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A Case of Simultaneous Bilateral Germ Cell Tumors Arising from Cryptorchid Testes
0022-534 7/86/1362-04 70$02.00/0 THE JOURNAL OF UROLOGY
Vol. 136, August
Copyright© 1986 by The Williams & Wilkins Co.
Printed in U.S.A.
A CASE OF SIMULTANEOUS BILATERAL GERM CELL TUMORS ARISING FROM CRYPTORCHID TESTES MASAMICHI HAYAKAWA,* KIYOSHI MUKAI, KAZUHIKO NAGAKURA AND MAKOTO HATA From the Departments of Urology and Laboratory Medicine, National Defense Medical College, Tokorozawa, Japan
ABSTRACT
We report a rare case of simultaneous bilateral testicular germ cell tumors arising from uncorrected cryptorchid testes. Each side had a different histological type, which consisted of pure high grade seminoma on the left side, and teratocarcinoma with choriocarcinoma and yolk sac tumor elements in addition to seminoma on the right side. Patients with cryptorchidism are known to have a higher risk of germ cell tumors. Genetic factors also may have a role in the oncogenesis in our patient, since his older brother had had a seminoma in the left cryptorchid testis previously. Both patients had the HLA-Aw24 antigen. The characteristics of familial testicular tumors are discussed. It is well known that cryptorchidism is an important etiological factor of testicular geTm cell tumors. We report a case of bilateral germ cell tumors recognized synchronously in uncorrected cryptorchid testes. Family history was significant in that the older brother also suffered from seminoma in an uncorrected cryptorchid testis. CASE REPORT
A 47-year-old man was hospitalized because of painless masses in both groins 6 months in duration (fig. 1). The left mass measured 5.5 x 4.5 cm. and the right mass measured 9.5 x 6.0 cm. Both masses had a smooth surface without adhesion to the adjacent structures. A third mass, with an irregular surface and 10 cm. wide, was found in the right hypochondral region. Laboratory data included serum lactic dehydrogenase 1,455 units per 1. (normal 57 to 458 units per 1.), human chorionic gonadotropin 2,000 mlU/ml. (normal < 5 mIU/ml.) and afetoprotein 8,270 ng./ml. (normal < 20 ng./ml.). Clinical diagnosis was bilateral testicular tumors arising from cryptorchid testes, and bilateral orchiectomy was performed. Pathological examination revealed that the left tumor had the general architecture of a seminoma with a significantly increased number of mitoses (fig. 2). Therefore, diagnosis was anaplastic seminoma. The right testicular tumor also had areas of anaplastic seminoma as well as components of teratoma, embryonal carcinoma, choriocarcinoma and yolk sac tumor (fig. 3). Diagnosis was teratocarcinoma. lmmunocytochemical examination demonstrated human chorionic gonadotropin in the choriocarcinoma area (fig. 4) and a-fetoprotein in the yolk sac component. Postoperatively, the serum lactic dehydrogenase and human chorionic gonadotropin returned to normal but the a-fetoprotein remained high. A computerized tomography (CT) scan and lymphangiography demonstrated extensive retroperitoneal metastasis. Accordingly, the patient received 3 courses of chemotherapy, consisting of 10 mg. vinblastine on day 1, 30 mg. bleomycin on days 1 and 2, and 50 mg. cis-platinum on day 5 for each course. The right upper abdominal mass disappeared completely after the chemotherapy and serum a-fetoprotein returned to normal. The patient's older brother had undergone left orchiectomy for seminoma arising from the left uncorrected cryptorchid testis in 1967 when he was 46 years old. Retroperitoneal metastasis was treated b,Y postoperative radiation therapy. The Accepted for publication January 15, 1986. * Current address: Department of Urology, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, Japan.
result of HLA antigen typing from both brothers is shown in table 1. Both men had the HLA-Aw24 antigen. DISCUSSION
The etiology of testicular germ cell tumors is not certain and several factors have been proposed, including genetic factors, cryptorchidism, testicular dysgenesis and so forth. To infer the significance of a genetic factor in the etiology of testicular tumors it seemed worthwhile to collect and to examine a number of these tumors occurring in closely related family members. In 1984 Mills and associates reviewed the familial pattern of testicular cancer and concluded that the frequency of concordance of cell types of the tumor among family members was highest in monozygotic twin brothers compared to nontwin brothers and father-son pairs. 1 In addition to their reviewed cases we collected 13 reports of families, 2-s including our cases as intrafamilial testicular cancer in nontwin brothers, a monozygotic twin9 and a father-son pair. 10 The characteristics of testicular tumors occurring in a family are analyzed in table 2. Among the nontwin brothers there were 3 families consisting of 3 patients in 1 family and 4 brothers in 2. However, the tumors in the latter 2 families were not examined microscopically and, therefore, these cases were excluded from our study. Concordance of the histological pattern between pairs was
FIG. 1. Bilateral painless masses with smooth surface in both groins 470
BILATERAL GERlVI CELL ~Ul'vH)RS .?RO:tv! CR,YPT(#R.CI-ilD TESTES
noted most 1n tv1ins Ou:r results also indicated that same type of tumor was found more frequently in twins than in nontwin brothers and father-son pairs. regard to the histological pattern of cancer occurring else-where in the body, Macklin raised a that tumors of the same type and location were more frequent in monozygotic twins than in other familial relations. 11 The histological patterns were verified in 8 twin families (16 members), 28 nontwin families (59 members) and 7 father-son pairs (14 members) (table 2). Among the cases with multihistological patterns seminoma plus embryonal carcinoma was
In
FIG. 2. Left testicular tumor with features of seminoma. High powe1· view demonstrates many mitoses. Reduced from X450.
471
Serr_iJ.nom.a or ca:rcinoma vvas type in the intrafamilial testic-
ca,ov,,w;,o,,m
ular tumors. Anderson and associates collected 3 cases of cryptorchidism in 8 sets of twins with testis cancer, and postulated that some factors might be involved in the association of twinning, cryptorchidism and testis cancer. 3 Welvaart and Tijssen estimated that the incidence of cryptorchid testes in relation to testicular cancer was between 3.6 and 11.6 per cent. 12 The morbidity rate of cryptorchidism and cancer in twins is much higher (37.5 per cent) compared to the rates in nontwins (15.3 per cent) and father-son pairs (14.3 per cent) (table Because there seems to be some relevance between cryptorchid testes and familial testicular cancer, especially in twins, the finding of cryptorchidism in twin brothers has significant implication for early testicular cancer detection. All such male members should be taught self-examination of the testis. Our own patient suffered from testicle cancer simultaneously occurring with bilateral cryptorchidism. In 7 patients (7.9 per cent) bilateral testicular malignancies were found in all family members, 5 of whom had bilateral seminoma. To the contrary, only 1 to 2 per cent of testicular cancer is bilateral among nonfamilial testicular tumor patients. 13, 14 Genetic factors also have an interesting aspect in our case. The patient's older brother had suffered from serninoma, and both men had the HLA-Aw24 antigen. Can and Bach reported that this antigen was found more frequently in n,i·r.110-rffo with advanced testicular tun,ors than in those with ,v,,crn,,:,cu tumors.15 Vv obbes and associates described 2 nontwin brothers with Aw24 antigen who suffered from advanced nonseminomatous tumors. 4 A phenotype is knovvn to be decided its corresponding gene. Presently, it remains uncertain whether HLA-Aw24 antigen may be responsible for or related to the
Fm. S. A, right testicular tumor with area of teratoma and glandular structure. B, right testicular tumor with area of embryonal carcinoma and p,imitive glands. Reduced from X200.
FIG. 4. Right testicular tumor. A, area of choriocarcinoma. B, same area stained for human chorionic gonadotropin shows positive trophoblastic cells (dark staining). Reduced from X450.
472
HAYAKAWA AND ASSOCIATES TABLE
Pt. Brother
1. HLA antigen typing in both brothers
REFERENCES
1. Mills, P. K., Newell, G. R. and Johnson, D. E.: Familial patterns of testicular cancer. Urology, 24: 1, 1984. 2. Kulkarni, R., Netzloff, M. L. and Texera, C.: Familial cryptorchid-
Age
ABO and Rh
A
B
C
DR
47 62
AB+ A+
2,24 2,24
35,48 7, 35
3,3,-
2, 6MT-1, 2, 4 1, 2MT-1
HLA Antigens
3. TABLE 2.
Familial pattern of testicular germ cell tumor Twins
Nontwins
(%)
(%)
6 (75)
18 (51.4)
2 (28.6)
6.
2 0
16 1
4 1
7.
6 7 0 1 3 0
28 7 2 2 22 1
9 1 2 1 3 1
8.
Pos. (%) 6 9 1 16
9. 10.
Cryptorchidism and bilateral tumors
Cryptorchidism (No. pts.)
Twins Nontwins Father-son pairs Total No.(%)
(37.5) (15.3) (14.3) (19.5)
4.
5.
Histological similarity of tumor in family: Concordance in histological pattern (No. pairs) Discordance Unknown Histological patterns (No. diseased testes): Seminoma Embryonal Ca Chorioca. Teratoma > 1 Histological pattern Unknown TABLE 3.
Father-Son Pairs(%)
Neg.
Unknown
10
0 7 0
43 6
11.
Bilat. Tumors Pos. 1 3 3
Neg.
Unknown
12.
15 55
0 1 1
13.
10
7 (7.9)
advance of testicular tumor. The large number of well studied similar cases will elucidate the possibility of the relevance between HLA antigens and the development of the testicular tumor.
14. 15.
ism and testicular tumors in non-twin brothers. Ann. Clin. Lab. Sci., 13: 327, 1983. Anderson, K. C., Li, F. P. and Marchettc;>, D. J.: Dizygotic twinning, cryptorchism, and seminoma in a sibship. Cancer, 53: 374, 1984. Wobbes, T., Hoekstra, H.J., Sleyfer, D. T. H. and Koops, H. S.: Tumors of the testis in two brothers: a case report. J. Surg. Oncol., 17: 135, 1981. Finan, P. J.: Malignant testicular tumours in non-twin brothers. Postgrad. Med. J., 57: 469, 1981. Gawande, A. S.: Histologically similar testicular neoplasms occurring in brothers. J. Urol., 123: 963, 1980. Abratt, R. P.: Testicular cancer in two brothers, one of whom has achondroplasia. Brit. J. Urol., 54: 427, 1982. Lefevre, R. E., Levin, H. S., Banowsky, L. H., Straffon, R. A., Stewart, B. H. and Hewitt, C. B.: Bilateral testicular tumors of germ cell origin. J. Urol., 114: 556, 1975. Wilbur, H.J., Woodruff, M. W. and Welch, M. S.: Concomitant germ cell tumors in monozygotic twins. J. Urol., 121: 538, 1979. Vaccari, E.: Testicular seminoma in father and son. Case report of testicular malignancies occurring in closely related family members. Andrologia, 11: 250, 1979. Macklin, M. T.: An analysis of tumors in monozygous and dizygous twins, with a report of 15 unpublished cases. J. Hered., 31: 277, 1940. Welvaart, K. and Tijssen, J. G. P.: Management of the undescended testis in relation to the development of cancer. J. Surg. Oncol., 17: 219, 1981. Hamilton, J. B. and Gilbert, J.B.: Studies in malignant tumors of the testis; bilateral testicular cancer. Incidence, nature, and bearing upon management of the patient with a single testicular cancer. Cancer Res., 2: 125, 1942. Bach, D. W., Weissbach, L. and Hartlapp, J. H.: Bilateral testicular tumor. J. Urol., 129: 989, 1983. Carr, B. I. and Bach, F. A.: Possible association between HLAAW24 and metastatic testicular germ-cell tumours. Lancet, 1: 1346, 1979.
Vol. 136, August
Copyright© 1986 by The Williams & Wilkins Co.
Printed in U.S.A.
A CASE OF SIMULTANEOUS BILATERAL GERM CELL TUMORS ARISING FROM CRYPTORCHID TESTES MASAMICHI HAYAKAWA,* KIYOSHI MUKAI, KAZUHIKO NAGAKURA AND MAKOTO HATA From the Departments of Urology and Laboratory Medicine, National Defense Medical College, Tokorozawa, Japan
ABSTRACT
We report a rare case of simultaneous bilateral testicular germ cell tumors arising from uncorrected cryptorchid testes. Each side had a different histological type, which consisted of pure high grade seminoma on the left side, and teratocarcinoma with choriocarcinoma and yolk sac tumor elements in addition to seminoma on the right side. Patients with cryptorchidism are known to have a higher risk of germ cell tumors. Genetic factors also may have a role in the oncogenesis in our patient, since his older brother had had a seminoma in the left cryptorchid testis previously. Both patients had the HLA-Aw24 antigen. The characteristics of familial testicular tumors are discussed. It is well known that cryptorchidism is an important etiological factor of testicular geTm cell tumors. We report a case of bilateral germ cell tumors recognized synchronously in uncorrected cryptorchid testes. Family history was significant in that the older brother also suffered from seminoma in an uncorrected cryptorchid testis. CASE REPORT
A 47-year-old man was hospitalized because of painless masses in both groins 6 months in duration (fig. 1). The left mass measured 5.5 x 4.5 cm. and the right mass measured 9.5 x 6.0 cm. Both masses had a smooth surface without adhesion to the adjacent structures. A third mass, with an irregular surface and 10 cm. wide, was found in the right hypochondral region. Laboratory data included serum lactic dehydrogenase 1,455 units per 1. (normal 57 to 458 units per 1.), human chorionic gonadotropin 2,000 mlU/ml. (normal < 5 mIU/ml.) and afetoprotein 8,270 ng./ml. (normal < 20 ng./ml.). Clinical diagnosis was bilateral testicular tumors arising from cryptorchid testes, and bilateral orchiectomy was performed. Pathological examination revealed that the left tumor had the general architecture of a seminoma with a significantly increased number of mitoses (fig. 2). Therefore, diagnosis was anaplastic seminoma. The right testicular tumor also had areas of anaplastic seminoma as well as components of teratoma, embryonal carcinoma, choriocarcinoma and yolk sac tumor (fig. 3). Diagnosis was teratocarcinoma. lmmunocytochemical examination demonstrated human chorionic gonadotropin in the choriocarcinoma area (fig. 4) and a-fetoprotein in the yolk sac component. Postoperatively, the serum lactic dehydrogenase and human chorionic gonadotropin returned to normal but the a-fetoprotein remained high. A computerized tomography (CT) scan and lymphangiography demonstrated extensive retroperitoneal metastasis. Accordingly, the patient received 3 courses of chemotherapy, consisting of 10 mg. vinblastine on day 1, 30 mg. bleomycin on days 1 and 2, and 50 mg. cis-platinum on day 5 for each course. The right upper abdominal mass disappeared completely after the chemotherapy and serum a-fetoprotein returned to normal. The patient's older brother had undergone left orchiectomy for seminoma arising from the left uncorrected cryptorchid testis in 1967 when he was 46 years old. Retroperitoneal metastasis was treated b,Y postoperative radiation therapy. The Accepted for publication January 15, 1986. * Current address: Department of Urology, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, Japan.
result of HLA antigen typing from both brothers is shown in table 1. Both men had the HLA-Aw24 antigen. DISCUSSION
The etiology of testicular germ cell tumors is not certain and several factors have been proposed, including genetic factors, cryptorchidism, testicular dysgenesis and so forth. To infer the significance of a genetic factor in the etiology of testicular tumors it seemed worthwhile to collect and to examine a number of these tumors occurring in closely related family members. In 1984 Mills and associates reviewed the familial pattern of testicular cancer and concluded that the frequency of concordance of cell types of the tumor among family members was highest in monozygotic twin brothers compared to nontwin brothers and father-son pairs. 1 In addition to their reviewed cases we collected 13 reports of families, 2-s including our cases as intrafamilial testicular cancer in nontwin brothers, a monozygotic twin9 and a father-son pair. 10 The characteristics of testicular tumors occurring in a family are analyzed in table 2. Among the nontwin brothers there were 3 families consisting of 3 patients in 1 family and 4 brothers in 2. However, the tumors in the latter 2 families were not examined microscopically and, therefore, these cases were excluded from our study. Concordance of the histological pattern between pairs was
FIG. 1. Bilateral painless masses with smooth surface in both groins 470
BILATERAL GERlVI CELL ~Ul'vH)RS .?RO:tv! CR,YPT(#R.CI-ilD TESTES
noted most 1n tv1ins Ou:r results also indicated that same type of tumor was found more frequently in twins than in nontwin brothers and father-son pairs. regard to the histological pattern of cancer occurring else-where in the body, Macklin raised a that tumors of the same type and location were more frequent in monozygotic twins than in other familial relations. 11 The histological patterns were verified in 8 twin families (16 members), 28 nontwin families (59 members) and 7 father-son pairs (14 members) (table 2). Among the cases with multihistological patterns seminoma plus embryonal carcinoma was
In
FIG. 2. Left testicular tumor with features of seminoma. High powe1· view demonstrates many mitoses. Reduced from X450.
471
Serr_iJ.nom.a or ca:rcinoma vvas type in the intrafamilial testic-
ca,ov,,w;,o,,m
ular tumors. Anderson and associates collected 3 cases of cryptorchidism in 8 sets of twins with testis cancer, and postulated that some factors might be involved in the association of twinning, cryptorchidism and testis cancer. 3 Welvaart and Tijssen estimated that the incidence of cryptorchid testes in relation to testicular cancer was between 3.6 and 11.6 per cent. 12 The morbidity rate of cryptorchidism and cancer in twins is much higher (37.5 per cent) compared to the rates in nontwins (15.3 per cent) and father-son pairs (14.3 per cent) (table Because there seems to be some relevance between cryptorchid testes and familial testicular cancer, especially in twins, the finding of cryptorchidism in twin brothers has significant implication for early testicular cancer detection. All such male members should be taught self-examination of the testis. Our own patient suffered from testicle cancer simultaneously occurring with bilateral cryptorchidism. In 7 patients (7.9 per cent) bilateral testicular malignancies were found in all family members, 5 of whom had bilateral seminoma. To the contrary, only 1 to 2 per cent of testicular cancer is bilateral among nonfamilial testicular tumor patients. 13, 14 Genetic factors also have an interesting aspect in our case. The patient's older brother had suffered from serninoma, and both men had the HLA-Aw24 antigen. Can and Bach reported that this antigen was found more frequently in n,i·r.110-rffo with advanced testicular tun,ors than in those with ,v,,crn,,:,cu tumors.15 Vv obbes and associates described 2 nontwin brothers with Aw24 antigen who suffered from advanced nonseminomatous tumors. 4 A phenotype is knovvn to be decided its corresponding gene. Presently, it remains uncertain whether HLA-Aw24 antigen may be responsible for or related to the
Fm. S. A, right testicular tumor with area of teratoma and glandular structure. B, right testicular tumor with area of embryonal carcinoma and p,imitive glands. Reduced from X200.
FIG. 4. Right testicular tumor. A, area of choriocarcinoma. B, same area stained for human chorionic gonadotropin shows positive trophoblastic cells (dark staining). Reduced from X450.
472
HAYAKAWA AND ASSOCIATES TABLE
Pt. Brother
1. HLA antigen typing in both brothers
REFERENCES
1. Mills, P. K., Newell, G. R. and Johnson, D. E.: Familial patterns of testicular cancer. Urology, 24: 1, 1984. 2. Kulkarni, R., Netzloff, M. L. and Texera, C.: Familial cryptorchid-
Age
ABO and Rh
A
B
C
DR
47 62
AB+ A+
2,24 2,24
35,48 7, 35
3,3,-
2, 6MT-1, 2, 4 1, 2MT-1
HLA Antigens
3. TABLE 2.
Familial pattern of testicular germ cell tumor Twins
Nontwins
(%)
(%)
6 (75)
18 (51.4)
2 (28.6)
6.
2 0
16 1
4 1
7.
6 7 0 1 3 0
28 7 2 2 22 1
9 1 2 1 3 1
8.
Pos. (%) 6 9 1 16
9. 10.
Cryptorchidism and bilateral tumors
Cryptorchidism (No. pts.)
Twins Nontwins Father-son pairs Total No.(%)
(37.5) (15.3) (14.3) (19.5)
4.
5.
Histological similarity of tumor in family: Concordance in histological pattern (No. pairs) Discordance Unknown Histological patterns (No. diseased testes): Seminoma Embryonal Ca Chorioca. Teratoma > 1 Histological pattern Unknown TABLE 3.
Father-Son Pairs(%)
Neg.
Unknown
10
0 7 0
43 6
11.
Bilat. Tumors Pos. 1 3 3
Neg.
Unknown
12.
15 55
0 1 1
13.
10
7 (7.9)
advance of testicular tumor. The large number of well studied similar cases will elucidate the possibility of the relevance between HLA antigens and the development of the testicular tumor.
14. 15.
ism and testicular tumors in non-twin brothers. Ann. Clin. Lab. Sci., 13: 327, 1983. Anderson, K. C., Li, F. P. and Marchettc;>, D. J.: Dizygotic twinning, cryptorchism, and seminoma in a sibship. Cancer, 53: 374, 1984. Wobbes, T., Hoekstra, H.J., Sleyfer, D. T. H. and Koops, H. S.: Tumors of the testis in two brothers: a case report. J. Surg. Oncol., 17: 135, 1981. Finan, P. J.: Malignant testicular tumours in non-twin brothers. Postgrad. Med. J., 57: 469, 1981. Gawande, A. S.: Histologically similar testicular neoplasms occurring in brothers. J. Urol., 123: 963, 1980. Abratt, R. P.: Testicular cancer in two brothers, one of whom has achondroplasia. Brit. J. Urol., 54: 427, 1982. Lefevre, R. E., Levin, H. S., Banowsky, L. H., Straffon, R. A., Stewart, B. H. and Hewitt, C. B.: Bilateral testicular tumors of germ cell origin. J. Urol., 114: 556, 1975. Wilbur, H.J., Woodruff, M. W. and Welch, M. S.: Concomitant germ cell tumors in monozygotic twins. J. Urol., 121: 538, 1979. Vaccari, E.: Testicular seminoma in father and son. Case report of testicular malignancies occurring in closely related family members. Andrologia, 11: 250, 1979. Macklin, M. T.: An analysis of tumors in monozygous and dizygous twins, with a report of 15 unpublished cases. J. Hered., 31: 277, 1940. Welvaart, K. and Tijssen, J. G. P.: Management of the undescended testis in relation to the development of cancer. J. Surg. Oncol., 17: 219, 1981. Hamilton, J. B. and Gilbert, J.B.: Studies in malignant tumors of the testis; bilateral testicular cancer. Incidence, nature, and bearing upon management of the patient with a single testicular cancer. Cancer Res., 2: 125, 1942. Bach, D. W., Weissbach, L. and Hartlapp, J. H.: Bilateral testicular tumor. J. Urol., 129: 989, 1983. Carr, B. I. and Bach, F. A.: Possible association between HLAAW24 and metastatic testicular germ-cell tumours. Lancet, 1: 1346, 1979.