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Reprinted from
Cancer Research, Volume 8, Number 12, December, 1948.

PRIITIAA THA ,2KATAT! .2HHeTY WO.

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Reprinted from
Cancer Researcu, Votume 8, Nuweer 12, Decesner, 1948

Tumors of Fishes, Amphibians, and Reptiles*
H. G. Schlumberger** and Balduin Lucké
(From the Laboratory of Pathology, School of Medicine, University of Pennsylvania, Philadelphia 4, Pennsylvania)

_ ‘The study of tumors occurring spontaneously in
animals and the experimental study of neoplasia are
Se . Such studies in the past have dealt
large , with tumors in the higher vertebrates, mam-
mal: ls and birds; much less attention has been paid to
‘tile But neoplastic processes are ubiquitous among
vertebrates, and comparison has shown that tumors
in cold-blooded animals are essentially identical in
regard to their structure and behavior with the cor-
_ responding tumors of warm-blooded animals. Since
no comprehensive account of spontaneous tumors of
the former group exists, it was thought advisable to
_assemble the available literature as a guide to source
material and as an aid to future investigations. This
has been done in the present paper. In a comple-
mentary paper are reviewed the lines of experimental
investigation which have been pursued (123a).

I. TUMORS OF FISHES

" Fishest are the most numerous class of vertebrates
(73). Because of their economic importance, many
species are caught in vast quantities. During the
marketing and preparation of the catch for food, any
existing tumors are apt to be noticed. For these
reasons information about the neoplastic diseases of
fishes is more adequate than for amphibians and
All the major varieties of tumors that occur

in mammals, including man, and in birds have been
recorded in fishes. These tumors will now be taken
up in the following order: Tumors of epithelial tis-
sue, tumors of mesenchymal tissues, pigment cell
tumors, tumors of nervous tissues and hamartomas.

TUMORS OF EPITHELIAL TISSUES

In this group are included: papilloma, adenoma,
tumors of dental origin, epithelioma, adenocarcino-
ma, “tumors” of the thyroid.

x PAPILLOMA
_ The most common benign epithelial tumors of

Sen
* This study was aided by a grant from the Donner Foun-
dation. A grant from the National Institutes of Health to
ented to Me cont of ene
** Now at Ohio State University, Columbus, Ohio.
+n this review nomenclature for species follows current
usage; where necessary the older names used in the reports

not

657

fish hitherto recorded are which have
been reported in at least 16 different species (Table
1). The tissue of origin in all is surface epiderm;t
papillomas of the viscera have not as yet been ob-
served. The tumors vary in appearance; some are
finely lobulated, rather flat elevations; others, small
round warty growths, and still others, large cauli-
flower-like masses. They are usually solitary, but
multiple tumors are not rare. Histologically the
tumors have typical papillomatous arrangements
and show no tendency to invade the subjacent
tissues.

Of particular interest are the more common tu-
mors, some of which are perhaps transmissible.
Among them are the small, multiple, wart-like papil-
lomas described by Fiebiger (47). They developed
in a group of climbing perch (Anabes scandens)
which had been kept in the same aquarium for two
years. The tumors were scattered over various parts
of the body and ranged in size from that of a poppy-

658 *

Cancer Research

Taste 1:* Parrttoma

Species Site Author
Gudgeon Gobio (several species) (4) Skin Schroeders, 1908
Barbel Barbus Auviatialis (several) Lips Keysselitz, 1908
Climbing Perch Anabas scandens (several) Body surface Fiebiger, 1909a
Halibut Hippoglossus hippoglossus Snout Johnstone, 1912
Stint Osmerus eperlanus (37) Lips, buccal cavity, fins Breslauer, 1916
Gudgeon Gobio nigronatatus (2) Skin Anitschkov & Pavlovsky, 1923
Gudgeon Gobio blenniodes Skin Anitschkov & Pavlovsky, 1923
Plaice Pleuronectes platessa Body surface Johnstone, 1925
Plaice Limanda limanda (3) Body surface Johnstone, 1925
Goldfish Carassius auratus (2) Fins Sagawa, 1925
Crucian Carp Carassius carassius Skin of operculum Takahashi, 1929
Sole Solea solea (2) Skin of trunk Thomas, 1930
Eel Anguilla anguilla (3) Lower lip Thomas & Oxner, 1930
Brown trout Salmo irutia Skin of back Thomas, 1932e
Electric eel Electrophorus electricus Skin Coates, Cox & Smith, 1938
Slippery Dick Iridio bivittata (30) Skin Lucké, 1938
Sucker Calostomus commersonnii Skin near tail Lucké & Schlumberger

(not published)

* In this and the succeeding tables, the number of tumor-bearing animals, when in excess of one, follows the name of the species.

inclusions which were surrounded by an achromatic
halo, and could be readily distinguished from nu-
cleoli. In what appeared to be their earlier stages
they were dense and compact; later they became
fluffy and less distinct. The author compared them
with the inclusions of vaccinia and other virus di-
seases.

In 37 specimens of the stint Osmerus eperlanus
Breslauer (16) found tumors that likewise occurred
mainly on the lips, less commonly on the mucosa of
the oral cavity or on the fins. The fish were taken
from the brackish water of an inlet of the Baltic sea.
Upper and lower lips were affected equally; fre-
quently the tumors were in apposition. Some were
cauliflower-like growths, others were flat, varying
in size from small nodules to masses as large as the
head of the affected fish. Histologically all had a
papillomatous structure. Usually they showed no
tendency to invade, but occasionally the arrange-
ment of the cells suggested early malignancy. Cyto-
plasmic inclusions were sometimes, but not regular-
ly, encountered.

It may be pertinent here to discuss the tumors re-
ported by Schroeders (179) and by Anitschkov and
Pavlovsky (3) in several species of gudgeon Gobio,
a small marine fish. The descriptions of the latter
authors particularly exemplify the difficulty of classi-
fying certain skin tumors of fishes; 3 tumors which
they regarded as distinct types may represent merely
different stages of the same neoplastic process. In
their first case there were numerous small nodules
and flattened elevations, the larger and more fully
developed ones distinctly papillomatous, with their
bases and the subjacent corium the site of a pro-
nounced inflammatory reaction; the authors likened
these growths to the chronic inflammatory papillary

-

hyperplasia of the skin and mucous membranes in
man. In the second case a large rather flat solitary
growth was found on the dorsum of the fish, Gobio
nigronatatus. Histologically this had the character
of a benign papilloma and was not associated with
an inflammatory process. In the third case a rela-
tively massive, broadly sessile, cauliflower-like tu-
mor, 2 x 1 x 1 cm., occupied the dorsum of a small
Gobio blenniodes. It differed from the growth of the

second case in the markedly irregular hyperplasia
of its epithelial covering and in the delicacy of the

supporting connective tissue trabeculae. The tumor _

did not infiltrate the subjacent tissues, and although
the authors regarded it as a papillary carcinoma, the
evidence for malignancy is inconclusive. The tumors
reported by Schroeders (179) are in the same genus
of fish, Gobio, and have the character of benign
papillomas. In the absence of information regarding
the further development and fate of these tumors, it
is impossible to be certain of their true nature.
Mention must here be made of a non-neoplastic
disease of fish, which has sometimes been confused
with true tumor, the so-called pox-disease. It is par-
ticularly common in carp and may attain epidemic
proportions. The disease has no relation to the
various kinds of pox of man. Numerous milk-white,
flattened elevations are present on the epidermis of
the affected fish; so that it appears as if splashed
with melted paraffin which has solidified. All parts
of the body, including eyes and fins, may be af-
fected. Microscopically the lesions present a simple
hyperplasia of the epiderm; the corium usually re-
mains unchanged and sends no papillae into the
epithelial mass; however, a papillary structure is
occasionally attained by the larger and more per-
sistent growths. On histologic grounds no sharp dis-

Schlumberger and Lucké—Tumors in Fishes

659

tinction can be drawn between these lesions and true
neoplasms, but clinically the lesions of pox, unlike
true tumors, usually regress and disappear entirely.
A detailed and well illustrated account of this di-
sease is given by Plehn (162).

To the cases of papilloma reported in the litera-
ture we are able to add new examples from two other
species, The first concerns 2 large tumors which

affected a common sucker Catostomus commersonnii

caught in a Wisconsin Lake. The fish was 8 years
old (as determined from examination of its scales),
its total length was 31 cm., the sex was uncertain.
The tumors were located on the right side; the larger
measured 6.1 x 5.5 x 4.0 cm. and involved almost
the entire lower half of the tail fin, the smaller tu-
mor, which measured 20 mm. in diameter, was lo-
cated on the tail, immediately in front of the caudal
fin (Fig. 1). Both neoplasms were firm, hemispheri-
cal masses which had the typical lobulated appear-

ance of papilloma (Fig. 2). Histologically, a delicate

arborescent stroma supported great masses of epithe-
lial cells (Fig. 3). Tall columnar cells formed the
layers adjacent to the connective tissue stroma;
toward the center of the epithelial masses the cells
become polyhedral and in places suggest “pearl”
formation (Fig. 4). The nuclei were conspicuous,
and usually contained one or two prominent nucleoli.
_ Among some of the epithelial masses were groups of
large clavate cells (see footnote ¢); mucous cells
were not found. The tumors were sharply circum-
scribed, and nowhere extended into the subjacent
tissue; there was no inflammatory reaction.
Another kind of papillomatous growth occurred in
a small fish, the slippery dick Jridio bivittata, which
inhabits tropical and semitropical waters (116).
Thirty tumor-bearing specimens were found among
approximately 6,000 of these fish examined at the
Dry Tortugas, Florida. The tumors had the appear-
ance of flattened nodular elevations of the skin; they
were grayish in color and soft in consistency, and
often they attained large size (Fig. 5), were most
usual on the lateral surfaces and commonly de-
stroyed the fins. Histologically, delicate fibrous pro-
jections of the corium were covered with many layers
of epithelial cells (Fig. 6). The growths frequently
extended into the corium, but infiltration of the
deeper tissues was not observed. The cells of most
tumors were much larger than the cells of the normal
epiderm; the cytoplasm was faintly granular; the
nuclei large and round or oval (Fig. 7). The nature
of this neoplastic disease is uncertain; whether these
growths are true or merely exaggerated

neoplasms
non-neoplastic epidermal proliferations is yet to be
determined. In some respects they seem to be related

to the tumors of gudgeons discussed above. Since
fish affected with these tumors can readily be kept
in indoor sea water aquaria, they should prove ex-
cellent material for experimental investigation.

Abstracts of other reported cases of papilloma

Scuroepers, 1908: In several species of gudgeon
Gobio the author observed “fibro-epitheliomata.” In
some fish the tumors were solitary, in others multiple.
In all instances they were sharply circumscribed, papil-
lomatous, and yellow-white in color.

Jounstone, 1912: An irregular cauliflower-like
growth was observed on the snout of a halibut Hi,
glossus hippoglossus, weighing 120 pounds.
there was marked proliferation of the corium,
lying epithelium was intact with little evidence

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Jounstone, 1925: About 1 dozen whitish
averaging 5 mm. in diameter, were scattered
unpigmented side of a plaice Pleuronectes
growths were found to be impregnated with

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found on three plaice, Limanda limanda caught in
North Sea. One fish had a single tumor, 5 cm. in

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Cancer Research

mors were due to chronic irritation of the postopercular
skin by sand particles drawn into the mouth and ex-
pelled through the gill vent in the act of breathing.

Tuomas and Oxner, 1930: A tumor was located
on the lower lip in each of 3 eels Anguilla anguille.
The lesions showed simple epithelial proliferation with
a tendency to reduplication of the basal cell layer;
the basement membrane was preserved.

Tuomas, 1932: A 32 cm. brown trout Salmo trutta
bore an irregular tumor at the level of the posterior
margin of the operculum. It measured 22 x 11 x 5 mm.,
was not sharply demarcated, and in both gross and
microscopic structure was a typical papilloma.

Coates, Cox and Smirn, 1938: A tumor appeared
in the right mid-dorsal region of a six foot adult
electric eel Electrophorus electricus caught in the Ama-
zon river basin and maintained in good health in a
fresh water tank at the N. Y. Aquarium for a period
of more than four years. The growth began as a small
elevation of the skin, pinkish-gray in color and a few
millimeters in diameter. Its maximum size of 2 x 2.5
cm, was reached in about ten weeks, when it was ex-
cised. No recurrence took place in the remaining year
and a half of life. The growth was a grape-like pedun-
culated mass composed of squamous epithelium com-
mingled with very many mucous cells. The epithelium
was supported by a central narrow fibrous core of
connective tissue.

ADENOMA

Adenomas have been reported in 11 species of
fish (Table 2). In 3 species the neoplasms involved
structures which have no exact counterpart in man,
namely, the parabranchial bodies. These are two
small, often quite rudimentary organs, which lie in
front of the true gills, and, like them, are hidden
from view by the opercula or gill covers. They are
composed of an extremely vascular tissue; the nu-
merous capillaries are surrounded by large cells
with clear or coarsely granular acidophilic cyto-
plasm. The function of the parabranchials is un-
known; some investigators consider them to be en-
docrine organs.

Tumors of these structures have been observed in
codfish Gadus morhua from St. Pierre and Miquelon,

and in 2 kinds of coalfish from the Pacific. In the
coalfish Pollachius brandti and Theragra chalco-
gramma in which the normal parabranchials vary in
weight from 0.1 to 0.4 gm., tumors of 9 and of 16
gm., respectively, have been described (199). The
tumor cells formed alveolar masses supported by a
scanty but richly vascular stroma. The cells re-
sembled those of the normal parabranchial bodies,
having a clear cytoplasm when they were adjacent —
to the blood vessels, but with a granular cytoplasm
when more centrally located. The nuclei were large
and vesicular; mitoses were common. Necrosis of
the densely packed cells in the central part of the
alveolar mass led to the formation of pseudoacini.
Usually the tumors were not well delimited and infil-
trated the neighboring tissues. The investigators
who studied these growths at first hand fail to agree
as to their character. Takahashi (199) considered
them to be adenocarcinomas; Peyron and Thomas
(150) believed that they were benign or, at ete of
low-grade malignancy.

Besides these tumors, adenomas have bik re-
ported in various organs of 8 other species of fishes.
The tissue of origin was the liver in 3 species, and the
kidney, intestine, and ovary in the others. Most of
these tumors were solitary; some attained a very
large size, the tumor reported by Plehn in the liver
of a trout was twice the size of a man’s fist.

Biesele (13) studied the chromosomes in an ova-
rian tumor of a goldfish. Unfortunately no histologic
data are given and the author speaks of the growth as
an “adenoma or adenocarcinoma.” The average vol-
ume of the neoplastic chromosomes was twice that of
chromosomes in the cells of a healing skin wound
and in the nongerminal cells of a normal ovary. The
normal nuclei never possessed more than 4 nucleoli,
whereas 8 were found in the tumor cell nuclei.
Biesele concluded that the chromosomes of the gold-
fish tumor must be regarded as diplochromosomes.

An adenoma of the catfish Ameiurus nebulosus,
which has not previously been described, occurred
in the right kidney of a female whose total length

Taste 2: ADENOMA

Species
Sand shark Prionace glaucus

Site Author

Liver Schroeders, 1908
Trout Salmo irutia Liver Plehn, 1909
Ling Molva molva Ovary Johnstone, 1915
Codfish Gadus morhua (2) Parabranchial body Peyron & Thomas, 1929
Coal Fish Pollachius brandti (2) Parabranchial body Takahashi, 1929
Coal Fish Theragra chalcogramma Parabranchial body Takahashi, 1929
Purple Trout Salmo mykiss Intestine Thomas, 1931la
Rainbow Trout Salmo gairdnerii Liver Haddow & Blake, 1933
Platyfish Platypoecilus maculatus (several) Kidney Jahnel, 1939
Goldfish Carassius auratus Ovary Biesele, 1943
Catfish A meiurus nebulosus Kidney Lucké & Schlumberger

(not published)

Pts ;

MII the liver of a shack Prienace glences couche i
__ the Black Sea. The surface of the liver was covered
__ with whitish, spherical nodules ranging in size from a
__ pin-head to a walnut. Similar nodules were found

; ‘Schlumberger and Lucké—Tumors in Fishes

661

was 35 cm. The growth measured 8 x 8 x 6 mm., was
pale gray, and sharply delimited, though not encap-
sulated; its cut surfaces were moist but not bloody.
It was composed of acini that were irregular in size
and shape, and often greatly dilated. The lining
epithelial cells varied from low cuboidal to tall col-
_ umnar elements; their nuclei were large, vesicular,

and had prominent nucleoli; mitotic figures were un-

_ common. Papillary projections extended into some
of the cystic spaces; the scanty stroma was poorly
____ vascularized. This tumor was found in a fish which
ae also had massive epitheliomas of the lip and mouth.

ae _ Abstracts of other reported cases of adenoma
1908: Multiple adenomas were

_ Clear, glairy fluid was found in the cysts. Some areas
__ of fibrosis were also present in this lesion which may be

classified as a papillary cystadenoma of the ovary.
‘PLenn, 1924: The liver of a lake trout Salmo trutta

: was the site of a mass of cysts filled with clear fluid or

gelatinous material. The largest of the cysts measured
15 cm. in diameter; the entire tumor was twice as
large as a man’s fist. Between the cysts were remnants
__ of normal liver, strands of connective tissue, and iso-
lated bile ducts. The growth was regarded by Plehn a:
a cystadenoma of the liver.

Peyron and Tuomas, 1929: The authors observed
tumors of the parabranchial bodies in two codfish
Gadus morhua. In one, a large tumor, 4 x 3 x 1.5
cm., occurred on the right side, elevated the operculum,
and protruded beyond its posterior margin; the gills

- were compressed. In the other case the tumors were

bilateral and the size of a cherry. The histologic ap-
pearance has been discussed above.

TAKAHASHI, 1929: In two specimens of coalfish
Pollachius brandti each parabranchial body was the seat
of a tumor. In both, the growths on the right were the
size of a small heh’s egg, those on the left were twice
as large. In another variety of coalfish Theragra chal-

cogramma a large tumor was present in the left para-
branchial body. This tumor was soft in consistency,
poorly circumscribed, and contained many cystic and
necrotic areas. The surface was ulcerated. The his-
tologic structure was as already described.

THomas, 1931 a: In a purple trout Salmo mykiss,
a in total length, the author found a broadly ses-

sile, hemispheric tumor in the intestine midway between
stomach and anus. It measured 20 x 18 x 8 mm., was
gray-white and moderately firm; there was no ulcera-
tion of the surface. Histologically, the entire thickness
of the intestinal wall was infiltrated by the cystic neo-
plasm. The lining epithelium of the cysts was strati-
fied, the cells basophilic with occasional abnormal mi-
toses. Blood vessels were not numerous; collections of
lymphocytes were abundant.

Happow and Bake, 1933: The authors described
a hepatoma found near the anterior margin of the liver
of a 4 to 5 year old rainbow trout Salmo gairdnerii.
It was spherical, about 1.5 cm. in diameter, and paler
and more firm than the surrounding hepatic tissue. No
metastases were present. Microscopically the tumor
was composed of actively proliferating polyhedral cells,
only slightly different from the parent liver cells. The
arrangement of the cells resembled that of normal liver,
except for the presence in the tumor of an abundant
fibrous stroma. Although the adenoma was not en-
capsulated, it had not infiltrated adjacent structures.

JAHNEL, 1939: This author notes the frequent oc-
currence of cystic adenomas of the kidney in the tropical
aquarium fish Platypoecilus maculatus. No further de-
tails are given.

DENTAL TUMORS

Teeth are cutaneous appendages; in mammals
they may be regarded as modified papillae of the oral
mucosa. In elasmobranch fishes, such as sharks and
rays, the small placoid scales, which give the rough
granular feel to the skin of these animals, represent
phylogenetically the most primitive teeth of verte-
brates. Each scale has a pointed tooth-like shape;
its base is embedded in the dermis, its apex pro-
trudes above the surface. A central vascular con-
nective tissue pulp is surrounded by a layer of odon-
toblasts which form the hard dentin. The free sur-
face is coated by enamel, a product of modified
epithelial cells.

In Table 3 is given a summary of dental tumors
which have been observed in 4 species of fishes.

A neoplasm of “cutaneous teeth” was reported as
a “dermal odontoma” by Ladreyt (108). The tumor,

Taste 3: Dewrat Temors

: Species Site Author
Trout—species not given (2) Dental plates & hyoid bone Plehn, 1912
Croaker Micropogon opercularis Upper dental plate Roffo, 1925
Haddock Melanogrammus aeglifinus Maxilla Thomas, 1926
Cat shark Scyllium catulus Skin Ladreyt, 1929

662 ’

Cancer Research

a cylindrical mass, measuring 3 x 1.2 cm., arose in
the skin near the copulatory appendages of a cat
shark Scyllium catulus. It was very firm, and had a
small, very vascular cavity at its distal end. Histo-
logically, a thick layer of cutaneous epithelium cov-
ered a more or less homogeneous mass, which the
author believed represented enamelvor dentin. The
cavity noted grossly was occupied by greatly dilated
blood spaces that appeared angiomatous.

Corresponding more closely to odontomas of man
are the lesions described by Plehn (160) in the jaws
of two fresh-water trout. In both cases the tumors
consisted of large congeries of atypically formed
teeth. Innumerable, more or less confluent, nodular
tumors, had developed from all the tooth-bearing
surfaces, viz., both dental plates, the hyoid bones
and, in one case, the vomer. As the author showed
in a photograph, the tumors had attained such a
large size that the fishes could not close their mouths,
thus making feeding impossible.

Another example of an odontoma was reported by
Roffo (172) in a marine fish, the croaker Micropo-
gon opercularis. The tumor formed a firm, pale mass
on the upper dental plate. Histologically it con-
sisted of tooth germs irregularly scattered through a
connective tissue stroma. The paper is accompanied
by a number of excellent figures which show gross
appearance, roentgenograms, and histologic struc-
ture of the neoplasm.

Only one case of adamantinoma has been recorded,
by Thomas (202). The tumor formed a mass, 2.5
x 1 cm., that had infiltrated the maxilla and pro-
truded into the oral cavity of a haddock Melano-
grammus aeglifinus. Histologically it corresponded
in all details to the cystic adamantinomas of man.

EPITHELIOMA (EPIDERMOID CARCINOMA)

Some of the neoplasms reported in the literature
as epithelioma are only questionably malignant. In
this review we have placed certain tumors which

were reported as epitheliomas under the heading of
papilloma because of their structure and absence of
invasion. There remain a considerable number of
tumors of pavement epithelium that are invasive or
exhibit other evidence of malignancy, which prop-
erly may be regarded as epidermoid carcinomas.
They have been observed in 12 different species of
fishes (Table 4). The tissues of origin were the skin,
the lips or oral mucosa, and, in a single case, the
urinary bladder. In general, these tumors had the
structure of mammalian epidermoid carcinomas; in
some cases, as in that of Bashford, Murray and
Cramer (6) the resemblance to squamous cell car-
cinomas in mammals was reported as striking. It
must be remembered, however, that the epithelial
covering of fishes does not keratinize, hence the
typical cornified “pearls” of mammalian epitheli-
omas are not formed, although nonkeratinized col-
lections of concentrically arranged cells are frequent-
ly seen.

Several of the tumors under discussion resembled
papillomas, in their general appearance, but differed
in that they sent long, usually ill-defined pegs of
solidly packed cells into the corium or deeper tissues.
Thus, in the case reported by Murray (141) the
tumor invaded the underlying skeletal muscle. None
had metastasized at the time of examination.

The lips and oral mucosa are the most common
sites of epitheliomas in fishes; neoplasms have been
observed in these locations in 7 species. The first
record of an epithelioma in a fish reported by Mc-
Farland (136), deals with such a tumor. A lobu-
lated, papillary growth, 4 cm. in diameter, involved
the lower lip and adjacent mucosa of a catfish
Ictalurus catus; multiple small nodules were present
on the upper lip and the neighboring skin. Histo-
logically the neoplasm consisted of a fungoid mass
which was composed of epithelial cells supported by
a delicate vascular stroma. The larger tumor was
definitely invasive. The tumor reported by Clunet

Taste 4; Errrmetioma (Ertpermorm Carctwoma)

Species Site Author
Catfish Ictalurus catus Both lips McFarland, 1901
Carp Cyprinus carpio (2) Skin of head Dauwe & Pennemann, 1904
Carp Cyprinus carpio Not given Bashford, Murray & Cramer, 1905
Stickleback Spinachia s pinachia Skin of trunk Murray, 1908
Tench, Tinca tinca (2) Lips Fiebiger, 1909a
Carp Cyprinus carpio Fins & operculum Fiebiger, 1909a
Goldfish Carassius auratus Bladder Plehn, 1909
Barbel Barbus vulgaris Lower lip Clunet, 1910°
“LeNez” Chondrostoma soctia Oral mucosa Mazzarelli, 1910
Croaker Pogonias chromis (2) Lips Beatti, 1916
Whiting Merlangus merlangus Mandible Johnstone, 1924
Codfish Pollachius virens Lower lip Williams, 1929
Biajaca Cichlasoma tetracanthus Skin about orbit Puente-Duany, 1930
Catfish Ameiurus nebulosus (166) Lips, oral mucosa Lucké & Schlumberger, 1941

Schlumberger and Lucké—Tumors in Fishes

663

(31) was located on the lower lip of a barbel Barbus
vulgaris. It was the size of a hazel-nut and had in-
filtrated the floor of the mouth; structures sugges-
tive of epithelial pearls were present and mitoses
were numerous.

Fiebiger’s report (47) of epitheliomas on the lips
of two tench Tinca tinca is of interest in that the
tumors occurred in fish from the same pond. The
evidence of malignancy is not certain, for the author
states that a fairly well preserved basement mem-
brane surrounded the extensive epithelial pegs. In
one of Beatti’s (7) two cases of epithelioma in
_croakers, the basement membrane was intact in most
regions, though in some areas epithelial pegs pene-
trated deeply. In the other this was more marked,
and invasion of subcutaneous tissue had taken place.

We ourselves have been studying a transplantable

_ epithelioma of the lip and mouth of catfish Amei-

_ urus nebulosus taken from streams near Philadel-
phia (122). During a period of 2 years, 166 live
tumor-bearing fish were obtained.* Since our pre-
vious publication approximately 100 additional cases
have been studied. This neoplasm usually occurs as
a solitary or multiple, large, red, fleshy mass upon
the lips or dental plates (Figs. 8-11); less often it
involves other parts of the mouth or the skin. In
_ our series the lips and dental plates were affected in
all but 6 cases. All of the neoplasms are grossly
similar. They are broadly sessile, with a smooth or
coarsely nodular surface; in consistency they are
firm and resilient. Most of the tumors average from
1 to 2 cm. in diameter, but some are so massive as
to prevent closure of the mouth (Fig. 10). In ap-
_ proximately one-half of the cases, both lips or dental
plates are involved. In 53, or 60 per cent, of 89 fish
the tumors were in direct apposition (Figs. 9 and
11). Histologically the tumors consist of closely
packed masses of columnar or polyhedral cells, often
growing as papillary pegs supported by a delicate
richly vascular stroma (Fig. 12). The smaller tu-
mors grow outward, with little sign of invasion.
Larger growths commonly push broad solid pegs of
epithelial cells deep into the subjacent tissues; in
some, these pegs are bounded by a well preserved
basement membrane, but in the more massive tu-
mors they are definitely invasive, and flame-shaped
_ *Many of the tumor-bearing fish and several hundred
normal fish which were used for experimental purposes have
been furnished us through the kindness of Mr. C. R. Buller,
Chief Fish Culturist of the State Fish Hatchery, at Belle-
font, Pennsylvania, John J. Wopart, Jr., Superintendent of
the State Fish Hatchery at Torresdale, Pennsylvania, and
the late Dr. Robert O. Van Deusen, Director of the Phila-
delphia Aquarium. We wish to express our grateful apprecia-
tion to these gentlemen for the aid and advice given.

processes of loosely arranged cells extend far into
the subjacent tissues (Fig. 13). In the more in-
vasive tumors emboli of neoplastic cells are often
found, though no metastases have been observed.
It seems evident that the small, outward growing
tumors are early stages of a neoplastic process which
later assumes a more malignant character.

It has been possible to study living tumors almost
from the time of their inception. Tumor-bearing
fish were maintained under laboratory conditions
for periods up to 9 months; during this time we
observed that growth of most of the neoplasms was
relatively slow but progressive. The inception and

development of appositional growth was studied by

direct microscopic examination of the mucosal sur-
faces. The earliest evidence of neoplastic change
was the establishment of a more or less circum-
scribed patch of hyperemia on the mucosa. At this
time the mucosal surface was smooth and showed no
signs of proliferation; after approximately two weeks
the patch became slightly elevated; one or two
months later the local thickening had progressed to
the formation of a definite tumor.

Detailed microscopic study of the blood vessels
in vivo brought out the fact that they undergo pro-
found alterations during the development of the
tumor. At the site of future neoplastic growth they
gradually form irregular, wide meshed networks
that contrast sharply with the small, uniform capil-
lary loops of the adjacent normal mucosa. The
caliber of the blood channels in the neoplastic zone
varies greatly; some are dilated and bear saccular
expansions; others are constricted (Figs. 14 and 15).
Many of the proliferating vessels have thick walls,
whereas others are thin and delicate. In brief, the
neoplastic growth is preceded and accompanied by
a striking vascular reaction; the number, arrange-
ment, and structure of the vessels are conspicuously
atypical. The relation of blood-vessels to tumor
growth has previously been investigated mainly in
fixed tissue; the catfish epithelioma provides ma-
terial for such an investigation in the living animal.

Abstracts of other reported cases of epithelioma

Dauwe and PENNEMANN, 1904: Each of two
very large, old aquarium carp Cyprinus carpio developed
a tumor on the dorsum of the head, in front of the eyes
Microscopically the lesions were identical and consisted
of squamous epithelial cells that formed long pegs con-
taining central areas of necrosis. The authors regarded
the tumors as squamous cell carcinomas.

Basurorp, Murray and Cramer, 1905: These
authors mention an epithelioma in a carp Cyprinus
carpio but do not give the location. They state that
the tumor presented a striking resemblance to squamous

664 *

Cancer Research

cell c#¥cinoma of mammals. Multiple inoculations were
made into 6 carp with negative results.

Murray, 1908: In a male stickleback Spinachia
spinachia a flat cone-shaped tumor was located on one
side of the tail. The tumor, histologically a squamcus
cell carcinoma, arose from the skin and invaded the
myotomes of the affected side, penetrating to the verte-
brae. The surface was ulcerated, the cénter necrotic.

Fresicer, 1909 a: An epithelioma was found on
the lips of two tench Tinca tinca, both from the same
pond. One bore a tumor at the angle of the mouth on
the right that spread to both upper and lower lips. In
the other fish the neoplasm involved the entire upper
lip and extended backward on the left to the orbit. The
surface of each tumor was nodular, containing collec-
tions of pigment cells and visible blood vessels. His-
tologically there was pronounced epithelial hyperplasia,
but a fairly well preserved basement membrane sur-
rounded the epithelial pegs. Mucous cells and clavate
cells were present near the center of the cell masses.

Fresicer, 1909 a: In a carp Cyprinus carpio mul-
tiple wart-like masses the size of peas had almost de-
stroyed the right pectoral fin. They were also present
on the ventral and dorsal fins, and on the right oper-
culum. Histologically the tumors were malignant papil-
lary epitheliomas that invaded the corium and con-
tained many multinucleate giant cells.

Prenn, 1909: The abdomen of a goldfish was
greatly distended by a dilated urinary bladder, the
outlet of which was obstructed by a tumor. Histologic-
ally it was composed of neoplastic cells that tended to
form alveoli and had penetrated deeply into the sub-
jacent tissue.

Mazzaretur, 1910: A 4.5 x 3.5 cm. tumor arose
from the pavement epithelium of the mouth of a “Le
Nez” Chondrostoma soetta. The flattened epithelial cells
had large nuclei; some mucous cells were present. Local
liquefaction necrosis and cyst formation was observed
in the epithelial pegs.

Beattr, 1916: Tumors were found on the lips of 2
croakers Pogonias chromis. On the upper lip of one
there was a small cauliflower-like growth; another papil-
lomatous tumor was located on the forehead. The
stratified epithelium as well as the connective tissue of
the cutis were hyperplastic; the basement membrane
in most regions was intact, though at one point epithelial
pegs penetrated deeply. In the second fish the lower
lip was the site of a firm, diffuse swelling. The histo-
logic appearance of malignancy was more marked in
this case than in the former; the epithelial pegs in-

vaded the subcutaneous tissue more deeply. The tumors
may be classified as papillary epitheliomas with early
but definite signs of invasion.

Jounstone, 1924: In a whiting Merlangus mer-
langus, on the right side of the mandible and extending
a short distance into the mouth, was a 1 x 1 cm. tumor.
Histologically it was a typical epithelioma with ex-
tensive proliferation of epithelial pegs but an intact
basement membrane.

WitiiAMs, 1929: The author reported a bilobed
growth which had spread over the anterior portion of
the lower jaw of a codfish Pollachius virens caught near
the coast of Iceland. It may have arisen in the mucous
cells which are abundant in the integument of fish.
Evans, of the Pathology Department in Liverpool,
thought that it corresponded to human epithelioma ade-
noides cysticum.

Puente-Dvany, 1930: A periocular tumor was found
in the orbit of a small Cuban fresh water fish, the
biajaca Cichlasoma tetracanthus; though the neoplasm
had produced exophthalmos, the overlying skin was
intact. Histologically, the epiderm was thickened,
epithelial pegs penetrated into the dermis. In some
areas these pegs fused with masses of clear, polyhedral
cells having small round nuclei. These cells were the
characteristic feature of the tumor; their origin was
uncertain. The growth was recorded as an epithelioma,
possibly arising on an inflammatory basis.

ADENOCARCINOMA

Malignant tumors of gland-cell origin are the pre-
dominant cancers in man. By contrast, but few
examples, 7 in all, have hitherto been reported in
fishes. This fact does not permit us to conclude that
this kind of cancer is uncommon in fishes; it may —
mean that an adequate search has not yet been
made. This supposition is the more plausible because
most adenocarcinomas originate in the viscera, and
not on the body surface as do the epitheliomas.

The tumors occurred in 6 different species (Table
5). All but one of the tumors were located within
the body cavity. As shown in the table, in 2 cases
the tumors had their origin in the kidney of eels
Anguilla anguilla; both neoplasms were relatively
large 7 x 3.5 cm., and both were invasive and destruc-
tive. A tumor in a red tai Pagrosomus major, arose
behind the right kidney, but had no direct connec-
tion with it. It was large, 9 x 3.5 cm., uniformly

Taste 5: ADENOCARCINOMA

Species Site Author
Eel Anguilla anguilla Kidney Schmey, 1911
Eel Anguilla anguilla Kidney Plehn, 1924
Coalfish Pollachius brandti Glandula digitiformis Takahashi, 1929
Coalfish Theragra chalcogramma Mouth & operculum Takahashi, 1929
Red Tai Pagrosomus major Body wall Takahashi, 1929
Pike Esox lucius Ovary Haddow & Blake, 1933
Moray Muraena helena Palate Ladreyt, 1935

Schlumberger and Lucké—Tumors in Fishes

665

soft, pale gray, and invaded the body wall. The
component cells were cuboidal and had large spheri-
cal nuclei; the stroma was abundant. Takahashi
(199) regarded it as an adenocarcinoma of unknown
origin.

The ovarian tumor in a pike Esox lucius reported
_ by Haddow and Blake (68) was a soft mass, 7 x 3
_ m., near the anterior pole of the left ovary; several
smaller nodules accompanied the main tumor.
Microscopically, the structure was that of an adeno-
aca apparently derived from germinal epi-

rae tee « cancer of the digitiform or rectal gland in

the coalfish Theragra chalcogramma reported by
Takahashi (199) is of interest because of its exten-
sive metastases and its origin in a structure having
no homologue in man or the higher vertebrates. This
gland is a short tubular body, the duct of which
opens into the lower end of the intestine; its func-

direct extension were present in the liver, stomach,
intestine, spleen, urinary and swim bladders.

Abstracts of other reported casés of Adenocarcinoma

Scumey, 1911: A retroperitoneal mass 7 x 3.5 cm.
was found in an eel Anguilla anguilla approximately 3
years old. The tumor could be readily freed from the
abdominal musculature, but could not be separated
from the left kidney. Microscopically it consisted of

irregularly arranged tubules and cysts which passed
over into normal renal substance without sharp demarca-

PLEHN,
3 cm. in length, was greatly distended by a
7 x 3.5 cm. The lesion was apparently malignant,
destroyed the posterior half of the kidney and
the anterior portion, but no metastases were
No histologic description accompanied the re-

AKAHASHI, 1929: At the left angle of the mouth
coalfish Theragra chalcogramma was a tumor that
extended into the skin of the operculum on the
same side. The neoplastic epithelial cells were grouped
orm alveoli and invaded the adjacent structures.
tissue of origin was not identified.

Lapreyt, 1935: The palate of a moray Muraena
helena was ‘the site of a large tumor which had its origin
in the glands scattered throughout the mucosa, The
malignancy of the tumor was manifested by partial
absence of a basement membrane, atypical structure of
the cells, and extensive local invasion. Metastases were

Bs

1924: The abdomen of an eel Anguilla

#2) ee

glands in the palate. Tests showed that the venom of
the cancerous glands was less active than that of the
normal ones, but the effects it

produced—hyperemia
and cellular degeneration—were qualitatively the same.
THYROID “TUMORS”

No tumor or tumor-like lesion of fishes has re-
ceived more attention than that of the thyroid
gland. Such “tumors” are most frequently observed
in trout reared in hatcheries and less often in other
species living in ponds or aquaria (98, 131, 178, 190,
194) (Table 6). Attention was first called to this
condition by Bonnet (14) who described an epi-
demic that destroyed over 3,000 lake trout Salmo
lacustris in a fish hatchery between February and
June of 1883. All had tumors at the ventral junc-
tion of the gills.

Scott (182), who observed enlargement of the
thyroid of brook trout Salvelinus fontinalis reared
in a single pond, was the first to identify it as “car-
cinoma” (1891). The lesion began as a local hypere-
mia of the oral mucosa followed by nodular rough-
ening in the midline of the ventral wall of the
pharynx just behind the tongue. The nodules in-
creased in size, and ultimately filled the oral cavity,
protruding beyond the opercula. On section the
masses were found to be composed of distended ir-
regular acini lined by cuboidal or columnar cells.
Some of the alveoli were filled with colloid; the
lumen of others was small and the cells arranged
in papillary folds. Islands and acini of thyroid
cells were found scattered throughout the adjacent
tissues.

The view that these tumors are true cancers has
been maintained by numerous investigators (25, 58,
78, 153, 156, 195). In 1914 Gaylord and Marsh
published their monograph entitled “Carcinoma of
the Thyroid in the Salmonoid Fishes” (53), based
on tumors observed in several thousand trout at
U.S. government fish hatcheries. A study of the his-
tologic descriptions and many excellent photomicro-
graphs reveals, however, that the large majority of
the tumors are examples of hyperplasia and colloid
storage, without evidence of malignant change.
Nevertheless, it cannot be denied that among the
thousands of goiters there probably were instances
of adenocarcinoma. Gaylord and Marsh themselves
reported two cases in which metastases were found.
In one, the metastatic nodule was present in the wall
of the rectum, where it was covered by intact rectal
mucosa. In the other the metastasis was on the tip
of the lower jaw and may merely represent aberrant
thyroid tissue. This is made more likely in view of
the studies of Gudernatsch (66) who pointed out

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Cancer Research

thatthe teleost thyroid is not encapsulated and
that its follicles do not form a distinct organ but are
scattered over a wide area. Although the main bulk
of the thyroid develops about the stem of the ventral
aorta between the first and second gill arches, groups
of follicles are not uncommonly found among the
adjacent muscle bundles and bone lamellae. This
natural arrangement may be erroneously interpreted
by the unwary as evidence of invasiveness.

In a series of papers published in 1910-1914
Marine and Lenhart (127-130) reported the results
of their observations of this disease among brook
trout in a large fish hatchery in Pennsylvania. They
denied that the lesion is a carcinoma (128): “In
view of the facts that young fish are more affected
than old fish, that iodine stops the hyperplasia and
causes it to return to the colloid state, that removal
of the fish from the ponds to the open brook also
effects a cure, that the clinical incidence of tumors
is directly related to the water supply, and that the
severity of the disease as determined by histological
examination is likewise directly related to the water
supply, we cannot accept the prevailing opinion
that the disease is true cancer. On the other hand,
we believe that the disease as studied by us is an
extreme illustration of endemic goiter, the end stage
of which is cretinism.” The age incidence and de-
velopment of the lesion was summarized by Marine
(130): “It was found that the thyroid hyperplasia
began in the fry as soon as feeding was instituted,
and advanced overgrowth was present at the 4th

month of extra oval life; that the overgrowth pro-
gressively increased to the stage of clinical detecta-
bility, as ascertained by the reddening of the pharyn-
geal floor over the thyroid area, about the tenth
month in this hatchery; that visible goiters usually
manifested themselves about the beginning of the
second year, though they may be present as early as
the sixth month, depending on the favorableness of
conditions for overgrowth, and progressively in-
creased during the second and third years; that
older fish were more resistant and tended toward
spontaneous recovery.” Marine does not deny, how-
ever, that the hyperplasia of the thyroid may in
some instances progress to actual carcinoma.

In a recent monograph on the cause of thyroid
hyperplasia in animals and man, Duerst (40) ex-
pressed the belief that the functional demand made
upon the thyroid is in inverse proportion to the
oxygen tension of the air or, in the case of fishes, of
the surrounding water. He points out that carp and
tench require only 3 to 4 cc. of oxygen per liter of
water, while trout require 7 to 8 cc. When the
oxygen content of the water falls to 3 to 4 cc. per
liter the young trout develop thyroid hyperplasia,
at 1.5 cc. per liter they die of asphyxia; whereas
carp and tench survive at a 0.5 cc. per liter level.
The predominance of thyroid tumors in the Salmoni-
dae may be related to the high oxygen demands of
these fishes and the low oxygen tension present in
the tanks of the fish hatcheries. The fact, noted by
Marine, that the goiters occur particularly in young

Taste 6: Tayromw Tumors

Species
Lake trout Salmo lacustris (3,000)
Brook trout Salvelinus fontinalis (many)
Rainbow trout Salmo gairdnerii (3)
Amer. Salmon Salmo salar
Trout several species (several)
Trout several species (many)
Trout several species (6)
Lake trout Salmo lacustris
Trout several species (thousands)
Trout several species (thousands)
Dogfish Squalus sucklii
Sea Bass Serranus scriba & S. cabrilla (5)
Barbel Barbus Auviatialis (several)
Trop. Aquar. Fish Jordanella floridae (several)
Catfish Clarias dumerlii
Porgy Box vulgaris
Rainbow trout Salmo gairdnerii (many)
Aquar. Fish Danio albolineatus
Aquar. Fish Haplochilus chaperi (several)
Trout species not given
Salmon species not given
Aquar. Fish Rasbora lateristriata (several)
Aquar. Fish Helerandria formosa (several)
Aquar. Fish Rasbora laterisiriata (several)
Suckfish Echeneis naucrates (16)

Author
Bonnet, 1883
Scott, 1891
Gilruth, 1901
Gilruth, 1902
Plehn, 1902
Pick, 1905
Jaboulay, 1908
H. M. Smith, 1909
Marine & Lenhart, 1910, 1911, Marine, 1914
Gaylord & Marsh, 1914
Cameron & Vincent, 1915
Marsh & Vonwiller, 1916
Schreitmiiller, 1924
Schreitmiiller, 1924
Schreitmiiller, 1924
Johnstone, 1924
Leger, 1925
Klemm, 1927
Klemm, 1927
Peyron & Thomas, 1930
Peyron & Thomas, 1930
Smith, Coates, & Strong, 1936
Smith, Coates, & Strong, 1936
Smith & Coates, 1937
Lucké & Schlumberger (not published)

Schlumberger and Lucké—Tumors in Fishes

667

fish, and tend toward spontaneous regression in
older animals, may be related to the extensive involu-
tion which the thyroid normally undergoes when the
fish reaches sexual maturity—at the age of 3 or 4
years in trout. The involution of the thyroid is com-
pensated for, at least as concerns its oxygen regulat-
ing function, by an increase in the number of
erythrocytes in the circulating blood (40).

The possible relation of low oxygen tension in
water to thyroid hyperplasia in fish receives support

_ from the work of Marsh and Vonwiller (131). These

investigators found enlarged thyroids in five sea bass
_Serranus scriba and S. cabrilla that died in the
aquarium of Naples. Since these fishes were kept
in fresh sea water, in which the content of iodine is
high, depletion of the latter cannot account for the
- occurrence of the goiters, which histologically re-

___ sembled those of the Salmonidae.

Thyroid enlargements have been seldom observed
in marine fishes hence their appearance in a group of
shark suckers Echeneis naucrates is of interest. These
fish attach themselves to the belly of a shark by
_ means of a modified dorsal fin that has been trans-
formed into a suction plate. They are not strictly

these fish measuring nearly 3 feet in length were
caught off the coast of New Jersey and exhibited
for several weeks at a seaside resort. They were
then transferred to the Fairmount Park Aquarium
in the City of Philadelphia, where we had an op-
portunity to study them. The fish were kept in a
large tank of aerated sea water and fed a diet of
fresh

y sacrificed, at which time the tumor
measured 4 x 3 x 2.5 cm. almost filled the oral cavity,
and obstructed the free flow of water over the gills
(Fig. 16). Microscopically the tissue proved to be
thyroid, consisting in part of greatly dilated acini
filled with marginally vacuolated colloid and lined
by cuboidal or columnar epithelium, which formed
occasional low papillary projections (Fig. 18). Alter-
nating with the large colloid spaces were areas in
which the acini were very small. Thyroid tissue was
found between lamellae of bone (Fig. 17), but there
was nothing to suggest that this represented an in-
vasion of the bone. The histologic picture closely re-
sembled the hyperplasia with extensive colloid stor-
age frequently observed in non-toxic colloid goiters
of man. Bits of tissue were inoculated into the

anterior chamber of the eyes of three goldfish Caras-

larly affected. In all but one fish the goiters

confined to the oral cavity, measured between 1 and
3 cm. in diameter, and varied in color from pale
pink to bright red. In the single remaining fish the
thyroid had extended backward beneath each oper-
culum, lifting that structure away from the side of
the body. The animal rested upside down on the
bottom of the tank, apparently to avoid further

without effect. In none of the other marine fishes
kept under identical conditions in the aquarium did
goiters appear, nor were they known to occur in the
fresh water fishes exhibited in the same building.
The goiters of the shark suckers may be a response
to some metabolic idiosyncrasy of these fish. This
view is strengthened by the report of an official who
stated that during his service of over twenty years
he had frequently observed this lesion in the shark
sucker, but never in any other fishes.*

Abstracts of other reported cases of thyroid tumors

GrrrutH, 1902: A five year old salmon Salmo
salar and 3 rainbow trout Salmo iridens each bore a
tumor the size of a walnut, that projected beyond both
gill clefts and appeared to have started at the apex of
the second branchial arch. On section the tumors were
homogeneous, pale pink in color and soft in consistency.
A fibrous capsule surrounded them, and connective tissue
trabeculae extended from the capsule into the tumor
parenchyma. The alveoli were irregular and lined by
columnar or cuboidal epithelial cells. The tumors were
well vascularized and frequent hemorrhages were pres-
ent. Although the author identifies the mass as an en-
dothelioma, it probably represents a simple hyperplasia

* We wish to express our grateful appreciation of the late
Dr. Robert O. VanDeusen, superintendent of the Fairmount
Park Aquarium, who placed these and many other interest-
ing specimens at our disposal.

668 ad

Cancer Research

—
of the thyroid. The salmon was collected and described
for Gilruth by H. C. Wilkie, the 3 trout by L. F. Cryson.

PLEHN, 1902: A preliminary report on “adenocar-
cinoma” of the thyroid in trout. The author discusses
the normal anatomy of the gland in fishes and likens
the pathologic changes in her specimens to adenocar-
cinomas of the thyroid in mammals.

Pick, 1905: The fishes studied by Pick had been
bred in American fish hatcheries, and sent to him in
Germany. Despite the variability of the histologic find-
ings, Pick thought that the growths were unmistakable
epitheliomas. He believed that primary simple endemic
goiter undergoes a malignant transformation in conse-
quence of some external deleterious influences.

Japoutay, 1908: Six trout died following develop-
ment of a malignant tumor of the thyroid. The author
identified the tumors as adenocarcinomas that had in-
vaded the surrounding tissues. He implicated hereditary
factors as well as a contagious etiologic agent. The
former opinion he supported by the fact that fish raised
from eggs sent out of Germany suffered from the dis-

ease, whereas native trout under similar conditions:

remained well. Jaboulay believed that the infectious
agent was a myxosporidium present in the water and
taken into the digestive tract.

Situ, 1909: A large tumor of the thyroid gland
in a lake trout Salmo lacustris, was histologically a car-
cinoma of the alveolar type, not distinguishable from
similar tissue of human origin.

Cameron and VincEeNT, 1915: The authors found
a thyroid tumor in a dog fish Squalus sucklii which
they considered histologically similar to those re-
ported by Marine and Gaylord in trout. They pointed
out that whereas in teleosts the thyroid is scattered and
not encapsulated, in elasmobranch fishes it is definitely
encapsulated and forms a compact organ. This point
gives significance to their finding of invasion into the
surrounding tissues. A quoted report by Adami sug-
gests that histologically their specimen is a carcinoma.

Scurettmitter, 1924: The author described what
he considered were examples of malignant neoplasia
of the thyroid in Jordanella floridae and other oviparous
and viviparous toothed carp, in barbels, and in a catfish
(cited by Klemm).

Jounstone, 1924: On the floor of the mouth of a
porgy Box vulgaris on each side of the midline and
in the region of the thyroid was a 2.5 x 1.3 cm. tumor
which had lifted the operculum on that side. His-
tologically there were numerous large acini filled with
colloid and lined by tall columnar cells.

Lecer, 1925: Thyroid tumors were found in rain-
bow trout Salmo gairdnerii at a hatchery in Grenoble.
Leger states that most of them are adenomas, a few are
adenocarcinomas, and he presents an example of the
latter which had metastasized to the heart.

Kiem, 1927: Tropical aquarium fish of the spe-
cies Haplochilus chaperi (an oviparous toothed carp)
appeared unwell when they had attained a length of 1.5
to 2 cm. Examination revealed that the opercula were
lifted and breathing was rapid. On the pharynx a

reddened, hemispherical mass could be seen, 2.5 to 3
mm. in diameter, having the histologic characteristics
of a colloid goiter. A similar lesion was found in a
specimen of Danio albolineatus.

Peyron and THomas, 1930: The authors review
the problem of thyroid tumors in fishes, especially the
Salmonidae. Though inconclusive, they seem to favor
the view that most are malignant neoplasms and include
two cases of their own: one in a salmon, the other in a
trout, and both typical of the many other goiters de-
scribed in the literature.

SmitH, Coates and Srronc, 1936: These authors
observed thyroid hyperplasia in 2 species of tropical
aquarium fishes Rasbora lateristriata and Heterandria
formosa. They believed that the tumors are benign
adenomas; the discussion is brief.

SmitH and Coates, 1937: The authors present a
detailed morphologic study of the normal and hyper-
plastic thyroid in a tropical aquarium fish Rasbora
lateristriata that reaches a length of 3 cm. In the hyper-
plastic gland there is a great irregularity in the size and
an increase in the number of follicles. Cross sections
of the normal gland reveal not more than 10 follicles,
whereas in the thyroid tumor these may number 3,000.
Scattered collections of lymphoid cells were not un-
common in the tumor which also showed increased vas-
cularity. It infiltrated the adjacent muscle, cartilage,
and bone. The disease was usually fatal in two months,
as the tumor destroyed and replaced the gill structures.

TUMORS OF MESENCHYMAL TISSUES

In this group are included: fibroma, myxoma,
chondroma, osteoma, lipoma, leiomyoma, rhabdomy-
oma, hemangioma, osteo-sarcoma, lymphosarcoma,
and sarcomas not further classified. ;

FIBROMA

The most common neoplasms of the supporting
tissues of fishes are the benign and malignant tu-
mors of the connective tissue proper. Fibroma has
been reported in 18 species (Table 7). The subcu-
taneous tissue and trunk musculature are most fre-
quently involved; however, fibromas have been
found in the oral cavity, peritoneum, stomach and
esophagus. Guglianetti (67) reported a slow grow-
ing retro-orbital tumor in a goldfish Carassius aura-
tus that was under observation for 3 years. The
right eyeball protruded, the pupil was greatly di-
lated, and the lens opaque. The tumor measured
3.5 cm. in diameter, was elastic and rather soft in
consistency. Histologically the growth consisted of
connective tissue that was rich in nuclei and con-
tained several areas of necrosis.

Subcutaneous fibromas in goldfish have been
described by several authors (45, 175, 226). They
were often multiple and in one instance (226) in-
volved several fishes in the same pool. An infectious

: agent could not be demonstrated, nor could the tu-
mors be transplanted to other goldfish (45). The

: relationship of these growths to the subcutaneous
__ fibrosarcomas of goldfish cannot be determined from

_ the reports in the literature. A fibroma of the ovary
in a related species, the carp Carassius carassius
was reported by Freudenthal (52). The growth was
__ nodular, white, and did not adhere to surrounding
structures. Histologically the richly cellular paren-
;, consisted of connective tissue, was not in-

| filtative, and contained no demonstrable parasites,
"Bits of the tumor were inoculated intraperitoneally

____ into 2 other carp. One of these fish died on the fol-
_ lowing day; in the other no tumor tissue could be

a found when the animal was sacrificed 10 weeks later.

“The first report of a soft tissue tumor in a fish was
made by Crisp (33) at a meeting of the London
Pathological Society in December, 1853. The neo-
plasm was a fibroma weighing 4 pounds and loosely

attached to the peritoneum of a 10 pound carp. On
section it was found to consist of dense, white
bundles of fibrous tissue. The author called atten-
tion to the resemblance in origin and growth be-
tween this tumor and some of the tree fungi, point-

Schlumberger and Lucké—Tumors in Fishes 669
Taste 7: Finzoma
Site Author
Peritoneum Crisp, 1853
Body cavity Gervais, 1876
Subcutaneous Eberth, 1878
Subcutaneous Bland-Sutton, 1885
Stomach wall Bland-Sutton, 1885
Wall of stomach Ryder, 1887
Crucian carp Carassius carassius Abdominal wall & Piehn, 1906
mesentery
Coelom Plehn, 1906
Musculature Plehn, 1906
Oral cavity Fiebiger, 1909a
Esophagus Williamson, 1909
Orbit Guglianetti, 1910
: Peritoneum Johnstone, 1911
"Haddock > sea aeglifinus Subcutaneous Johnstone, 1911
Halibut Hippoglossus hip poglossus Retroperitoneal Johnstone, 1913
Halibut Hippoglossus hip poglossus Trunk muscle (multiple) Johnstone, 1914
Carp Cyprinus carpio Mesentery Ronca, 1914
Codfish Gadus morhua Orbit Johnstone, 1914
Goldfish Carassius auratus (several) Subcutaneous Wago, 1922
Plaice Pleuronectes a Dorsal fin Johnstone, 1922
Haddock Melanogrammus aeglifinus Subcutaneous (multiple) Johnstone, 1924
Turbot Rhombus maximus Dorsal fin Johnstone, 1924
- Codfish species not given Stomach wall Johnstone, 1925
Sardine Arengus pilchardus Peritoneum Johnstone, 1925
Goldfish Carassius auratus Skin (multiple) Sagawa, 1925
Goldfish Carassius auratus Back muscles Eguchi & Oota, 1926
_Halibut Hippoglossus hip poglossus Subcutaneous, on head Johnstone, 1926
__ Plaice Pleuronectes platessa Subcutaneous, on head Johnstone, 1926
___ Crucian carp Carassius carassius Ovary Freudenthal, 1928
_ Coalfish Theragra chalcogramma (2) Belly wall Takahashi, 1929
_ Rockfish Sebastodes inermis Body wall Takahashi, 1929
Codfish species not given Wall of duodenum Thomas, 1933a
__-‘Trop. Aquar. Fish Rasbora daniconius Region of dorsal fin Smith, Coates, & Strong, 1936
Brown trout Salmo trutia Intra-abdominal Kreyberg, 1937

ing out that these excrescences, both in man and
the lower animals, possessed a power of growth to
some extent independent of the body to which they
are attached.

Abstracts of other reported cases of fibroma

Gervais, 1876: A very large tumor was found near
the ovaries in the abdominal cavity of a carp Cyprinus
carpio. Histologically it was composed of connective
tissue.

ExertH, 1878: During a robbery at a fish hatchery
in Switzerland, a large lake trout Salmo lecustris was
injured by a blow on the head, but “the burglar failed
to capture the tasty morsel.” Though it bled from the

tologically the tumor was vascular, the
loose and somewhat gelatinous. In some
plasm resembled granulation tissue. The
fied it as a fibrosarcoma.

Bianp-Sutton, 1885: In a codfish Gedus morhua
a fibrous tumor lay in the loose tissue beneath the skin
of the abdomen. The growth had undergone calcifi-
cation.

670”

Cancer Research

BLAND-SuTTON, 1885: In the stomach of each of
two codfish Gedus morhua was a pale gray tumor
which on section was found to be composed of inter-
lacing bundles of glistening white: connective tissue.

Ryper, 1887: Described a fibroma near the pylorus
of a thwaite shad (cited by Thomas, 1931 b).

Penn, 1906: A tumor the size of a hen’s egg was
attached to the peritoneum of a crucian carp Carassius
carassius by a short pedicle. The mass was firm and
had a smooth surface; the cut surface was pale pink.
Histologically the tumor was a typical fibroma and was
made up of interlacing bands of connective tissue. A
few small areas of necrosis were present, no mitoses
were found. Several smaller fibromas were scattered
over the surface of the mesentery.

Prenn, 1906: A firm tumor the size and shape of
a hen’s egg was found in the coelom of a bream Abramis
brama. The neoplasm was composed of short spindle
cells and fibers; no mitoses were found, no inflammatory
cell infiltrates were present.

Piexn, 1906: A pink tumor 3 x 2.5 cm., was present
in the trunk muscles of a pike Esox lucius. The paren-
chyma was composed of connective tissue cells arranged
in bundles, with many fat cells scattered among them.
Mitoses were uncommon; occasional giant cells with
peripheral nuclei were present. The author called the
tumor a lipofibroma.

Fresicer, 1909 a: Arising from the oral mucous
membrane of a codfish Pollachius virens was a tumor
the size of a pigeon egg that consisted of bundles of
connective tissue covered by a thick layer of epithelium.

WittiamMson, 1909: The author reported a fibroma
of the esophagus in a codfish Gadus morhua.

Jounstone, 1911: A fibroma 5.8 x 3.3 x 2.3 cm.
was attached to the peritoneum in the region of the
caecum of a sardine Arengus pilchardus. The surface
was nodular and yellow-white in color. Histologically
the tumor was composed of interlacing bundles of con-
nective tissue.

Jounstone, 1911: Behind the operculum of a
haddock Melanogrammus aeglifinus was a well encap-
sulated tumor 7 x 6 x 6 cm. made up of bundles of
mature connective tissue.

Jounstone, 1913: A retroperitoneal fibroma weigh-
ing 2.5 kg. was found in a halibut Hippoglossus
hippoglossus. The tumor, which was soft and friable
and had a smooth, lobulated surface, was made up of
bundles of connective tissue.

Jounstone, 1914: Multiple fibromas were found
in the trunk muscles of a halibut Hippoglossus hippo-
glossus. They were well encapsulated and could readily
be shelled out.

Jounstone, 1914: In the left orbit of a codfish
Gadus morhua was a firm gray-white tumor 7 x 6 cm.
The overlying skin was intact; the eye was displaced
posteriorly and downward. The neoplasm was well en-
capsulated and consisted of interlacing bundles of con-
nective tissue.

Ronca, 1914: A tumor the size of a hen’s egg arose
in the mesentery of a carp Cyprinus carpio. White in

color, it was soft in consistency and was made up of
interlacing bundles of connective tissue.

Waco, 1922: Multiple tumors, 0.5 cm. in diameter,
were scattered over the body surface, fins, and eyes of
a goldfish Carassius auratus. Spheroidal or polypoid in
shape, they were smooth, not covered by scales, and
firm in consistency. The cut surface was red and trans-
lucent. Histologically there was an abundance of deli-
cate connective tissue and fusiform fibroblasts mingled

Though several fish with similar lesions were found in
the same garden pool, an infectious agent could not
be demonstrated. The author identified the tumor as
myxofibroma.

JouNsToNne, 1922: On the pigmented side of the
dorsal fin of a plaice Pleuronectes platessa was a firm
spherical tumor 3.5 x 3 cm.; on microscopic examina-
tion it proved to be a typical fibroma.

JoHNsTONE, 1924: Scattered over the trunk of a
haddock Melanogrammus aeglifinus were local thicken-
ings in the corium. Each of these measured about 5
mm. in diameter, and was covered by normal epidermis.
The author identified the lesions as fibromas. _

JouNstone, 1924: On the dorsal fin of a turbot
Rhombus maximus was a tumor that measured 1 x 1%
inches. Histologically it was a typical fibroma.

Jounstone, 1925: An immature female sardine
Arengus pilchardus bore a tumor 9 x 4 cm., which ap-
parently arose in the peritoneum. The viscera were
intact. Microscopically the tumor consisted of irregu-
larly arranged bundles of connective tissue abundantly
supplied with blood vessels.

SAGAWA, 1925: The author found multiple fibromas
on the skin of a goldfish Carassius auratus. The tumors
were firm and elastic, yellow-gray, sharply circum-
scribed, and varied from the size of a millet seed to that
of a pigeon’s egg. Histologically they were composed of
young connective tissue which, however, did not take
van Gieson’s stain. Myelinated nerve fibers were also
present. (These lesions may have been neurofibromas.)

Jounstone, 1925: The cardiac end of the stomach
of a 16 pound codfish bore a tumor 15 x 10 cm. On
section it was white, glistening, and firm in consistency.
Histologically the neoplasm was a fibroma.

Jounstone, 1926: On the nonpigmented side of
the head of a halibut Hippoglossus hippoglossus was a
mass 8 inches in diameter; the overlying skin was in-
tact. The tumor weighed 3 pounds, shelled out readily,
was well encapsulated, and histologically was a typical
fibroma.

Jounstone, 1926: Two tumors were present on
the head of a plaice Pleuronectes platessa. One on the
lower border of the operculum measured 44% x 3144
inches, the other was smaller, grew from the anterior
border of the right orbit, and partly covered the eye.
The overlying skin was intact. Both neoplasms con-
sisted of bundles of connective tissues; few vessels
were present.

Ecucnt and Oota, 1926: A firm elastic tumor

Schlumberger and Lucké—Tumors in Fishes

671

TAKAHASHI, 1929: Embedded in the trunk muscles
of a coalfish Theragra chalcogramma was a gray-white
tumor, 4 x 3.5 x 3.2 cm. The overlying skin was intact.

cf “TAKAHASHI, 1929: A cherry-sized, firm uniformly
__ white tumor was found in the body wall near the caudal
fin of a rockfish Sebastodes inermis. Histologically it

>» consisted of bands and whorls of connective tissue.

_ ‘THomas, 1933 a: A pedunculated fibroma 9 x 7.5
‘em, was found attached to the mucosa of the intestine,
near the pylorus. The host was a 9 year old codfish.
Smarn, Coates and Strone, 1936: A small tropical

aquarium fish Rasbora daniconius bore a sharply cir-

cumscribed, encapsulated, black tumor in the region
_ of the dorsal fin. It consisted of loosely arranged inter-
lacing bundles of elongated connective tissue cells.
_ _Kreyperc, 1937: In a brown trout Salmo trutta a
lobulated, firm, pink tumor was discovered
in the abdominal cavity. The mass measured 18 cm.
in diameter, and was attached to the serosa of the in-
testine by a narrow pedicle. The parenchyma was com-
posed of fibrous tissue, some of which was necrotic.
_ No mitoses were present.

SARCOMA (UNCLASSIFIED)

_ The intermutability of mesenchymal tissues, and
the complexity of tumors arising from these tissues,

_ render their classification difficult (195a, 23la).

Moreover, the boundary between non-malignant and
malignant mesenchymal tumors is frequently vaguer
than in epithelial tumors. Hence it is quite possible
that some tumors here listed as sarcomas actually
belong among the fibromas. It seems best therefore
to list these two groups in proximity. No attempt
has here been made to subdivide the sarcomatous
tumors, other than separating the osteosarcomas and
lymphosarcomas.

The sarcomas form the largest group of piscine
neoplasms, having been observed in 31 species
(Table 8). The predilection of the connective tis-
sues to undergo malignancy is not unique to fishes;

it also occurs in certain mammals such as the rat

(24). The majority of the tumors listed in Table 8
had their origin in the dermis or subcutaneous
tissues. However, this may not represent the true
relative organ incidence since such growths would
be more likely to attract attention than neoplasms
of the viscera.

Of particular interest are a number of sarcomas
that appear to arise on an environmental basis.

Three groups of investigators have reported in-
stances in which subcutaneous sarcomas appeared
in several goldfish Carassius auratus that had been
kept in the same tank. Roffo (171) observed a
small ulcerated tumor on the left side of a goldfish,
just anterior to the dorsal fin. Histologically the
neoplasm consisted of connective tissue arranged in
bundles, among which were pleomorphic cells, some
of which bore two or three nuclei. Similar tumors
developed in 7 of 20 fish kept in the same aquarium.
After the diseased fishes were removed and the tank
was disinfected, no further tumors developed. Mont-
pellier and Dieuzeide (138) reported that a single
tumor was present in the body surface of each of
five goldfish Carassius auratus that had been kept
in the same aquarium. Histologically the lesions
were identical, all were fibrosarcomas, the neoplastic
fibroblasts had elongated clear nuclei with promi-
nent nucleoli. Bits of one of the tumors were inocu-
lated into the caudal fins of three goldfish. After the
lapse of a year no tumors had developed. Six addi-
tional fish were inoculated and examined after a
shorter period. They likewise failed to show tumor
growth.

We ourselves (123c) have lately given an account
of 30 tumor-bearing goldfish all but two of which
were obtained from 3 small pools. It was found
characteristic of this neoplastic disease that it is
prevalent in certain pools and absent or rare in
others. Where prevalent, the number of tumor-bear-
ing fishes, as a rule, gradually increases. We have
presented evidence that the factors. which induce
the tumors are environmental rather than heredi-
tary. The neoplasms arise in the corium or subcu-
taneous tissue and are usually solitary. Their rate
of growth is generally slow, although some grow
rapidly and attain relatively large size (Figs. 20, 21).
The histological character of these growths exempli-
fies the difficulty of accurately classifying mesen-
chymal tumors. The smaller tumors resemble fibro-
mas or occasionally myxomas (Fig. 24), the larger
fibrosarcomas (Figs. 22, 23), but the paucity of
fiber-formation makes a purely fibroblastic origin
doubtful. The precise histogenesis of these neo-
plasms is as yet undetermined. We have tentatively
grouped them here with the sarcomas, although in
our paper we have referred to them simply as “mes-
enchymal tumors.”’ It is likely, though not as yet
certain, that these tumors are similar to the goldfish
tumors reported in the literature as fibrosarcomas or
fibromas.

672 Cancer Research
Taste 8: Sarcoma (Unclassified)

Species Site Author
Minnow Phoxinus laevis Corium of skin Bugnion, 1875
Goldfish Carassius auratus Dorsal fin Bland-Sutton, 1885
Goldfish Carassius auratus Not given Semmer, 1888
Pike Esox lucius Trunk muscle Ohlmacher, 1898
Brook trout Salvelinus fontinalis Trunk muscle Plehn, 1906
Chub Jdus idus Trunk muscles Plehn, 1906
Minnow Phoxinus laevis Trunk muscle Plehn, 1906
Crucian carp Carassius carassius Testicle Plehn, 1906
“LeNez” Chondrostoma nasus Muscles of back Plehn, 1906
Flounder Psetia macotica Subcutaneous (multiple) Schroeders, 1908
Scorpion fish Scorpaena porcus Subcutaneous Schroeders, 1908
Pike Esox lucius Kidney Plehn, 1909
Danubian trout Hucho hucho Liver Plehn, 1909
Codfish Pollachius virens Skin Fiebiger, 1912
Ray Raja macrorhynchus Fin ray Drew, 1912
Eel Anguilla vulgaris Mesentery Wolff, 1912
Codfish Gadus morhua Subcutaneous Johnstone, 1912
Plaice Pleuronectes platessa Subcutaneous Drew, 1912
Codfish Gadus morhua Trunk muscle Johnstone, 1915
Croaker Pogonias chromis Subcutaneous Beatti, 1916
Conger eel Conger conger Subcutaneous Johnstone, 1920
Codfish species not given ’ Mouth Johnstone, 1920
Dog salmon Oncorhynchus keta Body wall Kazama, 1922
Haddock Melanogrammus aeglifinus Subcutaneous Johnstone, 1922
Goldfish Carassius auratus Subcutaneous Schamberg & Lucké, 1922
Goldfish Carassius auratus Subcutaneous Johnstone, 1923
Codfish Gadus morhua Subcutaneous Johnstone, 1923
Ling molva molva Subcutaneous Johnstone, 1923
Turbot Rhombus maximus Subcutaneous Johnstone, 1923
Herring Clupea harengus Testis Johnstone, 1924
Eel Anguilla vulgaris (2) Peritoneum Plehn, 1924
Goldfish Carassius auratus Subcutaneous Roffo, 1924
Rainbow trout Salmo gairdnerii (2) Not given Leger, 1925
Codfish Pollachius virens Subcutaneous Johnstone, 1926
Codfish Pollachius virens Mandible Johnstone, 1926
Halibut Hippoglossus hippoglossus Body wall Johnstone, 1926
Croaker Micropogon opercularis (2) Subcutaneous Roffo, 1926
Codfish Gadus morhua Subcutaneous Thomas, 1927b
Codfish Gadus morhua Ovary Thomas, 1927b
Turbot Rhombus maximus Body wall Johnstone, 1927
Goldfish Carassius auratus Subcutaneous Dominguez, 1928
Dog salmon Oncorhynchus kela Body wall Takahashi, 1929
Dog salmon Oncorhynchus keta Body wall Takahashi, 1929
Hump-back salmon Oncorhynchus gorbuscha Body wall Takahashi, 1929
Coalfish Theragra chalcogramma Body wall Takahashi, 1929
Coalfish Theragra chalcogramma Subcutaneous Takahashi, 1929
Japanese bass Lateolabrax japonicus Subcutaneous Takahashi, 1929
Japanese bass Lateolabrax japonicus Pharynx Takahashi, 1929
Kisugo Sillago japonica Base of head Takahashi, 1929
Gurnard Lepidoptrigla alata Left body wall Takahashi, 1929
Codfish Gadus morhua Body wall Williams, 1931
Goldfish Carassius auratus (5) Subcutaneous Montpellier & Dieuzeide, 1932
Swordtail Xiphophorus hellerii (17) Retrobulbar Jahnel, 1939
Goldfish Carassius auratus (30) Subcutaneous Lucké, Schlumberger &

Breedis, 1948

One of the more malignant growths was success-
fully transplanted to the anterior chamber of the
eye of a tumor-bearing fish; all other attempts at
transplantation were unsuccessful.

A possible hereditary sarcoma has been reported
by Jahnel (80). A retrobulbar tumor appeared in
each of four sibling tropical aquarium fish, known
as swordtails, Xiphophorus hellerii. Seventeen other

siblings were traced, 9 of which developed tumors
in one or both orbits. Histologically the tumors
were identical, consisting of small round or spindle-

shaped cells with large vesicular nuclei; interstitial

tissue was almost absent. The tumor was markedly
invasive, infiltrated the orbital muscles and even
penetrated the skull. Mitotic figures were numerous.
In one animal a large tumor was present in the left

_ comas. It is possible however that they actually
were amelanotic melanomas. In this connection see
the recent papers by Levine and Gordon (111b), and
by Gordon (60a).

color was only present within and immediately beneath
e skin and was due to the normal pigment cells of
his region. Near the tip of the caudal fin was a small

been the result of such an infection, representing merely
_ chronic inflammation with foreign body giant cells. The
author identified the growth as a giant cell sarcoma.
_ Branp-Sutton, 1885: A tumor was present on the
_ posterior border of the dorsal fin of a goldfish Carassius
_ @uratus. The author states that it exhibited all the
histologic characteristics of a spindle cell sarcoma.
_ SeMMeER, 1888: In a brief communication the author
_ lists the cases of animal tumors that came to his
attention throughout 23 years at the Veterinary Institute
in Dorpat. He mentions a sarcoma in a goldfish, but
_ gives no details.
_ OHLMACHER, 1898: Immediately beneath the dorsal
fin, and embedded in the trunk musculature of a lake
pike Esox lucius, was a spherical white tumor 5 cm.
in diameter. It infiltrated the surrounding muscle
_and was intimately connected with the vertebrae, Lying
_ beneath the peritoneum were 12 widely scattered tumors
_ varying from 1 to 3 cm. in diameter. The visceral peri-
_toneum likewise bore 24 firm white nodules 1 to 2 cm.
in width; no lesions were found in the viscera. The
_ “primary” tumor in the abdominal wall resembled small
‘round cell sarcoma of man. It consisted of large collec-
_ tions of densely packed round or oval cells with promi-
ment nuclei surrounded by scanty cytoplasm. About
these collections of cells was a delicate fibrillary and
Tichly cellular connective tissue. The metastases were
_ similar in structure, except that the stroma was more
bun: This tumor should probably be regarded as
_ Penn, 1906: In the trunk musculature of a brook
trout Salvelinus fontinalis was a large cystic tumor that
contained 117 cc. of cloudy yellow fluid in which were
_ found leukocytes, and occasional bacteria. Similar tu-
mors in trout from the same lake had been described

fluid or a colloidal mass. Some areas were very cellular,
other regions were made up of fibrous tissue. The
author identified the lesion as a cystic fibrosarcoma.

PLEHN, 1906: An egg-shaped mass, 4 x 5.5 cm.,
was present deep in the back muscles of “le Nez,”
Chondrostoma nasus. The tumor, which was white,
spongy, and edematous, consisted of a delicate con-
nective tissue reticulum among which were occasional
multinucleate giant cells. Dilated lymphatics were
numerous,

ScHroepers, 1908: On the pigmented surface of a
flounder Psetta maeotica were 8 granular tumors,
yellow-gray in color. Some were almost spherical, with
a diameter of 5 cm., others, flat and oblong, and as
much as 10 cm. in length. The masses were soft and
infiltrated the adjacent skin and muscle. Histologically
the parenchyma was composed of round cells of uni-
form size, with many mitotic figures. (Lymphosar-
coma ?)

Scuroepers, 1908: A spindle cell sarcoma in the
tail muscles of a scorpion fish Scorpaena porcus grew
rapidly for two months when the fish was kept in an
aquarium. Cachexia became marked and the animal
died. Near the anal fin was an ulcerated area, 3 cm. in
diameter; on section the adjacent muscles were found
to be extensively infiltrated by the firm white tumor.
In the liver was a white nodule the size of a pea that
protruded above the surface and infiltrated the liver
tissue. Under the epicardium of the heart were 6 white
nodules, each the size of a pin-head. Two larger firm
nodules were found in the wall of the auricle, occupying
its entire thickness. Histologically the les
liver and heart were similar to the primary lesion which
consisted of bundles of connective tissue that were

674—

Cancer Research

growing between muscle fibers and had eroded the under-
lying bone.

Prenn, 1909 and 1924: A large tumor of the kid-
ney was found in a 10 pound pike Zsox lucius. It vad
mestastasized to the trunk muscles. Histologic studies
were of little value due to poor fixation of the tissue,
but the author regarded the tumor as a sarcoma.

PieHnn, 1909: On the surface of the liver of a large
Danubian trout Hucho hucho were white nodules vary-
ing from the size of a millet seed to that of half a
walnut. On section they were found not to be circum-
scribed, but had invaded the normal tissues. The author
identified the lesion as a spindle cell sarcoma.

Fresicer, 1912: According to the author this is the
first record of a fibrosarcoma in a salt water fish, the
three previous cases were found in fresh water fishes.
A cauliflower-like mass the size of an egg grew in the
subcutaneous tissue of a codfish Pollachius virens. It
was not sharply demarcated from the adjacent tissue;
the overlying skin was ulcerated, and hemorrhages were
numerous on the surface of its warty excrescences. The
round, elongated, and even branched tumor cells in-
filtrated the muscle.

Drew, 1912: A circular tumor, 4 x 1% inches, was
present on the dorsal surface near the lateral fin of a
ray Raja macrorhynchus. It was a broadly sessile, cauli-
flower-like mass covered by a layer of epithelium. The
parenchyma consisted of fibrous tissue apparently de-
rived from the perichondrium of one of the fin rays.
Nowhere was the tissue very cellular, but because of
its mode of growth the author classified it as a sarcoma.

Wotrr, 1912: A tumor the size of a man’s fist lay
between the layers of the mesentery of a large eel
Anguilla vulgaris. Histologically, nests of tumor cells
surrounded the blood vessels and were separated from
one another by bands of connective tissue. The author
identified the growth as a fibrosarcoma.

Jounstone, 1912: On the snout of a codfish Gadus
morhua was a gray-black non-encapsulated tumor, 7.5
x 4.x 3 cm. The superficial epidermis was destroyed.
Grossly it appeared to be a typical fibroma, but his-
tologic examination showed evidence of infiltration and
increased cellularity.

Drew, 1912: A plaice Pleuronectes platessa bore a
white ovoid mass, three-fourths of an inch in diameter,
on the operculum of the pigmented side. Histologically it
was made up of connective tissue. No further details
were given, and the growth was listed as sarcoma by the
author.

Jounstone, 1915: On the right side of an emaciated
codfish Gadus morhua between the first ventral and
second dorsal fin was an 8 cm. tumor that had invaded
the adjacent muscle fibers and undergone central lique-
faction necrosis. The tumor cells were spindle shaped;
occasional giant cells were present.

Beattt, 1916: Numerous subcutaneous nodules were
present on each operculum, on the snout, on the body,
and on one side of the tongue of a croaker Pogonias
chromis. The parenchyma consisted of densely grouped
spindle cells with abundant cytoplasm and small nuclei.

Jounstone, 1920: On the top and left side of the
head of a conger eel Conger conger were two firm, spheri-
cal tumors, each 10 cm. in diameter. Histologically
there was no evidence of encapsulation; the parenchyma
presented all the characteristics of a mixed cell sarcoma,

JoHNsTONE, 1920: Several tumors were present about
the left orbit and within the mouth of a codfish. On the
basis of their histologic structure the author classified
them all as sarcomas of mixed cell type.

KazaMA, 1922: Among 1,000 salmon Oncorhynchus
keta the author found a single tumor-bearing animal.
In a five year old fish, 85 cm. in length, there was a
tumor, 6.5 x 6 x 3 cm., which arose from the body wall
near the origin of the right pelvic fin. It was hemispheri-
cal, gray-white, and encroached on the peritoneal cavity.
The tumor was composed of fusiform cells that de-
stroyed and infiltrated the surrounding tissues; no mi-
toses were seen.

Jounstone, 1922: On the top of the head of a had-
dock Melanogrammus aeglifinus was a tumor which the
author called a sarcoma. No further details were
given,

ScHAMBERG and Lucké, 1922: A goldfish that had
lived in a garden pool for 15 years bore three tumors on
its right side. The growth which the authors regarded
as primary was on the back just anterior to the dorsal
fin; it measured 2.6 cm. in diameter and projected 1.5
cm. above the skin surface. The other tumors were
located near the tail, one measured 1 cm. in diameter,
the other 3 mm. All were dull white in color. Infiltra-
tion of the underlying muscle had occurred about the
largest tumor. Histologically the growths were com-
posed of loosely arranged spindle cells; the blood supply
was scanty; the vessels very thin walled. The two
smaller tumors did not infiltrate; the authors believed
they represented metastases; this interpretation is now
regarded as probably erroneous.

JoHNSTONE, 1923: At the base of the tail of a gold-
fish Carassius auratus was a tumor that measured 1 x 1.5
cm. Histologically it was made up of proliferating con-
nective tissue that had invaded the surrounding muscle.

JoHNsTONE, 1923: A mass 6 x 3 x 3 cm. was located
on the anterior border of the right orbit of a codfish
Gadus morhua. The connective tissue was abundant,
but in some areas there were large numbers of small
round cells, the neoplasm infiltrated the dermis and
muscle, but the skin was not ulcerated.

JoHNsTONE, 1923: On the right side of the head of a
ling Molva molva, arising above and behind the orbit,
was a tumor 11 x 5 cm. which grew forward over the
eye and almost covered the pupil. No histologic details
were given; it was classified by the author as a fibro-
sarcoma.

Jounstone, 1923: On the pigmented side of a turbot
Rhombus maximus was a tumor 8 x 3 cm.
the lesion consisted of connective tissue among which
were spindle cells. There was little evidence of malig-
nancy, although the author diagnosed it a sarcoma.

Jounstone, 1924: A creamy white tumor, slightly
nodular and measuring 34% x 1% inches, was loosely —

Schlumberger and Lucké—Tumors in Fishes

675

_ attached to the parietal peritoneum of a herring Clupea
harengus. It was fused with testis and was composed
of vesicular neoplastic cells. (Lymphosarcoma ?)
PLEHN, 1924: In each of two eels Anguilla vulgaris
there was a firm connective tissue tumor that arose in
_ the peritoneum and greatly distended the abdomen. The
author gives no details but considers the tumors to be
fibrosarcomas.

Lecer, 1925: In discussing thyroid tumors in trout
the author mentions 2 fibrosarcomas in rainbow trout
Salmo gairdnerii. They were red in color and very

42 vascular. No further details were given.

JoHNsToNE, 1926: On the top of the head of an
_ emaciated codfish Pollachius virens was a tumor that
_ measured 2 inches in diameter. On section the lesion

was soft and necrotic. No histologic studies were made,

but the lesion was listed by the author as a sarcoma.

x 5 inches and with raised edges, was observed on the

tion revealed that it was composed of loosely arranged
spindle cells.

Rorro, 1926: Each of two croakers Micropogon
opercularis bore a tumor. In one a nodular ulcerated
mass 2 cm. in diameter was found at the junction of the
head and thorax; in the other a similar mass was pres-
ent at the base of the tail. Histologically each was a
spindle cell sarcoma.

Tuomas, 1927 b: A subcutaneous tumor the size of
a hen’s egg was found in the trunk of each of 3 codfish
Gadus morhua. Several areas of necrosis were present;
the cells were large and fusiform, arranged in bands and
whorls that resembled the uterine fibroleiomyoma of
man. The author regarded the tumor as a fibrosarcoma.

Tuomas, 1927 b: Ina codfish Gadus morhua a tumor
the size of an almond was present near the right ovary.
The cells are fusiform; confluent vascular spaces lined
by a rudimentary endothelium were abundant. The tu-
mor was likened by the author to the fibrosarcomas of
birds and mammals.

Jounstone, 1927: Multiple small round cell sar-
comas were found in a turbot Rhombus maximus. Two
_ of the tumors were the size of a hen’s egg and were
located on the pigmented side of the fish; nine addi-
tional nodules were found scattered throughout the
musculature. None of the tumors were encapsulated;
the adjacent muscle was infiltrated. The cells were of
the small round cell type and appeared to be malignant.
The author believes that the numerous tumors were
multicentric in origin rather than metastatic. (Lympho
sarcoma ?)

Domincuez, 1928: A 25 cm. goldfish Carassius aura-
tus was observed to have had a nodule the size of a pea

on its dorsal fin for 3 years. During the last year and
a half the tumor had grown to a diameter of 1.5 cm.
Several days before death a few “secondary” nodules

fusiform cells with large oval nuclei.

TAKAHASHI, 1929: A tumor the size of a fist arose in
the trunk musculature of a dog salmon Oncorhynchus
keta. It was fluctuant, and was found to contain a
central area of liquefaction necrosis. Histologically the
tumor was composed of spindle cells that showed active
mitosis and infiltrated the surrounding musculature.

TAKAHASHI, 1929: On the left side of a dog salmon
Oncorhynchus keta, 15 cm. anterior to the tail fin, was
a tumor 9 x 7 cm., lying athwart the lateral line. On
the opposite side was a similar but smaller tumor. Both
were soft in consistency, showed liquefaction necrosis,
and infiltrated the surrounding muscle. The cells varied
in size and shape and were rich in cytoplasm.

9 tumor nodules ranging from 0.5 to 3 cm. in diameter.
There was no sharp demarcation from the surrounding
tissue and on histologic grounds the author identified the
tumor, which was very cellular and contained many
mitoses, as a round cell sarcoma. (Lymphosarcoma ?)
TAKAHASHI, 1929: In the middle of the trunk, above
the lateral line of a coalfish Theragra chalcogramma was
a tumor 4 x 3.5 cm. It was uniformly firm, and gray-
white. Microscopically the parenchyma consisted of
spindle cells, many of which were in mitosis. The sur-
rounding tissue was infiltrated by the tumor.
TAKAHASHI, 1929: An oval, subcutaneous tumor
larger than a hen’s egg was found in the occipital region
of a coalfish Theragra chalcogramma. Except at its base,

tissue; mitotic figures were uncommon. The tumor was
identified by the author as a spindle cell sarcoma.
TAKAHASHI, 1929: Eight tumors of varying sizes

the surrounding tissue.

TAKAHASHI, 1929: In the pharynx of a Japanese
bass Lateolabrax japonicus was a tumor, 7.5 x 3 cm.
Two similar lesions were present in
tissue of the right side. Histologically the
consisted of spindle cells with few mitotic figures

TAKAHASHI, 1929: On the dorsum of the neck region
of a kisugo Sillago japonica was a hemispherical, sof
elevation that measured 2.2 x 1.3 cm. and was gray-
white on section. It had infiltrated the adjacent tissues
and was identified by the author as a spindle cell sar-
coma,

TAKAHASHI, 1929: A vascular, gray, ulcerated tu-

cells were large and round with rather small nuclei. The

676m

Cancer Research

author regarded the tumor as a large round cell sarcoma.
(Lymphosarcoma ?)

WitiiaMs, 1931: An egg-shaped tumor, 12.8 x 8.8
cm., was present in the trunk muscles of a codfish Gadus
morhua. Histologically it consisted of small round cells
embedded in a connective tissue stroma, The tumor was
vascular and infiltrated the adjacent muscle. (Lympho-
sarcoma ?)

MYXOMA

Although in mammals fully developed mucous
tissue is found only in the umbilical cord, it has
been described as occurring in certain areas of some
fishes, particularly about the cranial cartilage of
selachians. Six cases of myxoma have been reported;
these were found in 5 species of fishes, all teleosts
(Table 9). Of these, four have been identified by
the authors as myxofibromas, the remaining two
were classified as myxosarcomas because of their
invasive character. “

The benign tumors arose in the subcutaneous
tissue; in one case they were multiple, and grouped
about the base of the fins. One of the invasive
tumors was retro-orbital, the other lay within the
trunk musculature; no metastases were found.

Abstracts of reported cases of Myxoma

PLEHN, 1906: The right eye of a 6 or 7 year old tench
Tinca vulgaris was displaced by a tumor arising below
the orbit. It was hemorrhagic, not sharply demarcated,
and infiltrated the surrounding tissues. Histologically,
some areas consisted of dense masses of spindle cells;
in other regions these were separated by a mucoid
ground substance in which were many delicate fibrils.

Scuroepers, 1908: On the pigmented side of a
flounder Psetta maeotica was a spherical pedunculated
tumor 9 x 12 x 7 cm. The overlying skin was intact.
The mass was elastic in consistency and translucent on
section, with numerous transecting fibrous bundles. Mi-
croscopically the large spaces between the interlacing
bundles of connective tissue were filled with an amor-
phous substance (mucin) that stained blue with hema-
toxylin. Within this were scattered stellate cells. Large
blood vessels coursed along the fibrous trabeculae.

ScHroepers, 1908: About 10 tumors were present at
the junction of the trunk and fins of a flounder Psetta
maeotica. Most were broadly sessile; in a few the over-
lying skin was ulcerated. Elastic in consistency, the
tumors on section were translucent and yellow-white.
Histologically, interlacing bundles of connective tissue,

mostly arranged perpendicular to the skin, formed a
coarse network, in the meshes of which was an amor-
phous ground substance containing stellate cells.

MacIntosu, 1908: A plaice Pleuronectes platessa
bore an elongated swelling on its right side. On dissec-
tion the tumor was gelatinous in consistency; the sur-
rounding muscle was atrophied and the growth could be
removed with ease. Histologically it was a loose, areolar
connective tissue, enmeshed in which were many small
cells and capillaries. The surrounding structures were
not infiltrated.

Jounstone, 1926: A tumor 2 inches in diameter,
irregular in shape, and glistening white in color, was
present in the body cavity of a sole Solea solea. His-
tologically the growth consisted of interlacing bundles
of connective tissue and areas of areolar tissue con-
taining stellate cells separated by large interspaces. _

Wit.iaMs, 1929: A tumor, 12.7 x 5.1 cm., was found
in the trunk musculature on the non pigmented side of
a turbot Rhombus maximus. The overlying skin was
ulcerated. Histologically typical myxomatous tissue in
filtrated the adjacent muscle.

CHONDROMA

Although the entire skeleton of selachians is com- —
posed of cartilage and this tissue is also abundant
in the teleost fishes, only 8 reports of tumors of
cartilage can be found in the literature (Table 10).
Of these 2 were in selachians; one arose from the
fin ray of a cat shark, the other from the lumbar
vertebrae of a dogfish. An explanation for this
dearth of material may be found in the fact that the
selachians are not commonly used for food and are
therefore seldom examined; however, the dogfish is
frequently dissected in biology laboratories. Mul-
sow (140) reported a chondroma attached to the
cranial bones in each of three crucian carp Caras-
sius carassius. All the tumors were massive and
nearly filled the cranial cavity. Unfortunately, no
further data are available, but if the animals were
siblings, the possibility that the tumors were com-
parable to multiple hereditary chondromas of man
would need to be considered. There is no record in
the literature of a malignant cartilagenous neoplasm
of fishes.

Abstracts of reported cases of chondroma

Mutsow, 1915: A chondroma was found attached to
the cranial bones in each of three crucian carp Carassius

Taste 9: Myxoma

Species Site Author
Tench Tinca vulgaris Subcutaneous Plehn, 1906
Flounder Psetia macotica Skin, head Schroeders, 1908
Flounder Psetia macotica Skin, trunk & fins Schroeders, 1908
Plaice Pleuronectes platessa Body wall MacIntosh, 1908
Sole Solea solea Peritoneum Johnstone, 1926

Turbot Rhombus maximus

Trunk musculature

Williams, 1929

Schlumberger and Lucké—Tumors in Fishes 677
| Tasiz 10: Caonproma
Species Site Author

Crucian carp Carassius carassius (3) Skull bones Mulsow, 1915
Barbel Barbus fluviatialis Mandible Surbeck, 1917

a pike Elops saurus Subcutaneous Surbeck, 1921
Minnow Phoxinus : Mandible André, 1927
Dogfish Squalus mitsukurii Lumbar vertebrae Takahashi, 1929
Codfish Pollachius virens Pre-orbital Thomas, 1932d
Cat shark Scylliorkinus canicula Skin Thomas, 1933b

fish Momichropis bimaculatus Operculum Nigrelli & Gordon, 1946

ee

carassius. The tumors were massive and nearly filled
the cranial cavity. These cases were cited by Thomas
(1932 b) and illustrated by Plehn, 1924.

_ Surpecx, 1917: In a very lean barbel Barbus fluvia-
tialis a tumor was found in the posterior region of the
mandible. Approximately 1.5 cm. in diameter, it was
td by the apposition of 2 spherical masses. The
in over the anterior nodule was ulcerated, the mass
1S , The posterior nodule was composed en-

: oo, 1921: A sea pike Elops saurus, 100 cm. in
Jength, bore a pedunculated tumor the size of 2 fists on
‘its ventral surface behind the pectoral fins. It con-
sisted of dense plaques of fibrous tissue and cartilage.
_ Anpré, 1927: A minnow Phoxinus had a peduncu-
| mulberry-like mass attached to the tip of the
mandible. The overlying skin was deeply pigmented,
the head was pulled down by the weight of the tumor.
Histologically, the tumor consisted of hyaline cartilage.
TAKAHASHI, 1929: A tumor, 10 x 7 x 5 cm., arose in
the region of the third to sixth lumbar vertebrae of a
dogfish Squalus mitsukurii. The overlying skin was ul-
cerated. The tumor, which consisted of hyaline carti-
lage, was fused with the third lumbar vertebra and
showed a central area of liquefaction necrosis the size of

_ THomas, 1932 d: Two symmetrical pre-orbital tu-
‘mors, each measuring 1.5 x 3 cm., were found in a 6
year old codfish Pollachius virens. Covered by intact
skin, they were broadly sessile upon the lachrymal bones,
but were separated from them and adjacent tissues by a
fibrous capsule. The tumors were very firm, partly
calcified, and consisted of typical cartilage cells em-
bedded in a fibrous matrix.

_ Tuomas, 1933 b: On the right flank below the pec-
toral fin of a cat shark Scylliorkinus canicula was a
tumor, the surface of which was partly denuded. It
arose from the connective tissue of the corium and
possessed a peripheral zone of hyaline cartilage; the
central portion was calcified.

Nicrevxr and Gorpon, 1946: When first observed the
tumor appeared as a small swelling at the anterior
margin of the right operculum of a jewel fish Hemi-
chromis bimaculatus. Within two months it had attained
size of 13 x 6 x 4 mm. The total length of the fish was
: the tumor proved to be an osteo-
(iiadiecmns consisting chiefly of hyaline cartilage ar-
ranged in a more or less irregular pattern. The fish was
——— of the

same species and strain that were kept in a 150 gallon
aquarium.
OSTEOMA

Osteomas are tumors frequently observed in 15
species of fishes (Table 11). The multiple osteomas
in a butterfly fish reported by William Bell in 1793
is probably the first recorded account of neoplasm
in a fish. The tumors in this case were the size of
hazel-nuts and involved several haemal and neural
spines. Since similar lesions were found in several
specimens, the fish were classified as a separate spe-
cies; viz., Chaetodon arthriticus. The tumor-bearing
fish are, however, now grouped with the normal
members of the species Platax pinnatus.

Several Japanese investigators (96, 175, 199)
have described localized bony overgrowths on the
ventral spinous processes (haemal spines) of the
sixth to eighth caudal vertebrae of the red tai, Pag-
rosomus major. The largest series, consisting of 102
fish, was reported by Takahashi (199). The growths
varied from the size of a pea to that of a large bean;
rarely were they as large as a walnut. In 28 cases
the tumor was single, in 64 there were 2 tumors; in
17, 3; and in 10, 4 or more. A line of fracture was
visible in several of the very small tumors. Taka-
hashi concludes that ossification of excess callus is
the initial step in the formation of these tumors.

Three specimens of Pagrosomus major were cho-
sen by us at random from the collection at the Na-
tional Museum in Washington, and one bore tumors
identical with those described by Takahashi (Fig.
25). Careful inspection of the roentgenograms (Fig.
26) and histologic sections failed to reveal convinc-
ing evidence of previous fracture. The cortex, which
is very thin in the normal spinous process, was
greatly thickened (Fig. 27). As the growths in-
creased in size the cancellous bone became more
prominent until only a thin cortical layer of dense
bone remained (Fig. 28). The marrow spaces were
filled with well vascularized adipose tissue; hema-
topoiesis does not occur in the bone marrow of
fishes, hence its absence in the osteomas could be

anticipated.

678” Cancer Research
Taste 11: Ostroma
Species Author

Butterfly fish Platex pinnalus Neural any haemal spines Bell, 1793

Scabbard fish Lepidopus sp. Dorsal fin rays Gervais, 1875

Butterfly fish Platax pinnalus Vertebral spines Gervais, 1875

Pike Esoxlucius _ Dental plate Bland-Sutton, 1885

Codfish Gadus morhua Superior maxilla Bland-Sutton, 1885

Codfish Gadus morhua Intervertebral disc Bland-Sutton, 1885

Pike Esox luctus Vertebra . Plehn, 1906

Flounder Psetia macotica Vertebral spines Schroeders, 1908

Carp Cyprinus carpio Skull bones Fiebiger, 1909c

Codfish Gadus morhua Vertebrae Williamson, 1913

Croaker Pogonias chromis Two vertebrae Beatti, 1916

Red Tai Pagrosomus major (6) Mandible, haemal spines Kazama, 1924

Red Tai Pagrosomus major (2) Haemal spines Sagawa, 1925

Codfish Gadus morhua Pre-maxilla Williams, 1929

Coalfish Theragra chalcogramma (8) Dorsal fin spines Takahashi, 1929

Flatfish Paralichthodes olivaceus Vertebral spine Takahashi, 1929

Red Tai Pagrosomus major (102) Haemal spines Takahashi, 1929

Rock fish Sebastodes inermis Dorsal fin Takahashi, 1929

Speckled trout Salvelinus fontinalis Fin rays Thomas, 1932b

Cat shark Scylliorhinus canicula Skin Thomas, 1933b

Red Tai Pagrosomus major Haemal spines Lucké & Schlumberger
(not published)

Angelfish Chaetodipterus faber (4) First haemal spine Lucké & Schlumberger
(not published)

Angelfish Chactodipterus faber Shoulder girdle Lucké & Schlumberger
(not published)

File fish Alutera schoepfi First interneural spine Lucké & Schlumberger
(not published)

In considering the etiology of these tumors the
following characteristics must be taken into ac-
count: their frequent occurrence in a particular spe-
cies, the predominance of the tumors in the spines
of the sixth to eighth caudal vertebrae, and the
predilection of the tumors for fishes over 20 cm. in
length. A traumatic origin, as suggested by Taka-
hashi, and Kazama (96) does not adequately ex-
plain all these features of the neoplasm. An eluci-
dation of the problem must await study of the tumor
in the living animal.

Chabanaud (27) has described a localized fusi-
form hypertrophy characteristic of certain spines of
the dorsal fin in several species of fishes—Corvina
ath . nigrita, and Sciaenoides perarmatus.

The enlargement of the spines was absent in very
young fish, but became manifest with increasing
age. The author concluded that these hypertrophies
were not accidental, but might be “integrated with
the metabolism of the species.”

Dr. L. P. Schultz, ichthyologist of the National
Museum in Washington, called our attention to
similar changes in the angelfish Chaetodipterus
faber. In old individuals of this species a localized
hypertrophy of the distal portion of the first inter-
haemal spine tends to develop (Figs. 29 and 30).
The enlargement may become massive, in some in-
stances measuring as much as 4.5 x 3 x 2.5 cm.
Histologic examination revealed that the tumor con-

sists of cancellous bone and concentrically arranged
bands of more condensed osseous tissue (Fig. 31).
A similar laminated structure is found in the otoliths
of fishes, where it is believed to result from periodic
(seasonal) fluctuations in the rate of growth. The
adipose tissue that had filled the marrow cavity was
still recognizable in some regions, but elsewhere had
almost disappeared. This overgrowth of bone prob-
ably represents a hyperostosis, rather than an
osteoma.

Reports of the sporadic occurrence of osteomas in
various species of fishes are not uncommon. The
tumors are usually found in the fin rays and verte-
bral spines, though the maxillae have been affected
twice, and Fiebiger (49) reports an osteoma the size
of a child’s fist that arose from the frontal bone of
a 900-gram carp Cyprinus carpio. A sagittal section
of the head revealed that much of the cranial cavity
had been obliterated by the growth.
the tumor consisted of bone and cartilage that in its
arrangement resembled normal endochondral bone
formation.

The collection of fishes in the National Museum
contains the bones of an angelfish Chaetodipterus
faber found in a Florida Indian kitchen-midden.
Several of the spines bear symmetrical hyperostoses,
and an irregular bony overgrowth which may be
classified as an osteoma is present on one of the
bones (cleithrum) of the shoulder girdle (Fig. 32).

Schlumberger and Lucké—Tumors in Fishes

679

_ Also in the collection is the skeleton of a file fish
_ Alutera schoepfi in which a large osteoma arises
tice from the first interneural spine (Fig. 33).

Abstracts of other reported cases of Osteoma

__ exactly the same tumours, and the fishermen informed

__ me they were always found in this fish: and therefore

__ conclude them to be natural to it. In Mr, Hunter’s col-
lection are two or three of these bones, but I never

____ knew what fish they belonged to . . . These tumours are
__ _Spongy, and so soft as to be easily cut with a knife; they

_ were filled with oil.” (See discussion at beginning of

this section.)

__ Gervais, 1875: In a scabbard fish Lepidopus sp.
there were numerous osteomas on the dorsal fin rays.

___ Gervais, 1875: The author points out that many

af are found in fossil as well as in living
fish. In both they are most common in the vertebrae
and fin rays. Gervais found a large osteoma in the fin

ray of a butterfly fish Platax pinnatus.

Bianp-Sutton, 1885: The author describes a bony
tumor that occurred on the dental plate of a pike Esox
Jucius. Scattered through the tissue were delicate spic-
ules of bone. f

_ Branp-Sutton, 1885: From the maxilla of a codfish
Gadus morhua there arose a heavy, bony, disc-shaped
tumor, 2 inches in diameter and half an inch in thickness.

Bianp-Sutton, 1885: An exostosis (osteochondro-

_™a?), 1 cm. in diameter, grew from the vertebrae of a
_ codfish Gadus morhua. It developed from the cartil-
aginous intervertebral discs.

_ Prenn, 1906: A stony-hard tumor the size of a wal-
nut arose from the last vertebra of a pike Esox lucius.
The author identified the growth as an osteoma.

_ ScHroepers, 1908: Multiple osteomas were found on
the vertebral spines of a flounder Psetta maeotica. The
tumors, 15 in number, ranged from the size of a pin-
head to that of a walnut and were attached to the bony
rays. All were covered by normal skin and were firm

im consistency. Histologically they resembled normal

WrirAMson, 1913: The author reports the case of a
bone tumor in a codfish Gadus morhua. The site of ori-
gin was a vertebral body.

Beattt, 1916: Multiple osteomas of two vertebrae in
a ctoaker Pogonias chromis were described. The author
states that he has seen several such lesions in this species
of fish.

Kazama, 1924: Osteomas were found in 6 of S00 red
tai Pagrosomus major examined. In one the tumor ap-
peared as a nodular mass as large as a thumb-nail at the
middle of the mandible. In the other
multiple, developing on the ventral
at the site of union with the anal fin. The author
gests that trauma evoked the lesions.

SaGawa, 1925: In each of 2 red tai Pagrosomus
a tumor the size of the tip of the little finger grew
spinous process of one of the caudal vertebrae.
tologically, the lesion was an osteoma.

WrtraMs, 1929: A protuberance 5 x 2 cm.,
from the anterior portion of the left premazxilla
codfish Gadus morhua. The overlying skin
The microscopic structure was that of
with Haversian canals and vascular spaces.

TAKAHASHI, 1929: The author reports 8
exostosis (osteochondroma ?) in Theragra chalcogram-
ma. In 6 fish, tumors occurred in the the dor
sal fin; some were as large as a small hen’s egg, and
one was certainly an osteoma. In the remaining 2 cases

present
near the posterior margin of the operculum.
TAKAHASHI, 1929: A spherical, firm, bony tumor
occurred on the spinous process of the third lumbar
vertebra of a flatfish Paralichthodes olivaceus. Pressure
by the tumor had produced local atrophy of the adja-
cent vertebral body.
Tuomas, 1932 b: A 5S year old speckled trout Salve-
linus fontinalis bore many firm, white nodules, between
3 and 7 mm. in diameter, at the base of the rays support-
ing the ventral portion of the caudal fin. The overlying
skin was normal, except for an absence of pigment in
some areas. Stages of transition between fibroblasts and
osteoblasts were noted. The appearance was that of
connective tissue in which a bony metaplasia was taking

THomas, 1933 b: On the back of a cat shark Scyllior-
hinus cannicula, immediately anterior to the dorsal fin,
was a firm white tumor 4 x 6 mm. Much of the tumor
consisted of osteoid tissue, yet in some areas osteoblasts
were present and true bone was formed.

ELE

oa #8

rT
Ha

5:
g,

OSTEOSARCOMA

Four tumors of fishes have been reported in the
literature as osteosarcomas (Table 12). One was
observed in a pike Esox lucius, the remaining 3 oc-
curred in codfish Gadus morkua and Pollachius
virens. The series is small and the diagnoses so
open to question that no conclusions can be drawn
as to the general characteristics of this tumor among
fishes. The tumors were all single; no metastases

Species Site Author
Pike Esox lucius Anal fin secs ag i
Codfish species not given Operculum urray,
Codfish Pollachius 5 Vertebra Williams, 1929
Codfish*"Gadus morhua Pectoral"fin Thomas, 1932b

eo:
680,

Cancer Research

were observed. There is no evidence of malignant
transformation of one or several of the multiple
osteomas noted in the preceding section.

Abstracts of reported cases of Osteosarcoma

WAHLGREN, 1873: A nodular growth 8 x 5.5 cm. was
present on the anal fin of a 3-foot pike Esox Iucius. The
overlying skin was intact. On section the tumor had the
appearance of bacon and was traversed by irregular
bony trabeculae. Microscopically the soft tissue con-
sisted of small, irregular cells with one or more nuclei.
The cells were surrounded by partially hyalinized con-
nective tissue.

Murray, 1908: In the subcutaneous tissue of the
operculum of a codfish was a hemispherical bony tumor
measuring 2 cms. Histologically it was composed of
irregular rounded masses of osseous tissue separated by
strands of spindle cells. Thin walled, irregularly ar-
ranged capillaries were numerous.

WittraMs, 1929: Arising from one of the vertebrae
of a codfish Pollachius virens was a tumor that infiltrated
the adjacent muscle in all directions. Histologically it
consisted of bone trabeculae and spindle cells.

Tuomas, 1932 b: Immediately behind the left pec-
toral fin of a young codfish Gadus morhua was a tumor
4.5 x 2 x 1.5 cm. that bulged into the peritoneal cavity
and infiltrated the adjacent trunk muscles. The neo-
plasm was soft, the cut surface was gray-white and
marked by many punctate hemorrhages. Among the
pleomorphic cells were plaques of osteoid tissue and
multinucleated giant cells.

LIPOMA

The fat storage depots of fishes correspond with
those of man, though the subcutaneous tissues are
not as heavily infiltrated. Nevertheless, in a catfish
Pygidium totae found in Lake Tota, Colombia, these
subcutaneous stores reach enormous proportions
(Fig. 34). Dr. L. P. Schultz, ichthyologist of the
National Museum, Washington, D. C., is undecided
whether the adiposity is characteristic of this species,
or whether it represents an abnormality. Histologic-
ally the tissue is composed of adult fat cells, the
subjacent trunk musculature is not invaded, and the
overlying skin is normal, without evidence of atro-
phy (Fig. 35). If this subcutaneous accumulation
of fat is pathologic for the fish, it should probably
be classified as a lipodystrophy rather than as a
true lipoma.

_ Discrete lipomas have been reported 7 times in
the literature; each tumor in a different species of
fish (Table 13). All but 2 of the tumors were com-
posed of adult fat cells. Takahashi (199) observed
a lobulated lipoma, the size of a small nut, in the
subcutaneous tissue behind the left eye of a Japa-
nese samlet Plecoglossus altivelis. The tumor was
well encapsulated, the fat cells varied in size, and
the nuclei were oval or star-shaped. In 1929 Wil-
liams (228) reported a smooth spherical encap-
sulated tumor that had displaced the right eye of a
dragonet Callionymus lyra. Histologically, it con-
sisted of fat cells which the author believed had
undergone malignant transformation. The connec-
tive tissue supporting stroma was myxomatous.

Abstracts of other reported cases of Lipoma

BERGMAN, 1921: On the trunk of a lake pike Esox
lucius there was a subcutaneous tumor the size of a
man’s fist. Histologically the lesion was a lipoma.

BERGMAN, 1921: Beneath the skin of the pigmented
surface of a plaice Pleuronectes platessa was a tumor
that measured 6.5 x 3.5 x 3 cm. It was easily separated
from the surrounding tissue and had produced a groove
in the back musculature by pressure atrophy. It weighed
25 gm., was firm but elastic, and floated in water; its
parenchyma was composed of adult fat cells.

Kazama, 1924: Within the ventral trunk rnicaliatite
of a flounder Paralichthys olivaceus was a tumor about
the size and shape of a little finger. It was encapsulated,
soft in consistency, and made up of fat cells.

WritiaMs, 1929: Protruding into the posterior por-
tion of the body cavity of a halibut Hippoglossus hippo-
glossus was a tumor that measured 27.6 x 12.5 cm. It
arose between the muscle bundles of the trunk. The cut
surface appeared oily, was pale yellow, and had the con-
sistency of cheese. Histologically the tumor was com-
posed of well differentiated fat cells.

Tuomas, 1933 d: A coalfish Pollachius carbonarius,
approximately 7 years old, bore a tumor, 3 x 2.5 x 2 cm.,
on the lower border of the liver. The surface was
smooth and greenish, and covered by normal peritoneum.
On section it was soft in consistency, homogeneous and
without apparent fibrous trabeculae. The tumor con- —
sisted of adult fat cells, among which were islands of
hematopoietic tissue.

LEIOMYOMA
The four cases of smooth muscle tumors reported

Taste 13: Liroma

Species Site Author
Plaice Pleuronectes platessa Subcutaneous Bergman, 1921
Pike Esox Ilucius Subcutaneous on trunk Bergman, 1921
Flatfish Paralicthys olivaceus Trunk muscle Kazama, 1924
Halibut Hippoglossus hippoglossus Trunk muscle Williams, 1929
Dragonet Callionymus lyra Subcutaneous on head Williams, 1929
Jap. samlet Plecoglossus altivelis Subcutaneous Takahashi, 1929

Coalfish Pollachius carbonarius

Liver

Schlumberger and Lucké—Tumors in Fishes

681

in fishes (Table 14) are not convincingly neoplastic
im character. In the three instances involving the
of hyperplasia than of true tumor; one was asso-
ciated with a parasitic infestation of the pyloric
appendages. Plehn (157) reported a leiomyoma in
a shiner Alburnus lucidus that arose in the trunk
musculature, was infiltrated by lymphocytes, and
_ contained minute hemorrhages. If the diagnosis of
leiomyoma was correct, the tumor probably had its
_ origin in the smooth muscle of blood vessels.

_ Abstracts of reported cases of Leiomyoma

_ Penn, 1906: On the ventral surface near the cardiac
_end of the stomach of an 8 or 9 year old rainbow trout
_ Salmo gairdnerii was a bean-sized mass. The overlying
Mucosa was intact. Histologically the cells were identi-

_ cal with the normal musculature of the intestine; only
_ the irregular arrangement was abnormal. No mitoses or

_ inflammatory cell infiltrates were present.

- Prenn, 1906: In the trunk musculature of a shiner
| Allburnus lucidus between 1 and 2 years old, was a firm
ame | cm. wide. Histologically it con-

_ sisted of interlacing bundles of smooth muscle containing
small “round cell” infiltrates and minute hemorrhages.
_ Mitoses were uncommon.

2 _ Pesce, 1907: The stomach wall near the pylorus of
sa a trout Salmo carpio was greatly thickened. The pyloric
a were filled with cestodes. Histologically the
‘cellular detail and organization differed greatly from
__ what is regarded as normal in this region. The irregular
_ fasciculi embedded in loose connective tissue meshes

were diagnosed as fibroleiomyoma.
_ Tuomas, 1933 c: In a male, 3 year old herring
- Clupea harengus, 18 cm. long, the pyloric segment of the
_ anterior gastric pouch was markedly hypertrophied. It
~ formed a cone-shaped, white mass that was covered by
The lumen of the stomach was normal.
“Histologically the mucosa and serosa were intact, the
wall from two to three times its normal thickness.
_ Oblique, regularly arranged connective tissue trabeculae
formed partitions in the mass which consisted chiefly
of smooth muscle fibers. There was no evidence of in-

vasion of the surrounding structures.

is. RHABDOMYOMA

2 Rhabdomyoma has been reported in 8 species
(Table 15). The record of twice as many tumors
_____ of striated muscle as of smooth muscle is probably

: due to the common location of rhabdomyoma in the
trunk musculature where they are more readily ob-

served. Histologically the tumors closely resemble
similar tumors found in man. Noteworthy is the
report by Young (235) of a rhabdomyoma in each
of two turbot. The fishes had been sent from Eng-
land to New Zealand and kept there for ten years
in separate tanks. Tumors measuring 3%4 by 1%
inches developed in both turbot at approximately
the same time and in the same location on the non-
pigmented side of the body. The neoplasms were
soft and yellow, and histologically consisted of large
striated muscle fibers, many of which were edema-
tous and had partly disintegrated.

The only rhabdomyoma that did not arise in the
trunk musculature was reported by Fiebiger (48).
It was found in the viscera of a codfish Pollachius
virens and measured 12 x 9 x 6 cm. The tumor was
encapsulated and could easily be separated from
the surrounding organs. Small cysts and groups of
cells that resembled hepatic cells were present among
the striated muscle bundles. This suggests that the
growth may have been primarily a teratoid tumor
in which the muscle fibers formed the predominant
element.

Abstracts of other reported cases of Rhabdomyoma

Apa, 1908: A red trout Salmo clarkii bore a 3 cm.,
spherical tumor on its left side 4 cm. behind the dorsal
fin. It was embedded in the musculature and projected
1.5 cm. above the general body surface. The tumor was
well circumscribed and separated readily from the sur-
rounding tissue. Histologically it was composed almost
wholly of multinucleate giant cells. Several of these
were of great length and resembled regenerating muscle.
In not a few, the part of the cell farthest from the
grouped nuclei showed definite striations.

BERGMAN, 1921: On the right side of a stint Osmerus
eperlanus, directly behind the head, was a tumor, 1.5 x
1 x 1.2 cm. The gray-white mass had the consistency
of normal muscle and extended to the vertebral column.
Histologically it was well circumscribed by a thin fibril-
lar capsule. The parenchymal cells were transversely
striated muscle fibers and myeloblasts in various stages
of development.

Kortmer, 1928: A tumor was present in the trunk
musculature of an adult tench Tinca tinca. The over-
lying scales in this region were approximately twice
normal size. Microscopically the tissue consisted of
irregularly arranged striated muscle fibers that formed
a typical rhabdomyoma.

Lapreyt, 1930: Near the posterior border of the
right pectoral fin of a wrasse Labrus mixtus was a pea-

E Taste 14: Letowroma

: Species Site Author
Rainbow trout Salmo gairdnerii Stomach wall Plehn, 1906

Shiner Alburnus lucidus Trunk muscle Plehn, 1906

‘Trout Salmo carpio Stomach wall Pesce, 1907

Wall of stomach Thomas, 1933c

68P Cancer Research

Taste 15: Reaspomyoma

Species Site Author
Red trout Selmo darkii Trunk muscle Adami, 1908
Codfish Pollachius virens Viscera Fiebiger, 1909b
Stint Osmerus eperianus Trunk muscle Bergman, 1921
Turbot Rhombus maximus Trunk muscle Young, 1925
Tench Tince tinca Trunk muscle Kolmer, 1928
Wrasse Lebrus mixtus Trunk muscle Ladreyt, 1930
Herring Clupes harengus Trunk muscle Williams, 1931
Halibut Hippoglossus hip poglossus Trunk muscle Thomas, 1932a

sized tumor. The overlying skin was ulcerated, the sur-
rounding musculature infiltrated by the neoplasm. His-
tologically it consisted of fusiform and giant cells as
well as myocytes. The author attempted to trace the
evolution of the connective tissue cells into mature
muscle fibers.

WiiuraMs, 1931: In a herring Clupea harengus, 24
cm. in length, a tumor 3.1 cm. in diameter arose in the
dorsal musculature immediately anterior to the dorsal
fin. The overlying skin was intact. Histologically only
the muscle fibers in the periphery showed striations.

Tomas, 1932 a: Along the ventral border of a hali-
but Hippoglossus hippoglossus was a tumor measuring
1.7 x 1.5 cm. On section it was pearly white and finely
fasciculated. There were no metastases. Histologically
the posterior portion of the tumor consisted of undif-
ferentiated cells, but toward the anterior region the
normal myomeric architecture was approached. A pseu-
docapsule was present, the result of pressure on the
adjacent myomeres which were infiltrated by the tumor.
The author discussed the embryology of fish striated
muscle and recognized many of the transitional forms
in this tumor.

HEMANGIOMA

Hemangiomas have been reported in 11 species
(Table 16). The earliest, and to date most interest-
ing account of such tumors is that of Plehn (157).
She observed three cases in the stickleback Gasteros-
teus aculeatus and states that these growths occur
frequently in this fish. The tumors, which were
deep red in color, arose on the ventral surface of
the head, spread forward to the angle of the mouth,
and thence over the operculum to the level of the
eyes. They seemed to cause little functional em-

barrassment. The proliferation and dilatation of the
vessels began in the corium and subcutaneous tis-
sue, then infiltrated the tissues between the gill
arches and hyoid bone. Solid cords of endothelial
cells finally penetrated to and partly replaced the
subjacent muscle.

Johnstone has reported 7 of the 12 recorded cases
of vascular tumors in fishes. He identified 5 as
examples of angiosarcoma; however, histologic data
in support of this diagnosis are meager. Several of
the lesions reported by investigators may represent
a local inflammatory response rather than a true
neoplasm; Drew, for example, found a copepod
within the lesion in one of his cases.

Abstracts of other reported cases of Hemangioma

Murray, 1908: In the pectoral girdle of a codfish
Gadus morhua there was a flat, dark-colored growth
about 1.5 cm. in diameter. Microscopically it consisted
of capillaries distended with blood.

Drew, 1912: A reddish tumor was present in the mid-
line on the ventral surface of the head of a spotted ray
Raja maculata at the level of the fifth gill arch. His-
tologically the appearance was identical with that of a
hemangioma of man. The body of a copepod was found
within the tumor.

Drew, 1912: A nearly spherical tumor, 1 inch in
diameter, was found in the region of the basi-hyal bone
of a conger eel Conger conger. It was white and covered
by an irregularly thicknened and ulcerated epidermis.
The central portion of the tumor was necrotic. The
neoplasm was made up of masses of endothelial cells
which in some regions arranged themselves in long
columns that suggested capillary formation.

Drew, 1912: A soft, red tumor was present on the

Taste 16: Hemanoroma

Species Site Author
Stickleback Gasterosteus aculeatus (3) Subcutaneous, head Plehn, 1906
Codfish Gadus morhua Pectoral girdle Murray, 1908
Spotted ray Raja maculaia Subcutaneous Drew, 1912
Conger cel Conger conger Region of basi-hyal Drew, 1912
Gurnard Trigla lineata Operculum Drew, 1912
Stickleback Pungitius pungilius Iris Johnstone, 1915
Mackerel Body wall Johnstone, 1924
Codfish species not given Swim bladder Johnstone, 1925
Ling Molea molea Body wall Johnstone, 1925
Plaice Plewronectes platessa Body wall Johnstone, 1925
Codfish Pollachius virens Trunk musculature Johnstone, 1926
Hake Merluccius merluccius Submucosa of rectum Johnstone, 1926

Schlumberger and Lucké—Tumors in Fishes

683

2% _ inner surface of the operculum of a gurnard Trigla
2 lineata. Histologically it consisted of a mass of dilated

___ Jounstone, 1924: In the body wall of a mackerel
_ Scomber scombrus was a soft, red tumor, 5 x 1.5 cm.,
that infiltrated the adjacent musculature. It was com-
_ posed of dilated capillaries supported by proliferating
_ Jounstone, 1925: In the swim bladder of a codfish
was a tumor that apparently arose from the plexus of
_ vessels normally present in this region. It consisted of
_ numerous dilated vessels supported by a loose connective
tissue stroma infiltrated by collections of lymphoid

_opngtngg 1925: A firm mass, 2 x 4 inches, was
the trunk musculature of a ling Molva molva.
A central dark area was interpreted by the author as
____ ¢lotted blood; the periphery consisted of many dilated
___-wessels, capillaries, and proliferating angioblasts.

ern A the

accompanying connective tissue stroma.

Jounstone, 1926: The last 3 inches of the rectum
of a hake Merluccius merluccius was swollen, deep red
in color, and resembled a huge blood clot. On section
the mucosa and submucosa were almost replaced by

_ dilated vascular spaces, ay of which contained ac-

’ LYMPHOSARCOMA

A discussion of lymphosarcoma in fishes must be
introduced by pointing out that circumscribed col-
-lections of lymphoid tissue in the form of nodes, do

ae eT Be

not occur in these animals. They are found in the
phylogenetic scale only in some birds (aquatic) and
in all mammals (93). In elasmobranch fishes, hema-
topoiesis takes place in the spleen, the mesonephros,
the submucosa of the intestine, and the subcapsular
tissue of the gonads. In teleosts the mesonephros is
generally the dominant hematopoietic organ; the
spleen and submucosa of the intestine have only an
accessory role. This distribution of the hematopoie-
tic tissue accounts for the frequent location of lym-
phosarcoma in the kidney; i.e., in 15 of the 20 re-
ported cases (Table 17).

In the older reports lymphosarcoma has not al- _
ways been separated from other forms of sarcoma; it
is probable that several of the tumors which in this
review are included in the latter group are in fact
lymphosarcomas.

Plehn (162) observed that the kidney of a gold-
fish Carassius auratus was increased to 20 times its
normal size. The organ was firm and white; the
normal renal tissue had been almost wholly replaced
by lymphoid elements. Metastases were found in
the liver. The author believes that renal insuffi-
ciency accounted for the generalized edema that
was present. In a herring Clupea harengus, measur-
ing 30 cm. in length, Johnstone (91) found an
intracoelomic tumor, 5 x 2.5 cm. Histologically it
was composed of connective tissue stroma packed
with lymphoid cells. It is probable that the sub-
capsular tissue of the gonads was the primary site
of the neoplasm. Recently, Nigrelli (142) has re-
ported several interesting cases of metastasizing
lymphosarcomas. Twelve fully grown pike Esox
luctus, kept in one tank, succumbed at various inter-
vals at the N. Y. Aquarium during the years 1940
and 1941. Both sexes were represented. There were
no external manifestations of disease, but autopsies
showed comparatively massive growths in the kid-
neys, with metastasis to the spleen and liver. His-
tologically the tumors were identified as lymphosar-
comas composed mainly of large lymphoblasts sup-
ported by irregular strands of fibrous stroma and a
delicate reticulum.

Another metastasizing tumor was found in a male

Taste 17: Lywrmosarcoma

Species Site Author
Filatfish Retro-orbital Johnstone, 1912
Goldfish Carassius auratus Kidney Plehn, 1924
- Herring Clupea harengus Peritoneum Johnstone, 1926
Conger eel Conger conger Kidney Williams, 1931
Amer. salmon Salmo salar Kidney Haddow & Blake, 1933
Pike Esox lucius Subcutaneous Haddow & Blake, 1933
Trop. Aquar. Fish Rasbora lateristriata Peritoneum Smith, Coates, & Strong, 1936
Pike Esox lucius (12) Kidney Nigrelli, 1947
Characin Astyanax mexicanus Branchial! region Nigrelli, 1947

684 °

Cancer Research

a
characin Astyanax mexicanus measuring 50 mm. in
total length and about four years old. The growths
occurred in the branchial region and had caused
exophthalmia. The tumor probably originated in a
paired mass of lymphoid tissue normally present in
the posterior region of the branchial cavity. There
was considerable local invasion extending even to
the myocardium. Metastases were present in the
corium of the skin, the gills, kidneys, pancreas, and
liver.

Abstracts of other reported cases of Lymphosarcoma

Jounstone, 1912: The left eye of a plaice Platichthys
flesus was displaced by a retro-orbital tumor, measur-
ing 2x 2 cm. The growth consisted of connective tissue
stroma in which were embedded masses of lymphocytes
separated by large spaces, apparently lymph channels.

WitiiaMs, 1931: A very large bulge was seen in the
ventral wall of a conger eel Conger conger; the over-
lying skin was intact. Dissection disclosed a ret i
toneal tumor, 16 x 9 cm., in the region of the kidney.
Within the kidney the lymphoid tissue was greatly in-
creased and the renal tubules were widely separated;
mitoses were numerous.

Happow and Brake, 1933: In each kidney of a 5
year old American salmon Salmo salar there was a mass,
4.4 x 2.4 cm., that diffusely invaded these organs, re-
sulting in almost complete destruction of the renal
units. The haemal arch was occluded by a mass of
tumor tissue, apparently by direct extension from the
veins of the renal portal system.

Happow and Brake, 1933: Many subcutaneous tu-
mors were found about the bases of the fins and within
the buccal cavity of a partly decomposed pike Esox
lucius. The neoplastic tissue was gray in color and did
not infiltrate the surrounding musculature; visceral me-
tastases were absent. Grossly the lesions appeared mu-
coid or fatty in character; histologically they appeared
to be lymphoid in origin. The authors suggest lympho-
sarcoma as a possible diagnosis.

Smairn, Coates and Stronc, 1936: Neoplastic lym-
phoid tissue produced a mass that was first noted in the
upper abdomen near the liver in a tropical aquarium
fish Rasbora lateristriata. The intra-abdominal swell-
ing could be seen distinctly during life through the
semitransparent abdominal wall. After approximately
2 months the tumor had extended cephalad, involving
the gill on the right side and pressing the operculum
outward.

TUMORS OF PIGMENT CELLS

Fishes are provided with an abundance of pig-
ment cells, not only in the epidermis and subcutane-
ous tissues, but in the peritoneum, mesentery, vis-
cera, and central nervous system. The most common
of these cells in fishes as in other vertebrates are the
melanophores which elaborate melanin. The guano-
phores, laden with guanin crystals, and the iridio-

cytes, bearing crystals of inorganic salts, are respon-
sible for the white background and the iridescence
so characteristic of fish coloration. In addition,
most fishes also possess yellow-pigmented xantho-
phores and red-pigmented erythrophores (allo-
phores).

The close relationship of these variously pig-
mented cells has been generally accepted by investi-
gators, and their origin usually sought in a common
undifferentiated mesenchymal cell (8). In 1909
Borcca suggested that these cells may be derived
from the neural crest. In recent years investigators
working with amphibian and avian embryos have
accumulated convincing evidence that in these ani-
mals the neural crest does supply the pigment cells
(42). In the light of these findings it is probable
that the pigment cells of fishes have their origin in
neurectoderm.

MELANOMA

The most frequently observed pigment cell tu-
mors of fishes are the melanomas located in the skin
and subcutaneous tissues. They have been reported
in 12 species (Table 18). Whether they are pre-
dominantly benign or malignant cannot be clearly
established. Johnstone (82, 83, 85) and Prince
(165) reported cases in which the lesions were
multiple, but whether they represent metastases is
difficult to determine. Besides these sporadic ex-
amples, melanotic tumors are commonly found in
hybrids of the tropical aquarium fishes Xiphophorus
hellerii and Platypoecilus maculatus. First reported
by Haiissler (1928) and Kosswig (1929) they have
been thoroughly investigated by Gordon and his co-
workers (59 to 63, 169). Swordtails Xiphophorus
hellerii possess only micromelanophores, or no mel- —
anophores at all; platyfish Platypoecilus maculatus
bear both micro- and macromelanophores. It is the
platyfish macromelanophore factor introduced into
the hybrid that produces melanosis and melanotic
neoplasms. Although the dominant inherited factor
responsible for melanosis is that for macromelano-
phores of the platyfish, alone it is ineffectual. The
swordtail strain also plays its part in the production
of the lesion, since it contributes hereditary factors
that initiate the multiplication of the macromelano-
phores in the hybrids.

According to the descriptions of Reed and Gor-
don (169), the neoplastic disease begins as a densely
pigmented spot in the caudal fin. It increases in
size and merges with other pigmented regions until
a large area is involved. This stage has been ob-
served in day-old fish as well as in embryos 6 days
before hatching (59). Subsequently a local swell-

Schlumberger and Lucké—Tumors in Fishes

685

Taste 18: Metanoma

Site Author

Skin Prince, 1892

Skin of head Johnstone, 1911

Skin of head Johnstone, 1912

Skin of fins Johnstone, 1912

Skin of fins Johnstone, 1913

Skin (multiple) Johnstone, 1915

Skin Bergman, 1921

Skin of pigmented surface Johnstone, 1925

Skin Hatissler, 1928 & 1934

Skin Kosswig, 1929

Body wall Takahashi, 1929

Skin Takahashi, 1929

Skin Ingleby, 1929

Skin Reed & Gordon, 1931

Skin Haddow & Blake, 1933

Branchial region Dollfus, Timon-David &
ies Mosinger, 1938
Silverside Menidia beryllina peninsulae Skin Nigrelli & Gordon, 1944
_ Killifishes hybrids (11) Eye Levine & Gordon, 1946
_ Killifishes hybrids (many) Skin Gordon, 1948

ing develops due to proliferation of the pigmented
cells. The transition from melanosis to neoplasm
not abrupt, and in the early stages a distinction
between the two cannot be made. It should be

_ pointed out here that non-neoplastic melanosis is
not uncommon in fishes and has recently been re-

_ ported by Smith and Coates (189) in the lung fish.
_ The neoplastic cells may be devoid of pigment, a
condition frequently observed in the metastases of
human melanomas; or they may be very heavily

&

The growth of these melanomas in tissue culture
was studied by Grand, Gordon, and Cameron (63).
Recently Levine and Gordon (111b) have re-
ported on the occurrence of pigmented ocular tu-
mors in xiphophorin fishes. The species distribution
of the neoplasms was as follows: 1 Platypoecilus
maculatus, 1 Xiphophorus pygmaeus, 6 hybrid P.
maculatus—X . hellerii out of a brood of 15, 2 hybrids
out of a brood of 16, and 1 hybrid from a private
collector. All fish were full grown, at least 6 months
old and some over a year old, before the tumor
developed. The average life span of the normal
fish is about a year and a half. Exophthalmia de-
veloped gradually and was associated with blindness
of the. affected eye. The neoplasms were composed
chiefly of pigmented epithelioid cells. They arose
in the choroid, invaded the retina, later they per-
forated the eyeball and grew into the retroorbital
tissues. No bacterial or virus agent could be identi-
fied. Although the authors stated in their paper that
the tumor is not controlled by a genetic factor, more
recent work has convinced Dr. Gordon that the tu-

4 mors develop on a genetic basis (60a).

These tumors closely resemble the ocular neo-
plasms reported by Jahnel (80) and identified by
him as fibrosarcomas; these have been discussed in
the section on sarcoma. He likewise sought a genetic
basis for their occurrence.

A hitherto undescribed type of pigmented tumor
was found in a grouper Epinephelus gigas, by Doll-
fus, Timon-David, and Mosinger. It is of such in-
terest that we shall quote an abstract made by
Foulds (35a) in full. “The primary growth was al-
most certainly of branchial origin. In addition to
tumors in the branchial region there were smaller
subcutaneous tumors in the caudal, anal, and dorsal
fins and in the liver and spleen. Some of the tumors,
especially in the branchial region, were plainly epi-
thelial, resembling basal cell tumors of mammals.
Some of the cells were pigmented and, since pigmen-
tation seemed associated with an eosinophilic de-
generation, it appeared as if the melanin granules
represented a degenerative phenomenon. In the liver
and spleen, however, though almost all the tumor
cells were pigmented there was no sign of a degenera-
tive process; careful examination revealed rare tu-
mor nodules with cells like those in the branchial
tumors. None of the tumor cells resembled the
melanocytes characteristic of lower vertebrates.
Transitions were found between epithelial cells de-
void of pigment and melanotic cells in which the
abundance of pigment was explicable only by an
active production of melanin. The most likely hy-
pothesis is that the tumor cells of epithelial origin
acquired secondarily the power of forming melanin.
Previously described melanomas in fishes were pre-
dominantly sarcomatous in appearance. It is sug-

686 Cancer Research

"gested that the present tumor reopens the problem
of the histogenesis of melanoblastomas and that of
the specificity of the melanin-forming function.”

Abstracts of other reported cases of Melanoma

Prince, 1892: In a cachectic female haddock Melano-
grammus aeglifinus there was a brown tumor, 20 x 5
cm., just below the lateral line. The surface was ulcer-
ated, the surrounding skin inflamed. Three pigmented
spots were present near the tumor. Histologically both
pigmented and nonpigmented cells were seen; the under-
lying muscle was not invaded.

Jounstone, 1911: On the right side of the head,
behind the eye of a thorn-back ray Raja clavata, was
a black, elliptical tumor, 7.5 x 6 x 2 cm. The animal
was so emaciated that the skeleton was visible. The
skin over the neoplasm was intact, though infiltrated
by tumor cells. Histologically the growth was made up
of irregular interlacing bundles of spindle cells that
were heavily laden with pigment and had infiltrated the
surrounding tissues. No metastases were found.

Jounstone, 1912: A thorn-back ray Raja clavata, 2
feet in length, bore a spherical tumor 7 cm. in diameter.
The growth, which was located on the dorsum of the
head at eye level, was black and very soft. The pig-
mented tumor cells were short spindles that infiltrated
the adjacent tissues. At the posterior margin of one
eye was a firm white tumor apparently a fibroma,

Jounstone, 1912: Melanotic tumors were found in
the skin of two rays Raja batis. One of the fish was
caught off the coast of Ireland, the other near Scotland.
In one the growth was found on the pectoral fin; it
was small and was not examined histologically. In the
other fish a flat black tumor, 10 x 6 x 1 cm., was present
near the center of the dorsal surface of the left pectoral
fin. Several 1 cm. nodules were scattered elsewhere on
the fin surface; all were covered by normal epithelium.
The tumor cells were pleomorphic, rich in melanin
granules, and infiltrated the adjacent tissue.

JouNsToNE, 1913: Melanotic sarcomas were found in
two rays Raja batis. In one a flat pigmented lesion rose
a millimeter or more above the surface of a pectoral
fin. In the other, caught off the coast of Ireland at a
depth of 70 fathoms, and measuring 5 ft. in width,
there were many melanotic tumors scattered over the
surface. The largest was on the back, measured 15 x 7
x 2.5 cm., and was very soft. On section, the densely
pigmented spindle cells deeply invaded the adjacent
muscle.

JouNnstone, 1915: Scattered over the body surface
of a halibut Hippoglossus hippoglossus were numerous
tumor nodules. Histologically, they consisted of spindle
cells, some multinucleate, others containing melanin
granules. The tumor cells infiltrated the surrounding
muscle tissue.

BeroMan, 1921: On the right side of the tail of an
eel-pout Zoarces viviparus was a black tumor the size
of a hazel nut. Cross sections of the body revealed
strands of black tissue extending to the vertebrae and
diffusely infiltrating the muscle. Most of the cells were

spindle shaped with a homogeneous cytoplasm that oc-
casionally contained a few pigment granules. Other
cells were branched, rich in pigment, and not distinguish-
able from melanophores. The author believed that the
nonpigmented cells were melanophores that had de-
veloped too quickly for the pigment to form.

Jounstone, 1925: Behind the pectoral fin on the
pigmented side of a plaice Pleuronectes platessa was a
circular tumor 3 x 0.5 cm. with raised edges and a
mammillated surface, which was variegated black and
orange. The corium was increased in width by the
tumor cells, which resembled short thick connective
tissue cells; the masses of pigment were mostly extra-
cellular. The surrounding muscle was infiltrated.

HaUsster, 1928: Melanomas, derived from melano-
phores in hybrids of the swordtail Xiphophorus hellerii
and platyfish Platypoecilus maculatus, Mexican killi-
fishes, were large and infiltrative, though no metastases
were noted. The author reports 8 cases, involving 20
of the F, generation; there was one case in a male F;.
All tumors were located near the midline on the ventral
surface.

Kosswic, 1929: Melanotic tumors were observed in
hybrids of female Xiphophorus hellerii and male Platy-
poecilus maculatus. In Fy, the hybrids were much
blacker than the male Platypoecilus because the black
factor—Gene N—acts differently on the female Xipho-
phorus than on the female Platypoecilus. By again
breeding a dark hybrid with Platypoecilus, the pigmen-
tation became even more pronounced, and the prolifera-
tion of the melanophores formed small melanomas on
the surface; they also infiltrated the internal organs.

TAKAHASHI, 1929: In the middle of the left side of
the body near the lateral line of a coalfish Theragra
chalcogramma was a tumor that measured 9 x 5 x 5 cm.
It was mottled gray and black, rather soft in consistency
and sharply demarcated, except at its base. The tumor
cells were round, spindle, or starshaped, embedded in
an abundant vascular connective tissue stroma. On the
left side of another coalfish, more emaciated than the
last, was a soft, uniformly black tumor, infiltrating the
skeletal muscle. A subperitoneal, black, pea-sized nod-
ule of the same histologic structure was probably a
metastasis. The cells were oval, many contained pig-
ment granules.

TAKAHASHI, 1929: On the left side of a chub mack- .

erel Pneumatophorus colias was a tumor, 3 x 4 x 1.5
cm., which on section was yellow-brown in color. The
tumor parenchyma consisted of smal] round or oval
cells some of which contained small amounts of melanin.

actively infiltrated the surrounding tissue.
IncLeBy, 1929: A black warty tumor, apparently
arising in the subcutaneous tissue, was found in a

branched cells loaded with masses of pigment which in
most instances completely obscured the nuclei. The

é
+
ee ey ee a oe a

_ Schlumberger and Lucké—Tumors in Fishes

athor suggested. that the tumor represented 8 homo-
_ logue of the pigmented mole in man.

Happow and BLake, 1933: The authors report two
skin tumors in a thornback- ray Raja clavate. Both
_ neoplasms were sessile and lobulated. The larger mea-
sured 4 x 2.1 cm., was distinctly paler than the normal
skin, but contained scattered deposits of melanin; the
‘smaller, measuring 2 x 1.5 x 0.5 cm., was heavily laden

ate Recs weciel Each tumor was traversed by
coarse fibrous trabeculae and rifted with many thin-
_ walled blood sinuses. The melanin was present mainly
in the form of intracellular granules, though some was
found. in the tissue spaces.

Haisster, 1934: A second report by this author
about melanomas that occurred in hybrids of Xipho-
phorus and Platypoecilus. In the 5 cases presented the
‘tumors were found in the region of the tail and were
_ derived from macromelanophores. Whether the tumors
_ were benign or malignant was not established.
Nucretir and Gorpon, 1944: A melanotic tumor
“Was found in a silverside Menidia beryllina peninsulos.
_ The fish measured 4.7 cm. in length; the tumor covered
an area of 5 x 1.5 x 1.0 mm. and extended along the
‘sides of the body. In the normal fish a broad band of
_ melanophores forms a syncytium in the region of the
: lateral line; these may have been the cells of origin of
the tumor. Histologically, the pigment cell overgrowth
in this fish appeared to be quite like the melanotic

i tumors reported in hybrid killifishes by Reed and Gor-
don. The tumor contained melanin-bearing cells of dif-

ferent sizes, corresponding somewhat to the variations

| encountered. The cells spread laterally

Pe corium, though in some areas they penetrated the

epidermis as well as the underlying fascia, muscle, and
bone.

Nii

ERYTHROPHOROMA

eee sewing from the red pigment containing
_ erythrophores (allophores) have been reported in a
trout, a flatfish, a tunnyfish, a gurnard, and in
hybrid killifish (Table 19). The most detailed ac-
count is that of Smith (188) describing the lesions
in a flatfish Pseudopleuronectes americanus. A red
tumor, 3 x 2 cm., was situated on the pigmented
side 4 cm. behind the right operculum, where it in-
_ yaded the subjacent tissues to the depth of the ex-

i: ene maecies Similar though smaller lesions

were scattered over the body: 2 near
margin of the main mass, and 2 on
mented side. Visceral tumors were also
10 in the liver, 10 in the kidneys, and

throughout the thickened corium as far as the under-
lying muscle bundles. Frozen sections of fresh tumor
tissue showed small pigment granules, varying in
color from vermilion to orange, and present in many
of the cells. Smith regarded the large skin lesion as
the primary site of the tumor and the smaller
nodules as metastases.

In 1929 Kosswig reported erythrophoromas in
two male fish produced by back-crossing an F, red
finned black killifish hybrid to a pure line red-finned
platyfish. In subsequent experiments (104) he ob-
tained a similar lesion in an F, hybrid of Xipho-
phorus montezsuma and X. hellerii. Kosswig inter-
preted the lesion as a dominant mutation in a soma-
tic cell. Only in a single F, hybrid of X. hellerii
and Platypoecilus maculatus did typical erythro-

Abstracts of other reported cases of Erythrophoroma

TAKAHASHI, 1929: On the left side just behind the
head of a gurnard Chelidonichthys kumu was a tumor,
8.5 x 7 x 7 cm., which infiltrated the muscles down to
the vertebrae and bulged into the coelom.
it was greenish-brown and firm.
filtrated the surrounding tissue,
large vesicular nuclei and a scanty cytoplasm which in
some instances contained yellow-green pigment granules.
By chemical methods the cells were identified as allo-
phores, a term accepted as synonymous with “erythro-
phore.”

Tuomas, 1931 b: A subperitoneal erythrophoroma
was found in a tunny fish Gymnosarda alleterate, The
tumor was of the same size and color as a small orange,
lay at the level of the liver, and was covered by peri-

Taste 19: Exvrmeornoromus

Species Site Author
Gurnard Chelidonichthys kumu Skin Takahashi, 1929
_ Killifishes (Platypoecilus maculatus (9) Skin Kosswig, 1929, 1931
horus hellerii
Tunny a alleterata Peritoneum Thomas, 1931b
Trout species not given Skin Thomas, 1931b
P americ. Skin Smith, G.N., 1934

Skin

Smith, Coates & Strong, 1936

688

Cancer Research

toneum. Beneath the mesothelial cells of the peritoneum
there was considerable proliferation of branched ery-
throphores. The protoplasmic prolongations were uni-
formly stippled by granules of red pigment.

Tuomas, 1931 b: An orange-red tumor infiltrated
the posterior portion of the anal fin of a trout; the
branching erythrophores were embedded in a dense con-
nective tissue stroma. A small tumor, identical with
that on the fin, found on the surface of the peritoneum,
was interpreted by the author as a metastasis.

Smirn, Coates and Stronc, 1936: In a hybrid of
X. hellerii and P. maculatus the authors found a tumor
arising from the red pigment cells. Brick red in color,
it grew in the region of the dorsal fin, invaded the skin
and adjacent tissues but none of the deeper structures.
Microscopically the pigmented tumor cells were large,
round or fusiform, and bore occasional dendrites.

GUANOPHOROMA

Only a single example of a neoplasm taking origin
from guanophores is on record. Takahashi (199)
described a tumor, 7 x 5 x 1.5 cm., on the left side
near the caudal fin of a “fat cod” Hexagrammos
atakii. On section the tissue was silver-white and
had a peculiar sheen. Histologically, it was densely
infiltrated by short, yellow-white, needle shaped,
doubly refractile guanine crystals of great brilliance.
The crystals were present not only in the pleomor-
phic tumor cells but also in the interstitial tissues.

XANTHOPHOROMA

The only tumor purported to take its origin from
the xanthophores in the skin of a fish was reported
by Schroeders (179). An irregular orange-colored
tumor, the size of a bean, was located on the right
side of the trunk beneath and partly upon the dorsal
fin of a blenny. In the vicinity of this tumor were
several nodules the size of pin-heads. Histologically
the tumor consisted principally of large epithelioid
cells with vesicular nuclei and an orange-yellow pig-
ment in the cytoplasm. Single and multinucleated,
branched giant cells that also contained the pigment
were scattered through the tissue. The author be-
lieved that the cells were derived from the endo-
thelium of the lymphatic spaces and blood vessels.
The center of the mass was hemorrhagic and necro-

tic. Whether it was a true neoplasm or a granulo-
matous reaction to injury must remain undecided.

TUMORS OF NERVOUS TISSUES

Only 7 papers dealing with tumors of the nervous
system of 9 species of fishes were found in the
literature (Table 20). There is as yet no record of
a neoplasm of the brain or spinal cord: Takahashi
(199) and Haddow and Blake (68) each report a
ganglioneuroma arising in a spinal ganglion of a
flatfish. Thomas (203) observed a similar tumor in
a codfish and subsequently described a neuroepi-
thelioma of the olfactory plate in a gilthead (210).

One of us (118) has studied the common nerve
sheath tumors of the snappers Lutianidae. A total
of 76 tumor bearing fishes were collected, which
were members of three species: the gray snapper
Lutianus griseus, the dog snapper L. jocu, and the
schoolmaster, L. apodus. The neoplasms generally
occurred along the course of the larger subcutaneous
nerves, particularly those of the head and dorsal
regions, as solitary or multiple relatively large firm
white masses (Fig. 36). Histologically, they closely
resembled the human neoplasms of the nerve sheath
group and were composed of two kinds of tissue: one
compact and richly fibrocellular (corresponding to
the Antoni A type); the other loose, reticulated,
and poorly cellular (Antoni B type). Palisade for-
mations of nuclei and fibrils were found in approxi-
mately one third of the tumors (Fig. 37). In some
regions the neoplasms were very cellular, the com-
ponent cells forming characteristic whorls (Fig. 38).

Neurilemmomas of the autonomic nervous system _
have been reported by Young and Olafson (236) in
25 brook trout Salvelinus fontinalis. The tumors
were tiny and not readily visible to the naked eye.
The pancreas and mesentery were most extensively
involved. The tumors were uniform and characteris-
tic in their structure. A peripheral band of collagen
surrounded concentric layers of fibrous tissue; at
the center of the growths there often was a group
of polyhedral cells with a variable amount of eosino-
philic and finely granular cytoplasm. No inclusion
bodies were seen, nor were bacteria found in the

Taste 20: Tumors or Nervous Tissues

Species Site Author

Codfish Gadus morkua Body wall Thomas, 1927a
Flatfish Limanda yokohamae Spinal ganglion Takahashi, 1929
Gilt head Sporus auratus Olfactory plate Thomas, 1932c
Flatfish Lepidorhombus megastoma Spinal ganglion Haddow & Blake, 1935
Goldfish Carassius auratus Subcutaneous Picchi, 1933
Snapper Lutianus griseus

Lutianus apodus }(76) Subcutaneous Lucké, 1942

Lutianus jocu
Brook trout Salvelinus fontinalis (25)

Pancreas & mesentery

Young & Olafson, 1944

: Schlumberger and Lucké—Tumors in Fishes

689

_ tissues. The authors believe that the occurrence of
_ the tumors among inbred trout of all ages in a single
___ hatchery suggests that hereditary factors may play
a role in the genesis of the neoplasm.

Abstracts of other reported cases of tumors
of Nervous Tissues

_ Tomas, 1927 a: A tumor, the size of a fetal head,
_ projected from the lateral body wall in the anal region
_ of a codfish Gadus morhua. Histologically, the neo-
_ plasm consisted of fibrillar tissue among which were
_ Scattered islands of ganglion cells. The author believed
eS co fibrillar tissue represented a syncytium of Schwann

TAKAHASHI, 1929: Adjacent to several of the thoracic
in a plaice Limanda yokohamae was a tumor
x 2x 2.5 cm. The growth was soft, gray, and in-

jacent tissue. It consisted of myelinated
among which were many glial and nerve
nerve cells were very large, with relatively
nuclei bearing large nucleoli. The anatomic posi-

origin in a spinal ganglion.

s

1932 c: An adult gilthead Sparus auratus
large tumor that reached from the anterior
the orbit to the maxilla. Extensive destruc-
of and ethmoid bones had taken place;
skin was ulcerated. Epithelial rosettes and
present in some regions, lending a pseudo-
to the tissue. Many of the acini were
by columnar cells that frequently bore tufts of
connective tissue trabeculae were
of nerve cells that gave origin to neurofibrils,
traced throughout the section. The
identified the tumor as a neuroepithelioma of the

i

ue

Ht

Happow and Brake, 1933: A tumor that occupied

whole thickness of the distal end of the
found in a flatfish Lepidorhombus megastoma.
could not be determined accurately, but
it apparently lay in the position of a spinal ganglion.
_ The was composed of a fibrillar groundwork of
_ mervous tissue containing scattered groups of ganglion
cells. Osmic acid preparations demonstrated the neuro-
fibrils as nonmedullated. The ganglion cells were im-
perfect, degenerated, and vacuolated, possessing bipolar
- continuity with the nerve fibers of the tumor substance.

i

:
:

a many-layered capsule of pigmented cells; the central
| region was composed of long fine fibrils that did not
stain with van Gieson’s reagent; blood vessels were
scarce and thin-walled. The author identified the tumor
as a schwannoma. The growth did not recur after it
was removed. Pieces of the tumor were injected into
various cold-blooded animals—fishes, frogs, and sala-
_ manders, but in none was there any evidence of growth.

HAMARTOMA

Tumors arising in developmental faults have been
recorded only twice in fishes. However, it should
be noted that grossly abnormal development is not
infrequently observed among fishes raised in hatch-
eries (124). Similar anomalies have been reported
in amphibians (125, 181) and reptiles (34, 75).

Charlton observed a mackerel Scomber scombrus
in which no pineal organ could be identified and the
area was occupied by a series of epithelial folds. In
5 or 6 places, bead-like masses of hyaline cartilage
were found among the epithelial cells. The author
identified the lesion as a chondro-epithelioma that
had destroyed the pineal body but caused little dam-
age to the brain. A tissue malformation, this lesion
may perhaps be classified as a hamartoma.

Labbé, in 1930, found a whiting Merlangus mer-
langus in which the normal horizontal convolutions
of the intestine were absent, their place being occu-
pied by a tumor. The latter consisted of embryonic
epithelial cells separated by connective tissue trabe-
culae that were poorly vascularized. The author con-
cluded that this was a tumor of embryonic cell rests,
i.e., of cells which would have formed the mucosa of
the intestine if differentiation had proceeded nor-
mally. Like the preceding case, this may represent a
local tumor-like developmental fault.

TAXONOMIC DISTRIBUTION OF
TUMOR-BEARING FISHES

It is well known that there are distinct differences
in natural susceptibility to neoplastic growth for
different taxonomic groups. For example, Ratcliffe
(168a) in his extensive survey of tumors in captive
wild animals and birds found that in mammals the
digestive tract, and in birds the genito-urinary or-
gans, are the predominant sites. Moreover, the organ
incidence of the various orders, families and species
also showed interesting differences. Thus, among
birds the grass parrakeet, Melopsittacus undulatus,
had by far the highest incidence of renal tumors.
Many other comparable examples are given for do-
mesticated animals by Feldman (46a).

In fishes, differences in organ or tissue suscepti-
bility are also present. As a class, they are more sus-
ceptible to neoplastic processes of their connective
tissues than of other tissues. Tumors of nerve sheath
are more common in the snapper family, Lutianidae,
than among other groups; epithelioma of the lip is
the most frequent tumor of a species of catfish,
Ameiurus nebulosus, and multiple osteoma of the
haemal spines more often affects the red tai, Pagro-
somus major, than other species. However, the same
kind of tumor may be found in different species of

*

Cancer Research

690
>_—

fishes, taxonomically and geographically separated.
For example, epithelioma of the lip has been re-
ported in both salt and fresh water fishes; among
the catfish in the streams of Pennsylvania (122,
136), the barbels in German rivers (97), the tench
in a German pond (47), the eels from the brooks
and coastal waters of France (217), the stints from
the brackish water of the Jasmunder Bay on the
Baltic Sea (16), the coalfish in the North Atlantic
(228), and the croakers from the South Atlantic (7).

On the contrary, a single species may be affected
by a variety of tumors in different organs. For ex-
ample, in the pike, Esox /ucius, tumors have been
observed in the bones, muscle, subcutaneous tissue,
dental structures, ovary, kidney and thyroid; the
tumors include osteomas, osteosarcomas, fibrosar-
comas, lipomas, adenocarcinomas and lymphosar-
comas.

For convenience of reference, all tumor-bearing
fishes of which we were able to find records in the
literature, or which we have ourselves observed,
have been assembled in Table 21. The classification
of the fishes is one used by most ichthyologists.*
The table is arranged according to orders, families
and species of fishes, variety and site of tumor,
author and date of publication. Only the zoological
names are given; the common names may readily
be found by referring to the tables of the various
tumors. Inspection of Table 21 shows at once the
great preponderance of tumor-bearing bony fishes
over cartilagenous fishes; this may be readily ac-
counted for by the numerical superiority and greater
economic importance of the former group. Among
the bony fishes, nearly one-half of all species affected
are representatives of only 5 families, namely the
salmoids (Salmonidae—salmon, trout), the cypri-
noids (Cyprinidae—carp, dace, minnows, chubs,
barbels), the codfishes (Gadidae), the flatfishes
(Bothidae), and the flounders (Pleuronectidae).
Members of these families are not likely to be more
susceptible to neoplastic growth than other species;
rather they are caught in vast numbers for food and
hence more often examined.

Il. TUMORS OF AMPHIBIANS

Nearly all amphibians belong to one of two or-
ders: the Urodeles which retain their tails through-
out life such as the salamanders, and the Anura

* We are grateful for advice on this and other matters
concerning classification and nomenclature to Dr. Carl L.
Hubbs of the Scripps Institution of Oceanography and Dr.
Robert R. Miller of the National Museum.

which are tailed only in the larval stage (frogs,
toads). Although frogs and salamanders have been
used in laboratories throughout the world for a
century, remarkably few tumors have been reported
in these animals, perhaps because they have not
been looked for by investigators interested in on-
cology. There is no good reason for believing that
amphibians are less susceptible to neoplastic growth
than fishes or other vertebrates. For example, sys-
tematic search for tumors in one species of the com-
mon laboratory frog, Rana pipiens, has revealed that
these animals are commonly affected with adeno-
carcinoma of the kidney.

URODELES

In the literature there are only 7 reports dealing
with spontaneous tumors in urodeles (Table 21).
The recorded tumors comprise carcinomas in 3 spe-
cies, fibromas in 2, and melanomas in one species.
This apparent rarity of tumors in urodeles is the
more surprising since these animals, above all other
vertebrates, have retained the capacity to regenerate
complex tissues such as leg, tail and lens. Various
“explanations” have been offered, but none appear
biologically sound. It has been suggested, for ex-
ample, that the ability of the salamander to regener-
ate lost limbs is evidence of the retention into adult
life of such highly potent morphogenetic fields that
an aberrant cell will be forced to differentiate by the
organizer effect of the adjacent tissues and hence
uncontrolled growth cannot occur. The failure of
carcinogens to evoke a neoplastic response similar
to that observed in mammals has been interpreted
by some as evidence that urodeles are more resistant
to tumor growth than are other classes of verte-
brates. But as stated above the probability is great
that tumors are not as rare as they seem to be in
these animals; they simply have not been sought,
hence have not been found.

Perhaps because of the paucity of spontaneous tu-
mors, few experimental studies of neoplasia have
been carried out on these animals. They have been
limited largely to attempts at the production of
tumors by means of carcinogenic agents, as in the ex-
periments by Martella (132), Koch and his associ-
ates (99), Fedotov (46), Finkelstein (51), Shev-
chenko (186) and Tokin (218). Other experi-
mental studies are those of the Champys (28) on a
transmissible epithelioma in the newt, believed to be
caused by a virus, and the work of the Brunsts
(186a) on melanomas of the axolotl which probably
arise on a hereditary basis. A detailed account of
these various experiments is given elsewhere (123a).

Schlumberger and Lucké—Tumors in Fishes

t Tastz 21: Taxowomrc Distazevrion or Tomon-Beastvo Fisuzs

ELASMOBRANCHII (Cartilagenous Fishes)
SELACHII (Sharks; Rays)

EUSELACHII
_ SCYLLIORHINIDAE (Cat Sharks)
2 Scylliorhinus catulus ..»» Dermal odontoma, skin Ladreyt, 1929
e 24 canicula .... Chondroma, skin Thomas, 1933b
_ GALEORHINIDAE (Gray Sharks)
Prionace glaucus Adenoma, liver Schroeders, 1908
ey ' TECTOSPONDYLI
_ SQUALIDAE (Dog Fishes)
- Squalus suckleyi Goiter, thyroid Cameron & Vincent, 1915
mitsukurii Chondroma, lumbar vertebra Takahashi, 1929
BATOIDEI
RAJIDAE (Rays; Skates)
Raja Fibrosarcoma, fin ray Drew, 1912
“ clavata .... Melanoma, skin Johnstone, 1911
= 304 ..». Melanoma, skin Johnstone, 1912
” = ..-. Melanoma, skin Haddow & Blake, 1933
“ maculata ..-. Hemangioma, skin Drew, 1912
“ batis .... Melanoma, skin Johnstone, 1912
ae .... Melanoma, skin Johnstone, 1913
PISCES (True Fishes)
TELEOSTEI (Bony Fishes)
ISOSPON DY LI (Soft-rayed Fishes)
ELOPIDAE (Tarpon)
Elops saurus Chondroma, subcutaneous Surbeck, 1921
CLUPEIDAE (Herrings)
harengus Lymphosarcoma, peritoneum Johnstone, 1926
Rhabdomyoma, trunk muscle Williams, 1931
2d ” Leiomyoma, wall of stomach joe eg
Arengus pilchardus Fibroma, peritoneum ohnstone,
* op Fibroma, peritoneum Johnstone, 1925
ee : eae Fibrosarcoma, body wall Kazama, 1922
eta ma, y
“ ” Fibrosarcoma, body wall Takahashi, 1929
bed ad Fibrosarcoma, body wall Takahashi, 1929
= gorbuscha Fibrosarcoma, body wall Takahashi, 1929
Salmo salar Goiter, thyroid Gilruth, 1901
“ “ Goiter, thyroid Wilkie, 1902
Ed * Lymphosarcoma, kidney Haddow & Blake, 1933
“ gairdoerii Goiter, thyroid Gilruth, 1902
ee = Leiomyoma, stomach wall Plehn, 1906
bed « Adenoma, thyroid Leger, 1925
“ “ Fibrosarcoma, not given Leger, 1925
“ “ Adenoma, liver Haddow & Blake, 1933
“ lacustris Fibroma, subcutaneous Eberth, 1878
. ° Goiter, thyroid Bonnet, 1883
“ “ Adenocarcinoma, thyroid Smith, H. M., 1909
“ trutta Adenoma, liver Plehn, 1909
- 2d Papilloma, skin Thomas, 1932e
7 bd Fibroma, coelom Kreyberg, 1937
“" mykiss Adenoma, intestine Thomas, 1931a
“ carpio Leiomyoma, stomach wall Pesce, 1907
“ clarkii Rhabdomyoma, trunk muscle Adami, 1908
“ — several species Adenocarcinoma, thyroid Gilruth, 1901
“ “ “ Goiter, thyroid Pick, 1905
“ “ “ Adenocarcinoma, thyroid Jaboulay, 1908
e « “ Goiter, thyroid Marine & Lenhart, 1910
rg * 34 Goiter, thyroid Gaylord & Marsh, 1914
“ “ “ Goiter, thyroid Peyron & Thomas, 1930
. >. Odontoma, jaws Plehn, 1912
“- @. Erythrophoroma, skin Thomas, 1931b

692 Cancer Research
—.
Taste 21: Taxonomic Distraisution or Tumor-Beantnc Fisues—Continued
Salvelinus fontinalis Goiter, thyroid Scott, 1891
" " Fibrosarcoma, trunk muscle Plehn, 1906
. ” Osteoma, fin rays Thomas, 1932b
* sas Neurofibroma, autonomic nerves Young & Olafson, 1944
Hucho hucho Fibrosarcoma, liver Plehn, 1909
PLECOGLOSSIDAE
Plecoglossus altivelis Lipoma, subcutaneous Takahashi, 1929
OSMERIDAE (Smelts)
Osmerus eperlanus Epithelioma, lips Breslauer, 1916

ANGUILLIDAE (True Eels)
Anguilla anguilla

CONGRIDAE (Conger Eels)
Conger conger
ae “ae

“ i

MURAENIDAE (Morays)
Muraena helena

CHARACINIDAE (Characins)
Astyanax mexicanus

ELECTROPHORIDAE (Electric woud

Electrophorus electricus

CATOSTOMIDAE (Sucker)
Catostomus commersonnii

CYPRINIDAE (Carps, Dace, Minnows, Chubs)

Cyprinus carpio
“ “
“oe “oe
“ “
“ “
ae “
Carassius carassius
“oe
“ ae
“oe “
“oe o
1 auratus
“ “oe
“ “oe
oe oe
“ “
“ “
“ ae
o “oe
“ “
“ “oe
“ “
“ “

Rhabdomyoma, trunk muscle

APODES (Eels; Morays)

Adenocarcinoma, left kidney
Fibrosarcoma, mesentery
Fibrosarcoma, peritoneum
Adenocarcinoma, kidney
Papilloma, lower lip

Hemangioma, region of basi-hyal
Fibrosarcoma, subcutaneous, head
Lymphosarcoma, kidney

Adenocarcinoma, palate

HETEROGNATHI
Lymphosarcoma, head

GYMNONOTI
Papilloma, skin

EVENTOGNATHI
Papilloma, skin

Fibroma, peritoneum
Fibroma, mesentery
Epithelioma, skin
Epithelioma, not given
Osteoma, skull bones
Epithelioma, fins & operculum
Fibroma, mesentery

Fibroma, abdominal wall & mesentery

Fibrosarcoma, testicle
Chondroma, skull bones
Fibroma, ovary

Papilloma, skin
Fibrosarcoma, dorsal fin
Fibrosarcoma, not given
Epithelioma, bladder
Fibroma, orbit
Fibrosarcoma, skin
Fibroma, subcutaneous
Fibrosarcoma, subcutaneous
Lymphosarcoma, kidney
Fibrosarcoma, subcutaneous
Papilloma, fins

Fibroma, skin

Fibroma, subcutaneous

Neurofibroma, subcutaneous
Fibrosarcoma, cutaneous

Bergman, 1921

Schmey, 1911

Wolff, 1912

Plehn, 1924

Plehn, 1924

Thomas & Oxner, 1930

Drew, 1912
Johnstone, 1920
Williams, 1931

Ladreyt, 1935

Nigrelli, 1947

Coates, Cox, & Smith, 1938

Lucké & Schlumberger, unpubl.

Crisp, 1854

Gervais, 1876

Dauwe & Pennemann, 1904
Bashford, Murray & Cramer, 1905
Fiebiger, J., 1909c

Fiebiger, J., 1909a

Ronca, 1914

Plehn, 1906

Plehn, 1906

Mulsow, 1915

Freudenthal, 1928

Takahashi, 1929
Bland-Sutton, 1885

Semmer, 1888

Plehn, 1909

Guglianetti, 1910

Schamberg & Lucké, 1922
Wago, 1922

Johnstone, 1923

Plehn, 1924

Roffo, 1924

Sagawa, 1925

Sagawa, 1925

Eguchi & Oota, 1926
Dominguez, 1928

Montpellier & Dieuzeide, 1932
Picchi, 1933

Lucké, Schlumberger & Breedis, 48

- Schlumberger and Lucké—Tumors in Fishes

i: =e thelioma, lips
.--. Rhabdomyoma, trunk muscle
.... Fibrosarcoma, trunk muscle
Epithelioma, trunk muscle
Fibroma, coelom
Leiomyoma, trunk muscle
Fibroma, dorsal fin
.... Adenocarcinoma, thyroid
a .... Lymphosarcoma, peritoneum
.... Goiter, thyroid

NEMATOGNATHI ead
c AMETURIDAE (Horned Pout; Channel Cats)
‘Ictalurus |

Epithelioma, lips _
Epithelioma, lips, oral mucosa
Adenoma, kidney

Adenocarcinoma, thyroid

HAPLOMI (Pikes; Mud Minnows)

Osteosarcoma, anal fin
Osteoma, dental plate
Fibrosarcoma, trunk musculature
Fibroma, musculature

E
é
g

Lymphosarcoma, subcutaneous
Lymphosarcoma, kidney

a a Res 2 geese

CYPRINODONTES (Toothed Carp)
ga ‘valde Melanoma, skin

hellerii

- .... Melanoma, skin
- ...- Melanoma, skin
- .... Erythrophoroma, skin
” ..+» Melanoma, skin

...! Melanoma, eye

Adenoma, kidney
Fibrosarcoma, retrobulbar
Adenocarcinoma, thyroid

Goiter, thyroid
Adenocarcinoma, thyroid

ANACANTHINI (Codfishes; Hakes)

¢ 4 POECILIIDAE (Top Minnows)

iu

CYPRINODONTIDAE (Killifishes)

i

_ GADIDAE (Codfishes)

Gadus morhua .... Fibroma, subcutaneous
i .... Fibroma, stomach wall
“6 .«+» Osteoma, maxilla

Taste 21: Taxonomic Disretevtion or Tumos-Brastxc Fisues—-Continued

Anitschkov & Paviovsky, 1923

Smith, Coates, & Strong, 1936
Smith, Coates, & Strong, 1936
Smith, Coates, & Strong, 1936
Klemm, 1927

McFarland, 1901

Lucké & Schlumberger, 1941
Lucké & Schlumberger, unpubl.

Schreitmilller, 1924

Walgren, 1873
Bland-Sutton, 1885
Ohlmacher, 1898

Piehn, 1906

Plehn, 1906

Plichn, 1909

Marine & Lenhart, 1910

Haddow & Blake, 1933
Nigrelli, 1947

Hatissler, 1928 & 1934

Kosswig, 1929

Reed & Gordon, 1931

Smith, Coates, & Strong, 1936
Gordon, 1937

Levine & Gordon, 1946
Jahnel, 1939

Jahnel, 1939

Smith, Coates, & Strong, 1936

Klemm, 1927
Schreitmiller, 1924

693 —

Cancer Research

Taste 21: Taxonomic Distarvution oF Toneon-Buanme Fisnes—-Continued

“ “
“ “
o “
“ ae
“oe oii
“ ci
a o
ae “
“ “
“ o
“e “oe
oe sp.
o “e
“ “
o “e
Melanogrammus aeglifinus
a “ae
“ee “
ae i
“ “
Molva molva
“ “e
“e “
Pollachius brandti
fi “
- carbonarius
‘as virens
“ “
“a “
oe ae
ti «ae
“ if
oe “
Theragra chalcogramma
oe “
“ee “
o “
MERLUCCIIDAE (Hakes)
Merluccius merluccius
Merlangus merlangus
BOTHIDAE

Lepidorhombus megastoma
PLEURONECTIDAE (Flounders)

Hippoglossus hippoglossus

Osteoma, vertebral disc
Hemangioma, pectoral girdle
Fibroma, oesophagus
Fibrosarcoma, subcutaneous
Osteoma, vertebra

Fibroma, orbit

Fibrosarcoma, trunk muscle
Fibrosarcoma, subcutaneous
Ganglioneuroma, body wall
Fibrosarcoma, subcutaneous
Fibrosarcoma, ovary
Osteoma, pre-maxilla
Adenoma, parabranchial body
Fibrosarcoma, body wall
Osteosarcoma, pectoral fin
Osteosarcoma, operculum
Fibrosarcoma, mouth
Fibroma, stomach
Hemangioma, swim bladder
Fibroma, duodenum
Melanoma, skin

Fibroma, subcutaneous
Fibrosarcoma, subcutaneous, head
Fibroma, subcutaneous
Adamantinoma, maxilla
Adenoma, ovary
Fibrosarcoma, subcutaneous
Hemangioma, body wall
Adenoma, parabranchial body
Adenoma, glandula digitiformis
Lipoma, liver

Fibroma, oral cavity
Rhabdomyoma, mesentery
Fibrosarcoma, skin
Fibrosarcoma, subcutaneous
Hemangioma, trunk
Fibrosarcoma, mandible
Osteosarcoma, vertebra
Epithelioma, lower lip
Chondroma, pre-orbital
Adenoma, parabranchial body

Adenocarcinoma, mouth, operculum

Fibroma, body wall
Fibrosarcoma, body wall
Fibrosarcoma, subcutaneous
Osteoma, fin rays
Melanoma, subcutaneous

Hemangioma, rectum
Epithelioma, mandible
Hamartoma, intestine

HETEROSOMATA (Flounders; Flatfishes)

Osteoma, vertebral spines
Myxoma, skin, head

Myxoma, skin, trunk & fins
Fibrosarcoma, subcutaneous
Fibrosarcoma, subcutaneous
Fibroma, dorsal fin
Rhabdomyoma, body wall
Fibrosarcoma, body wall
Myxoma, trunk muscles
Ganglioneuroma, spinal ganglion

Papilloma, snout

Bland-Sutton, 1885
Murray, 1908
Williamson, 1909
Johnstone, 1912
Williamson, 1913
Johnstone, 1914
Johnstone, 1915
Johnstone, 1923
Thomas, 1927a
Thomas, 1927b
Thomas, 1927b
Williams, 1929
Peyron & Thomas, 1929
Williams, 1931
Thomas, 1932b
Murray, 1908
Johnstone, 1920
Johnstone, 1925
Johnstone, 1925
Thomas, 1933a
Prince, 1892
Johnstone, 1911
Johnstone, 1922
Johnstone, 1924
Thomas, 1926
Johnstone, 1915
Johnstone, 1923
Johnstone, 1925

Thomas, 1933d
Fiebiger, J., 1909a
Fiebiger, J., 1909b
Fiebiger, J., 1912
Johnstone, 1926
Johnstone, 1926
Johnstone, 1926
Williams, 1929
Williams, 1929
Thomas, 1932d
Takahashi, 1929
Takahashi, 1929
Takahashi, 1929
Takahashi, 1929
Takahashi, 1929
Takahashi, 1929
Takahashi, 1929

Johnstone, 1926
Johnstone, 1924
Labbé, 1930

Johnstone, 1923
Johnstone, 1924
Young, 1925
Johnstone, 1927
Williams, 1929
Haddow & Blake, 1933

Johnstone, 1912

;
Se ee

- Schlumberger and Lucké—Tumors in Fishes

695

es _ Taste 21: Taxonomic Distarsution or Tumoa-Brastno Frsues—Continued
a ..+» Fibroma, retroperitoneal Johnstone, 1913
vi «++» Fibroma, trunk muscle Johnstone, 1914
Bode --++ Melanoma, skin Johnstone, 1915
—S .... Fibroma, subcutaneous Johnstone, 1926
. ...+» Fibrosarcoma, body wall Johnstone, 1926
. Lipoma, trunk muscle Williams, 1929
.. Rhabdomyoma, body wall Thomas, 1932a
platessa Myxoma, body wall MacIntosh, 1908
- Fibrosarcoma, subcutaneous Drew, 1912
ee Lipoma, body wall Bergman, 1921
ee Fibroma, dorsal fin Johnstone, 1922
2 Melanoma, pigmented skin Johnstone, 1925
3 ...» Papilloma, skin Johnstone, 1925
.... Hemangioma, body wall Johnstone, 1925
™ .... Fibroma, subcutaneous, head Johnstone, 1926
thy flesus .... Lymphosarcoma, retro-orbital Johnstone, 1912
la limanda Papilloma, body surface Johnstone, 1925
pleuronectes americanus é Erythrophoroma, skin Smith, G. M., 1934
yokohamae . Ganglioneuroma, spinal ganglion Takahashi, 1929
ys olivaceus nA - oa em gem Kazama, 1924
pues teoma, spine Takahashi, 1929
DAE (Soles)
.... Myxoma, peritoneum Johnstone, 1926
.... Papilloma, skin Thomas, 1930
THORACOSTEI (Sticklebacks; Pipe Fishes; Sea Horses)
OSTEIDAE (Sticklebacks)
osteus aculeatus .... Hemangioma, subcutaneous, head Plehn, 1906
hia spinachia .... Epithelioma, skin Murray, 1908
jus pungitius .... Hemangioma, iris Johnstone, 1915
LABYRINTHICI
DAE (Climbing Perch)
scandens .... Papilloma, skin Fiebiger, 1909a
PERCOMORPHI (Mullets; Barracudas; Tunnyfish; Bass; Snappers; Croakers, etc.)
[DAE (Mackerels)
scombrus .... Hemangioma, body wall Johnstone, 1924
- .... Hamartoma, pineal Charlton, 1929
orus colias . Melanosarcoma, skin Takahashi, 1929
AE (Tunnies, Albacores)
alleterata Erythrophoroma, peritoneum Thomas, 1931b
DAE (Hairtails)
: Osteoma, fin rays Gervais, 1875
Melanoma, subcutaneous Nigrelli & Gordon, 1944
[DAE (Sea Basses)
scriba Goiter, thyroid Marsh & Vonwiller, 1916
cabrilla Goiter, thyroid Marsh & Vonwiller, 1916
colabrax japonicus .... Fibrosarcoma, subcutaneous Takahashi, 1929
OG. - eS iraesemag oe at a ‘
e ..++ Melanoma, bran region Dollfus, Timon-
PIANIDAE (Snappers
n griseus. Neurofibroma, subcutaneous Lucké, 1942
_ apodus Neurofibroma, subcutancous Lucké, 1942
— jocu Neurofibroma, subcutancous Lucké, 1942
IDAE (Porgies
go ..e+ Osteoma, mandible, haemal spines Kazama, 1924
te ..s» Osteoma, haemal spines Sagawa, 1925
” .... Adenocarcinoma, body wall Takahashi, 1929
sd .... Osteoma, haemal spines Takahashi, 1929
ee i ...+ Osteoma, hacmal spines Lucké & Schlumberger, unpubl,
auratus Neuro-epithelioma, olfactory plate Thomas, 1932¢

696 Cancer Research
——
Tastz 21: Taxonomic Distersurion or Tumor-Beartnc Fisurs—Continued
GIRELLIDAE
Box vulgaris .. Goiter, thyroid Johnstone, 1924
SCIAENIDAE (Croakers, Roncadores)
Pogonias chromis ... Epithelioma, lips Beatti, 1916
Fibrosarcoma, subcutaneous Beatti, 1916
- “9 Osteoma, vertebrae Beatti, 1916
Micropogon opercularis Odontoma, upper dental plate Roffo, 1925
23 - Sarcoma, subcutaneous Roffo, 1926
SILLAGINIDAE
Sillago japonica .... Fibrosarcoma, base of head Takahashi, 1929
PLATACIDAE
Platax pinnatus Osteoma, vertebral spines Bell, 1793
- = Osteoma, vertebral spines Gervais, 1875
EPHIPPIDAE
Chaetodipterus faber Osteoma, first haemal spine Schlumberger & Lucké, unpubl.

CATAPHRACTI

SCORPAENIDAE (Scorpion Fishes, Rock —

Sebastodes oo Fibroma, body wall Takahashi, 1929
Scorpaena po Fibrosarcoma subcutaneous Schroeders, 1908
HEXAGRAMMIDAE (Greenlings)
Hexagrammos otakii Guanophoroma, subcutaneous Takahashi, 1929
TRIGLIDAE (Gurnards) :
Trigla lineata Hemangioma operculum * Drew, 1912
Lepidotrigla alata Fibrosarcoma, body wall Takahashi, 1929
Chelidonichthys kumu Allophoroma, subcutaneous Takahashi, 1929
CHROMIDES
CICHLIDAE
Cichlasoma tetracanthus Epithelioma, skin Puente-Duany, 1930
Hemichromis bimaculatus Osteochondroma, operculum Nigrelli & Gordon, 1946
PHARYNGOGNATHI
LABRIDAE
Iridio bivittata Papilloma, skin Lucké, 1938
Labrus mixtus Rhabdomyoma, trunk muscle Ladreyt, 1930
DISCOCEPHALI
ECHENEIDIDAE (Remoras, Shark- _— j
Echeneis naucrates Goiter, thyroid - Lucké & Schlumberger, unpubl.
JUGULARES
CALLIONY MIDAE (Dragonets)
Callionymus lyra Lipoma, subcutaneous Williams, 1929
BLENNIIDAE
Blennius sp. Xanthoma, skin Schroeders, 1908
ZOARCIDAE
Zoarces viviparus Melanoma, skin Bergman, 1921
PLECTOGNATHI
MONACANTHIDAE
Alutera schoepfi Osteoma, interhaemal spine Schlumberger & Lucké, unpubl.
PEDICULATI
LOPHIIDAE
Lophius piscatorius Melanoma, skin Ingleby, 1929

Abstracts of reported tumors in Urodeles

VAILLANT and Pettit, 1902: A Japanese giant sala-
mander Megalobatrachus maximus was kept in a Paris
zoological garden from 1859 until its death in 1897.
The presence of a tumor on the palmar surface of the
right forefoot was first noted in 1874. It measured 10
cm. in diameter and had the appearance of a cluster of

grapes; the nodules varied from 0.5 to 2 cm. in width.
The overlying epidermis was intact and on histologic
examination appeared normal. The tumor parenchyma
was very vascular and composed of interlacing bundles
and whorls of pleomorphic connective tissue cells. The
nuclei of the neoplastic cells differed greatly in size, some
were large and vesicular, others small with abundant

Schlumberger and Lucké—Tumors in Fishes

69

~

chromatin. The authors identified the growth as a
fibroma.

: _ Pick and Pott, 1903: An elliptical tumor, 14 x 10 x
6 cm., was found to be broadly sessile on the testicle of
a Japanese giant salamander, Megalobatrachus maxi-
mus. The tumor contained many cysts, some of which
__ ‘Were as large as an apple. Two firm gray nodules, 1 cm.
in sage ag were present near the middle and at the
___ lower pole of the testicle. Histologically the cysts were
lined by pleomorphic epithelial cells that formed papil-
lary projections into the cyst cavities. The two smaller
Masses consisted of small alveoli, clumps, and strands
‘of neoplastic cells that were occasionally found free in
vascular spaces; in one area direct invasion of a vein
could be demonstrated. The authors identified the
tumor as a testicular carcinoma showing vascular in-
vasion and local metastasis.
Murray, 1908: An adenocarcinoma arose in the skin
_ glands of a newt, Triton cristatus, appearing as a mam-
_ millated mass at the angle of the jaw, and as nodules
_ scattered over the tail. The pits seen on the surface
__ of the tumors led into tubules that passed through the

waded, therefore the author suggested that perhaps the
_ tumors were benign. Nevertheless, throughout his de-

_ seription he refers to them as carcinomas.
_ Krontovsky, 1916: In an axolotl Siredon mexican-
wm, the author found a “malignant chromatophoroma.”
It was composed of atypical cutaneous melanophores
which were undergoing active proliferation and invad-
ing the neighboring tissues. Finkelstein (51), who
___ cited this case, points out that the tumor-bearing animal
___ was found at Kiev in 1916, (See also the comments of
___ Brunst [186a]). During thé years 1920-1930 there were
- in the aquarium of the Kiev Roentgenological Institute
with a hereditary tendency to melanoma.
_ Finkelstein suggests that perhaps these animals are pro-
geny of the original mutant described by Krontovsky.
- ScHwarz, 1923: On the forefoot of a Japanese giant
salamander Megalobatrachus maximus the author found
a pedunculated, almost spherical tumor that measured
2 cm. in diameter. Histologically, it was covered by
_ stratified squamous epithelium, but the bulk of the
tumor was composed of dense interlacing bundles of
connective tissue; nuclei were not abundant. The neo-
‘plasm was rather well vascularized and showed no evi-

dence of malignancy.

Cuampy and Cuampy, 1932 and 1935: Studied a
carcinoma of the skin in Triton alpestris, which was
transmissible to other newts of the same
1931 the authors observed that 3 out of 5
in one tank simultaneously developed cutaneous
which were found to be carcinomas composed of
as

if
f
i
ial

3 tumor-bearing animals were removed from

;
:
E
E
2
:
E
[
g

and were then replaced by another group of 8 animals.
Se tS eo re) eee
newts belonging to the homologous species
developed tumors; individuals of other ae ale were
not affected. No tumors developed in the animals placed
in the contaminated tank after the first month. Frag-
ments of the tumor were inoculated subcutaneously into
several newts; most of the animals died, but, in several,
tumors were found about 2 years later at some distance
from the site of inoculation. The authors believe that
the experiments indicate the existence of a carcinogenic
virus.

SHEREMETIEVA-BruNst and Brunst, 1948: Among
hundreds of axolotls Siredon mexicanum the authors
in 1932 found a male and a female of the gray variety
that had minute black spots on the sides of their bodies.
These gradually increased in size and progressed to mela-
notic tumors. The animals were mated and in successive

surrounding muscle and connective tissue. The cell of
origin appeared to be the melanophore which is normally
present in the corium. Histologically the growths re-
sembled the melanomas of hybrid killifishes (q.v.). The
tumor was found to be transplantable to other axolotls,
either gray or albino. The Brunsts regard this melanoma
as arising on a genetic basis.

ANURA

A considerable variety of spontaneous tumors
have been recorded in frogs of several genera and

) "Pante 22: Tewons or Tailed Amphibians —

OA AE, SES ory Subcut Vaillant & Pettit, 1902
mander Me; achus mus roma taneous
: — Megalobatrachus maximus Carcinoma Testicle Pick & Poll, 1903
| | ae newt Triton cristatus Adenocarcinoma Skin glands § Murray, 1908
Axolotl Siredon mexicanum Melanoma Subcutaneous Krontovsky, 1916
Giant salamander Megalobatrachus maximus Fibroma Subcutaneous Schwarz, 1923
Alpine newt Triton alpestris (3) Carcinoma Skin Champy & Champy, 1935
Axolotl Siredon mexicanum (many) Melanoma Skin Sheremetieva-Brunst &

Brunst, 1948

.

Cancer Research

Taste 23: Tomors or Tailless Amphibians (Anvra)

Species Tumor Site Author

frog Rana sp. Adenoma Skin Eberth, 1868

Meadow frog Rane virescens Osteegenic sarcoma (?) Femur Ohlmacher, 1898

European edible frog Rana esculenta Fibroma Mouth Vaillant & Pettit, 1902

Leopard frog Rana pipiens Adenocarcinoma Kidney Smallwood, 1905 a

European edible frog Rana esculenta Carcinoma Ovary Plehn, 1906

frog Rane sp. (2) Adenocarcinoma Skin Murray, 1908

frog Rana sp. (2) Adenoma Skin Pavlovsky, 1912

frog Rane sp. Adenocarcinoma Skin Paviovsky, 1912

European edible frog Rana esculenta Hypernephroma Kidney Carl, 1913 -

frog Rana sp. Adenoma Skin Pentimalli, 1914

edible frog Rana esculenta Adenoma Skin Secher, 1917/19

European edible frog Rana esculenta Adenocarcinoma Skin Masson & Schwartz, 1923

Painted Escuerzo Ceratophrys ornata Fibrosarcoma Leg Volterra, 1928

American Bull frog Rana catesbiana Adenocarcinoma Skin Duany, 1929

European edible frog Rana esculenta Sarcoma (?) Leg Gheorghiu, 1930

Leopard frog Rana pipiens Adenocarcinoma Kidney Downs, 1932

Brown-throated frog Rana fusca (17) Adenoma Skin Pirlot & Welsch, 1934

Brown-throated frog Rana fusca Myxofibrochondroma (?) Leg Pirlot & Welsch, 1934

Leopard frog Rana pipiens (1200) Adenocarcinoma Kidney Lucké, 1934, 1938

American Bull frog Rana calesbiana Neurosarcoma Sacral plexus Lucké & Schlumberger
(not published)

Green frog (tadpole) Rana clamitans Myxosatcoma Tail Lucké & Schlumberger
(not published)

European edible frog Rana esculenta Hepatoma Liver Willis, 1948

species. The reports include adenomas in three
species, hepatoma in one, carcinoma in four, sar-
coma in three, and fibroma, myxoma and chondroma
each in one species.

The more common and up to the present the most
extensively studied tumor is the renal adenocar-
cinoma of the leopard frog, Rana pipiens (112, 113,
114). Over 1200 examples of such tumors have
been examined in our laboratory since 1933. The
tumors occur as solitary or multiple ivory-white
masses, and may involve one or both kidneys (Fig.
39). The larger growths not uncommonly metasta-
size, especially to the liver and lungs (Fig. 40).
Histologically, the majority of the tumors have the
appearance of adenocarcinomas (Fig. 42), and are
thus representative of the most common variety of
cancer in man. The component epithelial cells are
atypical and usually much larger and basophilic
than normal kidney cells (Fig. 41). Mitotic figures
aré common. The stroma is scanty and poorly
vascular. A capsule is lacking and even in very
small tumors marginal extensions infiltrate the ad-
jacent kidney. In the larger tumors the entire kid-
ney is often destroyed.

In a relatively small group of the tumors, the
appearance is less atypical, and the growths resemble
adenomas rather than adenocarcinomas. But there
are many gradations, and it is probable that all of
these renal tumors are malignant.

A distinctive characteristic of the frog carcinoma
is the frequent presence of acidophilic intranuclear
inclusions which in their general appearance are like

those found in herpes and certain other diseases
known to be due to viruses (Fig. 43). In their
typical form, they are conspicuous and clearly recog-
nizable. It is obvious, however, that there must be
developmental stages and the character of these is
still a matter of doubt. The inclusions are invariably
confined to the cells of the tumors and do not occur
in normal renal epithelium, nor in the cells of other
organs. Experiments have supported the indications,
first given by the presence of the intranuclear in-
clusions, that the tumor is in fact very probably
caused by a species-specific virus (115).

Our experience with regard to the occurrence of
metastasis is worthy of record. In the first series of
158 tumor-bearing frogs no metastases were found,
and the conclusion was reached that this cancer,
though locally destructive, does not become dis-
seminated. Yet tumor emboli are frequently en-
countered in vascular spaces (Fig. 44). In a second
series of 362 additional cases, metastasis was found
in 22 frogs; and to date we have observed over 75
tumor-bearing frogs with metastasis, nearly all of
them in animals with relatively large tumors. This
experience emphasizes that large series of animals
must be studied before an opinion about the charac-
ter of a neoplasm should be expressed.

The frog tumors have served for many different
kinds of experiments, such as manner of growth in
the anterior chamber of the eye of homologous and
of heterologous species (116, 120). By serial trans-
plantation the tumor has been maintained for 14
generations (176a). It has been transplanted to

_ Schlumberger and Lucké—Tumors in Fishes

699

ie tadpoles (19, 22), and studied in tissue culture
_ (117). The frog being poikilothermic lends itself
____ particularly well to studies on the effect of tempera-
____ ture on the tumor as regards its rate and manner of
_ growth (121), and as regards induction and aug-
mentation of metastasis (123b). These experimental
__ investigations are reviewed elsewhere (123a). Here
____ iit must suffice briefly to mention a few other studies
___ to indicate the lines of research that have been pur-
_ gued. Witschi (232) and Briggs (18, 20) have
‘studied the abnormal growths which appear in tad-

eggs exposed to carcinogens, and has introduced
carcinogens into tadpoles (17). Duran-Reynals
_ (41) and Schlumberger (176a) have injected sev-
_ eral carcinogens into adult frogs.
__ To the cases reported in the literature two ad-
: ‘ditional anuran tumors may be added. One tumor
occurred in a second-year tadpole of the green frog
_ Rana clamitans. It formed a mass measuring 7 x 5
_ _X 6 mm. on the dorsal fin, parts of which were de-
__stroyed by the growth (Fig. 45). Sections revealed
that portions of the dorsal myomeres had been in-
_ filtrated and destroyed (Fig. 49). Histologically
__ the tumor had the structure of myxosarcoma, being
composed of large stellate and spindle shaped cells
_ which were embedded in an abundant mucinous
_ matrix (Fig. 47). No inflammatory reaction was
_ present. The growth corresponded in every way to
___ @ true neoplasm. The tumor is unique in that no
ee neoplasms in larval amphibians have been recorded.
_.___ The other tumor occurred in an adult bullfrog in
which it formed a swelling in the left flank. On dis-
section, the growth was found to measure 2 x 1 x |
cm. It probably had its origin in one of the nerves
of the sacral plexus. It protruded into the coelomic
cavity, and through the muscles of the back which
it had invaded and partly destroyed (Fig. 48). His-
tologically, the mass was composed of interlacing
_ bundles and whorls which resembled neoplastic con-
nective tissue (Fig. 49, 50). In general appearance
___ the tumor was similar to the more malignant nerve
_ sheath tumors of man.

_ Abstracts of other reported cases of anuran tumors
___ Exserti, 1868: About 60 nodules, small but varying
___ im size, were found on the dorsal and ventral surfaces
of a frog. The tumors were located in the corium, were
covered by an intact epithelium, and did not infiltrate
the adjacent tissues or metastasize. Histologically the
tumors were composed of stratified squamous epithelium
arranged to form tubules and acini that superficially
_ resembled the normal skin glands. Eberth discussed the
possible relation of parasites to the neoplasms, since

trematodes and nematodes frequently inhabit the cu-
taneous glands of frogs. Transplantation experiments
yielded negative results.

OHLMACHER, 1898: The left femur of a frog Rana
virescens presented a spindle shaped swelling that oc-
cupied the entire length of the femur and reached a
maximum diameter of 8 mm. The periosteum was in-
tact. Histologically the tumor consisted of trabeculae
of bone and cartilage surrounded by large spaces. In
the latter were rapidly proliferating mononuclear cells
that appeared to be derivatives of the bone marrow.
The author concluded that the lesion was a “medullary
osteosarcoma.” However, the description is more sug-
gestive of callus formation after fracture. Murray (141)
described a similar lesion in a frog and concluded that
it probably represented callus rather than bone tumor.

VAILLANT and Perttrr, 1902: In their report of a
tumor in a python the authors briefly mention a fibroma
which they found in a frog, Rana esculenta. The tumor
cemeed ) ie eet a
mou

SMALLWoop, 1905: Bilateral renal tumors were
found in a leopard frog Rana pipiens and were inter-
preted as having arisen in the adrenals and secondarily
invaded the kidneys. Histologically the tumor was com-
posed of cuboidal or columnar epithelial cells arranged
as dilated and tortuous tubules, into the lumens of
which the neoplastic cells often extended as papillary
projections. This tumor was first reviewed by Murray
(141) who failed to see any resemblance between the
tumor cells and those of the normal adrenal. Subse-
quently one of us (112) obtained a slide of the tumor
from Dr. Smallwood. A study of this section revealed
that the lesion was a renal adenocarcinoma and bore no
relation to the adrenal glands.

PLeHN, 1906: Between the ovaries and fat bodies of
Rana esculenta were bilateral white cherry-sized tumors;
5 or 6 smaller nodules were scattered among the eggs
in the ovaries. The neoplastic cells were large, pleo-
morphic, with vesicular nuclei; multinucleated giant
cells were common. Normal and abnormal mitotic fig-
ures were abundant. Plehn believed that the tumors
were carcinomas and represented a neoplastic growth
of the primitive egg cells.

Murray, 1908: A hemispherical nodule was present
on the inner aspect of the thigh of an adult male frog.
The overlying skin was stretched, but apparently intact.
The neoplastic squamous epithelial cells formed irregu-
lar tubules and acini separated by delicate connective
tissue septae. The epithelium resembled that seen by
Eberth in the benign adenomas. In this case, however,
the structures were more bizarre and the subjacent
muscles were infiltrated by the tumor cells. Murray
regarded this growth and another similar one as adeno-
carcinomas of the skin.

Paviovsky, 1912: The author presented two cases of
adenoma and one of adenocarcinoma of the skin in
frogs at a meeting of the Russian Pathological Society.
The tumors were similar in that the neoplastic tubules
communicated with the surface and were lined by tall

700 ,

Cancer Research

=

columnar epithelium of embryonal type; these cells did
not resemble those normally found in the serous or
mucous glands of the frog’s skin. In the case identified
as an adenocarcinoma the tumor cells invaded the sur-
rounding connective tissue.

Cart, 1913: A tumor, about the size of a cherry,
projected ventrally from the hilum of the left kidney
in an adult female Rana esculenta. The growth was
round, firm, red-brown, with a slightly uneven surface.
The neoplastic cells were pleomorphic, with large nuclei,
and resembled those of the adrenal. This appearance was
heightened by their occasional arrangement as cords of
cells; no glycogen, chromaffin, or fat was demonstrated.
Carl identified the lesion as a malignant adrenal tumor;
no metastases were found. Attempts to transmit it were
unsuccessful.

PeENTIMALLI, 1914: Scattered over the skin of the
trunk and extremities of a frog were 24 nodular ade-
nomas, the largest of which was the size of a small pea.
The overlying skin adhered to some, over others it was
ulcerated; the cut surfaces of the tumors were very
bloody. Histologically the neoplasms were adenoma-
tous, with frequent papillary proliferations extending
into the cysts. No metastases were found; transplants
failed to grow.

Secuer, 1917/19: An irregular cauliflower-like mass
about 1 cm. in diameter was present on the outer sur-
face of the thigh in Rana esculenta. The tumor re-
sembled those described by Murray, though it was less
infiltrative and apparently benign. The neoplastic epi-
thelial cells were arranged as solid sheets or acini; the
latter occasionally became small cysts. No metastases
were present; parasites could not be found.

Masson and ScHwartz, 1923: Three tumors, ranging
from 5 to 15 mm. in diameter were located on the right
thigh, the right flank, and the lower right abdomen of
Rana esculenta. They were spherical, pale pink in
color, firmly attached to the epiderm but not to the
subjacent musculature. Columnar neoplastic epithelial
cells lined tubular spaces and were supported by a layer
of cuboidal cells. Some of the tubules were cystically
dilated; elsewhere the cells formed solid strands. The
connective tissue stroma was infiltrated by inflammatory
and neoplastic cells which in some instances had pene-
trated as far as the endothelium of the lymph sacs.
The writers were undecided whether the tumors were
multicentric in origin or if a single one was the primary
growth, the others secondary. Transplants did not grow.

Vorterra, 1928: A firosarcoma had produced con-
siderable swelling of the left hind foot in an exotic frog
Ceratophrys ornata. The tumor was dense, white, and
homogeneous in appearance; the overlying skin was
ulcerated; the bones of the foot were largely destroyed.
Numerous metastatic nodules were present in the liver,
two of them were as large as hazel-nuts. The neoplastic
cells were spindle-shaped elements gathered into com-
pact bundles; in many places the cells extended to the
endothelial lining of the vessels. Mitoses were abund-
ant, and frequently atypical.

Dvany, 1929: Two cutaneous tumors were found in

a bullfrog Rana catesbiana that had been brought to
Havana some years before from the United States.
The smaller growth, about the size of the frog’s eye,
was situated between and slightly behind the eyes.
rectly back of this was another tumor as large as the
animal’s head. The neoplastic epithelial cells formed
tubules that somewhat resembled the normal skin glands;
the underlying tissues were not invaded. No metastases
were found in the viscera, but the author raised the
question whether the smaller nodule may have been a
metastasis or extension from the larger He
identified the tumor as an adenocarcinoma and noted its
similarity to those described by Murray and by Masson
and Schwartz. ;

GHEoRGHIU, 1930: The author found a tumor the
size of a nut in the right gastrocnemius muscle of
esculenta. The lesion involved the skin, was
consistency, and dull white in color. The cells were
pleomorphic, though in some areas those of spindle
shape predominated. Filaria as well as numerous bac-
teria were found throughout the sections. The tumor
was easily transplantable and had been carried
12 generations. About 80 per cent of the grafts “took”;
they grew rapidly for from 15 to 20 days, then ulcerated,
and the frogs died, probably from infection. The nature
of these tumors is questionable; it is quite possible, as
Cramer (32) pointed out, that the “tumors” were in-
fectious granulomas.

Downs, 1932: A yellow-brown tumor almost filled —
the coelomic cavity and compressed the liver of Rana

formed bizarre tubules which were identified as of in-
testinal origin. A section of the tumor was examined by —
one of us (112) and a striking resemblance to the renal
adenocarcinoma noted. That the lesion was actually
such a tumor is highly probable since remnants of kid-
ney tissue were seen in the section.

Prrtot and Wetscu, 1934: The authors found 17
cases of cutaneous adenoma among 1800 frogs Rana
fusca. The tumors were frequently multiple and varied
in diameter from 1 to 15 mm. Stratified columnar epi-
thelial cells with large vesicular nuclei lined the irregu-
lar acini. Mitoses were numerous, but the basement
membrane was intact and there was no evidence of local
invasion or metastasis. Another growth observed by
these investigators was a 15 x 7.5 mm. tumor adherent
to the overlying skin of the leg in Rana fusca; the
femur was intact. Masses of spindle-shaped connective
tissue cells alternated with regions that were relatively
acellular, and composed chiefly of fibrils. Islands of
cartilage were present, In some areas a transition from
connective tissue to cartilage was apparent. Three frogs
were inoculated with the tumor tissue; in all there was
a severe inflammatory reaction associated with resorp-
tion of the implant. These authors identified this tumor
as a myxofibrochondroma, but their description leaves
one in doubt as to the nature of the growth.

Wits, 1948: A solitary white tumor, 3 cms. in
diameter, was found in the liver of an adult European

‘Schlumberger and Lucké—Tumors in Fishes

701

edible frog Rana esculenta. Microscopically, it had an
alveolar structure and the general appearance of a well
differentiated hepatoma.

Several pseudotumors have been reported in the
literature. Gebhart (54) and Wagner (225) de-
_ scribed connective tissue hyperplasia of the pylorus
_ of frogs. The first writer implicated coccidia as the
etiologic agent, whereas Wagner believed that fibro-
sis followed encystment of nematode worms and
their eggs. Montpellier and Dieuzeide (137) wrote
of a localized epithelial proliferation in three speci-
mens of Discoglossus pictus that had been kept in
_ the same tank. A characteristic histologic feature
- was the presence of large eosinophilic cytoplasmic
inclusion bodies in the epithelial cells. However,
the lesions gradually disappeared, and the authors

concluded that they were not true tumors. The dis-

Ill. TUMORS OF REPTILES

In 1908 Murray (141) wrote that no malignant
neoplasms had been reported in reptiles up to that

time. Scott (183) examined the records of over
6,000 autopsies performed on reptiles of various
kinds at the London Zoological Gardens from 1900
to 1925. In only two did he find a neoplasm; both
occurred in turtles. Bergman (11) found a macro-
scopic tumor in only one of 2,200 snakes which he
examined; Patay (145a) however, observed a tu-
mor-bearing individual in one of a group of 54 large
ring snakes. Our experience with fishes and amphi-
bians leads us to suspect that a careful study of
large numbers of reptiles will reveal a tumor inci-
dence not far different from that in other verte-

;

The reptiles alive today are but a small remnant
of the vast numbers that dominated the earth in the
Mesozoic age. Among the most spectacular were
the giant dinosaurs, in three of which tumor-like

lesions were found in the caudal vertebrae. These
__ have been variously interpreted as osteomyelitis,
excess callus following fracture, and hemangioma.
Moodie (139), who discussed one of these in detail

and cited two others reported by Hatcher (71) and
Holland (76), believed that they were hemangiomas.
However, the descriptions of Hatcher and Holland
strongly suggest that the lesions noted by them were
bony overgrowths following fracture, rather than
neoplasms. Although the dinosaurs were reputedly
capable of living for a thousand years, evidence of
disease is rarely found in their fossil bones (139).
Moodie also reported an osteoma of the third dorsal
vertebra in a mosasaur, a large aquatic reptile that
lived during the latter part of the Cretaceous.

TURTLES (CHELONIA)

The first tumor in a turtle of which we can find
any record is an adenoma of the thyroid reported by
Pick and Poll (154) in 1903. It was an egg-shaped,
encapsulated mass, 6 x 4 x 2.5 cm., on the ventral
aspect of a Brazilian fresh water turtle, Platemys
geoffroyana (Hydraspis hilarii). The connective tis-
sue stroma was moderate in amount and divided the
parenchyma into elongated lobules. The latter was
composed of tubular acini lined by tall columnar
epithelial cells which rested upon 2 to 5 layers of
small polyhedral cells with relatively large nuclei.

In a brief report on the causes of death in the
London Zoological Gardens during 1911, Plimmer
(163) records “a glandular cancer in the stomach of
a tortoise.” A more detailed description of this case
was found by Scott (183) among the post-mortem
records of the Zoological Society of London. This
record identified the animal as an elephantine tor-
toise in which “there was a large mass, 8 x 5 inches
of new growth springing from the mucosa of the
stomach which was very red and swollen. The
growth was white and gelatinous.” There is no
account of histologic studies.

In 1913 Plimmer (164) reported the death of a
West African fresh water turtle, Sternothacrus
niger. “Death from rupture of the heart. The heart
measured 134 x 144 inches. The pericardium was
full of blood. The heart muscle was converted into
a soft whitish growth, full of very large multinu-
cleated cells.”” Since no mention is made of tumors
elsewhere in the body, that found in the heart may

; Taste 24; Tomons ov Toxries (Cuetonta)

q Species Tumor Site Author

Turtle Platemys geo, Adenoma Thyroid Pick & Poll, 1903

Giant tortoise Testudo eephantina Adenocarcinoma Stomach Plimmer, 1912

Black terrapin Sternothaerus niger Rhabdomyoma (?) Heart Plimmer, 1913

Green turtle Chelonia mydas (3) Papilloma Skin Lucké, 1938

‘ Green turtle Chelonia mydas (6) Papilloma Skin Smith & Coates, 1938, 1939

4 Green turtle Chelonia mydas (many) Papilloma Gall bladder Smith, Coates & Nigrelli, 1941

4 Horsfield’s tortoise Testudo horsfeldi Fibroadenoma Lung Tevetaeva, 1941

_ ‘Musk-turtle Sternothaerus odoratus (2) Papilloma Skin Schlumberger & Lucké

2 _ (not published)

3

4s ARCH FO

‘ Scegitttn, )>
4 PS 43 Queen's @

7Q2

Cancer Research

have been primary. The presence of the large multi-
nucleated cells suggests that it may have been a
rhabdomyoma. —

One of us (116) has studied the multiple large
papillomas of the skin and eyes in the edible green
turtle Chelonia mydas. Three spécimens, caught off
Cape Sable, were available for examination. The
tumors were located on the tail, flippers (Fig. 52),
the axillae, neck, eyelids, corneas. In one instance
bilateral corneal growths had produced blindness
(Fig. 51). The tumors were hemispherical and had
a rough warty surface which was ulcerated in some
areas. They were sessile or had a broad peduncu-
lated base, and ranged in size from small warts a
few millimeters in diameter to masses 20 cm. in
width. The tumors were rubbery in consistency and
on section were white and bloodless. Histologically
they were papillomas, with arborescent connective
tissue papillae covered by several layers of keratiniz-
ing squamous epithelium (Figs. 53, 54).

The connective tissue component became more
prominent as the tumor increased in size, and its
cellularity gave evidence of active proliferation.
Although this never yielded the picture associated
with malignant connective tissue tumors, numerous
spherical masses, from 3 to 5 cm., were found in the
lungs of one of the turtles (Fig. 57). These were
composed of dense fibrous tissue covered by ciliated
columnar respiratory epithelium (Figs. 58, 59).
Whether they were primary tumors of the lung or
whether they represented a metastatic dissemination
of the neoplastic connective tissue of the skin papil-
lomas cannot be determined with certainty, but an
origin in situ appears most probable. In this con-
nection may be mentioned the brief note of Tsvetae-
va (219) reporting a fibroadenoma of the lung in a
Turkestan turtle, Testudo horsfeldi. Whether the
animal bore any skin papillomas was not stated.
Since many papillomas (warts) of man and other
animals are of proved virus etiology, it is interesting
to consider a similar etiology for these tumors of
turtles.

Smith and Coates (191, 192) observed similar
fibroepithelial growths in six specimens of Chelonia
mydas. Besides the more common papillary struc-
tures, they also noted occasional smooth elevations
which on section were composed of interlacing bands
of connective tissue varying in density and covered
by a slightly thickened epithelium. The investigators
regarded these as fibromas. At times both types of
growth coexisted. In a subsequent paper (192) the
authors reported that in more than half of 250 tu-
mors occurring in the six turtles examined they
found ova of the parasitic trematode Hapalotrema

constrictum (later [193] reclassified as Distomum
constrictum). The authors believe that the ova
were probably deposited in the preexisting vascular
tumor tissue by the migrating flukes, and remained
there without affecting the subsequent growth of the
tumor. They concluded that the ova were not of
primary importance in the etiology of the neoplasm.

Recently, however, Nigrelli (142) reported find-
ing as many as 50 leeches, Ozobranchus branchiatus,
in various stages of growth on a bit of the papilloma
only 4% inch square. The largest leeches measured
10 mm. in length, 5 mm. in width; all were strongly
contracted. In the regions where the leeches were at-
tached, the vascularity of the tumors was increased.
The hirudin secreted by the leeches may have a
direct stimulating effect on the growth of the tumor,
or may affect it indirectly by improving the circula-
tion. The author suggested further that the leeches
may act as vectors for viruses or other parasites
that may be causative in the development of the
papillomas.

In these turtles Smith, Coates, and Nigrelli (193)
observed a papillomatous disease of the gall bladder
associated with the presence in that organ of the
trematode Rhytidodoides similis. Occasionally the
tumors formed discrete patches which surrounded
and occluded the orifice of the cystic duct. Not in-
frequently the entire mucosa was thickened and
rugose, the wall edematous and infiltrated with
lymphoid elements. These changes were accompa-
nied by capillary dilatation and connective tissue
proliferation. The mucosal glands were dilated and
tortuous but in none of the 100 affected gall blad-
ders examined was there any evidence of malignant
change. Although most of the worms lay free in the
bile of the gall bladder, some were found attached
to the papillomatous portions of the mucosa. The
authors believe that the growths are the result of
mechanical or chemical factors associated with the
presence of the parasite.

Two musk turtles Sternothaerus odoratus bearing
skin papillomas were obtained by us from the Phila-
delphia Zoological Gardens. In one there was a
growth, 5 x 5 x 8 mm., on the dorsum of the tail
(Fig. 55) and another on the right front flipper.
In the second animal a single tumor, 4 x 5 x 5 mm.,
was present on the left hind flipper. The three small
tumors were very firm in consistency and deeply
lobulated. On section they closely resembled the
common warts of man. A loose, well vascularized
connective tissue core was covered by multilayered
stratified squamous epithelium showing hyperkera-
tosis and parakeratosis (Fig. 56). Long pegs of epi-
thelial cells extended deeply into the underlying

Schlumberger and Lucké—Tumors in Fishes 703

Seiatiettive tins, but there was no evidence of
malignancy. Bits of the tumors were transplanted
_to the subcutaneous tissue of three musk turtles and
three mud turtles, Kinosternum subrubrum. After
nine months the transplants had failed to grow, and
there was no evidence of recurrence at the site of

| —_s CROCODILES (CROCODILIA)
Only two instances of neoplasia in the Crocodili-
dae have been reported. In a discussion following
the presentation of a paper on tumors in cold-
blooded animals by Pick (153) at a meeting of the
- Berliner medizinische Gesellschaft in 1905, v. Han-
Semann (72) said, “I wish to add that I saw a
Iesion, very similar to that just described by Herr
‘Heller in lizards, in a very large crocodile (the spe-
cies was not given) in our (Berlin) Aquarium. We
operated on the animal and it turned out that we
were dealing with quite ordinary warts. Soon there-
after the animal died, whether as a result of the
operation or from some other cause I cannot say.
Nevertheless, I have the impression that the warts
per se had nothing to do with its death.”
_ Amore detailed account of a neoplasm i in a young
_porose crocodile Crocodilus porosus is given by Scott
and Beattie (183). The first symptoms were an
inability to rise, and a tendency to fall on its right
side. A diagnosis of cerebellar tumor was made and
the animal was destroyed. At autopsy a tumor
somewhat larger than a cherry stone was found on
the ventral surface of the cerebellum. On micro-
scopic examination a few glial fibers were seen, but
the mass was mainly composed of small round cells
_and a few larger, often multinucleated cells. Occa-
‘sional mitotic figures were present; the neoplasm
had invaded the adjacent nervous tissue. The en-
tire right auricle of the heart was filled with a tumor
that had also invaded the wall of the right ventricle
and the interventricular septum. Histologically, it
_vogeegan to the growth found in the cerebellum.

In the portal spaces of the liver were numerous
groups of neoplastic cells; the latter were also dif-
fusely scattered throughout the disorganized paren-
_ chyma. The authors concluded that the tumor was

Species Tumor
monitor Varanus dracoena Enchondroma
Lacerta agilis Papilloma
Lacerta muralis fiumensis (several) Papilloma
Lisard Lacerta viridis (several) Papilloma
Tegu Tupinambis teguixin Squamous cell
carcinoma

Miss Tubleombis nicrepuncieh Squamous cell
_ Pegu bu gropu us cho

a round cell sarcoma, primary in the liver, with
metastases in the heart and cerebellum. Examina-
tion of the photomicrograph reveals nothing to sug-
gest that the liver cell itself was the neoplastic cell
of origin. It may be that the tumor arose in the

LIZARDS (SAURIA)

in captivity. All but one of the lesions were neo-
plasms of surface epithelium. The exception was a
case described by Bland-Sutton (12) of multiple
enchondromas in an Indian monitor, Varanus draco-
ena. The animal, which also suffered from rickets,
had large tumors in the fifth and seventh cervical
vertebrae. Two tumors were present in the distal
metaphysis of the right humerus, one in the left
humerus. Each of two metacarpal bones bore a
tumor near its distal end, and four were found in
the hyoid bone. Histologically the neoplasms were
composed of hyaline cartilage. It may be noted that
the possible etiologic relation of rickets to general-
ized chondromatosis in man was suggested by Vir-
chow in 1863.

In a male lizard Lacerta agilis, Koch (100) found

Lacerta muralis fiumensis. The lesions attained a
considerable height and histologically bore a cer-

Plehn (159) observed similar lesions in another
species of lizard, Lacerta viridis, The papillomas

Taste 25: Towons oF Lisanne (Saveta)

Site Author
Bones Bland-Sutton, 1885 |
Skin Koch, 1904
Skin Heller, 1906
Skin Plehn, 1910
Skin Schwarz, 1923
Mouth Ratcliffe, Schlumberger, &

Lucké (not published)

wo4

Cancer Research

occurred in several portions of the body and varied
greatly in size. Though they occasionally presented
firm swellings of considerable dimensions, thev never
penetrated deeply nor did they infiltrate the sur-
rounding tissues.

A squamous cell carcinoma arising in the skin of
the right forefoot of a tegu, Tupinambis teguixin,
has been reported by Schwarz (180). The tumor
was approximately spherical, measured 3 cm. in
diameter, and had almost destroyed the metacarpal
and proximal two phalanges of the fifth digit. The
two proximal phalanges of the fourth toe were also
extensively injured. The tumor parenchyma con-
sisted of neoplastic epithelial cells that showed sug-
gestions of keratinization and “pearl’ formation. A
vascular connective tissue stroma traversed the
masses of tumor cells and even appeared to infiltrate
the adjacent muscle. Large areas of necrosis were
present throughout the neoplasm. Although* the
overlying skin was intact, the author believes that
the tumor arose locally from the epidermal cells.
The tumor was operatively removed, but the animal
died a few weeks later; no metastases were found
at autopsy. :

In collaboration with Dr. Herbert L. Ratcliffe,
pathologist to the Philadelphia Zoological Garden,
we have studied a squamous cell carcinoma of the
mouth in a black-spotted teguixin, Tupinambis ni-
gropunctatus. When first observed, the tumor,
which arose from the left upper gum, had a smooth,
lobulated, pink surface and was very firm in con-
sistency. It measured 2.5 x 2 x 1 cm., and during
the following months increased fairly rapidly in
size, doubling its dimensions in a year. At the end
of that time a similar tumor appeared in the cor-
responding location on the right upper gum. In the
following 18 months both tumors increased in size
and exhibited central areas of necrosis and ulcera-
tion (Fig. 60). At intervals the animal became list-
less and refused its food. When this occurred a
partial excision of the tumors was performed. This

was followed by a return of the animal’s desire for
food.

Several biopsies were taken, the vascularity of the
tumor causing considerable bleeding. Attempts at
tissue culture of this material were unsuccessful be-
cause oral bacteria were a constant contaminant.
Transplants were made to the subcutaneous tissue
of 23 lizards and the gums of four alligators, but the
tumor failed to grow. A similar negative result fol-
lowed transplantation to the anterior chamber of
the eyes of 9 alligators, 9 green frogs, one bull frog,
6 chickens, 12 chicks, and 9 rats.

After being under observation for 2 years and 8
months the animal died from an accidental injury.
At autopsy there was local infiltration of the adja-
cent tissues by the tumor, but no metastases. His-
tologically the neoplasm was composed of squamous
epithelial cells supported by delicate connective tis-
sue trabeculae. The neoplastic cells adjacent to the
trabeculae were radially arranged and columnar in
shape. Elsewhere they were polygonal, the baso-
philic cytoplasm was abundant, with prominent in-
tercellular bridges. Frequently cell aggregates were
found that resembled the epithelial “pearls” of
human squamous cell carcinoma (Fig. 61). The
nuclei were pleomorphic, and showed a marked ten-
dency to produce giant forms with one or more
prominent nucleoli (Fig. 62). Mitotic figures were
numerous.

SNAKES (SERPENTES)

The recorded instances of tumors in snakes are
very few, but several are of great interest. One such
is the adenocarcinoma of the pancreas of Say’s pine
snake Pituophis sayi, which was reported by Rat-
cliffe (167). Grossly the pancreas was diffusely en-
larged; upon histologic examination the parenchyma
was found largely replaced by neoplastic epithelial
cells. In a later publication Ratcliffe (168) reported
that in a series of 136 snakes which had died in
captivity, he found in the pancreas of 45 individuals

Taste 26: Tomors or Swaxes (Sexrentes)

Species Tumor Site Author

Python Python sebae Adenocarcinoma Ovary Bland-Sutton, 1885

Python Python sebae Cystic adenoma (?) Stomach Vaillant & Pettit, 1902

Ring snake Tropidonotus natrix Adenocarcinoma Kidney Patay, 1933

Say’s pine snake Piiuophis sayi * Adenocarcinoma Pancreas Ratcliffe, 1935

Water snake Homalopsis buccata Papillary carcinoma Bile duct Bergman, 1941

Pine snake Pituophis melanoleucus Melanoma Skin Ball, 1946

Pine snake Pituophis melanoleucus Melanoma Labial folds _— Ball, 1946
Rhabdomyoma Palate Ball, 1946

Reticulated python Python reticulatus Melanoma Skin _ Schlumberger & Lucké

(not published)
Reticulated python Python reticulatus Melanoma Skin Lucké & Breedis

(not published)

Schlumberger and Lucké—Tumors in Fishes

705

BN sist the cocrdaaec hich ho ind
served in the pine snake. The
‘most frequently in the Crotalidae (rattle-snakes,
water moccasins) and Colubridae (pine snakes, black
acer). The author traced the development of the
to necrotic foci of unknown etiology. The
$ was apparently followed by an abortive
_ and atypical regeneration of the terminal ductal epi-
thelium, producing small, adenoma-like cell masses.
continued to proliferate while degeneration of
r and islet epithelium progressed until some-
} the entire organ was replaced by atypical duct
: Whether, or at what stage, the process
es to be an atypical regeneration and assumes
character of a neoplastic tumor is difficult to
determine. At the time of his report Ratcliffe re-
ed the lesions as early tumors; he has recently

us that he now considers them to be re-
4 rather than neoplastic. Continuing his
of this disease, he examined 261 snakes be-
to the most susceptible species, 60 to 90 days
‘capture. In contrast to the high incidence of
lesion in animals that had died in captivity only
of the sacrificed snakes showed evidence of

neoplasia.

report by Ball (4) of a malignant melanoma
: hot two pine snakes Pituophis melanoleucus
has recently appeared; we have had the opportunity
of examining the tumors. The animals were a male
and a female, kept in the same cage at the San
Diego Zoological Gardens. In the female snake a
dark rapidly growing tumor was noted on the tail
after the animal had been in captivity for three
years. The tail was amputated, but subsequently
two black tumors appeared on the head and one on
the abdomen. Two years after the primary tumor

mal died six months later. At autopsy the tumor
measured 11 x 6 x 5 cm. and had encroached on the
coelomic cavity. Two metastatic nodules, approxi-
‘mately 2 cm. in diameter, were found in the liver.
Histologically the neoplastic cells were spindle
shaped with an abundant cytoplasm that frequently
contained large numbers of fine pigment granules.
The cells were arranged in interlacing bundles; the
nuclei occasionally showed some evidence of palisad-
In the male animal a tumor was first noted after
almost six years of captivity. The growth, which
‘appeared on the upper labial fold, increased very
‘Tapidly in size and the snake was sacrificed 8 months
after the tumor was first seen. Histologically it re-
sembled that of the first animal and was identified as

a melanosarcoma. No metastases were found. How-
ever, a non-pigmented tumor 1.5 cm. in diameter
was discovered on the palate. It was composed of
large elongated cells with a fibrillar cytoplasm in
which cross striations were occasionally seen. Scat-
tered through the section were plump giant cells
with multiple, centrally located nuclei. This tumor
unquestionably was different from the others; it had
all the structural characteristics of a

The melanomas of the pine snakes lend added
interest to our recent findings of similar neoplasms
in two reticulated pythons, Python reticulatus. The
first python* was a female, 18 feet in length, and 50
to 60 years of age, which had been on exhibition in
the National Zoological Garden of Washington, D.
C., for thirteen years, when a nodule the size of a
walnut was noticed on the left lateral surface of the
trunk. It was located halfway between the head and
tip of the tail. During the following year the tumor
grew rapidly, and when examined by us measured
11.5 x 8x 3.5 cm. (Fig. 63). The mass was a varie-
gated red-brown in color; the surface was faintly
lobulated. The periphery was covered by expanded
scales, but toward the center these were destroyed
by a shallow ulceration. The tumor was quite vas-
cular and bled profusely when we removed small
portions for examination. It was firm in consis-
tency; on section the surface was a mottled red, yel-
low, and black. Six months later the tumor had in-
creased somewhat in size and the area of ulceration
was larger. The animal was killed as unfit for exhi-
bition.

At autopsy the tumor was found to have pene-
trated to the vertebral bodies. Its lateral spread had
been somewhat restricted by the stout connective
tissue septae that normally separate the larger
muscle bundles (Fig. 64). Protruding into the coel-
omic cavity 20 cm. caudal to the heart, was a black,
broadly sessile mass that measured 7 x 5 x 6 cm.
(Fig. 66) and was covered by smooth transparent
mesothelium. On section it was granular, black in
color, and the pigment it contained rubbed off and
discolored the fixing fluid. On the dorsal surface of
each kidney were 6 to 7 widely scattered, roughly
circular, umbilicated, yellow-white nodules varying
from 0.5 to 1.2 cm. in diameter (Fig. 65).

Histologically the primary neoplasm was com-
posed of interlacing bundles of spindle shaped cells
(Fig. 67) which in some areas contained large num-

*We wish to express our appreciation to Dr. W. M.
Mann, director of the National Zoological Garden, for plac-
ing this animal and the facilities of the Reptile House at our

disposal.

>

a.

Cancer Research

bers of pigment granules (Fig. 68). Elsewhere, the
cells were less elongated and the nuclei more vesicu-
lar, with prominent nucleoli; this appearance was
most marked in the metastatic nodules in the kidney
(Fig. 69). Occasionally there was a suggestion of
palisading (Fig. 70) similar to that observed in the
melanomas of the pine snakes. This resemblance of
reptilian melanomas to the neurilemmomas of man
may therefore perhaps be traced to the origin of
both in neurectoderm.

In view of the successful transplantation of mouse
tumors to the yolk sac of the chick embryo (201),
the finely minced python tumor was inoculated into
the yolk sac or onto the chorio-allantoic membrane
of 80 embryos. The chick embryos all died within
48 hours after inoculation; in some, death was the
result of bacterial infection; in others, the snake tis-
sue appeared to be toxic to the embryo.*

The second python, also a female, was 20 feet
long, and had been at the Philadelphia Zoological
Garden for 20 years. No information as to age is
available, other than that the snake was “full-
grown” when received at the Garden. About a year
before its death, the keepers noted a swelling in the
right side of the upper jaw, and two black tumors
on the body. The snake became weak, declined
food, and had to be sacrificed.** At autopsy, the
tumor was found to arise from the region of the
angle of the jaw; it extended forward, was covered
externally by unbroken skin, had a firm consistency,
and measured 6 x 3 x 2 cm. The cut surfaces of the
tumor were pale and had a fibrous appearance. A
second tumor, 2 x 2 cm. in diameter, was located on
the side of the body, about 8 feet from the tip of the
tail. It was somewhat elevated, the covering skin
was unbroken; its consistency was relatively soft
and its color deep black. A similar, much smaller
growth, 0.5 cm. in diameter, was found under the
skin about 4 feet from the head. None of the tumors
had invaded the neighboring tissues, and no metas-
tases were found. Histologically, the tumors were
composed of spindle-shaped cells, grouped in inter-
lacing bundles. Melanin was fairly abundant in the
two smaller growths, but the tumor of the jaw was
almost amelanotic. The tumors were regarded as
multiple non-malignant melanomas. Attempts to
transplant them into the anterior chamber of the eye
of a number of alligators, turtles and frogs were
unsuccessful.

Two other reports of tumors of pythons belonging
to a different species are on record. Bland-Sutton
(12) observed in a python Python sebae which was
destroyed at the London Zoological Garden that the
viscera were studded with an enormous number of

firm yellow-white tumor nodules. The liver con-
tained many similar nodules, varying from the size
of a pea to that of a large walnut. In the lung were
twenty pea-sized nodules; each kidney bore a mass
the size of a walnut, and the ovaries were the seat
of several that had attained the size of an orange.
Histologically the tumor was identified as a “medul-
lary cancer made up of alveoli containing masses of
irregular cells.” The source of the metastases could
not be determined with accuracy, but the author
believed that the ovaries were probably the primary
site of the tumor.

More difficult to interpret is the case recorded by
Vaillant and Pettit (222) in a python Python sebae,
which died 8 days after a swelling near the middle
of its body first became apparent and about 40 days
after the animal had become indifferent to food. At
autopsy a spheroidal mass that measured 28 cm. in
diameter was found attached to the gastric mucosa
and extending into the esophagus. The tumor ap-
parently precipitated intussusception of the small
intestine by the pyloric end of the stomach, account-
ing for the rapid increase in size of the swelling and
the death of the snake. The neoplasm was very
cystic; though most of the cysts were quite small,
one or two contained almost a liter of foul purulent
fluid. Connective tissue septae separated the cysts
which were often lined by epithelial cells. The na-
ture of this tumor is not recognizable from the
authors’ description. It may perhaps represent a
cystic adenoma, but it may not be a neoplasm. Less
difficult to interpret are two older reports of “tu-
mors” in pythons (79, 224). In these cases the
growths were almost certainly not true neoplasms;
rather, they were probably organized blood clots.

In contrast to the questionable nature of these
growths is the carcinoma of the kidney reported by
Patay (145a) in a ring-snake, Tropidonotus natrix.
The animal was a female, 75 cm. in length. The left
kidney measured 4 x 2.5 cm. Its lower portion was
occupied by a well circumscribed growth, approxi-
mately one-third the size of the entire organ. His-
tologically, the tumor consisted of atypical epithelial
cells which in some areas were arranged as acini into
which papillary projections protruded; elsewhere
the cells were undifferentiated. The author regarded

the tumor as a papillary adenocarcinoma, and
likened it to similar tumors in mammals.

* This work was carried out for us through the courtesy

of Col. Raymond Randall, director of the Division of Veteri-
nary Medicine, Army Medical Center, Washington, D. C.

** Dr. Herbert Ratcliffe, Pathologist of the Philadelphia
Zoological Garden, kindly gave us the snake for examination.

Schlumberger and Lucké—Tumors in Fishes

707

___ The last of the snake tumors on record is a papil-

_ lary carcinoma of the bile duct in an East Indian
_ watersnake Homalopsis buccata. It was the only
tumor found by Bergman in 2200 wild snakes ex-
amined (11). He suggests that the apparent rarity
_ of neoplasms in wild snakes may be attributed to the
fact that a tumor-bearing individual living under
natural conditions would probably be so handi-
_ capped that it would fall an easy prey to its enemies.

the wall and the neighboring tissues. Histologically
_ it consisted of atypical pleomorphic epithelial cells.
It is of interest that a trematode was found in close
_ proximity to this tumor, because in the gall bladders
_ of other reptiles, green turtles, trematodes have been

found associated with papillomatous growths (193).

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40

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——————--—-—«, Spontaneous Neoplasms in Fishes. III.
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Schlumberger and Lucké—Tumors in Fishes

711

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& Proc. New Zealand Inst., 24:201. 1891.
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193,

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1939.

, and Nicretu, R. F. A Papillomatous Di-
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———, and Strronc, L. C. Neoplastic Diseases in
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bid. 22:4-5. 1921. (Cited by Thomas.
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Taxanasui, K. Studie iiber Fischtumoren. All the
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' 16:212, 1926.

. Studie iiber die Fischgeschwiilste. Ztschr.
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. Studies on Tumors of Fishes from Japa-
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. Les Sarcomes Fibroblastique chez la Morue.
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. Contribution & I’Btude des Lesions Pré-
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. Adenome Kystique d I'Intestin moyen chez
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. Les Tumeurs des Poissons (Etude Anato-
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. Rhabdomyome chez un Filet. /bid., 21:
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. Deux Cas de Tumeurs Osseuses chez des
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. Chondromes Symétriques chez un Colin.
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. Papillome Tégumentaire chez un Truite.
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. Fibrome de I'Intestin Juxta-pylorique chez
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. Sur Deux Cas de Tumeurs Tégumentaires
chez la Rousette. /bid., 22:306-315. 1933b.
. Sur un Cas de Leiomyome de I'Estomac
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#12

Cancer Research

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———, and Oxner, M. Papillomes de la Lévre In-
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Wrrscut, E. Experimentally Produced in
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Family of Brook Trout. Am. J. Path., 20:413-41"
1944,

DESCRIPTION OF FIGURES 1 AND 2
Cutaneous papillomas in the common sucker, Catostomus commersonnii.

Fro. 1.—A large papilloma occupies the ventral half of
the caudal fin; just anterior to it is a smaller tumor.

Fic. 2,—Section through the smaller of the two papillomas.
The tumor has a typical papillary arrangement, the support-

ing connective tissue is scanty. The underlying structures are
not involved. For details of microscopic structure see Fie
ures 3 and 4. Mag. X 10.

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DESCRIPTION OF FIGURES 16 TO 19
Thyroid “tumors” in the shark sucker, Echeneis naucrates.

Fic. 16.—Gross appearance of a tumor protruding through
the floor of the mouth. The top of the head has been re-
moved by a section which passed through the level of the
eyes (visible in the photograph as bilateral heavy black
crescents).

Fic. 17.—-Thyroid tissue between the bony lamellae of a
branchial arch. On the left is normal epidermis. This ap-
parently aberrant location of thyroid tissue is normal for
teleost fishes. Mag. * 100.

Fic. 18.—Microscop'c appearance of tumor shown in
16. Many of the acini are very small, with only a
lumen lined by tall columnar cells. As the acini increase
amount of colloid increases. There are many marginal va
uoles in the colloid. Mag. « 70. ; hagas

Fic. 19.—Gross appearance of a tumor on the floor of the
mouth in the living fish. fig Meee

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NOTICE

The Index to Literature of Experimental Cancer
Research, 1900 to 1935, prepared by the Donner
Foundation, is now available. It is a bound volume
of over 1000 pages. The Donner Foundation has

generously distributed copie’ to the principal
medical libraries of the United States and Canada,

and to some European libraries. Individ wish-
ing a copy for their personal use may ob one by
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$10, which is less than the cost of ert gee

Bic

ERRATUM

In the paper by Bernhard, Rosenbloom and
Eichen, entitled “A Study of Inorganic Phosphorus
Release Accompanying Glycolysis of Blood in

At

Cancer,” Vol. 8, No. 6, p. 295, ae One

the first paragraph, “252 mgm. per cent” should
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