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Unbalanced Chromosomal Translocation Associated with Sertoli-Cell-Only Histology
0022-534 7/Sl/1453-0563$03.GO /0 THE JOURNAL OF UROLOGY
Voi. 145, 563-564, March 1991
Copyright© 1991 by AMERICAN UROLOG1CAL ASSOCIAT!ON INC.
Printed in U.S.A.
1
UNBALANCED CHROMOSOMAL TRANSLOCATION ASSOCIATED WITH SERTOLI-CELL-ONLY HISTOLOGY CHARLES E. SHAPIRO From the Department of Surgery/Urology, University of Southern California and Southern California Permanente Medical Group, Los Angeles, California
ABSTRACT
A case is reported of unbalanced chromosomal translocation resulting in loss of the long arm of the Y chromosome and Sertoli-cell-only histology. KEY WORDS:
chromosome abnormalities, infertility, Sertoli cells
The Sertoli-cell-only syndrome is a relatively uncommon cause of male infertility. A case is reported of unbalanced chromosomal translocation resulting in loss of the long arm (q) of the Y chromosome giving rise to this histological diagnosis. CASE REPORT
A 39-year-old man was evaluated for primary infertility. Medical history was remarkable for bilateral gynecomastia for which surgery was performed 10 years previously. Urological history was unremarkable. Physical examination revealed a normal-appearing man with small, irregular testes and a left varicocele. Laboratory evaluation included normal values for luteinizing hormone, testosterone and estradiol but elevated (2.5 times normal) folliclestimulating hormone. Semen analysis confirmed azoospermia but fructose was positive. Testicular ultrasound identified a calcification within the left testis. Peripheral blood karyotype (GTG and QFQ banding) revealed 46,X,-Yq,t(5;Y)(Yp5q;5p: ), that is an unbalanced translocation between the 5 and the Y chromosomes resulting in loss of the long arm (q) of the Y, a free short arm (p) of the 5 and attachment of the short arm (p) of the Y to the long arm (q) of the 5 (figs. 1 and 2). Bilateral testicular exploration revealed multiple, bilateral, adenomatoid tumors of the tunica vaginalis and a calcified left testicular nodule with heterotopic bone formation. Testis parenchymal biopsies showed Sertoli-cell-only histology. The karyotypes of living relatives (mother, 2 full brothers and 2 halfmaternal brothers) were normal, suggesting that this case represents a spontaneous mutation. DISCUSSION
found on the long arm (q). Proved as well as postulated translocations between the X and Y chromosomes and between the Y and an autosome have been reported. 6 •9 •10•13 The clinical appearance has varied from phenotypic female subjects with recurrent abortions 14 and gonadal tumors 15 to phenotypically normal male subjects with small testes and karyotypes of 46XX. 6 .1° Our patient was a phenotypically normal male subject except for small testes. It is our practice to obtain a karyotype on those patients presenting with primary infertility and azoospermia. Ordinarily testis biopsy would not have been done in view of the markedly elevated follicle-stimulating hormone. However, testis exploration and biopsy were necessary in this case because of the
FIG. L Peripheral blood karyotype
Primary testicular failure represents less than 10% of the etiologies of male infertility. 1 Within this category is the syndrome known as germinal cell aplasia or the Sertoli-cell-only syndrome. The histological appearance of this condition is well known but nonspecific, consisting of seminiferous tubules lined by Sertoli cells alone and devoid of germinal elements. 2 The etiology of the absence of germ cells may include congenital absence, and acquired absence from radiation or toxin exposure, mumps and cryptorchidism. 3 The Sertoli-cell-only syndrome has been reported in a number of chromosomal abnormalities, including 45X, 4 48XYYY 5 and 46XX male subjects. 6 The genetic content of the Y chromosome is being slowly elucidated and has been described elsewhere. 7- 10 Basically, the testis determining region is located on the short arm (p) of the Y chromosome, although the exact position of the gene and its mechanism of action have yet to be determined. 6 •11 •12 The spermatogenesis determining region is Accepted for publication August 31, 1990. Read at annual meeting of New York Section, American Urological Association, Amsterdam, The Netherlands, September 24-0ctober 1, 1988.
FIG. 2. Translocation 46,X,-Yq,t(5;Y)(Yp5q;5p:) 563
564
SHAPIRO
abnormalities on physical examination. In all likelihood, most patients with Sertoli-cell-only histology do not undergo biopsy because of the markedly elevated levels of follicle-stimulating hormone. This case is noteworthy given the variety of physical and operative findings in the face of a well defined chromosomal abnormality, and it tends to support several theories: the testis determining region is located on the short arm (p) of the Y chromosome; the spermatogenesis determining region is located on the long arm (q) of the Y chromosome and a chromosomal defect may be 1 etiology of the Sertoli-cell-only syndrome.
7. 8. 9. 10. 11.
REFERENCES
1. Greenberg, S. H., Lipshultz, L. I. and Wein, A. J.: Experience with 425 subfertile male patients. J. Urol., 119: 507, 1978. 2. McClure, R. D.: Endocrine investigation and therapy. Urol. Clin. N. Amer., 14: 471, 1987. 3. De Kretser, D. M., Burger, H. G., Fortune, D., Hudson, B., Long, A. R., Paulsen, C. A. and Taft, H.P.: Hormonal, histological and chromosomal studies in adult males with testicular disorders. J. Clin. Endocr. Metab., 35: 392, 1972. 4. Sakai, Y., Ogawa, A. and Ehara, T.: An infertile man with a 45X karyotype. J. Urol., 139: 1316, 1988. 5. Hori, N., Kato, T., Sugimura, Y., Tajima, K., Tochigi, H. and Kawamura, J.: A male subject with 3 Y chromosomes (48, XYYY): a case report. J. Urol., 139: 1059, 1988. 6. Palmer, M. S., Sinclair, A.H., Berta, P., Ellis, N. A., Goodfellow,
12.
13. 14. 15.
P. N., Abbas, N. E. and Fellous, M.: Genetic evidence that ZFY is not the testis-determining factor. Nature, 342: 937, 1989. Goodfellow, P., Darling, S. and Wolfe, J.: The human Y chromosome. J. Med. Genet., 22: 329, 1985. Page, D.: Zeroing in on the sex switch. Science, 239: 21, 1988. Tiepolo, L. and Zuffardi, 0.: Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm. Hum. Genet., 34: 119, 1976. Kolata, G.: Maleness pinpointed on Y chromosome. Science, 234: 1076, 1986. Koopman, P., Gubbay, J., Collignon, J. and Lovell-Badge, R.: ZY gene expression patterns are not compatible with a primary role in mouse sex determination. Nature, 342: 940, 1989. Sutcliffe, M. J. and Burgoyne, P. S.: Analysis of the testes of H- Y negative XOSxrh mice suggests that the spermatogenesis gene (Spy) acts during the differentiation of the A spermatogonia. Development, 107: 373, 1989. Davis, R. M.: Localisation of male determining factors in man: a thorough review of structural anomalies of the Y chromosome. J. Med. Genet., 18: 161, 1981. Khudr, G., Benirschke, K., Judd, H. L. and Strauss, J.: Y to X translocation in a woman with reproductive failure. A new rearrangement. J.A.M.A., 226: 544, 1973. Park, I. J., Heller, R. H., Jones, H. W., Jr. and Woodruff, J. D.: Apparent pseudopuberty in a phenotypic female with a gonadal tumor and an autosome-Y chromosome translocation. Amer. J. Obst. Gynec., 119: 661, 1974.
Voi. 145, 563-564, March 1991
Copyright© 1991 by AMERICAN UROLOG1CAL ASSOCIAT!ON INC.
Printed in U.S.A.
1
UNBALANCED CHROMOSOMAL TRANSLOCATION ASSOCIATED WITH SERTOLI-CELL-ONLY HISTOLOGY CHARLES E. SHAPIRO From the Department of Surgery/Urology, University of Southern California and Southern California Permanente Medical Group, Los Angeles, California
ABSTRACT
A case is reported of unbalanced chromosomal translocation resulting in loss of the long arm of the Y chromosome and Sertoli-cell-only histology. KEY WORDS:
chromosome abnormalities, infertility, Sertoli cells
The Sertoli-cell-only syndrome is a relatively uncommon cause of male infertility. A case is reported of unbalanced chromosomal translocation resulting in loss of the long arm (q) of the Y chromosome giving rise to this histological diagnosis. CASE REPORT
A 39-year-old man was evaluated for primary infertility. Medical history was remarkable for bilateral gynecomastia for which surgery was performed 10 years previously. Urological history was unremarkable. Physical examination revealed a normal-appearing man with small, irregular testes and a left varicocele. Laboratory evaluation included normal values for luteinizing hormone, testosterone and estradiol but elevated (2.5 times normal) folliclestimulating hormone. Semen analysis confirmed azoospermia but fructose was positive. Testicular ultrasound identified a calcification within the left testis. Peripheral blood karyotype (GTG and QFQ banding) revealed 46,X,-Yq,t(5;Y)(Yp5q;5p: ), that is an unbalanced translocation between the 5 and the Y chromosomes resulting in loss of the long arm (q) of the Y, a free short arm (p) of the 5 and attachment of the short arm (p) of the Y to the long arm (q) of the 5 (figs. 1 and 2). Bilateral testicular exploration revealed multiple, bilateral, adenomatoid tumors of the tunica vaginalis and a calcified left testicular nodule with heterotopic bone formation. Testis parenchymal biopsies showed Sertoli-cell-only histology. The karyotypes of living relatives (mother, 2 full brothers and 2 halfmaternal brothers) were normal, suggesting that this case represents a spontaneous mutation. DISCUSSION
found on the long arm (q). Proved as well as postulated translocations between the X and Y chromosomes and between the Y and an autosome have been reported. 6 •9 •10•13 The clinical appearance has varied from phenotypic female subjects with recurrent abortions 14 and gonadal tumors 15 to phenotypically normal male subjects with small testes and karyotypes of 46XX. 6 .1° Our patient was a phenotypically normal male subject except for small testes. It is our practice to obtain a karyotype on those patients presenting with primary infertility and azoospermia. Ordinarily testis biopsy would not have been done in view of the markedly elevated follicle-stimulating hormone. However, testis exploration and biopsy were necessary in this case because of the
FIG. L Peripheral blood karyotype
Primary testicular failure represents less than 10% of the etiologies of male infertility. 1 Within this category is the syndrome known as germinal cell aplasia or the Sertoli-cell-only syndrome. The histological appearance of this condition is well known but nonspecific, consisting of seminiferous tubules lined by Sertoli cells alone and devoid of germinal elements. 2 The etiology of the absence of germ cells may include congenital absence, and acquired absence from radiation or toxin exposure, mumps and cryptorchidism. 3 The Sertoli-cell-only syndrome has been reported in a number of chromosomal abnormalities, including 45X, 4 48XYYY 5 and 46XX male subjects. 6 The genetic content of the Y chromosome is being slowly elucidated and has been described elsewhere. 7- 10 Basically, the testis determining region is located on the short arm (p) of the Y chromosome, although the exact position of the gene and its mechanism of action have yet to be determined. 6 •11 •12 The spermatogenesis determining region is Accepted for publication August 31, 1990. Read at annual meeting of New York Section, American Urological Association, Amsterdam, The Netherlands, September 24-0ctober 1, 1988.
FIG. 2. Translocation 46,X,-Yq,t(5;Y)(Yp5q;5p:) 563
564
SHAPIRO
abnormalities on physical examination. In all likelihood, most patients with Sertoli-cell-only histology do not undergo biopsy because of the markedly elevated levels of follicle-stimulating hormone. This case is noteworthy given the variety of physical and operative findings in the face of a well defined chromosomal abnormality, and it tends to support several theories: the testis determining region is located on the short arm (p) of the Y chromosome; the spermatogenesis determining region is located on the long arm (q) of the Y chromosome and a chromosomal defect may be 1 etiology of the Sertoli-cell-only syndrome.
7. 8. 9. 10. 11.
REFERENCES
1. Greenberg, S. H., Lipshultz, L. I. and Wein, A. J.: Experience with 425 subfertile male patients. J. Urol., 119: 507, 1978. 2. McClure, R. D.: Endocrine investigation and therapy. Urol. Clin. N. Amer., 14: 471, 1987. 3. De Kretser, D. M., Burger, H. G., Fortune, D., Hudson, B., Long, A. R., Paulsen, C. A. and Taft, H.P.: Hormonal, histological and chromosomal studies in adult males with testicular disorders. J. Clin. Endocr. Metab., 35: 392, 1972. 4. Sakai, Y., Ogawa, A. and Ehara, T.: An infertile man with a 45X karyotype. J. Urol., 139: 1316, 1988. 5. Hori, N., Kato, T., Sugimura, Y., Tajima, K., Tochigi, H. and Kawamura, J.: A male subject with 3 Y chromosomes (48, XYYY): a case report. J. Urol., 139: 1059, 1988. 6. Palmer, M. S., Sinclair, A.H., Berta, P., Ellis, N. A., Goodfellow,
12.
13. 14. 15.
P. N., Abbas, N. E. and Fellous, M.: Genetic evidence that ZFY is not the testis-determining factor. Nature, 342: 937, 1989. Goodfellow, P., Darling, S. and Wolfe, J.: The human Y chromosome. J. Med. Genet., 22: 329, 1985. Page, D.: Zeroing in on the sex switch. Science, 239: 21, 1988. Tiepolo, L. and Zuffardi, 0.: Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm. Hum. Genet., 34: 119, 1976. Kolata, G.: Maleness pinpointed on Y chromosome. Science, 234: 1076, 1986. Koopman, P., Gubbay, J., Collignon, J. and Lovell-Badge, R.: ZY gene expression patterns are not compatible with a primary role in mouse sex determination. Nature, 342: 940, 1989. Sutcliffe, M. J. and Burgoyne, P. S.: Analysis of the testes of H- Y negative XOSxrh mice suggests that the spermatogenesis gene (Spy) acts during the differentiation of the A spermatogonia. Development, 107: 373, 1989. Davis, R. M.: Localisation of male determining factors in man: a thorough review of structural anomalies of the Y chromosome. J. Med. Genet., 18: 161, 1981. Khudr, G., Benirschke, K., Judd, H. L. and Strauss, J.: Y to X translocation in a woman with reproductive failure. A new rearrangement. J.A.M.A., 226: 544, 1973. Park, I. J., Heller, R. H., Jones, H. W., Jr. and Woodruff, J. D.: Apparent pseudopuberty in a phenotypic female with a gonadal tumor and an autosome-Y chromosome translocation. Amer. J. Obst. Gynec., 119: 661, 1974.