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Adult Wilms Tumor and Bilateral Germ Cell Tumors of Testes: A Case Report
0022-534 7/82/1286-1296$02.00/0
Vol. 128, December Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1982 by The Williams & Wilkins Co.
ADULT WILMS TUMOR AND BILATERAL GERM CELL TUMORS OF TESTES: A CASE REPORT TORU HARA, MAKOTO FUJIME, KAZUKI KAWABE, AKIRA UENO, KENKICHI KOISO T ADAO NIIJIMA
AND
From the Department of Urology, Faculty of Medicine, University of Tokyo, Tokyo, Japan
ABSTRACT
We report on an adult with Wilms tumor following bilateral germ cell tumors of the testes. Bilateral primary germ cell tumors of testes are uncommon and the concurrence of Wilms tumor in an adult is rare. To the best of our knowledge, the presence of both of these tumors in 1 individual has not been reported in the literature. Germ cell tumor of the testis and Wilms tumor have the common aspect of possessing totipotentiality in the histogenesis, although there have been no reports of both these tumors in 1 individual. Herein we report on an adult with Wilms' tumor that occurred 26 and 16 years after the treatment of initial and subsequent testicular germ cell tumors. The possible relationships of these 2 tumors, as well as the inciting effects of hormone and radiation therapy on the oncogenesis of Wilms tumor in the adult, are discussed.
forming a pseudocapsule, and there were no typical tumor lobules or cysts. Microscopic appearance of this tumor was predominantly of the blastemal pattern. Relatively small and oval or spindle-shaped immature cells, with scanty cytoplasm and large nuclei, were packed closely and could have been confused with other mesenchymal and anaplastic tumors (part A of figure). However, in the other areas the blastemal elements were subdivided by stromal tissues into circumscribed nodules and blastemal cells were rare (part B of figure). There were neither definite tubular elements nor striated muscles but a few abortive glomeruli-like structures were seen (part C of figure). Pathological diagnosis was undifferentiated or poorly differentiated nephroblastoma. Postoperative therapy included combined chemotherapy and irradiation, according to the National Wilms Tumor Study 2 regimens but it was not completed because of an acute attack of cholecystitis.
CASE REPORT
A 51-year-old man was hospitalized in July 1980 for dull pain and a mass in the right flank 1 month in duration. Relevant history revealed a left testicular tumor in 1954 and subsequent right testicular tumor in 1964. The left testicular tumor was teratocarcinoma, mixed with embryonal and seminomatous components. Left orchiectomy with para-aortic lymph node dissection was done, followed by 6,000 rad 60 cobalt irradiation to the para-aortic and left iliac areas (3,000 rad in each area). The right testicular tumor was pure seminoma. Right orchiectomy was done, followed by 4,000 rad 60 cobalt irradiation to the para-aortic and right iliac areas (2,000 rad in each area). Since 1964 supplemental injections of 125 mg. testosterone enanthate were done twice a month (total of 47.5 gm.). Physical examination revealed a tumor in the right flank, which had a smooth surface and solid consistency on palpation. Urinalysis revealed 30 to 40 red and 8 to 10 white blood cells per high power field. Serum creatinine was 1.6 mg./100 ml. and erythrocyte sedimentation rate was 37 mm. per hour. Excretory urography showed enlargement of the right kidney with distortion of the pyelocaliceal systems. The right ureter was not visualized. Computerized axial tomography demonstrated a tumor originating from the right kidney and renal angiography revealed the existence of hypovascular areas in the middle and lower portions of the right kidney. Chromosomal abnormality was not demonstrated in the peripheral blood. On August 5 radical right nephrectomy was done. Grossly, the tumor appeared to infiltrate into the renal capsule but no metastatic lesions were found in the surrounding tissues at operation. The capsule was already partially torn by invasion of the tumor. The stage of this tumor was estimated to be group 3, according to the criteria proposed by the National Wilms Tumor Study. 1 The resected specimen weighed 850 gm. and the tumor occupied the middle and lower portions of the kidney. On section the tumor looked partially gray-tan and well delineated, displacing the remaining normal tissues, and it contained focal areas of hemorrhage and necrosis. The junction between the tumor and kidney was sharp, with compressed renal tissue Accepted for publication March 26, 1982.
DISCUSSION
The occurrence of a Wilms tumor usually is limited to the first decade of life, although some cases have been reported in adults. The accurate incidence of this lesion in adults is difficult to ascertain. There is considerable variation in the incidence reported and there also is some confusion in the terminology related to this tumor. 2 A fundamental histologic feature of Wilms tumor is the presence of abortive or embryonic glomerulotubular structures with immature spindle stromal cells, which are not found in renal cell carcinoma. 3 In our case histopathological diagnosis might have been confused with anaplastic or sarcomatous renal tumors. While the origin of Wilms tumor from metanephric cells has been accepted by most authors, the specific mechanism of its development has not been elucidated sufficiently. In our case the concurrence of bilateral germ cell tumors of the testes and Wilms tumor suggests a congenital disorder because of the close relationship among gonads, mesonephros and metanephros in the embryo. The fact that the nodular foci of persistent nephrogenic blastema are encountered in newborns may support Cohnheim's4 "cell rest" theory of tumor formation in application to Wilms tumor. Potter has proposed that persistent nephrogenic blastema in the human is the result of ampullary failure, a deficiency of organizer effect at the ends of the ureteral buds. 5 This view of persistent blastema as an error of metanephric differentiation is interesting when the genitourinary anomalies known to occur with Wilms tumor are considered. 6 Our patient had received testosterone enanthate as supplemental hormone therapy. The effects of this earlier therapy cannot be ignored when considering the possible oncogenic effect of this tumor. There is a report of Wilms tumor in the adult triggered by androgen abuse. 7 Thus, it appears that the administration of certain hormones may have an inciting or
1296
AD:.J:Ur 'VIILiviS T):Jh1lOR AND EILATERAL TESTlCTJLAR TTJIVfORS
A, histopathologically, tumor shows relatively small and immature cells with oval nuclei and scanty eosinophilic cytoplasm. Immature cells are packed closely and could be mistaken for cells of other mesenchymal and anaplastic neoplasms. B, blastemal elements subdivided by stromal septa into circumscribed nodules. Two mixed elements of this tumor suggest Wilms tumor. C, rare and atypical glomeruloid structures that have neither definite tubular elements nor striated muscles. H & E, reduced from XIOO.
contributory effect on the oncogenesis of Wilms tumor, just as certain drugs may induce hepatoma. 8 However, in animal experiments there are no reports of hormone-induced nephroblastoma, although a few nephroblastomas in rats have been reported following irradiation. 9 Our patient received 3,000 plus 2,000 rad in 10 years to the para-aortic areas before the development of Wilms tumor. It is possible that a reacquisition of
embryonic characteristics might have been induced by that irradiation. There have been reports of neoplasms following irradiation. For instance, a mixed mullerian tumor of the uterus has been associated closely with prior irradiation. 10 In this regard one should also consider the possible interacting effects of irradiation and hormone therapies on the subsequent appearance of
1298
HARA AND ASSOCIATES
Wilms tumor. Other tumors that have been reported to occur with Wilms tumor are mixed liver tumor, 11 contiguous urological tumor, that is tumor of the renal pelvis and multicentric neoplasms in the ipsilateral ureter, 12 primary neoplasms, that is rhabdomyosarcoma, myelomonocytic leukemia and neuroblastoma, 13 leukemia, 14 fibrosarcoma, 15 bilateral retinoblastoma, 15 neurofibromatosis, 16 adrenocortical carcinoma17 and adenocarcinoma of the colon. 18 All of these tumors are rare. CONCLUSION
We have reported a case of adult Wilms tumor preceded by bilateral germ cell tumors of testes. We have postulated that these tumors might have developed from the same origin and that the Wilms tumor was promoted by earlier hormone and radiation therapy. This hypothesis is plausible in our case but, of course, there is no way to rule out the possibility of independent origins for these multiple neoplasms. REFERENCES
1. D'Angio, G. J., Beckwith, J. B., Breslow, N. E., Bishop, H. C., Evans, A. E., Farewell, V., Fernbach, D., Goodwin, W. E., Jones, B., Leape, L. L., Palmer, N. F., Tefft, M. and Wolff, J. A.: Wilm's tumor: an update. Cancer, suppl. 7, 45: 1791, 1980. 2. Babaian, R. J., Skinner, D. G. and Waisman, J.: Wilms' tumor in the adult patient: diagnosis, management, and review of the world medical literature. Cancer, 45: 1713, 1980. 3. Bodian, M. and Rigby, C. C.: The pathology ofnephroblastoma. In: Tumours of the Kidney and Ureter. Edited by E. Riches. Baltimore: The Williams & Wilkins Co., vol. 5, chapt. 18, p. 219, 1964. 4. Cohnheim, J.: Vorlesungen iiber algemeine Pathologie. Ein Handbuch fur Aerzte und Studirende, 2nd ed. Berlin: Verlag von August Hirschwald, vol. 1, p. 723, 1882.
5. Potter, E. L.: Normal and Abnormal Development of the Kidney. Chicago: Year Book Medical Publishers, 1972. 6. Bennington, J. L. and Beckwith, J.B.: Tumors of the kidney, renal pelvis, and ureter. In: Atlas of Tumor Pathology. Washington, D. C.: Armed Forces Institute of Pathology, fasc. 12, series 2, p. 38, 1975. 7. Prat, J., Gray, G. F., Stolley, P. D. and Coleman, J. W.: Wilms tumor in an adult associated with androgen abuse. J.A.M.A., 237: 2322, 1977. 8. Farrell, G. C., Joshua, D. E., Uren, R. F., Baird, P. J., Perkins, K. W. and Kronenberg, H.: Androgen-induced hepatoma. Lancet, 1: 430, 1975. 9. Berdjis, C. C.: Kidney tumors and irradiation pathogenesis of kidney tumors in irradiated rats. Oncologia, 16: 312, 1963. 10. Varela-Duran, J., Nochomovitz, L. E., Prem, K. A. and Dehner, L. P.: Postirradiation mixed miillerian tumors of the uterus: a comparative clinicopathologic study. Cancer, 45: 1625, 1980. 11. Fraumeni, J. F., Jr., Miller, R. W. and Hill, J. A.: Primary carcinoma of the liver in childhood: an epidemiologic study. J. Natl. Cancer Inst., 40: 1087, 1968. 12. Orlin, I.: Association of two contiguous urological tumors with adult Wilms tumor. J. Urol., 109: 362, 1973. 13. Valdes-Dapena, M. and Arey, J.B.: Multiple (4) primary neoplasms in a child with aniridia. Abstract. Amer. J. Path., 62: 22A, 1971. 14. Schwartz, A. D., Lee, H. and Baum, E. S.: Leukemia in children with Wilms tumor. J. Ped., 87: 374, 1975. 15. Pendergrass, T. W.: Congenital anomalies in children with Wilms tumor: a new survey. Cancer, 37: 403, 1976. 16. Bader, J. L. and Miller, R. W.: Neurofibromatosis and childhood leukemia. J. Ped., 92: 925, 1978. 17. Muller, S., Gadner, H., Weber, B., Vogel, M. and Riehm, H.: Wilms' tumor and adrenocortical carcinoma with hemihypertrophy and hamartomas. Eur. J. Ped., 127: 219, 1978. 18. Sabio, H., Teja, K., Elkon, D. and Shaw, A.: Adenocarcinoma of the colon following the treatment of Wilms tumor. J. Ped., 95: 424, 1979.
Vol. 128, December Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1982 by The Williams & Wilkins Co.
ADULT WILMS TUMOR AND BILATERAL GERM CELL TUMORS OF TESTES: A CASE REPORT TORU HARA, MAKOTO FUJIME, KAZUKI KAWABE, AKIRA UENO, KENKICHI KOISO T ADAO NIIJIMA
AND
From the Department of Urology, Faculty of Medicine, University of Tokyo, Tokyo, Japan
ABSTRACT
We report on an adult with Wilms tumor following bilateral germ cell tumors of the testes. Bilateral primary germ cell tumors of testes are uncommon and the concurrence of Wilms tumor in an adult is rare. To the best of our knowledge, the presence of both of these tumors in 1 individual has not been reported in the literature. Germ cell tumor of the testis and Wilms tumor have the common aspect of possessing totipotentiality in the histogenesis, although there have been no reports of both these tumors in 1 individual. Herein we report on an adult with Wilms' tumor that occurred 26 and 16 years after the treatment of initial and subsequent testicular germ cell tumors. The possible relationships of these 2 tumors, as well as the inciting effects of hormone and radiation therapy on the oncogenesis of Wilms tumor in the adult, are discussed.
forming a pseudocapsule, and there were no typical tumor lobules or cysts. Microscopic appearance of this tumor was predominantly of the blastemal pattern. Relatively small and oval or spindle-shaped immature cells, with scanty cytoplasm and large nuclei, were packed closely and could have been confused with other mesenchymal and anaplastic tumors (part A of figure). However, in the other areas the blastemal elements were subdivided by stromal tissues into circumscribed nodules and blastemal cells were rare (part B of figure). There were neither definite tubular elements nor striated muscles but a few abortive glomeruli-like structures were seen (part C of figure). Pathological diagnosis was undifferentiated or poorly differentiated nephroblastoma. Postoperative therapy included combined chemotherapy and irradiation, according to the National Wilms Tumor Study 2 regimens but it was not completed because of an acute attack of cholecystitis.
CASE REPORT
A 51-year-old man was hospitalized in July 1980 for dull pain and a mass in the right flank 1 month in duration. Relevant history revealed a left testicular tumor in 1954 and subsequent right testicular tumor in 1964. The left testicular tumor was teratocarcinoma, mixed with embryonal and seminomatous components. Left orchiectomy with para-aortic lymph node dissection was done, followed by 6,000 rad 60 cobalt irradiation to the para-aortic and left iliac areas (3,000 rad in each area). The right testicular tumor was pure seminoma. Right orchiectomy was done, followed by 4,000 rad 60 cobalt irradiation to the para-aortic and right iliac areas (2,000 rad in each area). Since 1964 supplemental injections of 125 mg. testosterone enanthate were done twice a month (total of 47.5 gm.). Physical examination revealed a tumor in the right flank, which had a smooth surface and solid consistency on palpation. Urinalysis revealed 30 to 40 red and 8 to 10 white blood cells per high power field. Serum creatinine was 1.6 mg./100 ml. and erythrocyte sedimentation rate was 37 mm. per hour. Excretory urography showed enlargement of the right kidney with distortion of the pyelocaliceal systems. The right ureter was not visualized. Computerized axial tomography demonstrated a tumor originating from the right kidney and renal angiography revealed the existence of hypovascular areas in the middle and lower portions of the right kidney. Chromosomal abnormality was not demonstrated in the peripheral blood. On August 5 radical right nephrectomy was done. Grossly, the tumor appeared to infiltrate into the renal capsule but no metastatic lesions were found in the surrounding tissues at operation. The capsule was already partially torn by invasion of the tumor. The stage of this tumor was estimated to be group 3, according to the criteria proposed by the National Wilms Tumor Study. 1 The resected specimen weighed 850 gm. and the tumor occupied the middle and lower portions of the kidney. On section the tumor looked partially gray-tan and well delineated, displacing the remaining normal tissues, and it contained focal areas of hemorrhage and necrosis. The junction between the tumor and kidney was sharp, with compressed renal tissue Accepted for publication March 26, 1982.
DISCUSSION
The occurrence of a Wilms tumor usually is limited to the first decade of life, although some cases have been reported in adults. The accurate incidence of this lesion in adults is difficult to ascertain. There is considerable variation in the incidence reported and there also is some confusion in the terminology related to this tumor. 2 A fundamental histologic feature of Wilms tumor is the presence of abortive or embryonic glomerulotubular structures with immature spindle stromal cells, which are not found in renal cell carcinoma. 3 In our case histopathological diagnosis might have been confused with anaplastic or sarcomatous renal tumors. While the origin of Wilms tumor from metanephric cells has been accepted by most authors, the specific mechanism of its development has not been elucidated sufficiently. In our case the concurrence of bilateral germ cell tumors of the testes and Wilms tumor suggests a congenital disorder because of the close relationship among gonads, mesonephros and metanephros in the embryo. The fact that the nodular foci of persistent nephrogenic blastema are encountered in newborns may support Cohnheim's4 "cell rest" theory of tumor formation in application to Wilms tumor. Potter has proposed that persistent nephrogenic blastema in the human is the result of ampullary failure, a deficiency of organizer effect at the ends of the ureteral buds. 5 This view of persistent blastema as an error of metanephric differentiation is interesting when the genitourinary anomalies known to occur with Wilms tumor are considered. 6 Our patient had received testosterone enanthate as supplemental hormone therapy. The effects of this earlier therapy cannot be ignored when considering the possible oncogenic effect of this tumor. There is a report of Wilms tumor in the adult triggered by androgen abuse. 7 Thus, it appears that the administration of certain hormones may have an inciting or
1296
AD:.J:Ur 'VIILiviS T):Jh1lOR AND EILATERAL TESTlCTJLAR TTJIVfORS
A, histopathologically, tumor shows relatively small and immature cells with oval nuclei and scanty eosinophilic cytoplasm. Immature cells are packed closely and could be mistaken for cells of other mesenchymal and anaplastic neoplasms. B, blastemal elements subdivided by stromal septa into circumscribed nodules. Two mixed elements of this tumor suggest Wilms tumor. C, rare and atypical glomeruloid structures that have neither definite tubular elements nor striated muscles. H & E, reduced from XIOO.
contributory effect on the oncogenesis of Wilms tumor, just as certain drugs may induce hepatoma. 8 However, in animal experiments there are no reports of hormone-induced nephroblastoma, although a few nephroblastomas in rats have been reported following irradiation. 9 Our patient received 3,000 plus 2,000 rad in 10 years to the para-aortic areas before the development of Wilms tumor. It is possible that a reacquisition of
embryonic characteristics might have been induced by that irradiation. There have been reports of neoplasms following irradiation. For instance, a mixed mullerian tumor of the uterus has been associated closely with prior irradiation. 10 In this regard one should also consider the possible interacting effects of irradiation and hormone therapies on the subsequent appearance of
1298
HARA AND ASSOCIATES
Wilms tumor. Other tumors that have been reported to occur with Wilms tumor are mixed liver tumor, 11 contiguous urological tumor, that is tumor of the renal pelvis and multicentric neoplasms in the ipsilateral ureter, 12 primary neoplasms, that is rhabdomyosarcoma, myelomonocytic leukemia and neuroblastoma, 13 leukemia, 14 fibrosarcoma, 15 bilateral retinoblastoma, 15 neurofibromatosis, 16 adrenocortical carcinoma17 and adenocarcinoma of the colon. 18 All of these tumors are rare. CONCLUSION
We have reported a case of adult Wilms tumor preceded by bilateral germ cell tumors of testes. We have postulated that these tumors might have developed from the same origin and that the Wilms tumor was promoted by earlier hormone and radiation therapy. This hypothesis is plausible in our case but, of course, there is no way to rule out the possibility of independent origins for these multiple neoplasms. REFERENCES
1. D'Angio, G. J., Beckwith, J. B., Breslow, N. E., Bishop, H. C., Evans, A. E., Farewell, V., Fernbach, D., Goodwin, W. E., Jones, B., Leape, L. L., Palmer, N. F., Tefft, M. and Wolff, J. A.: Wilm's tumor: an update. Cancer, suppl. 7, 45: 1791, 1980. 2. Babaian, R. J., Skinner, D. G. and Waisman, J.: Wilms' tumor in the adult patient: diagnosis, management, and review of the world medical literature. Cancer, 45: 1713, 1980. 3. Bodian, M. and Rigby, C. C.: The pathology ofnephroblastoma. In: Tumours of the Kidney and Ureter. Edited by E. Riches. Baltimore: The Williams & Wilkins Co., vol. 5, chapt. 18, p. 219, 1964. 4. Cohnheim, J.: Vorlesungen iiber algemeine Pathologie. Ein Handbuch fur Aerzte und Studirende, 2nd ed. Berlin: Verlag von August Hirschwald, vol. 1, p. 723, 1882.
5. Potter, E. L.: Normal and Abnormal Development of the Kidney. Chicago: Year Book Medical Publishers, 1972. 6. Bennington, J. L. and Beckwith, J.B.: Tumors of the kidney, renal pelvis, and ureter. In: Atlas of Tumor Pathology. Washington, D. C.: Armed Forces Institute of Pathology, fasc. 12, series 2, p. 38, 1975. 7. Prat, J., Gray, G. F., Stolley, P. D. and Coleman, J. W.: Wilms tumor in an adult associated with androgen abuse. J.A.M.A., 237: 2322, 1977. 8. Farrell, G. C., Joshua, D. E., Uren, R. F., Baird, P. J., Perkins, K. W. and Kronenberg, H.: Androgen-induced hepatoma. Lancet, 1: 430, 1975. 9. Berdjis, C. C.: Kidney tumors and irradiation pathogenesis of kidney tumors in irradiated rats. Oncologia, 16: 312, 1963. 10. Varela-Duran, J., Nochomovitz, L. E., Prem, K. A. and Dehner, L. P.: Postirradiation mixed miillerian tumors of the uterus: a comparative clinicopathologic study. Cancer, 45: 1625, 1980. 11. Fraumeni, J. F., Jr., Miller, R. W. and Hill, J. A.: Primary carcinoma of the liver in childhood: an epidemiologic study. J. Natl. Cancer Inst., 40: 1087, 1968. 12. Orlin, I.: Association of two contiguous urological tumors with adult Wilms tumor. J. Urol., 109: 362, 1973. 13. Valdes-Dapena, M. and Arey, J.B.: Multiple (4) primary neoplasms in a child with aniridia. Abstract. Amer. J. Path., 62: 22A, 1971. 14. Schwartz, A. D., Lee, H. and Baum, E. S.: Leukemia in children with Wilms tumor. J. Ped., 87: 374, 1975. 15. Pendergrass, T. W.: Congenital anomalies in children with Wilms tumor: a new survey. Cancer, 37: 403, 1976. 16. Bader, J. L. and Miller, R. W.: Neurofibromatosis and childhood leukemia. J. Ped., 92: 925, 1978. 17. Muller, S., Gadner, H., Weber, B., Vogel, M. and Riehm, H.: Wilms' tumor and adrenocortical carcinoma with hemihypertrophy and hamartomas. Eur. J. Ped., 127: 219, 1978. 18. Sabio, H., Teja, K., Elkon, D. and Shaw, A.: Adenocarcinoma of the colon following the treatment of Wilms tumor. J. Ped., 95: 424, 1979.