when one considers how much more disadvantageous
for the development of the cyema such a condition must be than such minor things
as polydactyly and brachydactyly, hare-lip, cleft palate, or club-foot and hand,
it becomes apparent that znternal must far more frequently be the cause of fetal
death than the external anomalies. The latter have long been recognized as prob-
able causes of fetal death and the subsequent termination of gestation merely
because they are so evident. It is true that external not infrequently are associated
with internal anomalies, but the effect of the latter upon the life of the cyema
probably has been underestimated largely because they can be revealed only by
painstaking examination. However, the frequent presence of marked internal
anomalies in the bodies of individuals who have passed middle life, or even the
proverbial threescore and ten, also indicates that the réle of external anomalies
in the termination of gestation probably has been overestimated. For aside from
such major defects as the various forms of cranio-rachischisis, it is difficult to see
how minor external anomalies, such as polydactyly or brachydactyly, hyper-
phalangism, cleft palate, or hare-lip or anarthroses and synarthroses, in them-
selves can lead to the death of the fetus and hence to the interruption of pregnancy.
The same thing is true of anomalous renal development, except in so far, perhaps,
as it is extremely pronounced or associated with anomalies in the organs of inter-
nal secretion. Cardiac anomalies, especially septal defects, and internal hydro-

1 The word abortion is here used in the general sense of an interruption of gestation, regardless of the time or the cause.

339

340 STUDIES ON PATHOLOGIC OVA.

cephalus, on the other hand, probably would very seriously affect the further
development of the cyema, even if not evident externally.

It is strange that we know so little regarding the anomalous development
of the chorion as a factor in the termination of pregnancy. That the cause for
the latter not infrequently may be sought in the ovum or spermatazoon one can
scarcely doubt, for otherwise one would have to assume that the human repro-
ductive cells are characterized by a unique immunity and perfection. That this
is not the case has been abundantly shown for the human spermatazoon, but we
are still quite ignorant concerning the occurrence of pathologic unfertilized ova.
Jones (1897), however, came to the conclusion that they were common, and
Detleftsen (1914) reported that abnormal ovaries commonly occur in guinea-pig
hybrids—that is, crosses between the domestic and the wild cavy species. Further-
more, Huber (1915) found abnormal fertilized ova which disintegrate even before
implantation in the rat.

Crosti (1896) believed that abortion in the first 8 or 10 weeks is always due
to defects inherent in the ovum, and Szasz (1903) stated that fetuses from the early
months of gestation may show malformations not found in the later months.
If this be true, then it demonstrates what one would seem to be able safely to
assume, that the existence of some fetal anomalies makes continued development
impossible. Such anomalies, hence, never should be met in the newborn, but
should be found in the early fetus only. This conclusion of Szasz would also seem
to be justified if fetal anomalies were more common in the earlier than in the later
months of pregnancy. This was the conclusion reached by Mall (1917), who
found that localized anomalies are twelve times as common in abortuses as are
monsters among fetuses at term. But since not only acardiac monsters, but also
small nodules, such as reported by Slemons (1917*) under the caption ‘Fetus
amorphous anideus,’’ may sometimes survive until term, it is difficult to sub-
stantiate the assertion of Szasz at present, except perhaps indirectly by the greater
infrequency of anomalies at term and by the occurrence of such heretofore unknown
specimens as No. 1843 (Meyer, 1919°), in which survival was manifestly impossible.
Such vesicles as this, wholly devoid of a eyema, apparently never can continue to
develop for any length of time, and, as far as I can learn, never have been observed
before; for the large hydatiform degenerations, composed of portions of a chorionic
vesicle and villi only, really belong in another category.

No one will doubt that the presence of certain developmental anomalies
tends to fetal death and hence also to early abortion, but until more material
is available it will be impossible to make reliable statistical deductions and
determine the relative frequency with which various anomalies occur in the
different months of pregnancy or even at the time of birth. However, there is no
doubt that small primary nodular forms, which are true developmental anomalies,
such as those shown in figures 205 and 206 (plate 18, Chap. XIII), are far more
frequent among young than among older specimens in the Carnegie Collection.
This, however, does not wholly confirm the statement of Szasz, though it is in entire
accord with Mall’s conclusion. If one considers the external form and the structure

SOME ASPECTS OF ABORTION. 341

of these small masses, one feels quite certain that some of them belong in the
category of rare, full-term specimens such as that. reported by Slemons. Few of
these probably survive till term on account of an insufficient blood-supply, and
the occasional survival of one in association with a normal, full-term fetus is an
extremely interesting occurrence.

One need only to regard the question of abortion historically and recall
the practices of primitive races to be reminded of the fact that in such a matter as
this human custom, conduct, and frailty play a very large rédle. Nor need attention
be directed to the practices of primitive or uncivilized peoples alone, even if Rob-
inson’s (1919) estimate that 1,000,000 criminal abortions are performed annually
in the United States can not be accepted without question. Since the number of
annual births in the United States, estimated on the basis of the registration area,
is only about 2,400,000, this would imply that 1 criminal abortion is performed
for every 2.4 births. Or, to put it another way, if somewhat less than 40 per cent
of all pregnancies terminate prematurely, as Pearson (1897) estimated, then,
according to Robinson, 1 out of every 4 pregnancies is terminated criminally.
But the highest estimates of the ratio of abortions to pregnancies are those of
Taussig (1910) and myself. Those of Taussig were based upon the experience
at a St. Louis gynecological clinic, and mine upon about 700 selected histories
from the Carnegie Embryological Collection. From these data it seems that
there is 1 abortion to about 1.7 to 2.3 pregnancies. Hence, if we accept Rob-
inson’s estimate of the incidence of criminal abortion in the United States as
1 to every 2.4 births, it would follow that in the women considered by Taussig or
myself about 70 per cent of all pregnancies which terminated prematurely were
terminated criminally! Furthermore, upon the basis of Pearson’s estimate of
prenatal mortality, the criminally induced actually would exceed the abortions
due to all other causes by over one-half, while upon the basis of Mall’s earlier
estimate of a prenatal mortality of about 20 per cent, the criminal abortions in
the United States, as estimated by Robinson, actually would exceed the grand
total of abortions from all causes by 200,000 cases annually!

It is regrettable that we are left partly to surmise regarding the exact incidence
of prenatal death. Ahlfeld (1898) estimated that there is 1 abortion for every 4
or 5 normal births. This would be 1 to every 5 or 6 pregnancies. A. Hegar (1863)
estimated that 1 out of 8 or 10 pregnancies ends prematurely. Michailoff (1897),
as reported by Chazan (1904), gave a frequency of 10.18 per cent, and Keyssner
(1895) a frequency of 15.1 per cent, or 1 abortion to every 5 or 6 births, an
estimate confirmed also by Williams (1917). According to Lechler (1883) and
Chazan (1904), this was also the figure reached by Busch and Moser (1840), upon
theoretical grounds alone.

Stumpf (1892) found 1 abortion for every 3.56 pregnancies, a mortality of
28 per cent, and Keyssner still less, or 1 abortion in 9 pregnancies, or a mortality
of but 11 per cent.

Since the causes responsible for postnatal mortality differ so widely from those
which operate before birth, it is wholly unlikely that a curve of postnatal mortality,

342 STUDIES ON PATHOLOGIC OVA.

if extended through prenatal life back to conception, as done by Busch and Moser
and by Pearson, would tell the truth. Indeed, it could do so only by the merest
chance, for the curve of postnatal mortality is based upon a totally different set of
conditions. Besides, it undoubtedly is true that the rate of mortality varies from
month to month in prenatal much as it does from decade to decade in postnatal
life, although probably in a totally different way. It could fail to do so only if a
perfect uniformity of conditions obtained throughout the period of gestation.
Since this is not the case, the curve of postnatal mortality is of course based upon a
totally different set of conditions.

Upon theoretical grounds, Pearson (1897) decided for a mortality of 37.6 per
cent, or 1 abortion in every 2.7 pregnancies, an estimate which Mall (1917°) regarded
as too low. This opinion of Mall would seem to be confirmed by Taussig (1910),
who, from data obtained in 201 gynecological dispensary patients, concluded that
there was 1 abortion to every 2.3 pregnancies, a mortality of 43.4 per cent; and
also by the present series of almost 700 cases, which indicates a prenatal mortality
of 58 per cent.

If we take the statement of certain social workers or propagandists, who
allege that a conservative statement of the total number of criminal abortions
annually performed in the United States is 250,000, then on the basis of Pearson,
1 in every 6, and on the basis of Mall’s earlier estimate, 1 in every 3 interrupted
pregnancies, is terminated criminally. However, Taussig (1910), on the basis of
histories obtained from 293 patients at the St. Louis gynecological dispensary,
reported that only 36 out of 371, or approximately 10 per cent, of the abortions
in these women were admittedly mechanical. The histories in the Carnegie Col-
lection present similar evidence, but these percentages undoubtedly are too low.

It should not be overlooked, however, that the surprisingly high percentages
of prenatal mortality in the above women undoubtedly do not represent the actual
life conditions of the whole population. They merely represent the conditions in
women who have aborted. How much the inclusion of all those women who never
had aborted would have lowered these percentages it is impossible to say, but one
scarcely can doubt that the lowering would be considerable. After a fuller con-
sideration of the literature, Schultz, page 183, estimated the prenatal mortality
among the general population at 22.0 per cent, a figure somewhat higher than
Mall’s earlier but considerably below his later estimate.

Since the women in the present series do not constitute a dispensary group,
but very largely also represent cases in private practice, one can not contemplate
the amazing prenatal mortality in these women without the profoundest concern,
not alone because of its significance upon the birth-rate, but also because of its
relation to the wellbeing of these women and the effect of such practices upon
public morals. Nor can one be quite certain that the indicated antenatal mor-
tality is on the decrease or that it is high in these women alone, for Malins (1903),
for example, believed that abortion is more common among the economically
more fortunate classes. This opinion seems to be shared also by others. Nothing
even remotely like it seems to be known in the case of the domestic animals,

SOME ASPECTS OF ABORTION. 343

except in such conditions as contagious abortion. Aside from this affection,
abortion in some domestic animals seems to be a rather rare phenomenon, having
occurred, according to Malins, only 131 times in a series of pregnancies which
resulted in 3,710 living colts. This is a ratio of only 1 abortion in every 29.1
pregnancies, or less than one-seventeenth the frequency found in the women in
the present series.

But it is very clear that we lack sufficient data upon which to base reliable
opinions regarding these matters. Social workers undoubtedly far overestimate the
prevalence of criminal abortion, though it should at once be admitted that profes-
sional obstetricians very likely underestimate its frequency, for their opinion is
based upon a rather different experience. However, that the estimate of the former
is entirely too high can be shown also by their estimate of the deaths due to abor-
tion. It has been stated publicly, for example, by enthusiasts for birth control
that there are 8,000 deaths due to abortions, annually, in New York alone, and
50,000 in the entire country. Since the total number of deaths from all causes
among all women between the ages of 15 and 40, regardless of whether they are
child-bearing women or not, as estimated on the basis of the registration area
according to the United States census for 1916, was only 139,642, one-third of all
deaths in women of these ages would, according to these advocates, be due to
criminal abortion!

No mention was made of the occurrence of previous abortions in 11.4 per cent
of the 697 selected cases of abortion in which the clinical histories were quite
complete and apparently reliable. This small percentage stands in marked con-
trast to the findings of Malins (1903), who stated that 63.4 per cent of the women
in a selected series of 2,000 hospital and private cases had not aborted before, and
that of the childless 3.2 per cent had aborted. Only 3 cases among the 697 were
specifically stated to have suffered no previous abortions. In the rest of the 11.4
per cent the matter was not mentioned. Only 1 of these 3 women had borne
children, and the remaining 2 were recorded as having had neither previous abor-
tions nor children.

Malins, who found 14.2 per cent sterile women in a series of 2,000 selected
private and hospital cases, stated that 3.1 per cent of these had aborted, but had
had no children. Although it is not recorded in 78 cases that the women had either
had children or abortions, one can not assume that they had neither, else the per-
centage of primiparze would be 11.4 as compared to 4.86 per cent in the series of
Franz (1898). Graefe (1896) found only 2 out of 38 cases in primipare, a per-
centage of 5.5 per cent, and stated that Litthauer found only one such case. How-
ever, such small groups as these really can not contribute anything of statistical
value, except when combined. Out of Hellier’s series of 1,800 married women
belonging to the laboring classes, 184, or over 10 per cent, never had been pregnant
before, and 1,616, or 89.7 per cent, had one or more abortions. The latter was
true of 92.9 per cent of the cases in the Carnegie series, and although repeated
abortion occurred in a considerable percentage of these women, only 5.6 per cent
had aborted more than 5 times.

344 STUDIES ON PATHOLOGIC OVA.

The above 78 cases also represent the women in this series of 697 cases who
may not have aborted previously. However, all of them had aborted once, or
they would not be represented in the Carnegie Collection. The only exceptions
to this statement may be a few instances of spurious pregnancy in which hemor-
rhage or membranous dysmenorrhea may have been taken for genuine evidence of
pregnancy because of an irregularity in the menstrual history.

A single previous abortion had occurred in 56.6 per cent of 608 cases, and
two previous abortions in 22.9 per cent. About 79 per cent of these women, as
contrasted to the 66 per cent of Stumpf’s series of 446 cases, had aborted once or
twice previously, and 69.1 per cent once or twice only. Hence the great majority
of the specimens in the present series came from cases of first and second abor-
tions, as indicated in table 13. However, one should, I presume, recall in this con-
nection that it always is easy for a woman to say that she has aborted only once
or not at all. Yet the records probably are not very defective in this regard, for,
as will appear later, most of the women were relatively young.

As shown in table 14, 394 out of 692 women, or 56.9 per cent, aborted before
the beginning of the fourth month of gestation. Hence it is evident that most
of the conceptuses from this series are small. Only 3 cases aborted during the last
2 months and 78.6 per cent before the beginning of the fifth month. The marked
increase in the frequency of abortion from the first to the second month, as well
as the marked decrease from the sixth to the seventh month, is not without signifi-
cance. The same factor probably is at least partially responsible for both.
Knowledge confirmatory of the fact that she is pregnant would come to a woman
with the advent of the second month, while the viability of the fetus would act
as a deterrent to interference with the gestation especially after the fifth month.

Only 33.4 per cent of the women of this series aborted in the third month, as
compared to 59 per cent in the series of Diihrssen (1887), and to 42.7 per cent of
Franz’s (1898) cases, taken only, however, from the first 7 months of gestation.
However, since only 3 of the present series of 692 cases aborted during the last 2
months, and only 14 during the last 3 months, it is quite immaterial whether or
not the cases in this series from the last 3 months are included, for 98.2 per cent
aborted before the seventh month. Although Franz stated that only 15.45 per
cent of the cases collected by him had aborted before the twenty-eighth week,
the summary given at the end of his paper would seem to make this percentage
76.9, which compares fairly well with the 98.2 per cent found in this series.

That no existing collection of specimens or of histories correctly represents
the actual facts in the world at large would seem to be indicated by a comparison
of the results obtained by different investigators, as given in table 15. With the
exception of the results of Stumpf and myself, and some of those of Lechler for the
third, fifth, sixth, and seventh months, the divergencies are striking—probably
irreconcilable—and suggest that a far larger series of cases than that dealt with
at present is necessary before any results closely approximating the truth can be
obtained. The only regard in which the findings of Franz, Hellier, Stumpf, and
myself are in surprising agreement is the average number of pregnancies to abor-

SOME ASPECTS OF ABORTION. 345

tions per woman. This was 4.77 in Franz’s, 4.59 in Hellier’s, 4.15 in Stumpf’s, and
4.58 in the present series. Hellier’s group came largely from the laboring classes
of Leeds. The Carnegie series comprises women from widely different stations
in life and from widely scattered communities, and those of Franz and Stumpf
came from different regions of the European continent. Since these four series
included 3,762 women, it would seem that one can assume that the average of these
groups, or 4.54 full-term pregnancies per abortion, probably approaches the truth
very closely indeed. This truly remarkable agreement found in women from three
countries also seems to imply that the proportion of births and abortions per woman
is largely, if not wholly, independent of nationality and environment.

A very large proportion of the women in the histories of whom the matter
was recorded were childless. This, as shown in table 16, was true of 143 out of 585
cases, or of 24.4 per cent. Hellier found the childless to form only 1.3 per cent of
his series of 1,800 gynecological cases from among the working classes of Leeds.
Approximately the same percentage of the present series as was childless had but
a single child. A somewhat smaller number had two children, the childless and
those who had one and two children forming 67.1 per cent of the whole group.
Yet one woman had borne 14 and another 16 times.

Franz found that primipare formed only 4.86 per cent of his series of 844
cases, but if we could assume that all the cases in the Carnegie series which were
reported as childless actually were primipare, then the percentage of the latter in
this collection would be 24.7. However, since such a marked discrepancy exists
between the percentage recorded by Franz and the latter figure, it is more than
likely that a considerable number of the women recorded as childless in this series
were not primipare after all. This is indicated also by the fact that only 78 out
of 697 women, or 11.2 per cent, of which number the 585 included in table 16 form
a part, were unrecorded as to offspring or previous abortions. Only 2 additional
cases were recorded as not having suffered an abortion previously. Consequently
only 80 out of these 697 women, or 12.9 per cent, apparently were in their first
pregnancy.

Franz found abortion twice as common in multipare as in nullipare. From
clinical cases Graefe (1896) concluded that women who had borne three times
aborted most frequently, but he added that this finding was not confirmed in his
private practice. Stumpf found the ratio of abortions to births 1 to 5.1 in primi-
pare, but only 1 to 2.21 in multipare having up to and including 5 children, and
1 to 2.22 in multipare having more than 5 children.

As shown in table 16, the average number of abortions per woman is practically
the same in the childless and in those having had one child, but with the second
child a rise of almost 16 per cent takes place, for the average number of abortions
per woman changes from 2.5 to 2.9. Another smaller advance is shown to occur
with the fourth child, although there are relatively slight fluctuations in women
having had 4 to 7 children. Since the number of women having borne 8, 9, and
10 children was so small, no conclusions could be drawn regarding them.

346 STUDIES ON PATHOLOGIC OVA.

In all groups except the first two, composed of women having none or but
one child, the average number of abortions lies between 2.9 and 3.6 per woman.
Moreover, this ratio is practically the same in the groups having borne 2, 4, and
even 6 children, but since the total number of cases involved in this table is only
585, the number in each group is necessarily small, being over 100 in the first
three groups only.

Upon comparing the total number of previous abortions suffered by 697
women with the total number of children borne by them, we find that there was
0.84 previous abortion for every child. However, if the 697 abortions represented
by the specimens which brought these women to our notice be included, then the
ratio becomes 1.3 instead of 0.84 abortion per child; yet Malins, on the basis of
2,000 selected private and hospital cases, found but 1 abortion to every 5 children.
A similar proportion is recorded also by Hellier, who, on the basis of 6,974 births
and 1,288 abortions in 1,800 married women, found one abortion for every 5.5
children. Keyssner (1895), on the basis of 9,381 births and 1,194 abortions, found
a ratio of but 1 abortion to every 8 births. Although the statistics of Keyssner
were taken from the clinics, polyclinies, and gynecological journals, and those of
Malins from selected private and hospital cases, one is at a loss to explain the
great disparity between them and those in the present series.

In this series of 697 women with 1,351 children and 1,843 abortions, there were
1.3 abortions for every child or 1 abortion for every 1.7 pregnancies. This result
differs somewhat from that recorded by Taussig for the cases in the St. Louis
Gynecological Clinic, which was 1 abortion for every 2.3 pregnancies. The lack
of correspondence between the estimate made by Taussig and that in the present
series is not surprising, for the Carnegie series is fairly representative, being com-
posed to a considerable extent of material obtained from the general practitioner.
However, it is surprising to find that this ratio of children to abortions is lower in
these women than in the cases from a dispensary, unless we accept the opinion of
those who hold that abortion is more common among the economically more
favored classes.

The relative constancy in the ratio of abortions to children in families with
3 to 7 children seems to imply that whatever the factors responsible for the inter-
ruption of pregnancy, they act with unexpected regularity in women of widely
differing ages and with decidedly different reproductive histories. This would
seem to imply that in these women there is no tendency to limit the family to any
particular number of children through interference with the gestation, for were
such the case abortion should be more frequent in connection with the particular
number to which it is attempted to restrict the size of the family. This could fail
to be true only if we could assume that this supposed limitation in the size of the
family were due to causes other than interference with the gestation.

Only 29.1 per cent of the 607 women whose ages were given were less than 25
years old, but, as shown in table 17, 56.1 per cent were less than 30 and 77.4 per
cent less than 35 years. In the series of Stumpf this was true of 23.3, 51.7, and
71.8 per cent, respectively. Upon considering the relation of the different age

SOME ASPECTS OF ABORTION. 347

groups as shown in table 18, nothing unusual appears. The average number of
abortions per child is highest in the 15 to 19 year group, in which it is 4.8. In
the 20 to 24 year group it has dropped to 1.6, and then, as might be expected, a
gradual decrease, both in the number of children and of abortions, is noticeable in
each half-decade from 15 to 50 years, where it is 0.14.

The number of abortions per woman ranges from 1.1 in the 15 to 19 year
group to 2.7 in the 40 to 44 year group. There is a decided drop in this average
in the 45 to 49 year group, but since this group contains only 3 cases, it must be
disregarded. In the 15 to 19 and 20 to 24 year groups, the average number of
abortions per woman exceeds the average number of children, but after that the
reverse is true, these ratios being almost equal in the 25 to 29 and 30 to 34 year
groups. The greatest disproportion between abortions and children is reached in
the 40 to 44 year group, in which the ratio is 2.08 children for every abortion.

Taussig found 870 full-term births in 293 women, the average number of
children per woman being considerably higher, or 2.9, instead of 1.9 as in this series.
The average number of abortions in 201 women was 1.8, instead of 2.6 as in this
series. Hellier (1901) found that 1,800 selected married women had borne 6,974
children, or an average of 3.87 each, and in Franz’s series of 4,255 women, the
average number of children per woman was still higher, or 4.77, as compared with
1.9 of the present series of 697 women.

The series of 446 cases of Stumpf form a striking contrast to the present one,
for, although the actual number of cases of pregnancy in essentially the above age
groups ranges from 89 in the group over 40 to 365 in the 26 to 30 year group, the
ratio of abortions per pregnancy differed markedly, as an inspection of table 18
will show. Aside from the entire lack of correspondence between the two sets of
percentages shown there, especially as far as women below 20 are concerned, in
whom the difference is practically 1,600 per cent, Stumpf found two maxima of
abortions to births, instead of a gradual decline as in the Carnegie series. Stumpf’s
first maximum occurred between 26 and 30, and the second after 40. It also is
peculiar that although Stumpf’s ratios are 200 to 1,600 per cent below mine in
women below the age of 40 years, they are 200 per cent higher than mine after
this age. Since the discrepancies are so great, it is very likely that a number
of unknown factors are involved. Hence it is hardly worth while to try to reconcile
the remarkable difference.

The 21 admittedly unmarried women in this series had 25 abortions, or 1.2
abortions per woman, and 11 children, or 0.5 child each. Both of these figures are
below the average for the professedly married women, yet, as might be surmised,
the ratio of abortions to children is considerably higher in this group of the un-
married than in the case of all groups of the married except the 15 to 19 year group.
It is 2.2 abortions per child. Since the average number of abortions per child in
the 15 to 19 year group of professedly married women is more than twice as high
as in the small group of the unmarried, it would seem that there is something in
the marital relationship of women of these years, or in the attitude toward abortion

348 STUDIES ON PATHOLOGIC OVA.

on the part of the married, which is responsible for this difference. However, until
a far larger group can be obtained, such a surmise remains unsupported.

In contrasting the number of abortions per woman in 344 women giving birth
to conceptuses classed as normal with those suffered by 264 women who aborted
conceptuses classed as pathologic, we find (table 19) that the former had sustained
an average of 1.7 abortions and the latter only 1.79, or practically the same number.
However, upon referring to table 20, it will be seen that a slight tendency to earlier
abortion of pathologic conceptuses is indicated. Yet table 21 indicates that abor-
tion of a conceptus classed as pathologic strangely enough seems to have had no
discernible effect in reducing the number of children per woman. This is, of
course, contrary to what one should expect, and undoubtedly contrary also to the
facts. The 256 women giving birth to conceptuses classed as pathologic really
had more children on an average than the 337 who had aborted conceptuses classed
as normal, for women giving birth to conceptuses classed as pathologic had an
average of 2.3 children, but those aborting conceptuses classed as normal only 2.1
children. Hence, one would seem to be led to the startling and impossible con-
clusion that pathogenicity of the conceptus, whatever its cause, does not reduce,
but enhances, fertility!

It may be recalled in this connection that Hellier found that 96.5 per cent of the
1,800 married women who had abortions “‘almost up to the maximum”’ nevertheless
later bore one or more children. -But the explanation for the above anomalous and
self-contradictory result probably lies in the fact that many conceptuses classed
as pathologic very likely are merely macerated normal specimens, the form of which
was changed during long retention.

The women aborting conceptuses classed as pathologic aborted somewhat
earlier, for 86.7 per cent of them had done so before the beginning of the fifth
month of gestation, as compared with 76.5 per cent of those who aborted specimens
classed as normal. Since the groups in table 20 contain 402 normal and 290
pathologic cases, this difference in percentages of early abortions might seem to
imply that conceptuses classed as pathologie actually had developed under un-
favorable conditions, died, and were aborted sooner. ° Since, as previously stated,
most of these are young, while those classed as normal are relatively older, one
may assume that young conceptuses are retained relatively longer after death
than older ones. This conclusion is borne out also upon comparing the menstrual
with the estimated or anatomic ages of specimens grouped as normal and pathologic.
From such a comparison it is evident that the specimens classed as pathologic
were retained relatively longer after death than those classed as normal, and that
had they been aborted as soon after their death as were those classed as normal, a
still larger percentage of them would have been aborted before the fifth menstrual
month than actually was the case.

From table 22 we learn that 50 per cent of the women aborting conceptuses
classed as pathologic and 60.9 per cent of those aborting conceptuses classed as
normal were below 30 years. Hence the women aborting conceptuses classed as
pathologic would seem to have been somewhat older.

SOME ASPECTS OF ABORTION. 349

Upon contrasting the conditions in the small group of negro women, as revealed
in tables 18 to 22, with those in whites, one is not justified in drawing any definite
conclusion regarding the possibility of racial differences, because the group of negro
women is so small; but nevertheless it strikes one’s attention that self-induction
of abortion is unrecorded among them. Psychic and accidental mechanical
causes also are unrecorded. Therapeutic intervention occurred in only 1.3 per
cent of the colored women, but in 6.6 per cent of the white. As shown in table
18, families with single children seem to be rarer among these negro women, but
the average number of children was less, a fact in agreement with the statement in
our last national census to the effect that, with the exception of the cities of Balti-
more and Washington, the average family among negroes in cities of a population
of 10,000 and over is somewhat smaller than that among whites.

Abortions among the negro women also seemed to fall somewhat later in
gestation than among the white, only 65.4 per cent of them aborting before the
fifth month, as contrasted with 79.7 per cent of the white women. The negro
women, however, did not differ materially in age-grouping, as shown in table 22.

Could one take the figures deduced from the records of specimens classed as
pathologic at their face value, one would be justified in concluding that but a very
small percentage of the abortions here concerned were due to interference on the
part of the patient. It also must be remembered that a smaller proportion of
abortuses classed as pathologic than of those grouped as normal probably result
from interference by the patient. This follows from the inference that a normal
gestation may be presumed to continue uninterrupted in its development far more
frequently than a pathologic one, a conclusion reached also by Giacomini and
by Mall.

As shown in table 23, abortion was recorded as self-induced in approximately
34 per cent of 198 histories selected from the Carnegie Collection, in which other
causes than disease are mentioned. But these percentages do not truly represent
the situation, for such interference no doubt occurred in a far larger percentage of
cases, for the simple reason that physicians are disinclined to record and report,
and patients still more disinclined to state, such a fact. That the alleged causes
are not always the true ones is a matter of common knowledge.

The interference was alleged to have been medicinal in only two of these cases.
In the rest it was said to have been mechanical. This was true of 68 out of 90
cases in which the termination of the gestation was alleged to have been due to
medicinal, accidental, or psychic causes or to mechanical interference on the part
of the patient. This is a percentage of 70.8. Associated diseases were mentioned
in only 54 out of 252 cases, or in 21.4 per cent. The abortion was recorded as
having been spontaneous in 2 cases only, although no cause was recorded in 463
of the 697 cases. Therapeutic abortions formed 24.7 per cent of those in which
a cause was assigned.

A comparison of the part played by various alleged causes of abortion as
recorded in histories classed as normal and pathologic is given in table 24. What
particularly strikes one’s attention is the fact that tumors and displacements of

350 STUDIES ON PATHOLOGIC OVA.

the uterus are recorded more frequently as a cause of abortion among specimens
classed as normal and self-induction more frequently among the pathologic cases.
In a higher percentage of these the presence of associated diseases was mentioned,
however, and miscellaneous and psychic causes also were recorded. Interference
might be presumed to occur more frequently in cases involving pathologic condi-
tions, yet it is recorded more frequently in connection with conceptuses classed
as normal. It is not unlikely that the explanation given for the apparent increase
in fertility with the increase in frequency of abortion applies also to this contra-
dictory result. However, therapeutic intervention was somewhat more common
among the pathologic in a somewhat larger percentage of which no cause for the
termination of the gestation was assigned. The latter was the case in 76.6 per
cent of 264 pathologie and in 63.3 per cent of 344 normal cases out of a total of
608. Miscellaneous causes, such as exertion, purgative drugs, coitus, etc., were
assigned as frequently in the one as in the other class of cases, but the total number
in each group is so small that these percentages probably are not very reliable.

That the abortion was inevitable in many, even if not in the majority, of the
so-called spontaneous or habitual cases, is corroborated by the fact that most of
the abortuses in the pathologic division are young, by far the greater majority of
the older fetuses falling among the normal. Moreover, many of the larger con-
ceptuses also are received fresh, and in the case of those which were received as
the result of such complications of pregnancy as toxemia, pernicious vomiting,
placenta previa, febrile conditions, and other similar causes, these causes are
recorded.

There often is no way of accounting for the termination of the so-called
spontaneous cases from an examination of the conceptuses alone. However, it
was very interesting to frequently find that the chorionic vesicle and the decidua
had undergone pronounced changes in the case of abortions which were reported
as spontaneous. Many of these fell into the first four groups of Mall’s classifica-
tion and showed the presence of hydatiform degeneration, thus contradicting the
statement of Hegar (1904) that hydatiform moles almost invariably occur only
later in pregnancy, and confirming the statement of Solowij (1899), who claimed that
clinical experience teaches that hydatiform moles are aborted in toto only in the
first months of pregnancy.

Indeed, pathologie conditions of the chorion and decidua seem to be especially
frequent causes for the termination of pregnancy during the early months, although
one must recall that decidual and possibly chorionic changes may be the con-
sequence of previous interference alone. It may long remain impossible to deter-
mine the true or original cause of antenatal death, for the secondary or immediate
cause may completely mislead one. Hegar (1902) concluded that the cause of
abortion not infrequently lies in the decidua alone, and that the death of the
cyema usually can be shown to be due to degenerate changes in the villi. He
came to this conclusion because he found no evidence of pathologic changes in
the chorions of some abortuses. That endometritis and other uterine conditions
pre-existent to the implantation may be responsible, especially for early abortions,

SOME ASPECTS OF ABORTION. 351

one can not doubt, for the changes in the endometrium and decidua frequently
seem to be so profound.

Certain alleged minor causes to which recourse is had by patients recur so
frequently in the histories that this fact alone suggests that they probably are not
the true or ultimate causes. Among such causes, a slip or a slight fall on the stairs
and minor psychic disturbances may be cited. That psychic disturbances may
interrupt gestation seems quite likely, but they probably merely are the immediate,
not the ultimate, cause of the abortion. They could be regarded as the ultimate
cause only if the conceptus is aborted well preserved, for otherwise one would have
to assume that psychic causes can produce uterine contractions sufficiently severe
to cause the death of the conceptus, and that later, after the conceptus has become
macerated, recurring similar psychic disturbances finally effect the expulsion of
the macerated specimen.

Since infectious diseases no doubt very often are the immediate rather than
the ultimate cause of abortion, as Harris (1919) found in the case of influenza, it
undoubtedly may be assumed that many of the abortions caused by such and simi-
lar complications would have occurred later. They remind one of the defective
fruit which persists insecurely upon the tree until a sudden gust of wind showers
it to the ground. The findings of Harris regarding the effects of influenza and
pneumonia upon gestation, seem to be confirmed also by the small series of cases
of abortion among the present series in which the abortion was attributed to an
infectious disease. But in considering the alleged causes of abortion, one must
bear in mind that when a woman knows of a plausible exonerating reason for the
termination of the gestation she has every incentive to state it. That this is the
case is indicated by the various strange and, to the initiated, highly improbable
or even impossible reasons often assigned for the interruption of a pregnancy.

Associated constitutional or venereal diseases were recorded in only 76 out of
697 selected histories. In 463 of these 697 cases the cause of abortion was not
given. In 52 out of the 76 cases in which associated diseases were present, other
causes for the termination of pregnancy also were recorded. Hence the suggestion
that the associated diseases probably were merely the immediate or incidental
causes in these cases seems decidedly probable.

What strikes one’s attention in the perusal of some of the histories is the long
period during which many of these young conceptuses really were in process of
abortion, as indicated not only by the anatomic as contrasted with the menstrual
age, but also by the repeated hemorrhages. Since in most of these cases the
abortion probably was inevitable from the beginning, it would seem that the
conclusion of Giacomini, reached also by Mall, that one should not temporize
with such cases, but promptly relieve the patient of an abnormal, dead or dying
conceptus, would seem to be justified. That some general practitioners apparently
are beginning to realize this situation is instanced by Dr. Bacon, who, in connection
with a recent specimen donated to the collection, wrote: ‘This makes the second
or third case in which I have apparently delayed an abortion and, when the gesta-
tion finally was ended, was rewarded with an abnormal child for my pains. |

352 STUDIES ON PATHOLOGIC OVA.

wonder if it really pays humanity?” However, the practitioner no doubt meets
with great and often insuperable difficulties in determining the exact status of
affairs, and in the present state of our knowledge he must temporize so as not
to be led into unjustifiable procedures. There is no doubt, however, that con-
servative symptomatic treatment, no matter how unavoidable because of our
inability to determine the condition of the conceptus, often is directly opposed to
the best interests of the patient.

No case confirmatory of that reported by Jackson (1838) came to my attention
among those in the Carnegie Collection. It seems strange that one of a pair of
human twins can be aborted weeks or even months before term and the other
continue in uninterrupted development to the end of normal gestation. Moreover,
since the authenticity of Jackson’s case rests solely upon the statement of “‘a very
intelligent lady’’ who was “‘too intelligent to be deceived and too honest to deceive,”
one scarcely can feel convinced by it alone. However, Jackson stated that Nan-
crede had observed a similar case in which one fetus was aborted at 444 months
and the other went to term, and Fuertes (1879) reported such an instance as one
of superfetation. In this case a woman of 27 years gave birth to a male child on
March 13 and to a female on July 27. The former, which lived only 15 days,
was regarded as having been born in the seventh month of pregnancy, and the
latter at full term. Bonnar (1865) also reported a series of cases of this sort in
connection with a review of the question of superfetation. It is true that the
alleged denouement in dystocia and also in cases of interrupted labor seems to suggest
that even vigorous contractions of the uterus are not inconsistent with retention
of attachment by the placenta, but expulsion of one with retention of the other
fetus for some months afterward would seem to fall into a somewhat different
category.

In examining the histories one is impressed by the frequent cases of so-called
habitual abortion. These sometimes begin with the married life of a young woman
and continue more or less interruptedly throughout her child-bearing period.
This is illustrated by the cases in which a birth at term was followed by several
abortions, and by another birth at term and again by abortions. Regarding
some of these cases, it is clearly stated that the patients took steps to terminate the
unwelcome pregnancies, and in others the histories concerned mothers who had
given birth to 6 or more, even up to 13 children, and then suffered one or more
successive abortions, without a history of previous abortions. This is illustrated
by the following seven cases, for example, in which the women had borne 6, 8, 9,
10, 11, 12, and 13 children, respectively. The first woman had experienced 4
successive abortions, the following 5 one abortion each, and the last, 3 successive
abortions. In some of these cases it is fairly evident that weariness with such
heavy burdens of child-bearing probably was responsible for the termination of
pregnancy, while in others abortion may have resulted from exhaustion due to
a large series of quickly succeeding gestations, and in still others to pathologic
or other causes. Experience with higher domestic animals, too, would seem to

SOME ASPECTS OF ABORTION. 353

suggest that abortion not infrequently follows too closely repeated pregnancies,
especially under the stress of advancing years.

If the condition of the uterine mucosa at the time of implantation of the
impregnated ovum may show variations in structure at all comparable to those
seen in decidue accompanying abortuses, then it is easily conceivable that the
fate of the conceptus may be determined by the structure of the implantation
site. Not infrequently a small area of the decidua about an abortus shows all
the transitions shown in figures 75, 76, 77 (plate 6, Chap. IV), and 135 (plate 13,
Chap. IX). The first figure shows the fine, clear, large, polygonal decidual cells,
practically wholly infiltrated, and hence presents a rather homogeneous appearance.
Figure 76 shows considerable infiltration and autolysis, and also marked change
from the usual polygonal cell found present in the post-menstruum by Hitschmann
and Adler (1908) to a fibroblast form. In figure 78 (plate 6, Chap. IV) the normal
decidual cells have become still more elongated, and in figure 135 the decidua is
represented by a decidedly fibrous mass totally different from what it once was.
I do not know how far these changes of fibrosis of the decidua may have progressed
before implantation occurred, but if the changes in the mucosa are at all pro-
nounced, one scarcely can believe that they can fail to profoundly affect the nutri-
tion and growth of the conceptus.

It may be urged that fibrosis of the decidua is but an effect of the death and
retention of the conceptus rather than an indication of the pathologic conditions
pre-existent in the mucosa. However, the many instances of abortuses in which
the decidua is very degenerate and also infiltrated would seem to argue against
such an assumption. Besides, many of the decidue found surrounding retained
specimens do not show comparable changes. Moreover, Orloff (1896), Iwanoff
(1898), and L. Fraenkel (1903, 1910°) found that restoration of the mucosa may
begin before the conceptus is expelled from the uterus. This fact also seems to
suggest that fibrosis probably is pathologic in significance. Moreover, in the
few cases of partial regeneration of the mucosa which came to my attention, the
decidua was not in the fibrous state shown in figure 135. Infiltration of the
decidua no doubt more frequently might arise after death of the conceptus, but
that it frequently is present long before this time would seem to be indicated
also by the fact that the presence of fibrosis does not seem to bear any definite
relation to the duration of the retention, and that the condition of the mucosa
before implantation can markedly influence the course of gestation is indicated also
by the findings of Punto (1906) in cases of pregnancy complicated by myomata.

354 STUDIES ON PATHOLOGIC OVA.

TABLE 13.—Total number of cases (608), grouped according to the number of previous abortions.

Number of abortions.

Normal white
Pathologic white
Normal colored
Pathologic colored

Normal white.,. 25: a2 < ¢.24.200.<%i50 4

Pathologic white................ 7 57 112 45 17 13
Normal colored............-.--- 1 4 8 8 9 3
Pathologic colored............... 1 4 8 2 1 4

Author.

Average
No. of cases 2,536 | 2,982

No.of Average No. of : ’ Average No. of
abortions per

abortions.

aa Oi

SOME ASPECTS OF ABORTION. 355

TaBLE 17.—Total number of cases (607), grouped according to the age of the mother.

Age of mother (years).

| Total
15 to 19 | 20 to 24 | 25 to 29 | 30 to 34 | 35 to 39 | 40 to 44 | 45 to 49
MN ONIMAL WIG sats, Aareleie oe oie temo bas sass 21 80 91 60 44 1 ae Beecae 314
A UOLORIG WILG ev ere ii srecicrcinto Nasaye cre 0 9 49 63 56 37 28 2 244
INormaAlicolored :(o.- <:16 3. x0 odincncecseses 4 4 9 if 4 Ai Abeer 29
PACH OORICICOLOLEds cai aoe creas ; 2 8 1 6 1 1 1 20
UND) ORS Oa een brit OC EOE oer 36 141 164 129 86 48 3
TaBLE 18.—Ratio of abortions to children in the various age-groups. Total number of cases, 576.
Average Average Ratio of average Stumpf (446 cases).
A 7 No. of No. of No. of No. of No. of abortions
ge group. cases. abortions cases. children to average No.
per woman. per woman. of children. Age. Average No.

Total....

TaBLE 20.—Total number of cases (692), grouped according to time of abortion by months, race, and
nature of the conceptus.

Month of gestation.

356 STUDIES ON PATHOLOGIC OVA.

TaBLE 21.—Abortions grouped according to the number of children, race, and the nature of the conceptus.
(Total number of cases, 593.)

No. of children.

TaBLE 22.—Abortions grouped according to the age of the mother, race, and the nature of the conceptus.
(Total number of cases, 607.)

Age of mother (years).

15-19 20-24

TABLE 23.—Total number of cases (697), grouped according to the causes of abortion.

Cause of abortion.

T
Un- Spon- Self- Ther- Accid. Psy- Assoc. aaa Miscel-

recorded.|taneous.|induced.| apeutic.| Mech. chic. | disease. position. laneous.

Pathologic white
Normal colored

TABLE 24.—Causes of abortion (252 cases).

Alleged causes of abortion. Pathologic (88 cases). Normal (164 cases).

p. et.
22.7
14.7
13.4
15.8

19.5

Accid. mech. . )

The cause was unrecorded in 76.6 per cent of 264 pathologic and in 63.3 per cent of 344 normal cases out of a total of 608.

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