616-006 : 597

NEOPLASMS I N FISH: A REPORT O F SIX CASES

WITH A SUMMARY OF THE LITERATURE.
ALEXANDER HADDOW (Davidson Research Fellow), and ISOBELBLAKE
(Investigator, Furunculosis Committee, Ministry of Agriculture
and Fisheries and the Fishery Board for Scotland).
Front the Department of Bacteriology, Uaiversity of Edinburgh.

(PLATES
XI.-XIV.)
FROM the middle of the nineteenth century reports have been accumu-
lating with reference to the occurrence of piscine tumours, and
within the last thirty years these contributions have increased in
number and significance, so that there now exists a fairly wide and
instructive literature on the subject. The following table represents
a selection from the more recent and well-authenticated sources.

Family or genas. Nature of tumour. Author.

~ ~ ~~

Trout (Salmo tsutta). . Rhabdomyosarcoma Adami (1908)

Cod(Oadusmorrhw) . . Spindle<ell sarcoma of air- Bashford (1904,1905)
bladder
Gurnard(Trigla) . . . Malignant adenoma Bashford and Murray
(1904)
Caraesiuavulgaris . . . Fibroma of ovary (1 spindle- keudenthal (1928)
cell sarcoma)
Flounder (Pleurmtesfleszrs). Lymphosarcoma
Cod(Gdwmorrhua)
Ling (MoZaa molaa)
.. ..
Sarcoma-3 cases
Papillary cystadenoma of
ovary Johnstone (1924)
Skate(Raicrbatis) . . Melanotic sarcoma-3 cases
Halibut (Hippogloasw arlyarisj Cutaneous papilloma
Fibroma
Whiting ( O d u s aeghyhus) .
Epithelial tumour of jaw
Cod(0adzlsmorrhw) . . Osteo-sarcoma of operculum
Angioma of pectoral girdle nlurray (1906)
15-spined marine stickleback Squamous-cell carcinoma
(Gmttwosttw spinachia)
Goldfish (Cypritaus auratus)
Barbus (Cyprininae) . .
. Lymphosarcoma of kidney
Fibrolipoma Plehn (1906,1924)
Tench (Tinca arL~ariS) .
. Myxosarcoma
Corvina. . . . . Dentigerous tumour Roffo (1925)
Pollachiusbrandti . . . Carcinoma arising from ac-
cessory branchi=-2 cases Takahashi (1929)
Adenoma in hypogastric
cavity

41
41 A. HADDOW A N D 1. BLAKE

TABLE-continued
- ~~

Family or genus. Nature of tumour. Author.

Dollachiw chalcograrnma :arcinoma arising from ac-

cessory branchite
Carcinoma in gill-flap region
r - 2 cases
3 indlecell sarcoma
elanosarcoma-2 cases
Dsteoma-8 cases
Pagmrnajor. . . Adeno-carcinoma
Osteoma-102 cases
Incorhynchw . . . Spindlecell sarcoma
Large roiind<ell sarcoma
Jollago japonica . . Spindlecell sarcoma rakahashi (1929)
Cateolabroxjaponieus .
Cepidotriga alala . .
9. 9, 99

Large-cell sarcoma
Srnall-cell sarcoma
Sebaatodee inermis . . Fibroma
Osteochondrofibroma
Plecoglosswr . . . Lipoma
Hexagramma otakii . Guanophoroma
9hhelidonichthys . . Allophoroma
Cimande Yokohama. . Neuroma gangliwellulare
Shar! . . . ..
Tory hena h i p p r h Multiple exostoses
Chondroma arising from car-
tilage of lumbar vertebra
Whiting (Gadtu aeglefintu) Odontoblastic epithelioma
Fiisiform sarcoma-4 cases
Abdominal gangliwneuroma
Herring (Clwpea harenguu) Rhabdomyoma
Cod(Gadusmorrhua) . . Small round-cell sarcoma Williams (1930)
Conger eel (Conger wulgaris) . Lymphosarcoma of kidney
Halibut(Hi poqlossusrmlgaris Lipoma
Dragonet (8allionymus Zyra) , Liposarcoma
Turbot (Rhombwr maximus) . Myosarcoma
Coal-fish (Gadus wireng) . , Osteosarcoma
Cod (Gadus morrhua) . Osteoma of jaw
Coal-fish (Qtadwr uirens) . Tumour of jaw comparable
with human adenoid cystic
e ithelioma of Brookes Williamson (1909,
&wing) 1911)
Catfish (Anawhichas lupus) Colloid carcinoma in abdomi-
nal cavity
Cod (Oadwr callarias) . E p i t h e 1i o m a of u r i n a r y
bladder
Turbot (Rhombus maximuu) Rhabdomyoma Young (1923-25)

CASEREPORTS.
I. Lymp?wsarcomain a salmon (Salmo salar).
This tumour occurred i n a mature salmon five years old which was returning
t o fresh water to spawn for the first time. T h e tumour apparently took origin
i n the lymphoid tissue of the anterior part of the kidney (fig. 1). The normal
teleost kidney is an extremely lyrnphocytic structure represented by an extensive
tract of small cells, supported by a fine reticulum of connective tissue, in
association with the usual renal elements (fig. 3). The functional kidney i n
fishes is t h e mesonephros, and i n teleosts the anterior part of t h e organ has an
individual differentiation and possesses a haemopoietic function in addition to
that of excretion (fig. 4). The primary growth in the present case was apparently
JOURNAL OF PATHOLOQY.-VOL. XXXVI. PLATEXI

NEOPLASIS
IN FISH

FIG. 1.-Case I. Lymphosarcoma in a salmon (Sukmo salar). Extensive invasion of the

kidney. Above the ovary on each side is seen the primary mass. x $.

Fro. 2 . 4 a s e I. Sectional view. Occlusion of the hEmal arch

by tumour tissue. x 4.
 JOURNAL O F PATHOLOGY.-VoL. XXXVI.
PLATEX I 1

NEOPLASMS
I N FISH

FIG.3. -Appearance of normal teleost FIG. &-Anterior part (haemopoietic)of

kidney. Renal elements and lymphocytic normal teleost kidney. x 325.
background. x 325.

FIG. 5.--Case I. Primary growth. x 325. FIG. 6.-Case I. Infiltration of kidney.

x 325.
 JOURNAL OF PATHOLOQY.-VOL. XXXVI. PLATEXI11

NEOPLASMS
IN FISH

FIG. 7.-Case 11. Hepatoma in rainbow FIG.8.-Normal liver tissue from case 11.
trout (Salmo irideuu). Note nuclear en- x 410.
largement. One cell in mitosis. x 410.

FIG. g.--Case 11. Area of tumour FIG.10.-Case 111. Ganglioneuroma in

showing stroma. x 410. megrim (Lepidwhombus [Zmtqopt-ptsrus]
me.qastoma). Ganglion cells and fibrils.
x 325.
JOURNAT, OF PATHOLOOP.-Vor.. XXXVI. PLATEXIV

NEorLAsm IN lisa

F ~ Q11.-Case
. IV. Melanomata in PIG.12.-Case IV. Surfaceappear-
thornback ray (Ilaia clavata). ance of smaller tumour. x 1.
Surface appearance of larger tumour.
x 1.

Fro. 13.-Case IV. Sectional views FIG.14. -Case IV. Structure of melanw
to show absence of invasion. x 1. mata, showing sinuses. x 90.
 NEOPLASMS IN FISH 43

derived from the lymphoid parenchyma of this structure, which had enlarged
and extended laterally to form two separate bodies, each measuring about 4‘4 by
2’4 cm. The microscopic appearance was uniform and is shown in fig. 5.
Extensive invasion of the kidney throughout its whole length was the striking
macroscopic feature of the case, and as far as could be ascertained no metastases
were ,present in other organs. The infiltration had resulted in almost complete
destruction of the renal units, leaving only discrete islets of tubular epithelium
(fig. 6). Fig. 2 demonstrates the appearance of the kidney and surrounding
structures on transverse section. The haemal arch is seen to be occluded by
a mass of tumour tissue, apparently by direct spread from the veins of the renal
portal system in the substance of the kidney.
11. Hepatomu i n a rainbow trout (Salmo irideus).
The tumour was found near the anterior margin of the liver of a 4-5 yeat
rainbow trout, found dead. . It was spherical, about 1’6 cm. i n diametar, and
paler and firmer than the surrounding hepatic tissue. The latter presented no
abnormality apart from patchy autolytic changes. No metastases were found,
Microscopically the tumour was seen to be composed of polyhedral cella only
slightly dedifferentiated from the parent liver cell (figs. 7 and 8). Mitmes were
numerous, averaging five in each high-power field of approximately 800 c e h .
The arrangement of the cells more or less resembled that of the normal
liver, except for the presence of an intersecting fibro-vascular stroma (fig. 9).
Although the adenoma was not encapsulated, no clear evidence of infiltration
could be found, either macro- or microscopically.
111. Gmglio-neurm i n a megrim (Lepidorhombus [Zeugopterus] megastoma).
Of considerable dimensions, this neoplasm was situated immediately behind
the body cavity and occupied almost the whole thickness of the body. It was
found impossible to determine the parent tissue with accuracy, but the growth
found attachment to, and apparently arose from, an area outside the vertebral
column, as if in the position of a spinal ganglion. The tumour was slightly
lobulated and possessed a fine fibrous tissue capsule. Microscopic examination
revealed a fibrillar groundwork of nervous tissue containing scattered groups of
ganglion cells. I n osmic acid preparations the neuro-fibrils were seen to be
non-medullated. Examination of the ganglion cells by high-power magnification
showed them to be imperfect, degenerate and vacuolated, although possessing
bipolar continuity with the nerve fibres of the tumour substance (fig. 10).
IT. Melanwnata in a thornback ray (Raia clavata).
These tumours were found in a two-year thornback ray which was apparently
in excellent general condition when caught. Both tumours were sessile and
lobulated : the larger, measuring 4 x 2 x 1 cm. in its greatest dimensions, waa
distinctly paler than the normal skin, but contained scattered deposits of melanin,
while the smaller tumour, measuring 2 x 18x 8 cm., was densely loaded with
melanin throughout. Figs. 11 and 12 show the surface appearance of the
tumours, and the sectional views shown in fig. 13 illustrate the complete absence
of any invasive tendency. Incidentally, these tumours are practically identical
i n appearance with the melanomata described and figured by Feldman (1933) as
occurring in the skin of hogs. Xicroscopically (fig. 14) the tumours were found
to be richly cellular and composed of packed collections of melanoblasts possessing
extremely large nuclei. Both tumours were traversed by coarse fibrous t r a b e c h
radiating from the base, and in addition were rifted with numerous thin-walled
blood sinuses. The melanin was distributed mainly as intracellular granules,
but clumps of pigment also occurred extracellularly. No mitoses were seen.
44 A. HADDOW AND I. BLAKE

V. Nultiple subcutaneous turnours in a pike (Esox lucius).

The neoplastic tissue in this case occurred aa outgrowths a t the bases of the
finsand in the buccal cavity of a female pike. The fish unfortunately was highly
decomposed. The tumour masses were grey in colour and covered with thin
skin. The same structures occurred also in the opercula, but in this situation
were almost completely destroyed by putrefaction of the gills. The tumours
were confined to the subcutaneous area and the muscle waa free from intiltration ;
there were no visceral metastases. The outgrowths appeared to the naked eye
as mucoid or fatty in nature, but microsqopic examination showed a highly
cellular structure, apparently lymphatic in origin.

VI. Ovarian tumour in a pike (Esox lucius).

This tumour occurred in a large pike found in a dying condition. The ova
from the right ovary had been shed. Near the anterior end of the left ovary
was found a large soft swelling measuring 3 x 7 cm., and accompanied by several
similar nodules of smaller size. The whole ovary was hemorrhagic, and the ova,
in some parts cystic, were not being shed. While the tissue was in a state of
poor preservation, there could be no doubt aa to the nature of the condition.
Microscopically the structure was that of an adeno-carcinoma, apparently derived
from an abnormal proliferation of the germinal epithelium.

DISCUSSION.
From the above review and contribution it is evident that tumour-
formation constitutes a tangible fraction of the pathology of both
fresh- and salt-water fish. A study of the families and genera involved
shows that teleosts preponderate, and this probably finds its chief
correlation in the fact that this order has an enormous numerical
superiority in the fish populations in existence a t the present time.
Examination of the sources of origin of the tumours indicates that
while examples are found in tissues from all of the primitive layers,
the majority are from derivatives of the mesoblast. I n the above
series of 180 cases, less than 10 per cent. are epiblastic in origin.
Tumours occur in most organs having homologues in other vertebrates,
and in addition Takahashi (1929) has described neoplasms (guano-
yhoroma, allophoroma), arising in the specific chromatophores of the
fish corium.
With regard to the frequency of these tumours,it may be stated
that the group of 142 examples collected by Takahashi occurred in
a population of approximately 10,000 fish, mainly derived from the
Japanese Sea. It must be recalled that an inordinate proportion of
these cases was represented by simple osteomata. Cases 1, 5 and 6
reported above were found in a group of 298 fish found dead and
dying, and composed of salmon, sea trout, brown trout, pike and
grayling. Case 2 occurred in a group of 116 trout-farm fish (SaEmo
fario, S. irideus,S.fontinalis) found dead. The accurate age-constitution
of these groups is not available, but it may be said that in the second
case the fish varied from young t o just mature, and that none were
old. T h u s the incidence, while significant, is of an order apparently
 NEOPLASMS IN FZSH 45

relatively low, and it may be of interest to contrast this with other

data in the comparative study of neoplasms. Feldman (1929) found
carcinoma present in 5 per cent. of 40,000 killed horses, mostly in
auimals over 1 5 years. H e reports Frohner as finding 650 cases of
carcinoma (13 per cent.) in 5000 horses, and Curtis found tumours in
9 per cent. of 880 birds. The spontaneous rate in guinea-pigs and
rabbits is apparentlyvery low. I t is of the utmost importance that
these data be viewed in the light of the lasin principle which has
emerged from the comparative study of cancer, and which has been
so adequately stressed by Cramer (1932), namely, that " the frequency
with which cancer is found in a group of individuals, whether animals
or man, depends on the age-constitution of the group ; it will be high
or low as the proportion of middle-aged and old individuals is high
or low."
With regard to the general characters of the cancer cell in fish,
it is evident that, while rapid division and invasion occur in the usual
way, widespread metastasis is exceptionally rare. It is possible that
this may be explained, in part at least, on an anatomical basis; for
instance, the lymphatic system of the fish is merely a diffuse arrange-
ment of capillaries and spaces possessing no organised lymphatic
glands.
Transplantation of tumour material has been attempted in only
a few cases and has been uniformly negative, mainly on account
of premature death of the inoculated fish. Using two crucians,
Freudenthal (1928) performed intraperitoneal inoculation of perfectly
fresh fibroma cells; one fish died shortly after, the other showed no
pathological feature on being killed after ten weeks. Takahashi also
records several unsuccessful attempts a t auto- and iso-transplantation.
I n the present study, a yearling rainbow trout was anesthetised in
24 per cent. urethane and inoculated intramuscularly with an emulsion
of cells from the hepatoma in case 2, but died from septicaemia a t the
end of a few days.
Diseased conditions due to trematode, nematode, cestode, protozoal
and similar agencies are so frequent in fish that parasitic inclusions
in relation to tumour-formation might be expected in an unusual
number of instances. Takahashi found this association to exist in
three of his cases, but it does not appear to be unduly frequent.
Tumours in the poikilothermE are of unusual intrinsic interest and
in addition their occurrence lends considerable support to the thesis
of the essential biological unity of neoplasms. It is from this aspect,
their relation to the comparative pathology of cancer as a whole, that
their description is of most value. This wider subject first received
systematic attention by Johne (1889) and Woods Hutchinson (1901),
but it was the classical studies of Bashford (1904) and Murray (1908)
on the zoological distribution of cancer which first laid a strong
foundation for the doctrine of the ultimate Etiological homogeneity
46 A. HADDOW A N D I. BLAKE

of malignant new growths. These studies pointed insistently to the

autonomy of the cell as the clue to what must be regarded a8 a
fundamental biological phenomenon, expressing itself only incidentally
as a problem of human pathology. I n the writer’s opinion this attitude
has been greatly strengthened by the descriptions of over 600 animal
neoplasms recorded in the recent monograph by Feldman (1932).
Legrand (1911) pointed out that the pathogenic cause can hardly be
a specific infective agent, on the ground that there is not in existence
a known organism so indifferent to the choice of its host as t o be
capable of infecting such a wide variety of the forms of life. It must
be admitted on the other hand that this argument has lost some of its
independent validity when we consider, for instance, the pathogenic
activity exerted over a wide range of the vertebrate phylum by the
closely related types and strains of iMycobacteriurn tuberculosis. Never-
theless, there can be no escaping the fact that the same etiological
factor may initiate the growth of different tumours, and that similar
tuniours may owe their origin to widely differing agencies. With this
fact we must consider the impressive evidence which has accumulated
in the past thirty years with regard t o the properties of the cancer cell
in transplantation, the results of the application of mendelian analysis
to the incidence of spontaneous neoplasms in mice, and the formidable
array of data which has accrued from the study of experimentaI
carcinogenesis.
The discovery of the action of X-rays in producing somatic geno-
variation is a more recent indication of the direction in which events
must inevitably move. There can be little doubt that the proposition
as enunciated byBashford will proceed to its logical conclusion, and
that cancer must soon be regarded essentially as a problem concerning
the genetic relationship between the somatic cell and the malignant
variant to which it gives rise.
We desire to thank Professor T. J. Mackie for his help and for the provision
of facilities, and acknowledgments are also due to Dr J. Ritchie, Dr A. Bowman,
Mr J. J. M. Shaw, F.R.C.S., and Mr R. Elmhint, from whom some of the
specimens were received. The expense incurred has been defrayed by a grant
made to one of us (A. H.) from the Moray Research Fund.

REFERENCES.
ADAMI,J. a. . . . . . . . Montreal Med. Jmrn., 1908, xxxvii. 163.
BASHFORD, E. F. . . . . .
Scientifi Reports on the Investigations of the
Cancer Research Fwnd, 1904, No.1.
9, ,, . . . . . .
The growth of cancer, Trans. Med. SOC.
London, 1905, xxviii. 210, and The Lancet,
1905, i. 837.
E. F., AND MURRAY,Proc. Roy. Soc., 1904, Ixxiii. 66.
BASHFORD,
J. A.
CRAYER,W. . . . . . . . The comparative study of cancer, Cancer
Review, 1932, vii. 241.
 NEOPLASMS IN FZSH 47

W. H.
FEZIDMAN, . . . . . Malignant growths in domesticated animals,
Journ.Amer. Vet. Med. ASSOC., 1929, Ixxv. 192.
2, I, . . . . . Neoplasms of domesticated animals, Hayo
Clinic Monograph, Philadelphia (W. B.
Saunders), 1932.
P. .
FREUDENTIIAL, . . . . Fibrom ( 1 Spindelzellensarkom) im Ovarium
einer Karausche (Carassiwr vulgaris), Zeita.
\
f. KrebsJorsch., 1938, xxvi. 414.
JOHNE . . . . . . . . . I n Birsch-Hirschfeld’s Lehrbuch der allgemeinen
pathologischen Anatontie, 1889 (quoted in
Sci. Reps. on the Investigations of the Cancer
Research Fund, X o . 1).
J.
JOHNSTONE, . . . . . . Journ. Marine Biol. Assoc. of the United King-
dom, 1924, xiii. 447.
LEGRAND. . . . . . . . Bull. de 1’Assoc. franc. pour l’4tude du ixmer,
1911, iv. 71.
MURRAY,J. A. . . . . . . The zoological distribution of cancer, 3rd Sci.
Rep. of the Imperial Cancer Research Fund,
1908, 41.
PLEHN,M. . . . . . . . . Ueber Geschwulste bei Kaltblutern, Zeits. f.
Krebsforsch., 1906, iv. 626.
,) . . . . . . . . . . Praktikum der Pischkrankhiten, Stuttgart,
1924.
ROFFO,A. H. . . . . . . . Sobre un tumor paradentario de la Corvina,
Bol. del. Inst. de ilfed. Exp., 1926, ii. 28.
TAKAHASHI, K. . . . . . . Studie uber die Fischgeschwulste, Zeits. f.
Krebsforsch., 1929, xxix. 1.
TEOMAS,L. . . . . . . . Epithelioma odontoblastique des maxillaires
chez une morue, Bull. de 1’Assoc. frang. pour
l’&ude d u cancer, 1926, xv. 464.
. . . . . . . . . . Les sarcomes fibroblastiques chez la morue,
ibid., 1927a, xvi. 79.
. . . . . . . . . . . Sur un cas de ganglioneurome abdominal chez
la morue, ibid., 1927 b, xvi. 202.
G.. . . . . . .
W~LLIAMS, Tumorous growths in fish, Report of the Lama-
shire Sea-Fisheries Laboratory, 1928,120.
3, ......... Report of the Lamashire Sea - Fisheries
Laboratory, 1930, 98.
WILLI,MSON,H. C. . . . . Annual Reports of the Fishery Board f o r Scot-
land (Scientt$c Investigations), 1909, 67 and
69; 1911, 14.
. .
WOODSHUTCHINBON . . Studies in Human and Comparative Pathology,
London, 1901.
YOUNG . . . . . . . . . Journ. Marine Bid. Aasoc., N.S., 1933 - 25,
xiii. 910.