- Email: [email protected]
Testicular Tumors in 2 Families
0022-534 7/81/1253-0432$02.00/0
Vol. 125, March
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1981 by The Williams & Wilkins Co.
TESTICULAR TUMORS IN 2 FAMILIES RICHARD E. PESCHEL, MARTIN SCHIFF
AND
ARTHUR H. KNOWLTON
From the Departments of Therapeutic Radiology and Urology, Yale University School of Medicine, Yale-New Haven Hospital and Department of Therapeutic Radiology, The Hospital of St. Raphael, New Haven, Connecticut
ABSTRACT
Testicular cancers in closely related family members are rare. We herein report the second incidence of pure seminoma occurring in a father and son. The increased risk of malignant tumors developing in the undescended testis is well established. We also describe the second reported incidence of testicular cancers occurring in 2 non-twin brothers, in which 1 of the cancers developed in an undescended testis. Malignant tumors of the testis are the third leading cause of cancer deaths in young male patients, ranging in age from 15 to 34 years. 1 Although apparently increasing in incidence these tumors are relatively rare, occurring in only approximately 5 male patients per 100,000 in the United States. 2 Clearly, the probability of such tumors occurring in> 1 closely related family member is extremely small. Only 6 previous cases of testicular cancers in a father and son have been reported. 3 Of these 6 cases only 1 involved a pure seminoma occurring in both family members. 4 We herein describe the second reported incidence of pure seminoma in a father and son. Only 1 incidence of testicular tumors in non-twin siblings with a history of cryptorchidism has been reported. 5 We present the second reported incidence of testicular cancers occurring in 2 non-twin brothers, in which 1 of the cancers developed in an undescended testis. CASE REPORTS
Family 1, case 1. A 62-year-old white man presented with an asymptomatic 5 cm. mass in the right testicle on physical examination. On September 6, 1961 a right orchiectomy via an inguinal incision was done. Pathological studies revealed pure seminoma. A chest x-ray, excretory urography (IVP) and routine blood studies were negative. The patient received postoperative radiotherapy to the pelvis and para-aortic lymph node regions (dose unknown). The patient was alive with no evidence of disease 19 years after the treatment. Family 1, case 2. The son of the patient presented in case 1 was well until he was 43 years old, when an enlarging mass developed in the right scrotum. Physical examination confirmed an abnormal 6 cm. mass occupying the right scrotum and a right radical orchiectomy was done on June 11, 1973. Pathological studies revealed pure seminoma. A lymphangiogram was suspicious for para-aortic adenopathy. A chest x-ray, lung tomograms and routine blood studies were normal. The patient received postoperative radiotherapy to the right pelvis and para-aortic lymph node regions (3,400 rad in 30 days) followed by mediastinal and bilateral supraclavicular irradiation (2,700 rad in 23 days). The patient presently is 7 years without evidence of disease. Neither the father (case 1) nor the son (case 2) had a history of an undescended testicle. There was no other history of cancer in the immediate family. The pathological studies in cases 1 and 2 were reviewed and confirmed by the pathology department at our hospital. Family 2, case 3. A 23-year-old white man presented with a 5-month history of a painful left testicular mass. Physical examination revealed an abnormal 5 cm. mass and a left radical orchiectomy was done on April 12, 1979. The pathological condition was a mixed germ cell tumor with seminoma, em-
bryonal carcinoma, and mature and immature teratoma. A chest x-ray showed a metastatic lesion in the left lung. An abdominal computerized axial tomography scan showed significant para-aortic and pelvic adenopathy. The ,8-human chorionic gonadotropin titer was 64,000 and the a-fetoprotein was abnormal. The patient received several cycles of cis-platinum, vinblastine and bleomycin with a partial response. On September 17, 1979 a retroperitoneal node dissection was done along with excision of a left lower lobe lung nodule. In December 1979 the patient suffered left hydronephrosis secondary to an enlarging abdominal mass. Local radiotherapy (1,800 rad in 15 days) and further chemotherapy were given. Progressive renal failure and widespread metastatic disease developed and the patient died on December 24, 1979. Family 2, case 4. The brother of the patient in case 3 was a healthy 25-year-old man who had an undescended left testicle at birth. After the diagnosis of testicular cancer was established in his brother in April 1979 this patient was encouraged to seek a urologic evaluation. The patient described a 6-month history of vague left abdominal discomfort. Therefore, resection of the undescended testis was done on June 25, 1979. A pure seminoma arising in an atrophic testis was found. A chest x-ray, lymphangiogram, lung tomograms and an abdominal computerized axial tomography scan all were negative. The ,B-human chorionic gonadotropin titer was 0. The patient received postoperative radiotherapy to the left pelvis and para-aortic node regions (2,550 rad in 23 days) and is now 9 months without evidence of disease. There was no other history of cancer in family 2. The pathological conditions in cases 3 and 4 were determined by the pathology department at our hospital.
Accepted for publication May 30, 1980. 432
DISCUSSION
The etiology of testicular cancer is unknown. Although genetic factors may have a role in this disease there is a paucity of data to support this hypothesis. The data on identical twins are sparse (8 cases). 6' 7 As reviewed by Raghavan and associates the total number of reported cases of testicular cancers in a father and son or in non-twin siblings is only about 20. 3 We have described only the second reported incidence of pure seminoma arising in the father and the son (cases 1 and 2). Whether this represents a chance event or some hereditary influence in patients with testicular cancer is problematical. Raghavan and associates have suggested that a form of genetic anticipation may occur in father-son testicular tumors in which successive generations have tumors of increased severity. 3 Only 4 of the reported 7 cases of father-son testicular cancers show increased tumor severity in the sons (table 1). 3• 4 •8- 11 Clearly, any conclusions made from such a small data base must be viewed with caution. Our case study (family 1) does not support the assumption of increased tumor severity in the sons.
r-i1ESTICULAR TTJI1/'lORS IN 2 FAMILIES TABLE
Father's Disease
References Silber and associates8 Arcadi4 Musa9 Fetterly10 Lapes and associates 11 Raghavan and associates3 Present study
TABLE
L Testicular tu1nors in fathers and sons Prognosis Worse in the Son?
Son's Disease
Seminoma
Teratoma chorioca.
Yes
Seminoma Teratoma Seminoma Rt. embryonal Ca and seminoma, It. seminoma Bilat. seminoma
Seminoma Chorioca. Embryonal Ca Teratoca.
No Yes Yes ?
Teratoca.
Yes
Seminoma
Seminoma
No
2. Cryptorchidism and testicular cancers in siblings
References
Relationship
Cryptorchidism in Siblings (No.)
Domrich 12 Salm and Adlington13 Villani 14 Ghosh and associates' Present study
Twins Twins Twins Non-twins Non-twins
Both Both Both 1 1
Most investigators report an increased incidence of malignant tumors in the undescended testis. 7 Table 2 summarizes the cases of cryptorchidism and testicular cancers occurring in siblings. 5 • 12- 14 In the 3 cases of twins both siblings had a history of cryptorchidism. In the 2 non-twin cases only 1 sibling had a history of an undescended testis. In both of these non-twin cases it was the history of an undescended testis in 1 sibling that led to a high suspicion of cancer after a testicular neoplasm had been diagnosed in another family member. Therefore, despite the lack of knowledge concerning the genetic influence
on testicular cancers, our second (cases 3 and 4) emphasizes the importance of a family history and the need to counsel close male relatives of a patient who may be at higher risk. Particular attention should be directed toward family members with a history of an undescended testis. REFERENCES 1. Cancer statistics, 1980. CA, 30: 23, 1980.
2. Mostofi, F. K.: Testicular tumors: epidemiology, etiology and patho-
logical features. Cancer, 32: 1186, 1973. 3. Raghavan, D., Jelihovsky, T. and Fox, R. M.: Father-son testicular malignancy. Does genetic anticipation occur? Cancer, 45: 1005, 1980. 4. Arcadi, J. A.: Testicular neoplasms in father and son. J. Urol., 110: 306, 1973 .. 5, Ghosh, P., Jacobs, H. and Rattner, W. H.: Testicular neoplasm in siblings. Urology, 7: 212, 1976. 6. Levey, S. and Grabstald, H.: Synchronous testicular tumors in identical twins. Urology, 6: 754, 1975. 7. Wilbur, H. J., Woodruff, M. W. and Welch, M. S.: Concomitant germ cell tumors in monozygotic twins. J. Urol., 121: 538, 1979. 8. Silber, S. J., Cittan, S. and Friedlander, G.: Testicular neoplasm in father and son. J. Urol., 108: 889, 1972. 9. Musa, M. B.: Germ-cell malignant tumours in father and son. Canad. Med. Ass. J., 112: 1201, 1975. 10. Fetterly, J. C.: Malignant tumors in father and son. Letter to the Editor. Canad. Med. Ass. J., 113: 92, 1975. 11. Lapes, M., Iozzi, L., Ziegenfus, W. D., Antoniades, K. and Vivacqua, R.: Familial testicular cancer in a father (bilateral seminomaembryonal cell carcinoma) and son (teratocarcinoma). A case report and review of the literature. Cancer, 39: 2317, 1977. 12. Domrich, H.: Uber Leistenhodencarcinoma bei Zwillingen Langenbecks. Arch. f. Clin. Chir., 197: 848, 1940. 13. Salm, R. and Adlington, S. R.: Seminoma in identical twins. Brit. Med. J., 2: 964, 1962. 14. Villani, U.: Tumore concordante de! testiculo in una coppia di gemelli monozigoti. Acta Genet. Med. GemelloL, 16: 172, 1967.
Vol. 125, March
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1981 by The Williams & Wilkins Co.
TESTICULAR TUMORS IN 2 FAMILIES RICHARD E. PESCHEL, MARTIN SCHIFF
AND
ARTHUR H. KNOWLTON
From the Departments of Therapeutic Radiology and Urology, Yale University School of Medicine, Yale-New Haven Hospital and Department of Therapeutic Radiology, The Hospital of St. Raphael, New Haven, Connecticut
ABSTRACT
Testicular cancers in closely related family members are rare. We herein report the second incidence of pure seminoma occurring in a father and son. The increased risk of malignant tumors developing in the undescended testis is well established. We also describe the second reported incidence of testicular cancers occurring in 2 non-twin brothers, in which 1 of the cancers developed in an undescended testis. Malignant tumors of the testis are the third leading cause of cancer deaths in young male patients, ranging in age from 15 to 34 years. 1 Although apparently increasing in incidence these tumors are relatively rare, occurring in only approximately 5 male patients per 100,000 in the United States. 2 Clearly, the probability of such tumors occurring in> 1 closely related family member is extremely small. Only 6 previous cases of testicular cancers in a father and son have been reported. 3 Of these 6 cases only 1 involved a pure seminoma occurring in both family members. 4 We herein describe the second reported incidence of pure seminoma in a father and son. Only 1 incidence of testicular tumors in non-twin siblings with a history of cryptorchidism has been reported. 5 We present the second reported incidence of testicular cancers occurring in 2 non-twin brothers, in which 1 of the cancers developed in an undescended testis. CASE REPORTS
Family 1, case 1. A 62-year-old white man presented with an asymptomatic 5 cm. mass in the right testicle on physical examination. On September 6, 1961 a right orchiectomy via an inguinal incision was done. Pathological studies revealed pure seminoma. A chest x-ray, excretory urography (IVP) and routine blood studies were negative. The patient received postoperative radiotherapy to the pelvis and para-aortic lymph node regions (dose unknown). The patient was alive with no evidence of disease 19 years after the treatment. Family 1, case 2. The son of the patient presented in case 1 was well until he was 43 years old, when an enlarging mass developed in the right scrotum. Physical examination confirmed an abnormal 6 cm. mass occupying the right scrotum and a right radical orchiectomy was done on June 11, 1973. Pathological studies revealed pure seminoma. A lymphangiogram was suspicious for para-aortic adenopathy. A chest x-ray, lung tomograms and routine blood studies were normal. The patient received postoperative radiotherapy to the right pelvis and para-aortic lymph node regions (3,400 rad in 30 days) followed by mediastinal and bilateral supraclavicular irradiation (2,700 rad in 23 days). The patient presently is 7 years without evidence of disease. Neither the father (case 1) nor the son (case 2) had a history of an undescended testicle. There was no other history of cancer in the immediate family. The pathological studies in cases 1 and 2 were reviewed and confirmed by the pathology department at our hospital. Family 2, case 3. A 23-year-old white man presented with a 5-month history of a painful left testicular mass. Physical examination revealed an abnormal 5 cm. mass and a left radical orchiectomy was done on April 12, 1979. The pathological condition was a mixed germ cell tumor with seminoma, em-
bryonal carcinoma, and mature and immature teratoma. A chest x-ray showed a metastatic lesion in the left lung. An abdominal computerized axial tomography scan showed significant para-aortic and pelvic adenopathy. The ,8-human chorionic gonadotropin titer was 64,000 and the a-fetoprotein was abnormal. The patient received several cycles of cis-platinum, vinblastine and bleomycin with a partial response. On September 17, 1979 a retroperitoneal node dissection was done along with excision of a left lower lobe lung nodule. In December 1979 the patient suffered left hydronephrosis secondary to an enlarging abdominal mass. Local radiotherapy (1,800 rad in 15 days) and further chemotherapy were given. Progressive renal failure and widespread metastatic disease developed and the patient died on December 24, 1979. Family 2, case 4. The brother of the patient in case 3 was a healthy 25-year-old man who had an undescended left testicle at birth. After the diagnosis of testicular cancer was established in his brother in April 1979 this patient was encouraged to seek a urologic evaluation. The patient described a 6-month history of vague left abdominal discomfort. Therefore, resection of the undescended testis was done on June 25, 1979. A pure seminoma arising in an atrophic testis was found. A chest x-ray, lymphangiogram, lung tomograms and an abdominal computerized axial tomography scan all were negative. The ,B-human chorionic gonadotropin titer was 0. The patient received postoperative radiotherapy to the left pelvis and para-aortic node regions (2,550 rad in 23 days) and is now 9 months without evidence of disease. There was no other history of cancer in family 2. The pathological conditions in cases 3 and 4 were determined by the pathology department at our hospital.
Accepted for publication May 30, 1980. 432
DISCUSSION
The etiology of testicular cancer is unknown. Although genetic factors may have a role in this disease there is a paucity of data to support this hypothesis. The data on identical twins are sparse (8 cases). 6' 7 As reviewed by Raghavan and associates the total number of reported cases of testicular cancers in a father and son or in non-twin siblings is only about 20. 3 We have described only the second reported incidence of pure seminoma arising in the father and the son (cases 1 and 2). Whether this represents a chance event or some hereditary influence in patients with testicular cancer is problematical. Raghavan and associates have suggested that a form of genetic anticipation may occur in father-son testicular tumors in which successive generations have tumors of increased severity. 3 Only 4 of the reported 7 cases of father-son testicular cancers show increased tumor severity in the sons (table 1). 3• 4 •8- 11 Clearly, any conclusions made from such a small data base must be viewed with caution. Our case study (family 1) does not support the assumption of increased tumor severity in the sons.
r-i1ESTICULAR TTJI1/'lORS IN 2 FAMILIES TABLE
Father's Disease
References Silber and associates8 Arcadi4 Musa9 Fetterly10 Lapes and associates 11 Raghavan and associates3 Present study
TABLE
L Testicular tu1nors in fathers and sons Prognosis Worse in the Son?
Son's Disease
Seminoma
Teratoma chorioca.
Yes
Seminoma Teratoma Seminoma Rt. embryonal Ca and seminoma, It. seminoma Bilat. seminoma
Seminoma Chorioca. Embryonal Ca Teratoca.
No Yes Yes ?
Teratoca.
Yes
Seminoma
Seminoma
No
2. Cryptorchidism and testicular cancers in siblings
References
Relationship
Cryptorchidism in Siblings (No.)
Domrich 12 Salm and Adlington13 Villani 14 Ghosh and associates' Present study
Twins Twins Twins Non-twins Non-twins
Both Both Both 1 1
Most investigators report an increased incidence of malignant tumors in the undescended testis. 7 Table 2 summarizes the cases of cryptorchidism and testicular cancers occurring in siblings. 5 • 12- 14 In the 3 cases of twins both siblings had a history of cryptorchidism. In the 2 non-twin cases only 1 sibling had a history of an undescended testis. In both of these non-twin cases it was the history of an undescended testis in 1 sibling that led to a high suspicion of cancer after a testicular neoplasm had been diagnosed in another family member. Therefore, despite the lack of knowledge concerning the genetic influence
on testicular cancers, our second (cases 3 and 4) emphasizes the importance of a family history and the need to counsel close male relatives of a patient who may be at higher risk. Particular attention should be directed toward family members with a history of an undescended testis. REFERENCES 1. Cancer statistics, 1980. CA, 30: 23, 1980.
2. Mostofi, F. K.: Testicular tumors: epidemiology, etiology and patho-
logical features. Cancer, 32: 1186, 1973. 3. Raghavan, D., Jelihovsky, T. and Fox, R. M.: Father-son testicular malignancy. Does genetic anticipation occur? Cancer, 45: 1005, 1980. 4. Arcadi, J. A.: Testicular neoplasms in father and son. J. Urol., 110: 306, 1973 .. 5, Ghosh, P., Jacobs, H. and Rattner, W. H.: Testicular neoplasm in siblings. Urology, 7: 212, 1976. 6. Levey, S. and Grabstald, H.: Synchronous testicular tumors in identical twins. Urology, 6: 754, 1975. 7. Wilbur, H. J., Woodruff, M. W. and Welch, M. S.: Concomitant germ cell tumors in monozygotic twins. J. Urol., 121: 538, 1979. 8. Silber, S. J., Cittan, S. and Friedlander, G.: Testicular neoplasm in father and son. J. Urol., 108: 889, 1972. 9. Musa, M. B.: Germ-cell malignant tumours in father and son. Canad. Med. Ass. J., 112: 1201, 1975. 10. Fetterly, J. C.: Malignant tumors in father and son. Letter to the Editor. Canad. Med. Ass. J., 113: 92, 1975. 11. Lapes, M., Iozzi, L., Ziegenfus, W. D., Antoniades, K. and Vivacqua, R.: Familial testicular cancer in a father (bilateral seminomaembryonal cell carcinoma) and son (teratocarcinoma). A case report and review of the literature. Cancer, 39: 2317, 1977. 12. Domrich, H.: Uber Leistenhodencarcinoma bei Zwillingen Langenbecks. Arch. f. Clin. Chir., 197: 848, 1940. 13. Salm, R. and Adlington, S. R.: Seminoma in identical twins. Brit. Med. J., 2: 964, 1962. 14. Villani, U.: Tumore concordante de! testiculo in una coppia di gemelli monozigoti. Acta Genet. Med. GemelloL, 16: 172, 1967.