THE JOURNAL o,· UROLOGY
VoL 114, October
Copyright© 1975 by The Williams & Wilkins Co.
Printed in U.SA.
BILATERAL TESTICULAR TUMORS OF GERM CELL ORIGIN ROBERT E. LEFEVRE,* HOWARD S. LEVIN, LYNN H. BANOWSKY, RALPH A. STRAFFON, BRUCE H. STEWART AND CLARENCE B. HEWITT From the Departments of Pathology and Urology, The Cleveland Clinic Foundation and The Cleveland Clini,· Educational Foundation, Cleveland, Ohio
ABSTRACT
Four cases of primary testicular tumor of germ cell ongm are reported. Three cases were bilateral, while the remaining case involved a unilateral tumor in a nontwin brother of 1 patient with bilateral tumors. Because of the increased likelihood of a second primary tumor developing in a patient who had a maligrnmtgerminal cell tumor and because the changes n1ay be subtle, localized to the testis and occur at'ter a fuinor:::free interval of many years, careful examination of the contralateral testis and long-term followup are_ indicated even, when syst~mic chen19ther_1,1py for malignancy lias been used. This is the seventh time familial occurrence of testis tumors in noii.:::rwiii'orothers has been reported but the first time that one of the brothers had bilateral tumors.
has
Since Livingstone reported the first case of bilateral testicular tumor in 1805 several comprehensive reviews have been published to determine its frequency. 1 Gilbert and Hamilton reported 148 additional cases, 2 and Abeshouse and associates reported another 53 cases, making a total of 209 reported cases. 3 Mostofi and Price reported an incidence of 1 per cent of bilateral germ cell tumors in approximately 6,000 cases. 4 The occurrence is rare, ranging from no cases in the 922 testicular tumors reported in 1946 by Friedman and Moore• to 1 in 1,700 cases reported by Hotchkiss and Laury• to the 2 per cent incidence reported by Gilbert and Hamilton. 2 Bilateral testicular tumors may occur simultaneously or successivel),'.-They-inay-oe 6T primary origin, metastatic or associated with systemic types of neoplasia. 7 · 9 Although these tumors are rare even fewer cases in siblings have been reported. Six cases of primary testicular tumors in identical twins, 10· 15 and 6 cases of primary testicular tumors in non-twins have been reported. 1 M 1 We herein report 4 cases of testicular tumor of germ cell origin. Three cases are bilateral and the fourth is a unilateral tumor in a non-twin whose brother had bilateral tumors. This report is the seventh one concerning non-twin brothers with primary testicular malignancies and the first m which 1 brother had bilateral testis tumors. CASE REPORTS
Case 1. A 17 -year-old white boy was admitted to the hospital in April 1963 with a 6-week history of Accepted for publication ,January 3, 1975. * Current address: Gould Medical Group, 600 Coffee Rd., Modesto, California 9.5:3,50.
painful swelling of the left testis. He had undergone 4 weeks of therapy for infection. Left inguinal orchiectomy was performed at another hospital before the boy was referred to us for further treatment. There was no history of trauma or cryptorchidism. The patient had undergone right inguinal herniorrhaphy when he was 5 years old. Physical examination revealed a healing left inguinal incision and surgically absent left testis. There was no gynecomastia and no lymphadenopathy. A chest roentgenogram, excretory urogram (IVP) and urinary gonadotropin determinations were normal. Pathologic diagnosis was teratocarcinoma with a microfocus of choriocarcinoma. There was no vascular invasion, no local spread, no interstitial cell hyperplasia and no lymphocytic reaction. On May 7, 1963 the patient underwent transperitoneal bilateral lymphadenectomy and all 29 lymph nodes were free of tumor. The patient received no chemotherapy or radiotherapy and had yearly chest roentgenograms and urinary gonadotropin determinations; the results were normal. The patient remained well until March 1972 when he was 26 years old and seen with a 2-day history of acute pain and swelling of the right testis. The right testis was enlarged, diffusely firm, irregular and tender. Urinary gonadotropin, IVP and chest roentgenograms were normal. On March 13 he underwent right inguinal orchiectomy and a right testicular prosthesis was implanted. Pathologic diagnosis was seminoma, with extensive infarction and hemorrhage. There was no vascular invasion, local spread or lymphocytic reaction but there was moderate interstitial cell hyperplasia. Postoperatively, the patient received 3,150 rads
556
BILATERAL TESTICULAR TUMORS OF GERM CELL ORIGIN
557
delivered tumor dose over 19 days to the right iliac carcinoma. The family history is significant in that lymph nodes. He has done well and is able to have his brother (case 4) also had a testis tumor. erections , although he has failure of emission. From January 15 to February 26, 1959 the Case 2. A 20-year-old white man was examined patient received 23 treatments of cobalt 60, with a because of a 3-month history of low back pain and delivered tumor dose of 4,400 rads to the left iliac painless swelling of the left testis. There was no nodes and 4,600 rads delivered dose to the parahistory of trauma, infection or cry ptorchidism. aortic lymph nodes . He was followed every 3 to 4 Physical examination showed a firm non-tender months with regular examinations of the right mass in the left scrotum, which did not transmit testis and did well until August 1961, when on light . There was no gynecomastia nor lymphade- routine examination some irregularity was palnopathy . An IVP and urinary gonadotropin deter- pated in the right testis. There was no lymphminations were normal but there was a small adenopathy or gynecomastia and the right testis nodule seen in the left lower lung field on roent- was hard, non-tender and not enlarged. with thickgenographic examination of the chest. On April 19, ening between the epididymis and testis. On Au1960 left inguinal orchiectomy was performed. gust 25, 1961 right orchiectomy and right inguinal Pathologic diagnosis was embryonal carcinoma and iliac node dissection were done. Pathologic with vascular invasion and extension to the line of diagnosis was teratocarcinoma with vascular inresection of the spermatic cord. vasion, local extension and intersti t ial cell hyperFrom April 29 to June 3 the patient underwent plasia. There were focal a reas of seminoma in situ 25 treatments of cobalt 60 radiotherapy, with 3,600 and focal choriocarcinoma. Two lymph nodes were rads to the left inguinal region at a depth of 4 cm. negative for tumor. He received no further radioand 4,800 rads to the para-aortic lymph nodes. therapy and chemotherapy . The patient was last During this radiation therapy he received his first seen in February 1971, at which time bilateral course of triple drug therapy (10 mg. chlorambucil testicular prostheses were implanted, and roentand 5 mg. methotrexate daily for 10 days and 0.5 genograms of the chest and urinary gonadotropin mg. actinomycin D daily for the middle 5 days) . determinations were normal. This triple drug chemotherapy was continued Case 4. This patient (brother of case 3) was seen every 3 to 6 months until March 1963. All chest at the hospital in July 1955 when he was 21 years old with a 1-year history of painless, gradual enroentgenograms during this time were normal. The patient was lost to followup until March largement of the right testis. There was no history 1968, when he was seen because of a 4-month of trauma, cryptorchidism or infection. A month history of painless swelling of the right testis. He before hospitalization he was rejected from an had been receiving treatment for infertility when ROTC program because of the testicular mass. he first noticed the swelling in November 1967. Physical examination revealed a hard irregula r Physical examination revealed no masses in the testis that was twice normal s ize . There was no left hemiscrotum and the right testis was hard, ly mpha denopathy or gynecomastia. A chest roentimmovable and did not transmit light. An IVP, genogram and IVP were normal. Left inguinal lymphangiograms, chest roentgenograms and uri- orchiectomy was done on July 22. Pathologic nary gonadotropin determinations were normal. diagnosis was teratocarcinoma with interstit ial cell On March 11, 1968 the patient underwent right hyperplasia. Postoperatively the patient received inguinal orchiectomy. Pathologic diagnosis was 34 t reatments of cobalt 60 with a delivered tumor teratocarcinoma . There was necrosis and hemor- dose of 5,000 rads to the para-aortic and right rhage but no vascular invasion , local extension or pelvic lymph nodes . At the time of t his report (16 lymphoid reaction. Interstitial cell hyperplasia and years lat er) he is well. .focal syntrophoblasts were present. For almost 2 DISCUSSION years the patient received 0.5 mg. actinomycin D Bilateral testicular tumors occur in a variety of per day for 5 days every other mont h. At this time there is no evidence of tumor recurrence or metas - recognized clinical settings . Bilateral neoplasms of possible interstitial cell or adrenal origin occur in tases. Case 3. A 19-year-old man not iced a painful cases of adrenogenital syndrome. 2 2 ApptQ~im8-Jely nodule in the left testis a month prior to admission 25 per ce11t of pa tients with malignant lymphoma to the hospital. T here was no history of urinary invoiving the testis have bilateral involvement. 4 tract infections, trauma or cryptorchidism. Physi- Three of7 patients with plasmacytoma of the testis cal examination showed a firm, non-tender mass in had bilateral involvement. 23 Mostofi and Price the left testis. There was no gynecomastia or found bilateral involvement in 4 of 6 clinically lymphadenopathy. A chest roentgenogram was manifest secondary carcinomas, which mimicked normal , and IVP, lymphan giogram and urinary primary testicular neoplasms.' However, the fate gonadotropin determinations were not done. A left and clinical implication of bilateral testicular neoinguinal orchiectomy with high ligation of the plasms of germ cell origin are less well known. In spermatic cord was performed on December 6, the :3 cases of bilateral testis tumors of germ cell 1958 . The patient was referred to this hospital for origin reported herein a variety of histologic patfurther therapy. Pathologic diagnosis was terato- terns was observed (see tah]e). Of the 6 neoplasms
t
558
LEFEVRE AND ASSOCIATES
Reuiew of cases Initial Tumor Case No.
Age (yrs.)
1-17
2-20
Tumor Teratocarcinoma with focal choriocarcinoma Embryonal carcinoma
Second Tumor - - - - - - - - · - - - - - - - - - - - - - - - Survi-
Therapv
Age
(yrs.)
Interval
val Tumor
Therapv
(yrs.)
Bilat. lymph node
26
9
Seminoma
Cobalt 60
dissection Cobalt 60, triple
28
8
Teratocareinoma
Actinomycin D
22
:l
Teratocarcinoma with focal choriocarcinoma and seminoma in situ
None
3-19
Teratocarcinoma
drug Cobalt 60
4-21 (brother of case 3)
Teratocarcinoma
Cobalt 60
4 were teratocarcinoma and 2 contained focal choriocarcinoma. Seminoma and embryonal carcinoma each occurred in 1 testis. Our experience contrasts somewhat with that of Mostofi and Price.• In their series seminoma was present bilaterally in 75 per cent of the cases and in the remainder seminoma occurred in 1 testis and embryonal carcinoma with teratoma occurred in the other. They also round that tumors were simultaneous in about a third of the cases and consecutive in the remainder, with an interval of 3 to 15 years between tumors. In our series 3 patients each had a second neoplasm 3, 8 and 9 years, respectively, after the original orchiectomy. In addition to orchiectomy 1 patient underwent bilateral retroperitoneal lymph node dissection, 2 patients received cobalt 60 therapy and 1 patient received chemotherapy for malignancy. These types of therapy did not prevent the occurrence of a second tumor in any case. The interval between the first and second tumors and the lack of extra-testicular tumor in any of these cases suggest that the second tumors developed de novo. Our 3 cases of bilateral germ cell tumors were found in a review of 166 cases of testicular tumors treated from 1950 to 1970. The rate of bilaterality of 1.8 per cent is within the range reported in other series. 2 - 4 , 24 Although small, this rate is si~ificant when compared to the expected incidence of unilateral testis tumor, which is 2.1 to 2.3 in 100,000 male subjects. 25 A patient who has had 1 testis tumor is far more likely to suffer another than the general population. In addition, the fact that all 3 ofour patients were extremely young (17, 19 and 20 years old) argues further for careful followup. That 1 patient (case 3) was asymptomatic and the testis on physical examination was only subtly irregular further emphasize the need for careful physical examination at regular intervals after orchiectom~, for a germinal cell tumor. There are too few cases for statistical evaluation of genetic predisposition to testicular tumor of germ cell origin. However, this possibility must be considered when in 1 family (cases 3 and 4) bilateral neoplasm developed in 1 brother within 3 years and in a second brother a testicular tumor of
(yrs.)
5
13
16
similar type developed. The cl testicular neoplasms in these brothers were teratocarcinoma. To our knowledge this is the third reported instance of similar testicular neoplasms developing in nontwin brothers. 21 · 25 Prior to this report only twins had had tumors of similar histologic pattern. It is of interest that despite the occurrence of malignant neoplasms of the testis, all patients reported herein have survived. The patients with bilateral neoplasms have survived 1, 5 and 13 years, and the brother with unilateral teratocarcinoma has survived 16 years. At present none of these patients receive therapy. It is also of interest that 2 patients had focal choriocarcinoma in 1 testis, attesting to the fact that focal choriocarcinoma does not have the dire prognosis of pure choriocarcinoma of the testis. REFERENCES 1. Livingstone, ,J .: A case of cancer of both testicles
2.
3.
4.
5. 6.
7.
8. 9.
10.
which terminated favorably by the supervention of surgery. Edinburg Med. Surg. J., l: 163, 1805. Gilbert, J. B. and Hamilton, ,J. B.: Studies in malignant testis tumors; incidence and nature of tumors in ectopic testes. Surg., Gynec. & Obst., 71: 731, 1940. Abeshouse, B. S., Tiongson, A. and Goldfarb, M.: Bilateral tumors of testicles: review of literature and report of case of bilateral simultaneous lymphosarcoma. J. Urol., 74: 522, 1955. Mostofi, F. K. and Price, E. B., Jr.: Tumors of the male genital system. In: Atlas of Tumor Pathology. Washington, D. C.: Armed Forces Institute of Pathology, 2nd series, fasc. 8, 1973. Friedman, N. B. and Moore, R. A.: Tumors of testis; report on 922 cases. Mil. Surg., 99: 573, 1946. Hotchkiss, R. S. and Laury, R. B.: Concomitant bilateral malignant testicular tumors. J. Urol., 63: 1086, 1950. Harper, ,J. G. M., Dewing, S. B. and Nagamatsu, G.: Bilateral carcinoma of the testis: a report of three cases. ,J. Urol., 71: 6:34, 1954. Patton, J. F. and Mallis, N .: Tumors of the testis. ,J. Urol., 81: 457, 1959. Pierson, E. L., Jr.: A case of bilateral tumors of the testicle. With some notes on the effect of castration of the adult male. J. Urol., 28: 353, 1932. Champlin, H. W.: Similar tumors of the testis
BILATERAL TESTICULAR TUMORS OF GERM CELL ORIGI N
11.
12. 13. 14.
15.
16. 17.
occurring m identical twins. J.A.M.A .. 95: 96 , 1930. Wells, H. G.: Cited by Macklin, M. T.: Analysis of tumors in monozygous and dizygous twins , with a report of 15 unpublished cases. J. Hered. , 31: 277 , 1940. Domrich, H .: Ober Leistenhodencarcinom bei Zwillingen. Arch . f. Klin. Chir., 197: 848, 1940. Salm, R. and Adlington, S. R.: Seminoma in identical twins. Brit. Med. J ., 2: 964, 1962. Stewart , J. R. and Bagshaw , M. A.: Malignant testicular tumors appearing simultaneously in identical twins: a case report. Cancer, 18: 895, 1965. Villani , U.: Tumore concordante de! testicolo in una coppia di gemelli monozigoti. Acta Genet. Med., 16: 172, 1967. Raven, R. W.: Tumours of the testis in two brothers. Lancet, 2: 870, 1934. Lownes, J.B. and Leberman , P.: Tumors of the testis in brothers. Urol. & Cutan. Rev., 43: 205 , 1939.
559
18. Willis , R. A.: Pathology of Tumors, 2nd ed. London: Butterworth Inc. , pp. 557- 558, 1953. 19. Hutter, A. M. , Jr. , Lynch, J . J. and Shnider, B. I.: Malignant test icular tumors in brothers: a case report.. J.A.M.A. , 199: 1009, 1967. 20. Myers, G. H. , Jr. and MacPherson, B. R.: Histologically s imila r testicular neoplasms occurring in brothers. J. Urol., 108: 757 , 1972. 21. Young, J. A. a nd Bohne, A. W.: Seminoma in non-twin brothers: a case report. J. Urol., 107: 1000, 1972. 22. Fore, W.W., Bledsoe, T., Weber, D. M. and Brooks, R. T. , Jr.: Cortisol production by testicular tumors in adrenogenital sy ndrome. Arch. Intern. Med. , 130: 59 , 1972. 23. Levin , H. S. and Mosto fi , F . K .: Symptomatic plasmocytoma of the testis. Cancer, 25: 1193, 1970. 24. Gill , R. D. and Howell, R. B.: Primary bilateral testicular tumor. ,J. Urol., 59: 940, 1948. 25. Campbell, M. F. and Ha rrison , J. H .: Urology , 3rd ed. Philadelphia: W. B. Saunders Co., p. 1211 , 1970.
t
VoL 114, October
Copyright© 1975 by The Williams & Wilkins Co.
Printed in U.SA.
BILATERAL TESTICULAR TUMORS OF GERM CELL ORIGIN ROBERT E. LEFEVRE,* HOWARD S. LEVIN, LYNN H. BANOWSKY, RALPH A. STRAFFON, BRUCE H. STEWART AND CLARENCE B. HEWITT From the Departments of Pathology and Urology, The Cleveland Clinic Foundation and The Cleveland Clini,· Educational Foundation, Cleveland, Ohio
ABSTRACT
Four cases of primary testicular tumor of germ cell ongm are reported. Three cases were bilateral, while the remaining case involved a unilateral tumor in a nontwin brother of 1 patient with bilateral tumors. Because of the increased likelihood of a second primary tumor developing in a patient who had a maligrnmtgerminal cell tumor and because the changes n1ay be subtle, localized to the testis and occur at'ter a fuinor:::free interval of many years, careful examination of the contralateral testis and long-term followup are_ indicated even, when syst~mic chen19ther_1,1py for malignancy lias been used. This is the seventh time familial occurrence of testis tumors in noii.:::rwiii'orothers has been reported but the first time that one of the brothers had bilateral tumors.
has
Since Livingstone reported the first case of bilateral testicular tumor in 1805 several comprehensive reviews have been published to determine its frequency. 1 Gilbert and Hamilton reported 148 additional cases, 2 and Abeshouse and associates reported another 53 cases, making a total of 209 reported cases. 3 Mostofi and Price reported an incidence of 1 per cent of bilateral germ cell tumors in approximately 6,000 cases. 4 The occurrence is rare, ranging from no cases in the 922 testicular tumors reported in 1946 by Friedman and Moore• to 1 in 1,700 cases reported by Hotchkiss and Laury• to the 2 per cent incidence reported by Gilbert and Hamilton. 2 Bilateral testicular tumors may occur simultaneously or successivel),'.-They-inay-oe 6T primary origin, metastatic or associated with systemic types of neoplasia. 7 · 9 Although these tumors are rare even fewer cases in siblings have been reported. Six cases of primary testicular tumors in identical twins, 10· 15 and 6 cases of primary testicular tumors in non-twins have been reported. 1 M 1 We herein report 4 cases of testicular tumor of germ cell origin. Three cases are bilateral and the fourth is a unilateral tumor in a non-twin whose brother had bilateral tumors. This report is the seventh one concerning non-twin brothers with primary testicular malignancies and the first m which 1 brother had bilateral testis tumors. CASE REPORTS
Case 1. A 17 -year-old white boy was admitted to the hospital in April 1963 with a 6-week history of Accepted for publication ,January 3, 1975. * Current address: Gould Medical Group, 600 Coffee Rd., Modesto, California 9.5:3,50.
painful swelling of the left testis. He had undergone 4 weeks of therapy for infection. Left inguinal orchiectomy was performed at another hospital before the boy was referred to us for further treatment. There was no history of trauma or cryptorchidism. The patient had undergone right inguinal herniorrhaphy when he was 5 years old. Physical examination revealed a healing left inguinal incision and surgically absent left testis. There was no gynecomastia and no lymphadenopathy. A chest roentgenogram, excretory urogram (IVP) and urinary gonadotropin determinations were normal. Pathologic diagnosis was teratocarcinoma with a microfocus of choriocarcinoma. There was no vascular invasion, no local spread, no interstitial cell hyperplasia and no lymphocytic reaction. On May 7, 1963 the patient underwent transperitoneal bilateral lymphadenectomy and all 29 lymph nodes were free of tumor. The patient received no chemotherapy or radiotherapy and had yearly chest roentgenograms and urinary gonadotropin determinations; the results were normal. The patient remained well until March 1972 when he was 26 years old and seen with a 2-day history of acute pain and swelling of the right testis. The right testis was enlarged, diffusely firm, irregular and tender. Urinary gonadotropin, IVP and chest roentgenograms were normal. On March 13 he underwent right inguinal orchiectomy and a right testicular prosthesis was implanted. Pathologic diagnosis was seminoma, with extensive infarction and hemorrhage. There was no vascular invasion, local spread or lymphocytic reaction but there was moderate interstitial cell hyperplasia. Postoperatively, the patient received 3,150 rads
556
BILATERAL TESTICULAR TUMORS OF GERM CELL ORIGIN
557
delivered tumor dose over 19 days to the right iliac carcinoma. The family history is significant in that lymph nodes. He has done well and is able to have his brother (case 4) also had a testis tumor. erections , although he has failure of emission. From January 15 to February 26, 1959 the Case 2. A 20-year-old white man was examined patient received 23 treatments of cobalt 60, with a because of a 3-month history of low back pain and delivered tumor dose of 4,400 rads to the left iliac painless swelling of the left testis. There was no nodes and 4,600 rads delivered dose to the parahistory of trauma, infection or cry ptorchidism. aortic lymph nodes . He was followed every 3 to 4 Physical examination showed a firm non-tender months with regular examinations of the right mass in the left scrotum, which did not transmit testis and did well until August 1961, when on light . There was no gynecomastia nor lymphade- routine examination some irregularity was palnopathy . An IVP and urinary gonadotropin deter- pated in the right testis. There was no lymphminations were normal but there was a small adenopathy or gynecomastia and the right testis nodule seen in the left lower lung field on roent- was hard, non-tender and not enlarged. with thickgenographic examination of the chest. On April 19, ening between the epididymis and testis. On Au1960 left inguinal orchiectomy was performed. gust 25, 1961 right orchiectomy and right inguinal Pathologic diagnosis was embryonal carcinoma and iliac node dissection were done. Pathologic with vascular invasion and extension to the line of diagnosis was teratocarcinoma with vascular inresection of the spermatic cord. vasion, local extension and intersti t ial cell hyperFrom April 29 to June 3 the patient underwent plasia. There were focal a reas of seminoma in situ 25 treatments of cobalt 60 radiotherapy, with 3,600 and focal choriocarcinoma. Two lymph nodes were rads to the left inguinal region at a depth of 4 cm. negative for tumor. He received no further radioand 4,800 rads to the para-aortic lymph nodes. therapy and chemotherapy . The patient was last During this radiation therapy he received his first seen in February 1971, at which time bilateral course of triple drug therapy (10 mg. chlorambucil testicular prostheses were implanted, and roentand 5 mg. methotrexate daily for 10 days and 0.5 genograms of the chest and urinary gonadotropin mg. actinomycin D daily for the middle 5 days) . determinations were normal. This triple drug chemotherapy was continued Case 4. This patient (brother of case 3) was seen every 3 to 6 months until March 1963. All chest at the hospital in July 1955 when he was 21 years old with a 1-year history of painless, gradual enroentgenograms during this time were normal. The patient was lost to followup until March largement of the right testis. There was no history 1968, when he was seen because of a 4-month of trauma, cryptorchidism or infection. A month history of painless swelling of the right testis. He before hospitalization he was rejected from an had been receiving treatment for infertility when ROTC program because of the testicular mass. he first noticed the swelling in November 1967. Physical examination revealed a hard irregula r Physical examination revealed no masses in the testis that was twice normal s ize . There was no left hemiscrotum and the right testis was hard, ly mpha denopathy or gynecomastia. A chest roentimmovable and did not transmit light. An IVP, genogram and IVP were normal. Left inguinal lymphangiograms, chest roentgenograms and uri- orchiectomy was done on July 22. Pathologic nary gonadotropin determinations were normal. diagnosis was teratocarcinoma with interstit ial cell On March 11, 1968 the patient underwent right hyperplasia. Postoperatively the patient received inguinal orchiectomy. Pathologic diagnosis was 34 t reatments of cobalt 60 with a delivered tumor teratocarcinoma . There was necrosis and hemor- dose of 5,000 rads to the para-aortic and right rhage but no vascular invasion , local extension or pelvic lymph nodes . At the time of t his report (16 lymphoid reaction. Interstitial cell hyperplasia and years lat er) he is well. .focal syntrophoblasts were present. For almost 2 DISCUSSION years the patient received 0.5 mg. actinomycin D Bilateral testicular tumors occur in a variety of per day for 5 days every other mont h. At this time there is no evidence of tumor recurrence or metas - recognized clinical settings . Bilateral neoplasms of possible interstitial cell or adrenal origin occur in tases. Case 3. A 19-year-old man not iced a painful cases of adrenogenital syndrome. 2 2 ApptQ~im8-Jely nodule in the left testis a month prior to admission 25 per ce11t of pa tients with malignant lymphoma to the hospital. T here was no history of urinary invoiving the testis have bilateral involvement. 4 tract infections, trauma or cryptorchidism. Physi- Three of7 patients with plasmacytoma of the testis cal examination showed a firm, non-tender mass in had bilateral involvement. 23 Mostofi and Price the left testis. There was no gynecomastia or found bilateral involvement in 4 of 6 clinically lymphadenopathy. A chest roentgenogram was manifest secondary carcinomas, which mimicked normal , and IVP, lymphan giogram and urinary primary testicular neoplasms.' However, the fate gonadotropin determinations were not done. A left and clinical implication of bilateral testicular neoinguinal orchiectomy with high ligation of the plasms of germ cell origin are less well known. In spermatic cord was performed on December 6, the :3 cases of bilateral testis tumors of germ cell 1958 . The patient was referred to this hospital for origin reported herein a variety of histologic patfurther therapy. Pathologic diagnosis was terato- terns was observed (see tah]e). Of the 6 neoplasms
t
558
LEFEVRE AND ASSOCIATES
Reuiew of cases Initial Tumor Case No.
Age (yrs.)
1-17
2-20
Tumor Teratocarcinoma with focal choriocarcinoma Embryonal carcinoma
Second Tumor - - - - - - - - · - - - - - - - - - - - - - - - Survi-
Therapv
Age
(yrs.)
Interval
val Tumor
Therapv
(yrs.)
Bilat. lymph node
26
9
Seminoma
Cobalt 60
dissection Cobalt 60, triple
28
8
Teratocareinoma
Actinomycin D
22
:l
Teratocarcinoma with focal choriocarcinoma and seminoma in situ
None
3-19
Teratocarcinoma
drug Cobalt 60
4-21 (brother of case 3)
Teratocarcinoma
Cobalt 60
4 were teratocarcinoma and 2 contained focal choriocarcinoma. Seminoma and embryonal carcinoma each occurred in 1 testis. Our experience contrasts somewhat with that of Mostofi and Price.• In their series seminoma was present bilaterally in 75 per cent of the cases and in the remainder seminoma occurred in 1 testis and embryonal carcinoma with teratoma occurred in the other. They also round that tumors were simultaneous in about a third of the cases and consecutive in the remainder, with an interval of 3 to 15 years between tumors. In our series 3 patients each had a second neoplasm 3, 8 and 9 years, respectively, after the original orchiectomy. In addition to orchiectomy 1 patient underwent bilateral retroperitoneal lymph node dissection, 2 patients received cobalt 60 therapy and 1 patient received chemotherapy for malignancy. These types of therapy did not prevent the occurrence of a second tumor in any case. The interval between the first and second tumors and the lack of extra-testicular tumor in any of these cases suggest that the second tumors developed de novo. Our 3 cases of bilateral germ cell tumors were found in a review of 166 cases of testicular tumors treated from 1950 to 1970. The rate of bilaterality of 1.8 per cent is within the range reported in other series. 2 - 4 , 24 Although small, this rate is si~ificant when compared to the expected incidence of unilateral testis tumor, which is 2.1 to 2.3 in 100,000 male subjects. 25 A patient who has had 1 testis tumor is far more likely to suffer another than the general population. In addition, the fact that all 3 ofour patients were extremely young (17, 19 and 20 years old) argues further for careful followup. That 1 patient (case 3) was asymptomatic and the testis on physical examination was only subtly irregular further emphasize the need for careful physical examination at regular intervals after orchiectom~, for a germinal cell tumor. There are too few cases for statistical evaluation of genetic predisposition to testicular tumor of germ cell origin. However, this possibility must be considered when in 1 family (cases 3 and 4) bilateral neoplasm developed in 1 brother within 3 years and in a second brother a testicular tumor of
(yrs.)
5
13
16
similar type developed. The cl testicular neoplasms in these brothers were teratocarcinoma. To our knowledge this is the third reported instance of similar testicular neoplasms developing in nontwin brothers. 21 · 25 Prior to this report only twins had had tumors of similar histologic pattern. It is of interest that despite the occurrence of malignant neoplasms of the testis, all patients reported herein have survived. The patients with bilateral neoplasms have survived 1, 5 and 13 years, and the brother with unilateral teratocarcinoma has survived 16 years. At present none of these patients receive therapy. It is also of interest that 2 patients had focal choriocarcinoma in 1 testis, attesting to the fact that focal choriocarcinoma does not have the dire prognosis of pure choriocarcinoma of the testis. REFERENCES 1. Livingstone, ,J .: A case of cancer of both testicles
2.
3.
4.
5. 6.
7.
8. 9.
10.
which terminated favorably by the supervention of surgery. Edinburg Med. Surg. J., l: 163, 1805. Gilbert, J. B. and Hamilton, ,J. B.: Studies in malignant testis tumors; incidence and nature of tumors in ectopic testes. Surg., Gynec. & Obst., 71: 731, 1940. Abeshouse, B. S., Tiongson, A. and Goldfarb, M.: Bilateral tumors of testicles: review of literature and report of case of bilateral simultaneous lymphosarcoma. J. Urol., 74: 522, 1955. Mostofi, F. K. and Price, E. B., Jr.: Tumors of the male genital system. In: Atlas of Tumor Pathology. Washington, D. C.: Armed Forces Institute of Pathology, 2nd series, fasc. 8, 1973. Friedman, N. B. and Moore, R. A.: Tumors of testis; report on 922 cases. Mil. Surg., 99: 573, 1946. Hotchkiss, R. S. and Laury, R. B.: Concomitant bilateral malignant testicular tumors. J. Urol., 63: 1086, 1950. Harper, ,J. G. M., Dewing, S. B. and Nagamatsu, G.: Bilateral carcinoma of the testis: a report of three cases. ,J. Urol., 71: 6:34, 1954. Patton, J. F. and Mallis, N .: Tumors of the testis. ,J. Urol., 81: 457, 1959. Pierson, E. L., Jr.: A case of bilateral tumors of the testicle. With some notes on the effect of castration of the adult male. J. Urol., 28: 353, 1932. Champlin, H. W.: Similar tumors of the testis
BILATERAL TESTICULAR TUMORS OF GERM CELL ORIGI N
11.
12. 13. 14.
15.
16. 17.
occurring m identical twins. J.A.M.A .. 95: 96 , 1930. Wells, H. G.: Cited by Macklin, M. T.: Analysis of tumors in monozygous and dizygous twins , with a report of 15 unpublished cases. J. Hered. , 31: 277 , 1940. Domrich, H .: Ober Leistenhodencarcinom bei Zwillingen. Arch . f. Klin. Chir., 197: 848, 1940. Salm, R. and Adlington, S. R.: Seminoma in identical twins. Brit. Med. J ., 2: 964, 1962. Stewart , J. R. and Bagshaw , M. A.: Malignant testicular tumors appearing simultaneously in identical twins: a case report. Cancer, 18: 895, 1965. Villani , U.: Tumore concordante de! testicolo in una coppia di gemelli monozigoti. Acta Genet. Med., 16: 172, 1967. Raven, R. W.: Tumours of the testis in two brothers. Lancet, 2: 870, 1934. Lownes, J.B. and Leberman , P.: Tumors of the testis in brothers. Urol. & Cutan. Rev., 43: 205 , 1939.
559
18. Willis , R. A.: Pathology of Tumors, 2nd ed. London: Butterworth Inc. , pp. 557- 558, 1953. 19. Hutter, A. M. , Jr. , Lynch, J . J. and Shnider, B. I.: Malignant test icular tumors in brothers: a case report.. J.A.M.A. , 199: 1009, 1967. 20. Myers, G. H. , Jr. and MacPherson, B. R.: Histologically s imila r testicular neoplasms occurring in brothers. J. Urol., 108: 757 , 1972. 21. Young, J. A. a nd Bohne, A. W.: Seminoma in non-twin brothers: a case report. J. Urol., 107: 1000, 1972. 22. Fore, W.W., Bledsoe, T., Weber, D. M. and Brooks, R. T. , Jr.: Cortisol production by testicular tumors in adrenogenital sy ndrome. Arch. Intern. Med. , 130: 59 , 1972. 23. Levin , H. S. and Mosto fi , F . K .: Symptomatic plasmocytoma of the testis. Cancer, 25: 1193, 1970. 24. Gill , R. D. and Howell, R. B.: Primary bilateral testicular tumor. ,J. Urol., 59: 940, 1948. 25. Campbell, M. F. and Ha rrison , J. H .: Urology , 3rd ed. Philadelphia: W. B. Saunders Co., p. 1211 , 1970.
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