A Transplantable Nephroblastoma (Wilms' Tumor) and Other Spontaneous Tumors in a Colony of Rats CHARLES T. OLCOTT, M.D. (From the Department of Pathology, The New York hospital, Cornell Medical Center, New York, N. Y.) INTRODUCTION Rat A (Table 1), in which the nephroblastoma One of the most distinctive and widespread developed, was a member of the eighteenth filial types of the so-called “mixedtumors―is the renal generation of the inbred family and received neoplasm, first reported by Wilms in 1899 (10), 1 : 1,000 silver nitrate solution by mouth before and perhaps best described as a nephroblastoma. and after nephrectomy, instead of water. The left @ This tumor is found in chickens (3, 4), swine (3), kidney was removed when the rat was months cattle (3), rabbits (1, 8, 9), and rats (@), as well old; one kidney was removed with or without re as in man. In spite of many attempts to transplant duction of the other one in sixteen additional rats, TABLE 1 INCIDENCE OF TUMORS Tumors Sex and age No. of au- No. of inrat (months) topsies tumors (no.) Type of Tumor Male rats: Under 6 73 1 A6t Nephroblastoma 7—12 57 0 13—18 71 1 F't Fibrosarcoma of pelvis 19-24 46 2 G6t Myxoma near salivary gland H* Sarcoma of lung 25—30 17 0 Female rats: Under 6 52 0 7—12 42 1 Jt Fibrosarcoma of leg 13—18 76 3 Kt Myosarcoma of uterus L6 Malignantlymphoma in retroperitoneal tissues, liver and lung M*t Myelogenous leukemia 19-24 62 2 N6t Lymphangioma of neck 25—30 10 0 P Angioendothelioma under skin of neck S Animals given dilute solutions of silver salt.s instead of drinking water. t Animals of closely related family group. this tumor (@), no report of a successful transfer TABLE 2 is available. The tumor to be described was trans PERCENTAGE INCIDENCE OF TUMORS planted in series. Totalno.Percentageautopsiestumorsof no.Total Groups of rats tumors26441.524262.530672.320031.530772.319931.5506102.0 METHODS AND RESULTS Males Females The nephroblastoma was one of ten clearly de Rats receiving silver fined neoplasms found, with a number of non Rats receiving water neoplastic hyperplasias, among about 500 rats Rats of inbred family Other rats examined at autopsy. It will be seen from Tables 1 Total Animals @ and that neither the ingestion of silver by about three-fifths of the rats (5—7) nor the consan but no tumor developed in them. The rat was well guinity induced by brother-sister mating of a for 70 days after the operation, at which time the family of the Sherman-Mendel strain of white rat weight had decreased from @46to p210 gm., and for eighteen filial generations appreciably affected the animal became listless and was killed. the incidence of neoplasms. Microscopically, the tumor abutted on the renal Received for publication May 16, 1950. 6@5 Downloaded from cancerres.aacrjournals.org on October 1, 2021. © 1950 American Association for Cancer Research. 6@26 (1ancer Research pelvis at one point. In other places there was a and the animal became lethargic and was killed stilooth line of division between the tumor and the 45 (lays after the injection. There were many light @ normal renal parenchyma, with a thin but definite gray to red pedunculated masses up to cm. in fibrous capsule between them. The opposite edge diameter in the peritoneum, and microscopic foci of the mass was very poorly defined, and many of invasion of the liver and spleen. The tumor nests of characteristic tumor cells invaded the (Fig. 5) was identical with that in rat B. The site surrOufl(Iiflg tissue. This surrounding area was of intramuscular injection in the thigh showed no composed of areolar and fibrous tissue in which tumor on gross or microscopic study, but there were areas of edema, hemorrhage, and necrosis. was some necrosis and calcification. No attempt The tumor (Fig. 1) was arranged in moderate was made to transmit this tumor of the second sized to very large nests; these were separated transplanted generation further. from one another I)y strands of normal-appearing Two other rats of an entirely unrelated stock fibrous tissue, which were often invaded by mdi were inoculated with tumor material from rat B vidual anaplastic cells representing the sarcoma at the time that rat C was injected. Rat D, a fe like elellientS of the tumor to be described. The male about 5 months old, was injected intraperi sheets of tumor cells (Fig. @2)were largely corn toneally with I cc. of tumor suspension. There was posed of cells of ovoid to spindle shape, with pale no gain of weight or abdominal swelling. When cytoplasm and vesicular nuclei in which there this rat was killed 67 days later, the peritoneum were no conspicuous masses of chromatin. Mitoses was shiny and there was no evidence of tumor. were present in small numbers. In addition to the Tumor material from rat B was injected into sarcomatous cells, there were numerous tubular the thigh muscles of rat E, a female about S structures (,Fig. 3). rfhese hollow areas were lined months old. There was no sign of tumor at au l)y cells in regular palisade arrangement. Except topsy 67 days later. for this arrangement, these cells were very similar COMMENT III appearance to the main cellular component of the tumor. Some of the tubular structures had a The cells of the tubular and sarcoma-like areas slight resemblance to primitive glomeruli. of the original tumor appeared identical, except A portion of the tumor from rat A was ground for their different arrangement. In the trans with a pestle and mortar. About 3 cc. of the result planted and retranspianted tumor, the cells were ing cloudy suspension was injected into the sub found only in sarcomatous arrangement. It is cutaneous tissue and into the peritoneum of rat B, postulated that the whole complex tumor arose a male litter-mate of A, who had never received from one type of cell and is “mixed―inthe mor silver solution. A subcutaneous mass was first rec phological, but not in the embryological, sense. ognized 37 (lays after inoculation, and the rat was It appears significant that this tumor was killed 95 days after inoculation, when apparently transplantable only to closely related animals. in good health except for the mass. At autopsy, mnany nodules of tumor tissue in the peritoneum SUMMARY were observed, some as much as 3 cm. in diam A spontaneous nephroblastoma with sarcoma eter. Some of them were a(lherent to the liver. tous an(l tubular elements arose adjacent to the Microscopically (Fig. 4), the tumor again con remaining kidney of a rat from which one kidney siste(l of large sheets that invaded edematous had been remOve(l. The tumor was transplanted areolar tissue which contained lymphocytes in to a secOn(1, and retransplanted to a third, closely moderate numbers. None of the tubular structures related rat. In both cases, the cells of the trans described III rat A were noted in Rat B. The sar Initted tumor were uniformly sarcomatous. The coma-like cells of this transplanted tumor seemed tumor could not be transplanted to unrelated rats. in some places to be slightly longer and thinner Nine other spontaneous tumors are cited. than those of the original tumor, but they were in other respects indistinguishable from them. REFERENCES Material from the tumor in rat B was ground, 1. BELL, E. T., and HENRIcI, A. T. Renal Tumors in the strained through gauze, and inoculated into three Rabbit. J. Cancer Research, 1: 157—67,1916. rats—C, D, an(I E. 2. BuLL.ocK, F. 1)., and CURTIS, M. R. Spontaneous Tumors Rat C was a male litter-mate of rats A and B, of Rats. J. Cancer Research, 14: 1—115,1930. @%‘hOhadnever received silver solution; at 7 3. FELDMAN, @V.H. Neoplasms of Domestic Animals, pp. months of age this rat was inoculated with 1 cc. of 357—72. Philadelphia and London: W. B. Saunders, 1932. 4. MCKENNEY, F. 1). Embryonal Nephroma in the Chicken. tumor suspension into the peritoneum and 0.5 cc. Report of Two Cases. Am. J. Cancer, 15: 122—28,1931. into the thigh. The abdomen enlarged greatly, 5. OLCOTT, C. T. Experimental Argyrosis. III. Pigmentation Downloaded from cancerres.aacrjournals.org on October 1, 2021. © 1950 American Association for Cancer Research. @@@ , @:1 1.'@@ ,@.. .@--. ,,‘.. @ IF .. s_.,... - - p. ‘,@. “-ft S .@ @.. ‘@#i@ ‘-“4, I j $5 5 FIG. 1.—Original nephroblastoma in rat A showing ad FIG. 4.—Sarcoma-like area from first transplanted tumor jacent tubular and sarcoma-like structure. X 225. in rat B. X 1,080. FIG. 2.—I)etail of sarcoma-like area of tumor in rat A. FIG. 5.—Sarcoma-like area from second transplanted x 1,080. tumor in rat C. X 1,080. FIG. 3.—Detail of tubular area from rat A. X 1,080. Downloaded from cancerres.aacrjournals.org on October 1, 2021. © 1950 American Association for Cancer Research. 6@8 (1ancer Research of the Eyes of Rats Following Ingestion of Silver during Arch. Path., 49: 138—49, 1950. Long Periods of Time. Am. J. Path., 23:783—91, 1947. 8. POLSON, C. J. Tumours in the Rabbit. J. Path. & Bact., 6. ———. Experimental Argyrosis. IV. Morphological 30:603—14, 1927. Changes in the Experimental Animal. ibid., 24:813—33, 9. SCOTT, E. Tumors of the Kidney in Rabbits. J. Cancer 1948. Research, 2:367—71, 1917.