Tumors Characteristic for Certain Animal Species: a Review

CANCER RESEARCH

VOLUME17 OCTOBER 1957 NUMBER9

Tumors Characteristic for Certain Animal Species A Review*

HANS G. ScHLUMBERGERf

(Department of Pathology, College of Medicine, Ohio State University, Columbus, Ohio)

The tumors of man may originate in virtually mon. The low incidence of tumors of the gastro every organ or tissue, as witness the hundreds of intestinal and genitourinary tracts is probably real morphologically distinct neoplasms that have been and not solely due to the lesser accessibility of identified. Among the domestic and common lab these organs for inspection. In several of the more oratory animals, a large variety of tumors has common food fishes such as herring (Clupeidae), also been reported. This observation has tended cod (Gadidae), and mackerel (Scombridae), which to obscure the fact that in each species some tu are caught in vast numbers, the reported cases of mors occur much more frequently than others and neoplasia are few, are of connective tissue origin, may be regarded as a species characteristic (Table and without apparent species specificity. 1). These tumors merit consideration in any truly These fishes may be contrasted with members comprehensive study on the natural history of the of the snapper family (Lutianidae), in which single species. or multiple nerve sheath tumors are of frequent It is the aim of this paper to review these neo occurrence. In 2 months LÃ¼cke(52) was able to plasms and to interest biologists, who examine collect 76 specimens that had single or multiple large numbers of animals not commonly studied neurilemomas. He estimated that they occur in by oncologists, in collecting and recording the 0.5-1 per cent of snappers seen in the Tortugas tumors encountered (24). The information so ob waters, where the commercial fishermen of Key tained will contribute to our knowledge of com West call them "cancer fish." No other tumors parative oncology, and may provide data on the have been seen in these fish, nor were similar tu interaction of genetic and environmental factors mors observed in other species found in those wa in the etiology of neoplasia. ters. Among goldfish, Carassius auratus, neurile ZOOLOGICAL DISTRIBUTION momas also appear to be characteristic of the Fishes.â€”Tumors have been reported in over species. Approximately 10 per cent of the goldfish 120 species of fishes (75). Although isolated in in a large urban lagoon in Cleveland exhibit nerve stances have been described in which one or an sheath tumors (71). They usually appear as mul other viscus was affected, neoplasms of the skin tiple neoplasms of the skin but may occur singly and subcutaneous tissue are by far the most com- in the abdominal cavity. Some are invasive and * This paper is based upon an address to the Arizona show cytological changes characteristic of malig Division of the American Cancer Society in Phoenix, January nancy. The writer has also collected goldfish with 11, 1957. Studies by the author were supported in part by similar tumors from ponds in Atlantic City, N.J., grants-in-aid from the National Cancer Institute of the and Columbus, Ohio. The difficulty in determin U.S.P.H.S. and the American Cancer Society. ing the histogenesis of the less well differentiated t Present address: Medical Center, University of Arkansas, tumors is considerable, and it is very probable that Little Rock, Ark. most of the instances of fibrosarcoma reported in Received for publication May 20, 1957. goldfish are, in fact, cases of neurilemoma. De- 823

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spite careful dissection of many hundreds of adult in each instance the affected animals were limited goldfish from various parts of the United States, to a restricted area of the geographic range of the tumors other than the neurilemoma were encoun species. Small papillary tumors were found on the tered only twice. One was a cutaneous papilloma, lips of barbels, Barbus fluviatialis, caught in the the other an osteochondroma arising from the Mosel River, Germany, by Keysselitz (43). In basisphenoid bone of the skull. the neoplastic epithelial cells he described intra Papillary epithelial tumors of the lips have been nuclear inclusions surrounded by an achromatic reported as common in several species of fishes; halo and readily distinguishable from nucleoli. TABLE1 DISTRIBUTIONOFSPECIES-CHARACTERISTICTUMORS* SpeciesFISHES:EelAnguilla Reference

anguillaCatfishAmeiurus Schaeperclaus (70) nebulosusRed LÃ¼cke&Schlumberger (53) taiPagrosomus majorNorthern spinesLymphoid Takahashi (86) pikeEsox IndusMuskellungeEsox tissueLymphoid Nigrelli (60) masquinongySnapper1, tissuePeripheral Ritchie (unpublished)

Sp.GoldfishCaramasitininna nervesPeripheral LÃ¼cke(52) aura/usKillilis!, nervesSkinSkinKidneySkinLymphoid Schlumberger (71) hybridX. maculatilaAMPHIBIANS:AxolotlSiredonhelleri x P. Gordon (32)

mexicamimLeopard Brunst (78) frogRana pipiensREPTILES:Green LÃ¼cke(50) turtleCkelonia mydasBIRDS:ChickenGaUus Smith & Coates (82)

domesticusDuck tissueLiverKidneyPituitaryNasal Olson & Bullis (63) breed)Anser(Campbell dom.ParakeetMelopstittacusplatyrhynchos hepatomaAdenocarcinomaAdenomaCampbell (11)

vndulatusMAMMALS:HorseEquus Schlumberger (unpubl.) carcinomaCarcinomaMelanomaCarcinomaAdenoma& (72)

cabattusCattleBoa sinusesSkinEyeLiverLungKidneyBreastSkinUterus KÃ¤rnbach(42) McFadyean (55) taurusSheepOnus Russell et ai. (69) ariesSwineSui carcinomaAdenoma& Tamaschke (87) carcinomaNephroblastomaMixed& (87) scrofaDogCants Monlux et al. (56) tumorMastocytomaAdenoma Mulligan (59) familiarisRabbitOryclolagus " (58)

runiculus & carcinoma Green & Saxton (84) floridanusMouseMusSylvilagus SkinBreastBreastLiverTumorPapillomaEpitheliomaOsteomaLymphosarcomaLymphosarcomaNeurilemomaNeurilemomaMelanomaMelanomaAdenocarcinomaPapillomaLymphomatosisMalignantFibroma &papillomaAdenocarcinomaFibroadenomaFibrosarcomaShope (79, 80) musculusRatUnit Horn & Stewart (40) Bullock & Curtis (8) us rattusOrganLipsLipsHaemal " (7) Deer Capreolus capraea Liver Hepatoma Krause (45) * Other examples on which data are still incomplete are given in the text. In identifying tumors as species-characteristic, due regard must be given to the age of the animals collected, the care with which they were examined, and the number available for study.

Among the stint, Osmerus eperlanus, from an in kidney. Smaller growths were found in the liver, let of the Baltic Sea, Breslauer (5) in 1916 found spleen, and retroperitoneal tissue. The writer has 37 specimens with cauliflower-like growths that found a similar tumor in another fish of this spe occasionally were as large as the head of the af cies, and Haddow and Blake (36) have also re fected fish. Histologically, they were papillomas ported a case. with occasional intracytoplasmic inclusions. It is For several years Ritchie has been conducting of interest that recently Schaeperclaus (70) ob an extensive investigation of lymphosarcoma in served similar tumors in eels, Anguilla anguilla, the muskellunge, a large relative of the northern also caught in the Baltic Sea. Although previously pike.1 About 10 per cent of these fish taken from rarely observed, the lesions began to attract the Lake Scugog in the neighborhood of Toronto, attention of fishermen in 1948 and by 1950 ap Ontario, bear the tumor. The lesions differ from proximately 5 per cent of the catch was affected. those of the pike, described by Nigrelli, in that Since then, the incidence has gradually declined. the tumors apparently arise in the subcutaneous In addition to eels, codfish, Gaeus sp., were oc tissue from where they invade the trunk muscula casionally affected. ture. Later the kidney, spleen, and liver become Catfish, Ameiurus nebulosus, found in streams diffusely enlarged, the result of a lymphoblastic near Philadelphia commonly bear epithelial tu infiltration, accompanied by lymphatic leukemia. mors that appear as solitary or multiple large red Occasionally, the skin lesions heal, and the fish fleshy masses on the lips or dental plates, where recovers; but the cells appear to be definitely neo- they may interfere with closure of the mouth (53). plastic, and in most cases the tumors progress Histologically, the tumor has the structure of a until the fish succumbs. Initial studies by Ritchie rather solid papilloma with a delicate vascular indicate that the tumor can be transplanted and connective tissue stroma. The growths may invade that it is contagious to muskellunge living in the adjacent structures, but mÃ©tastaseswere never same water with fish bearing the growth. No other observed. During a 2-year period 166 tumor-bear varieties of tumors were found in any of the af ing catfish were examined in addition to several fected or normal fish. hundred apparently healthy fish. Except for a The platyfish, Platypoecilus maculatus, and microscopic renal adenoma, no other tumors were swordtail, Xiphophorus hellerii, do not hybridize encountered. in their native rivers of Mexico, but do so readily Bony lesions, provisionally identified as oste- in aquaria. Among the hybrids, the black or spot omas, are common on the ventral spinous processes ted fish often develop melanomas, whereas the of the sixth to eighth caudal vertebrae of a Japa nonspotted siblings are free of tumors. The ge nese food fish, the red tai, Pagrosomus major. Taka- netics of this neoplasm has been extensively in hashi (86) examined over 100 fish with this growth ; vestigated by Gordon (32). It is the species-spe the high incidence of the osteomas is also indicated cific tumor of these hybrids. by the fact that among three P. major selected at Amphibians.â€”Tumors are not frequently ob random from the collection in the National Mu served in amphibians. Among urodeles, with the seum in Washington, one bore the characteristic exception of the axolotl, only a few reports de tumors (75). The earliest lesions are fusiform; as scribing single cases are on record (75). A renal they increase in size, they become nearly spheri adenocarcinoma in Nectwus maculosus was re cal, reaching a diameter of 1-2 cm. Histologically, cently studied in this laboratory; but this speci the growths are composed of cancellous bone and men, contributed by Professor W. J. Leach, is the may represent a species-characteristic excess cal only one with a tumor of any kind observed by lus rather than a true tumor. The great variety him over a period of many years in several hun of genetically controlled bony overgrowths of dred of these animals dissected by students. fishes and their possible significance for the prob In view of this dearth of material, the occa lem of neoplasia has been discussed by Breder (4). sional occurrence of melanomas in the skin of Lymphosarcoma is the most common tumor in axolotls, Siredon mexicanum, is of particular in two species of the genus Esox, viz., the northern terest. First reported in a single specimen by pike, E. lucius ( = E. estar), and the muskellunge, Krontovsky (46), a similar tumor in each of a E. masquinongy. Nigrelli (60) studied twelve pair of grey axolotls and in another unrelated fe northern pike ranging in age from 2 to 6 years male was studied by the Brunsts (78). Among the that were kept in the same tank and died at inter offspring of the pair, as well as in subsequent gen- vals over a period of 1 year. The primary tumor, 1Personal communication dated April 3, 1957, from Dr. composed of large lymphoblasts, apparently arose R. C. Ritchie, Department of Pathology, Banting Institute, in the lymphoid tissue normally present in the University of Toronto, Toronto, Ontario.

erations, slow-growing transplantable melanomas ports of tumors in these species are awaited with appeared on the skin. Another report is that of interest. Finkelstein (27), who stated that during the dec Birds.â€”Among domestic birds, the highest tu ade 1920-1930 there were in the aquarium of the mor incidence is found in the chicken. Several in Kiev Roentgenological Institute axolotls with a vestigators, each basing his figures on over 2,000 hereditary tendency to melanoma. autopsies, have reported that tumors occurred in With one outstanding exception, tumors are as 12.9-19.5 per cent of fowl examined (10, 33, 63). uncommon among frogs and toads as they are in However, other workers found an incidence of the urodeles (75). The exception is the renal adeno- only 2-3 per cent (18, 22, 77). This disparity carcinoma of the leopard frog, Rana pipiens, first may be largely due to the presence or absence of adequately described by LÃ¼cke(50) in a report the leukosis complex among the birds studied. based on 158 cases. Since then over 1500 cases The leukosis complex includes visceral lympho- have been examined by LÃ¼ckeand the writer, matosis, erythroblastosis, and myeloblastosis (41). while many more have been seen by other inves Of these, visceral lymphomatosis is the most tigators. Nearly all are found in frogs caught in common; it is also by far the most frequently their natural habitat, New England, particularly encountered fowl tumor, particularly in the United Vermont. In large shipments of these animals the States, where it has led to losses of considerable incidence is usually about 1-2 per cent but may economic importance. In one series of 7408 au be as high as 5 per cent. The neoplasms arise in topsies, Goss (33) found that 1445 (19.5 per cent) the renal tubular epithelium, are often multicen- birds bore tumors and that, of these, 1332 (92 per tric, metastasize, and have been carried in serial cent) were of the leukosis complex, chiefly vis transplantation through many passages (76). In ceral lymphomatosis. Even after exclusion of these tranuclear inclusions first suggested a possible tumors, over two-thirds of chicken cancers are virus etiology for the tumor, a view supported sarcomas rather than carcinomas; like lympho by the transmission experiments of several inves matosis, several are of proved virus etiology (28). tigators (6, 20, 51, 89). This tumor provides an In other domestic birds such as pigeons, ducks, excellent example of a species-characteristic neo and geese, tumors are rarely observed (22). Only plasm; although sporadic cases of renal adenocar- single and usually isolated cases are described. An cinoma probably do occur in other frogs, none has interesting exception has been reported by Camp yet been reported. Furthermore, the writer has bell, who found carcinoma of the liver in 22 of 76 examined several thousand Rana pipiens, but no ducks belonging to the Campbell breed (11). tumor other than the renal adenocarcinoma was Among cage and captive wild birds, sporadic found, nor has any been described in the litera cases of tumor-bearing individuals have been re ture, indicating that they must be extremely rare. ported (30, 37). However, in 1933 Ratcliffe (66) Reptiles.â€”The paucity of tumors reported in noted that, of 6898 birds autopsied at the Phila reptiles (75) is coupled with the fact that rarely delphia Zoo, 81 were found to have a tumor, and, has more than a single case been described in any of these, 42 were birds belonging to the order Psit- species. The large edible marine green turtle, Che- taciformes that comprised only 17 per cent of all Ionia mydas, is commercially important and may birds examined. A single species, the shell para receive closer scrutiny than most reptiles. In these keet, Melopsittacus undidatus, with 177 autopsied animals several investigators (75, 82) have ob specimens, made up 28 of the 42 cases. This inci served fibro-epithelial papillomas on the skin of dence of 15.8 per cent was unequaled by any other the head, neck, and flippers, as well as on the cor species of bird or mammal exhibited in the Zoo. neas, where they may produce blindness. The le A similar high incidence of tumors in this species sions range in size from 5-mm. warts to large was later reported from the Moscow Zoological tumors 20 cm. in diameter. It is possible that this Park (21). tumor is the characteristic neoplasm of C. mydas, During the past 4 years the problem of neo but before this can be established a systematic plasia in the shell parakeet has been under inves examination of a larger number of these turtles tigation in our laboratory. Among 497 tumor- than any hitherto reported must be carried out. bearing birds there were 159 cases of fibrosarcoma In snakes and lizards only about twenty cases arising chiefly in the skin, spleen, and liver; car of neoplasia have been reported in nearly as many cinomas exclusive of those in the pituitary num species. It may be of interest, however, that mel bered 130, of which 106 were primary in the kid anomas of the skin have been found in two pine ney. Neoplasia of the hematopoietic tissues was en snakes, Pituiphis melanoleucus (1), and in two countered 37 times, being much less common in pythons, Python reticulatus (75). Additional re the parakeet than in the chicken. An unexpected

finding was that tumors of the pituitary are rela appeared to be endemic on a ranch in Wyoming tively common in the shell parakeet (72); this (49). At a meat inspection center in Denver 908 organ was the site of a primary adenoma or car tumors were found in slaughtered cattle during cinoma in 156 instances. The tumors often pro the 2 years 1953 and 1954. Of the total, 722 were duce blindness by pressure on the optic nerves and ocular tumors collected during only a part of 1 are frequently associated with polydypsia, hyper- year, permitting a conservative estimate of 1400 glycemia, and obesity. The metabolic disturbances eye tumors for the 2-year period, to contrast with are also found in birds with subcutaneous trans 186 tumors from all other sites (56). In reports plants of the tumor (74). Although it is apparent of the Meat Inspection Branch for the years 1950- from the figures cited that both renal carcinoma 54, 82 per cent of condemnations for neoplasms and the pituitary tumor are characteristic of Melo- in cattle were for cases of ocular squamous car psittacus undulatus, the species-specificity of the cinoma (69). Among 2003 bovine neoplasms in pituitary tumor is made more striking by the in India, 42 per cent were diagnosed as carcinoma frequent occurrence of pituitary growths in other of the eye (12). Russell et al. (69) have estimated animals. the over-all incidence of ocular epithelioma among Mammals.â€”In contrast to the other vertebrate cattle in the United States at 0.8-1.6 per cent. classes where data on neoplasia are meager, the They observed that 75 per cent of the tumors descriptive literature about tumors in mammals is arise on the cornea or limbus. enormous. Nevertheless, of the more than 10,000 In sheep most reported series of tumors are mammalian species only about ten are repre quite small and show considerable variation in sented by more than a few reports of isolated relative organ incidence. In two of the largest cases. The species on which adequate information collections (56, 87), benign and malignant tumors is available are the domesticated and the common of the liver comprise 12 and 30 per cent, respec laboratory animals. In most of these there is def tively, of all neoplasms. Although infrequent in inite evidence for a species-specificity of certain the United States, Tamaschke (87) found tumors tumors. of the lung to be as common as the hepatic neo During the past several decades the horse pop plasms; of 32 cases, 26 were listed as adenomas. ulation of Western Europe and the United States Tumors of the adrenal cortex or medulla are also has declined rapidly. For this reason most of the relatively frequent in sheep; however, there is no surveys on large numbers of animals were re tumor that can be considered characteristic of ported during the first 30 years of this century these animals in the manner of melanoma in (84). Tumors of the nose and accessory sinuses horses and ocular carcinoma in cattle. are more common in horses than in any other spe Among swine, the kidney is the site of 30-50 cies. KÃ¤rnbach (42) found 100 instances of neo per cent of all neoplasms reported (27, 56, 87). plasia at this site; and in a series of 1447 equine By far the greatest number are embryonal neph- tumors collected from the literature by Tamaschke romas, comparable to the Wilms' tumor in chil (87), 304 were primary in the nose or sinuses; of dren. Histologically, they are composed of both these, 70 were carcinomas, 50 sarcomas, and the epithelial and mesenchymal elements; hence, the rest benign. In the same series other frequent descriptive term "adenosarcoma." The young age sites of cancer were the gastrointestinal tract with at which swine are slaughtered may in part ac 93 cases, the testis with 88, and the penis with count for the relative frequency of this tumor 81. However, the most striking incidence of a which in other animals and man is characteristi tumor in these animals is that of the melanoma cally found in young individuals. in grey horses. The site of the primary growth is Dogs, many of which reach an old age as pets, usually the skin about the anus and genitalia. Al are subject to a wide variety of tumors. Most though rare in horses of other coat colors, it common are benign and malignant lesions of the reaches an incidence of 80 per cent in greys over skin, comprising about 35 per cent of the total 15 years old (55). The effect of age on the oc (16, 59). Another 20 per cent are neoplasms of currence of the tumor has been repeatedly con the mamma, in which over half are mixed tumors firmed; it is virtually unknown in animals under composed of epithelium, connective tissue, and 6 years, rises to 36 per cent at 8-10 years, and 61 other mesenchymal elements. This high incidence per cent at 10-12 years of age. of mixed tumors is peculiar to the canine mam In cattle the high incidence of epithelial tumors mary gland. Thyroid carcinoma, now uncommon arising on the cornea or conjunctiva has long in the U. S. where iodized salt is widely used, is been recognized as characteristic for these ani still frequent in parts of Europe. Dobberstein (17) mals (26). In 1900 Loeb noted that ocular cancer has recently reported from Germany that it rep-

resents 41.5 per cent of all canine carcinomas in sultant papillomas usually undergo malignant his series. Mulligan has pointed out that the mast transformation. cells are more prone to neoplastic growth in dogs Many thousands of guinea pigs are annually than in any other species (58, 59). There is also sacrificed in laboratories throughout the world, a striking breed specificity, for in the Boston ter but few tumors are on record. In part this may be rier mastocytomas account for over 40 per cent attributable to the youth of most of the animals of all neoplasms, whereas in the fox terrier the when killed. Although less than 30 tumors had incidence is only 9 per cent. been reported by 1940, in that year Papanicolaou Cats appear to be less susceptible to neoplasia and Olcott stated they had found about 100 neo than dogs, but this may well be due to the cir plasms among 7000 guinea pigs, most of which cumstance that they are not taken to veterinary were senile. In a preliminary survey it appeared clinics for treatment and diagnosis as often as are that the commonest tumor was a fibromyoma of dogs. In a series of 226 tumors in cats, Cotchin the lower segment of the uterus.2 These investi (15) found that 30 per cent were carcinomas of gators have described nine tumors in detail: four the skin. Of fifteen mammary tumors, thirteen leiomyomas and one lipoma of the stomach, two were carcinomas; this contrasts with those of the neurilemomas and one liposarcoma of the intes dog, in which mixed tumors of the breast are tine (64), and a chondrosarcoma of the iliac bone more common. Among 156 cases of feline tumors (62). Another tumor of bone, an osteogenic sar collected from the literature by Tamaschke (87), coma of the femur, was reported by Leader (48), 25 were primary in the breast; of these, twenty who listed nineteen additional tumors described were carcinomas. Next in frequency were benign in the literature: eight sarcomas of various sites, and malignant tumors of the skin and liver, each eight adenocarcinomas of the mammary gland represented by fifteen cases. Neoplasia of the mye- (three were in males), an adenocarcinoma of the loid and lymphoid tissue is occasionally reported kidney, an adenoma of the adrenal, and an em- (25, 39). No tumor is sufficiently characteristic of bryoma of the ovary. A recent report by Congdon the cat to be designated as species-specific. and Lorenz (14) suggests that leukemia is of rela The common laboratory mammals used in can tively frequent occurrence, in one inbred strain cer research are all rodents, with the exception of attaining an incidence of 6.7 per cent. No valid the rabbit which is usually grouped with the Lago- conclusion concerning species-characteristic tu morpha, a closely related order of gnawing ani mors can be reached from the data now available. mals. Relatively few instances of neoplasia in the The laboratory mouse is the animal in which rabbit are described in the literature; in 1927, the problem of neoplasia has been studied most Poison (65) collected 66 cases, of which 29 were intensively. The literature is almost endless, and adenomas or adenocarcinomas of the uterus. In a the variety of neoplasms reported approaches that colony of 500 female rabbits observed over a pe in man. Many of the tumors are transplantable riod of 4 years, Greene (34) found 83 cases of (19), and some have a very high incidence among benign or malignant epithelial uterine tumors. inbred strains of mice (13). In the C58 strain ap The animals belonged to nine different breeds; proximately 85 per cent of the animals develop each had borne two to sixteen litters over a 12- leukemia after they are 6 months old, and there 75-month period, suggesting that pregnancy is is evidence that a viral agent is transmitted from significant for the induction of these tumors. Al mother to offspring during gestation (35). How though the most common tumor in domesticated ever, among noninbred mice, which compare more rabbits is the uterine adenoma or adenocarcinoma, closely with the individuals of a species occurring its frequency among wild rabbits is unknown. in nature, breast cancer is by far the most com Because of the short average life span of the latter mon malignant tumor (40). The breast lesion may in their natural environment, the incidence of all .be considered the species-specific neoplasm of the tumors is probably lower. An exception to this mouse (29, 57). are two virus-induced skin tumors of the wild The organ incidence of tumors in the rat is cottontail rabbit, Syhilagus floridanus. These are directly dependent on the degree to which the a fibroma, first described by Shope in 1932 (79), colony is infested by larvae of the cat tapeworm, and a wartlike papilloma reported by the same Taenia crassicottis (taeniaeformis). The larvae lodge author in the following year (80). In some regions in the liver and lead to changes in the connective of Kansas 25 per cent of the cottontail rabbits tissue that terminate in fibrosarcoma (7). In a may bear papillomas. In the natural host these *Personal communication dated March 25, 1957, from rarely become carcinomas, but when the virus is Dr. G. N. Papanicolaou, Department of Anatomy, Cornell transmitted to the domesticated rabbit the re University Medical School, New York.

large rat colony used in the study of the hepatic frequent occurrence in captive wild mammals (73). sarcomas, Bullock and Curtis found 2450 animals Carcinoma affects a wide variety of animals but with the specific liver tumor, as well as 489 rats particularly the Canidae (foxes, wolves) and the with other neoplasms that were independent of Procyonidae (raccoons). The high incidence among the parasites (8). Of these, the largest numberâ€” the Canidae is of interest in view of the frequent 94â€”were in the breast and, except for two car occurrence of thyroid cancer in dogs reported by cinomas and two carcinosarcomas, were repre Dobberstein in Germany (17). sented by benign fibroepithelial tumors. In 506 Evidence of the growing interest among pathol- inbred laboratory rats of the Sherman-Mendel ogists in the comparative study of neoplasia may strain, Olcott (61) found ten tumors; all but one, be found in the recent reports of tumors in whales. a nephroblastoma, were of nonepithelial tissues. At least nineteen neoplasms have been described ; Two groups of investigators (54, 92) examined a the greatest number were fibromas, of which Stolk total of 123,000 wild rats, Rattus norvÃ©giens,and (85) found seven on the skin or tongue. Rewell found 125 tumor-bearing animals, an incidence of and Willis (67) collected four ovarian tumors: a approximately 1 per thousand. Forty tumors were mucinous cystadenoma in a blue whale, and three primary in the breast; of these, 36 were adenomas granulosa-cell tumors in another blue whale and or adenofibromas, and only four were classified two fin whales. as adenocarcinomas. Tumors of the liver totaled 25 cases, of which 21 were sarcomas, nearly all ETIOLOGY associated with the tapeworm larvae. From these The term "species characteristic" carries an data it is apparent that in the rat, barring the implication of constitutional susceptibility. How infested liver, the breast is the most common site ever, the susceptibility need not be to neoplastic of neoplasia, but in the rat, unlike the mouse, the growth per se, but rather to a particular environ great majority of these are benign tumors of fibro mental factor or even a behavior pattern that, in epithelial origin. Also characteristic of the rat is turn, initiates the tumor. An example of the in the greater frequency of sarcoma as compared direction of heredity is seen in the development of with carcinoma, whether the site be the skin, intramandibular carcinoma in nearly 1 per cent liver, or other organ. of old mice of the 020 Amsterdam strain (90). The reported cases of neoplasia in species of In many strains of mice hair of cage mates is oc wild animals living in their native habitat or in casionally found cleaving the gingival and enam captivity are generally too few in number to per el-forming epithelium to produce cysts in which mit conclusions on species specificity. Among the carcinoma may arise. The high incidence of the best sources of data are the annual reports of the tumors in the 020 Amsterdam strain is linked in prosector to the Zoological Society of London in part to the more frequent occurrence of the the Society's Proceedings, the recent bibliography cysts, attributed to the inheritance in these mice of diseases in wild mammals and birds by Halloran of a greater disposition to gnaw the hair of cage (37), and the surveys of tumor incidence among mates. animals at the Philadelphia Zoo by Fox (30) and The relative importance of heredity and en Ratcliffe (66). vironment varies with the particular tumor and In captive and wild deer, at least eighteen in with the species affected. Pigment-cell tumors of stances of adenoma or carcinoma of the liver have killifish hybrids, axolotls, and horses appear to be been reported (38, 91). Krause studied seven cases independent of environmental factors. It is note and collected eight additional ones from the lit worthy that, in both the axolotl and in the horse erature (45). Most of his material was from the lightly pigmented (grey) individuals are particu roe deer, Capreolus capraea, of Germany. The ma larly affected. The genetic mechanism of mela jority of tumors were liver cell carcinomas; only noma has been most clearly elucidated in the kil an occasional one had its origin in bile duct epi lifish hybrids (platyfish X sword tail). Gordon (32) thelium. The sex distribution was about equal, observed that the swordtails, Xiphopharns hellerii, and most of the animals were over 5 years old. possess only micromelanophores, or no melano- Within recent years a fibroma of the skin has phores at all; platyfish, Platypoecilus maculatus, been frequently observed in wild deer from widely bear both micro- and macromelanophores. In the scattered regions of the United States. The tu platyfish the gene Sp controls the growth of the mors are multiple and range in size from 0.5 to macromelanophores; if the hybrid receives the 10 cm. in diameter; Shope (81) has been able to Sp gene but not some of the modifiers normally transmit them using cell-free filtrates. present in either parent, there is an accelerated Goiter and thyroid carcinoma are of relatively proliferation of the macromelanophores. This leads

to melanosis, often followed by the development neoplasms of the hematopoietic tissue in chickens of a melanoma. (2, 9, 23) and mice (35) ; of the connective tissue Other genetically controlled neoplasms that tumors of fowl (28), rabbits (79), squirrels (44), may be independent of environmental factors are and deer (81). Other virus-induced tumors are the liver tumors in the Campbell breed of ducks the kidney carcinoma of frogs (51), some breast and some tumors of inbred strains of mice. tumors of mice (3), and the epidermal papillomas In recent years the possible effects of geophys and carcinomas of rabbits (80). There is evidence ical and geochemical factors on the development that the lip tumors of the barbel, stint, and eel, and geographic distribution of cancer have come as well as the lymphosarcomas of the pike and under investigation (83, 88). Physical agents as muskellunge (Table 1), are initiated by a virus, ubiquitous as sunlight may act in conjunction but none of these tumors has yet been transmitted with a hereditary trait to induce neoplasia. The experimentally. A few of the viruses, such as nonpigmented conjunctiva and periorbital tissue those of the rabbit papilloma, squirrel fibroma, of the white-faced Hereford cattle are believed by and chicken sarcoma, will induce neoplasms in some investigators to be particularly susceptible related species under experimental conditions, but to the carcinogenetic ultraviolet rays in sunlight. many are species- and even strain-specific. A similar relation has been suggested to account Among tumors that occur with a sufficiently for the higher incidence of skin cancer in the high incidence to be regarded as species-specific, white than in the colored races of man. Except only the fibrosarcoma in the liver of rats has been for a case of osteogenic sarcoma in a muskrat (47), clearly linked to a metazoan parasite (7). The ionizing radiations have not yet been implicated carcinogenic effect of cat tapeworm larvae is not in the production of cancer among wild animals. limited solely to the rat, for it has been observed The muskrat, Ondatra zibethica, was caught near in mice and even in the muskrat (31). Neverthe the Oak Ridge National Laboratory in Tennessee. less, in the mice as well as in other rodents that Analysis showed that the animal's tissues were harbor the parasite, liver sarcomas are rare. This receiving at least 40 rep per day, largely from provides another illustration of the importance radiostrontium stored in the skeleton. The food of the particular genetic constitution in the pro plants in the area contained relatively large duction of neoplasia by an environmental factor. amounts of radioactive elements. Chemicals in the water may account for some SUMMARY of the lip tumors in fishes. This is particularly There is great variety in the nature and inci true of the epitheliomas on the lips of catfish from dence of tumors found among different animals; streams heavily polluted by chemical wastes (53). but when sufficient data are available, a certain Recently, Russell and Kotin have suggested a neoplasm often proves characteristic for a particu similar etiology for the lip papillomas of white lar species. Although these species-specific tumors croakers, Gengonemus lineatus, taken in Santa have a genetic basis, evocation of the neoplastic Monica Bay, California (68). The association of growth is often dependent upon infectious agents a genetic factor is likely, for in both instances or physical and chemical factors in the environ other species of fish caught at the same time and ment. place were free of tumors. However, the impor REFERENCES tance of the environment is indicated by the ab 1. BALL, H. A. A Melanosarcoma and Rhabdomyoma in sence of similar tumors among the same species of Two Pine Snakes, Pituophis melanoleucus. Cancer Re catfish and croakers caught elsewhere. search, 6:184-38, 1946. 2. BEARD, J. W. Virus of Avian Myeloblastic Leukosis. Occasionally the absence of a trace element Poultry Sci., 36:203-28, 1956. may be responsible for the initiation of cellular 3. BITTNER,J. J. Relation of Nursing to the Extrachromo- overgrowth. The classic example of this is the oc somal Theory of Breast Cancer in Mice. Am. J. Cancer, currence of goiter and thyroid carcinoma in ani 35:90-97, 1939. mals receiving an inadequate amount of iodine 4. BREDER,C. M., JR. The Problem of Directives to Cellular (73). The importance of the animal's hereditary Proliferation as Illustrated by Ontogenetic Processes in Certain Fishes. Growth, 16:189-98, 1952. constitution is manifested by the difference in the 5. BRESLAUER, T. Zur Kenntnis der Epidermoidalge- amounts of iodine required to prevent goiters in schwÃ¼lstevonKaltblÃ¼tern.Arch. f. mikr. Anat., 87:200- various species; e.g., under similar environmental 264, 1916. 6. BRIGGS,R. Transplantation of Kidney Carcinoma from conditions goiter is common in trout, rare in carp ; Adult Frogs to Tadpoles. Cancer Research, 2:309-28, frequent in dogs, rare in cats. 1942. Viruses have proved to be the causative agents 7. BULLOCK,F.D., and CURTIS,M. R. A Study of the Reac of several species-characteristic tumors, including tions of the Tissues of the Rat's Liver to the Larvae of

Taenia crassicollis and the Histogenesis of the Cysticercus mata in the Rabbit. I. Clinical History, Pathology, and Sarcoma. J. Cancer Research, 8:446-81, 1924. Preliminary Transplantation Experiments. J. Exper. Med., 8. . Spontaneous Tumors of the Rat. Ibid., 14:1-115, 67:691-708, 1938. 1980. 35 GROSS,L. Viral (Egg-borne) Etiology of Mouse Leukemia. 9. BUHMESTEH,B. R. Iuiiiiss.-iy of the Virus of Visceral Cancer, 9:778-91, 1956. Lymphomatosis. I. Use of Short Experimental Period. J. 36 HADDOW,A.,and BLAKE,I. Neoplasms in Fish: a Report Nat. Cancer Inst., 16:1121-27, 1956. of 6 Cases with a Summary of the Literature. J. Path. & 10. CAMPBELL,J. G. Neoplastic Disease of the Fowl with Bact., 36:41-47, 1933. Special Reference to Its History, Incidence, and Seasonal 37 HALLORAN,P. O'C. Bibliography of Diseases in Wild Variation. J. Comp. Path. & Therap., 66:308-21, 1945. Mammals and Birds. Am. J. Vet. Res. (Sp. Suppl.), 1955. 11. . Spontaneous Hepatocellular and Cholangiocellu- 38, HAMERTON,A. E. Report on Deaths Occurring in the lar Carcinoma in the Duck. An Experimental Study. Brit. Society's Gardens during 1931. Proc. Zool. Soc. Lond., pp. J. Cancer, 3:198-210, 1949. 613-38, 1932. 12. CHANDRASEKHARAN,K.P., and SASTHY,G. A. A Survey 39. HOLZWORTH,J., and NIELSEN,S. W. Visceral Lympho- of Animal Neoplasms in the Madras State. I. Bovines. sarcoma of the Cat. II. J. Am. Vet. Med. Assoc., 126:26-36, Indian Vet. J., 30:325-33, 1954. 1955. 13. COMMITTEE.Standardized Nomenclature for Inbred 40, HORN, H. A., and STEWART,H. L. A Review of Some Strains of Mice. Cancer Research, 12:602-13, 1952. Spontaneous Tumors in Noninbred mice. J. Nat. Cancer 14. CONGDON,C. C., and LORENZ,E. Leukemia in Guinea Inst., 13:591-603, 1952. Pigs. Am. J. Path., 30:337-59, 1954. 41. JUNGHEHR,E. Avian Leukosis Complex, pp. 453-507. In: 15. COTCHIN,E. Neoplasms in Cats. Proc. Roy. Soc. Med., H. E. BIESTERand L. H. SCHWABTE(eds.), Diseases of 46:671-74, 1952. Poultry. 3d Ã©d.Ames, Iowa: Iowa State College Press, 16. . Further Observations on Neoplasms in Dogs, with 1952. Particular Reference to Site of Origin and Malignancy. 42. KÃ„RNBACH,K.Die Neubildungen der NasenhÃ¶hleund der I and II. Brit. Vet. J., 110:218-30, 274-86, 1954. NasennebenhÃ¶hlendes Pferdes. Berlin: Schoetz, 1909. 17. DOBBERSTEIN,J. Vergleichende Pathologie der Ge- 43. KEYSSEUTZ,G. Ueber ein Epithelioma der Barben. Arch, schwÃ¼lste.Ztschr.f. Krebsforsch., 59:600-610, 1953. f. Protistenk., 11:326-33, 1908. 18. . Die GeschwÃ¼lstederVÃ¶gel.Verhandl. d. deutsch. 44. KILHAM,L.; HERMAN,C.M.; and FISHER,E. R. Naturally Occurring Fibromas of Grey Squirrels Related to Shope's Gesell, f. Path. 39th Session. Stuttgart: Gustav Fischer, 1956. Rabbit Fibroma. Proc. Soc. Exper. Biol. & Med., 82:298- 19. DUNHAM,L. J., and STEWART,H. L. A Survey of Trans- 301, 1953. plantable and Transmissible Animal Tumors. J. Nat. 45, KRAUSE,C. Ueber das Leberadenom und den Leberkrebs Cancer Inst., 13:1299-1377, 1953. der Rehe mit besonderer BerÃ¼cksichtigungder Histo 20. DURYEE, W. R. Precancer Cells in Amphibian Adeno- genÃ¨se.Arch. f. wiss. u. prakt. Tierheilk., 73:1-24, 1938. carcinoma. Ann. N.Y. Acad. Sc., 63:1280-1302, 1956. 46. KRONTOVSKY,A.S. A Comparative and Experimental 21. DVISHKOV,P.P., and ZVBTAEVA,N.P. A Contribution to Pathology of Tumors (in Russian). Kiev, 1916. the Comparative Pathology of Tumors in Animals. English 47.. KRUMHOLZ,L.A., and RUST,J. H. Osteogenic Sarcoma in summary. Proc. Moscow Zool. Park, 3:166, 1946. a Muskrat from an Area of High Environmental Radio- 22. EBER, A., and MALKE, E. Geschwulstbildungen beim strontium. Arch. Path., 67:270-78, 1954. HausgeflÃ¼gel.Zusammenfassender Bericht Ã¼ber392 bei 48., LEADER,S. A. Osteogenic Sarcoma of the Femur in a 16460 GeflÃ¼gelsektionenermittelte Neubildungen. Ztschr. Guinea Pig. Am. J. Cancer, 29:546-50, 1937. f. Krebsforsch., 36:178-92, 1932. 49. LOEB, L., cited by CRAMER,W. The Comparative Study 23. ECKEHT,E. A.; BEARD,D.; and BEARD,J. W. Virus of of Cancer. Cancer Rev., 7:241-61, 1932. Avian Erythroblastosis. I. Titration of Infectivity. J. Nat. 50. LÃœCKE,B.A Neoplastic Disease of the Kidney of the Frog, Cancer Inst., 16:1099-1120, 1956. Rana pipiens. Am. J. Cancer, 20:352-79, 1934. 24. Editorial Announcement. Cancer Research, 16:371, 1956. 51. . Carcinoma in the Leopard Frog: Its Probable 25. EYESTONE,W. H. Myelogenous Leukemia in the Cat. J. Causation by a Virus. J. Exper. Med., 68:457-68, 1938. Nat. Cancer Inst., 12:599-613, 1951. 52. . Tumors of the Nerve Sheaths in Fish of the 26. FELDMAN,W. H. Neoplasms of Domesticated Animals. Snapper Family (Lutianidae). Arch. Path., 34:133-50, Philadelphia: W. B. Saunders, 1932. 1942. 27. FINKELSTEIN*,E.A. Tumor Growth in Invertebrates and 53. LÃœCKE,B., and SCHLUMBERGER,H.G. Transplantable in Lower Vertebrates. Usp. sovr. biol., 17:320-48, 1944. Epitheliomas of the Lip and Mouth of Catfish. I. Pathol 28. FOULDS,L. The Filterable Tumours of Fowls: a Critical ogy. Transplantation to Anterior Chamber of the Eye and Review. Suppl. to Xlth Sci. Rep. Imp. Cancer Research into Cornea. J. Exper. Med., 74:397-408, 1941. Fund, London, 1934. 54. McCoY, G. A Preliminary Report on Tumors Found in 29. . Histologie Analysis of Mammary Tumors of Mice. Wild Rats. J. Med. Research, 16: (NS) 285-96, 1909. I-rV. J. Nat. Cancer Inst., 17:701-801, 1956. 55. McFADYEAN,J. Equine Melanomatosis. J. Comp. Path. & 30. Fox, H. Disease in Captive Wild Mammals and Birds. Therap., 46:186-204, 1933. Philadelphia: J. B. Lippincott Co., 1923. 56. MONLUX,A. W.; ANDERSON,W.A.; and DAVIS,C. L. A 81. GALLATI, W. W. Fibrosarcoma Associated with the Survey of Tumors Occurring in Cattle, Sheep, and Swine. Cystieercus of Taenia taeniaeformis in the Liver of a Am. J. Vet. Research, 17:646-77, 1956. Muskrat. Ohio J. Sci., 66:71-75, 1956. 57. MOULTON,F.R. (ed.). Symposium on Mammary Tumors 32. GORDON,M. Genetic and Correlated Studies of Normal in Mice. Washington D.C.: Am. Assoc. Adv. Sci., 1945. and Atypical Pigment Cell Growth. Growth, 10 (Suppl.): 58. MULLIGAN,R. W. Neoplastic Diseases in Dogs. II. Mast 153-219, 1951. Cell Sarcoma, Lymphosarcoma, Histiocytoma. Arch. 33. GOSS, L. J. The Incidence and Classification of Avian Path., 46:477-92, 1948. Tumors. Cornell Vet., 30:75-88, 1940. 59. â€”¿â€”â€”.Neoplasmsof the Dog. Baltimore: Williams & 34. GREENE,H. S. N., and SAXTON,J.A., JR. Uterine Adeno Wilkins Co., 1949.

60. NIGRELLI,R. F. Spontaneous Neoplasms in Fishes. III. 77. SCHNEIDER,M.On the Frequency of Spontaneous Tumors Lymphosarcoma in Astyanax&uA Esox. Zoologica, 32:101- in the Domestic Fowl. J. Exper. Med., 43:433-41, 1926. 8, 1947. 78. SHEHEMETIEVA-BRUNST,E.A., and BRUNST,V. V. Origin 61. OLCOTT,C.T. A Transplantable Nephroblastoma (Wilms' and Transplantation of a Melanotic Tumor in the Axolotl. Tumor) and Other Spontaneous Tumors in a Colony of In: M. GORDON(ed.), Biology of Melanomas. Spec. Pub. Rats. Cancer Research, 10:625-28, 1950. N.Y. Acad. Sc., 4:269-87, 1948. 62. OLCOTT,C. T., and PAPANICOLAOU,G.N. Studies on 79. SHOPE,R. E. A Transmissible Tumor-like Condition in Spontaneous Tumors in Guinea Pigs. III. A Chondro- Rabbits. J. Exper. Med., 66:793-802, 1932. sarcoma of the Iliac Bone with Metastasis to the Mammary 80. . Infectious Papillomatosis of Rabbits. Ibid., 68: Region. Cancer Research, 3:321-25, 1943. 607-24, 1933. 63. OLSON,C., JR., and BULLÃ•S,K.L. A Survey and Study of 81. . An Infectious Fibroma of Deer. Proc. Soc. Exper. Spontaneous Neoplastic Diseases in Chickens. Mass. Ag. Biol. & Med., 88:533-35, 1955. Exper. Sta. Bull. No. 391, 1942. 82. SMITH,G.M., and COATES,C.W. Fibro-epithelial Growths 64. PAPANICOLAOU,G.N., and OLCOTT,C. R. Studies of of the Skin in Large Marine Turtles, Chelonia mydas. Spontaneous Tumors in Guinea Pigs. II. Tumors of the Zoologica, 23:93-98, 1938. Stomach and Intestine. Arch. Path., 34:218-28, 1942. 83. STEINER,P. E. Cancer: Race and Geography. Baltimore: 65. POLSON,C. J. Tumours of the Rabbit. J. Path. & Bact., Williams & Wilkins Co., 1954. 30:603-14, 1927. 84. STICKER,A. Ueber den Krebs der Thiere. Insbesondere 66. RATCLIFFE,H. L. Incidence and Nature of Tumors in ueber die EmpfÃ¤nglichkeit der verschiedenen Hausthier- Captive Wild Animals and Birds. Am. J. Cancer, 17:116- arten und ueber die Unterschiede des Thier- und Men 35, 1933. schenkrebses. Arch. f. klin. Chir., 66:616-96, 1023-87, 67. REWELL,R. E., and WILLIS,R. A. Some Tumours Found 1902. in Whales. J. Path. & Bact., 61:454-56, 1949. 85. STOLK,A. Some Tumours in Whales. KÃ¶ninkl.Nederl. 68. RUSSELL,R. E., and KOTIN,P. Squamous Papilloma in the Akad. Wetensch.-Amsterdam, 66:275-78, 1952; 56:369- White Croaker. J. Nat. Cancer Inst. (in press). 74, 1953. 69. RUSSELL,W. O.; WYNNE,E. S.; and LOQUVAN,G. S. 86. TAKAHASHI,K. Studie Ã¼berFischtumoren. Ztschr. f. Studies on Bovine Ocular Squamous Carcinoma (Cancer Krebsforsch., 29:1-73, 1929. Eye). I. Pathological Anatomy and Historical Review. 87. TAMASCHKE,C.BeitrÃ¤gezur vergleichenden Onkologie der Cancer, 9:1-52, 1956. HaussÃ¤ugetiere.Wiss. Ztschr. d. Humboldt Univ., 1:37- 70. SCHAEPEHCLAUS,W.Die Blumenkohlkrankheit der Aale 77, 1951-52. und anderer Fische der Ostsee. Ztschr. f. Fisch, u. d. 88. TROMP,S. W. Possible Effects of Geophysical and Geo- Hilfswiss., 2: (NS) 105-24, 1953. chemical Factors on Development and Geographic 71. SCHLUMBEROEH,H.G. Nerve Sheath Tumors in an Iso Distribution of Cancer. In: F. C. ROULET(ed.), Trans. 5th lated Goldfish Population. Cancer Research, 12:890-99, Meeting Internat. Soc. Geograph. Path., Basel and 1952. N.Y.: S. Karger, 1955. 72. . Neoplasia in the Parakeet. I. Spontaneous Chromo- 89. TWEEDELL,K. S. Adaptation of an Amphibian Renal phobe Pituitary Tumors. Ibid., 14:237-45, 1954. Carcinoma in Kindred Races. Cancer Research, 16:410â€” 73. . Spontaneous Goiter and Cancer of the Thyroid in 18, 1955. Animals. Ohio J. Sci., 56:23-43, 1955. 90. VANRÃœSSEL,T.G., and MÃœHLBOCK,O.Intramandibulnr 74. . Neoplasia in the Parakeet. II. Transplantation of Tumors in Mice. J. Nat. Cancer Inst., 16:659-89, 1955. the Pituitary Tumor. Cancer Research, 16:149-53, 1956. 91. WINER, J. H., and SCHROEDER,C.R. Malignant Hepa- 75. SCHLUMBERGER,H.G., and LOCKE,B. Tumors of Fishes, toma in the White-tailed Deer, Odocoileusosceola. Am. J. Amphibians and Reptiles. Cancer Research, 8:657-754, Cancer, 38:268-70, 1940. 1948. 92. WOLLT,P. G., and WHERRY,W. B. Notes on Twenty-two 76. . Serial Intraocular Transplantation of Frog Car Spontaneous Tumors in Wild Rats (Jf. norvÃ©giens).3. cinoma for Fourteen Generations. Ibid., 9:52-60, 1949- Med. Research, 20: (NS) 205-15, 1911-12.

Hans G. Schlumberger

Cancer Res 1957;17:823-832.

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