0022-534 7/92/1483-0883$03.00/0 THE JOURNAL OF UROLOGY Copyright© 1992 by AMERICAN UROLOGICAL ASSOCIATION, INC.
Vol. 148, 883-885, September 1992
Printed in U.S.A.
SERTOLI-LEYDIG CELL TESTICULAR TUMOR: CASE REPORT AND REVIEW OF SEX CORD/GONADAL STROMAL TUMOR HISTOGENESIS PAULE. PERITO, GAETANO CIANCIO, FRANCISCO CIVANTOS
AND
V. A. POLITANO
From the Departments of Urology and Pathology, University of Miami School of Medicine and Jackson Memorial Hospital, Miami, Florida
ABSTRACT
We describe a case of well differentiated Sertoli-Leydig cell tumor in a testicle. Previously, this tumor has only been illustrated histologically. The existence of a male homologue to the female arrhenoblastoma containing Sertoli and Leydig cells again supports the current hypothesis of gonadal development, and the common steps found in the male and female pathways. KEY WORDS: testicular neoplasms, Leydig cell tumor, Sertoli cell tumor
Testicular tumors are currently subdivided according to microscopic appearance into germ cell and nongerm cell tumors in the World Health Organization classification. 1 Because testicular tumors are heterogeneous, histological subtypes vary from study to study. Nongerm cell tumors represent only 5 to 10% of all testicular tumors. 2 Sex cord/gonadal stromal tumors are included in this group, most being differentiated toward Leydig or Sertoli cell components. Only 4 to 5% of all testicular tumors in adults are sex cord/gonadal stromal tumors. 3 Little is understood concerning the etiology and pathogenesis of these tumors. Sex cord/gonadal stromal tumors have been discovered in cryptorchid testes but no causal relationship has been found in maldescended testes. 4 • 5 Interestingly, the tumor is common in domestic dogs, laboratory rodents and wild animals but the application of knowledge gained from animal sex cord/gonadal stromal tumors is not yet established. 6 We describe a case of well differentiated Sertoli-Leydig cell tumor in a testicle. Previously, this tumor has only been illustrated histologically. 1 To our knowledge the tumor has never been formally described and discussed. We also discuss its controversial embryonic origin and relationship to the female homologue, previously known as arrhenoblastoma.
CASE REPORT
H. E., a 66-year-old healthy white man, presented with complaints of a full feeling in the left testicle. Physical examination revealed a normal left testicle and spermatic cord, and a 1 X 1 cm. area of barely palpable induration in the posterior aspect of the right testicle. No lymphadenopathy, abdominal masses, signs of virilization or gynecomastia was noted. Bilateral testicular ultrasound revealed simple cysts in the left testicle and a discrete lesion with high density internal structures within the posterior portion of the right testicle, opposite the side of the symptoms. The serum (3-human chorionic gonadotropin level was within the normal adult range (less than 5 mIU/ml.), a-fetoprotein was 9.1 ng./ml. (normal adult less than 15) and testosterone was 414 ng./dl. (normal adult 270 to 1,070). Right scrotal exploration revealed a 1.8 x 1 x 1 cm. ovoid mass within the parenchyma of the testicle. Frozen section of the mass was reported as a testicular tumor. At this point right radical orchiectomy was performed. Postoperatively, abdominal computerized tomography was negative. The patient had no signs of metastases or recurrence at 1 year postoperatively. Pathology data. The specimen was a 5 x 4 x 3 cm. testis containing an ovoid 1.8 x 1 x 1 cm. mass (fig. 1). Cross sections revealed white fibrous tissue between pink soft nodules. There Accepted for publication February 21, 1992. 883
FIG. 1. Well circumscribed nodule, partially resected, shows nodular pattern on cut surface.
was no gross extension into the rete testis or spermatic cord. The tumor was well circumscribed and well demarcated from the adjacent testicular parenchyma. Microscopic findings revealed mature Sertoli and Leydig cell components intermixed with fibrous stroma (fig. 2, A). The Sertoli cell component was the predominant cell population in the tumor (fig. 2, B). In areas the Sertoli cells were focally arranged in solid tubules that resembled immature seminiferous tubules (tubular adenoma pattern). Sparse connective tissue stroma surrounded the tubules. No annular tubules similar to those reported in the Peutz-Jeghers syndrome were noted in the Sertoli cell component. The tubules were narrowed and became a single cell row (trabecular pattern), which was the predominant arrangement. The Leydig cell component was arranged into nests of polygonal acidophilic cells. Pathognomonic Reinke crystals were present (fig. 3). No foci of necrosis, nuclear atypia, vascular or lymphatic invasion were present in the tumor. Mitoses were rare. DISCUSSION
The fetal gonad is derived from 3 sources: 1) coelomic epithelium, 2) mesenchyme and 3) primordial germ cells. 7 Thickening of coelomic epithelium and mesenchyme produces a bulge in the medial side of the mesonephros known as the gonadal ridge. This is the indifferent gonad from which the supportive structures of the testis and ovary arise before germ cell migration into the gonadal ridges. It has been postulated that the supportive cells of the gonadal ridge develop from a common stem cell rather than 2 of the 3
884
PERITO AND ASSOCIATES
Fm. 2. A, Sertoli cells in solid tubules with scanty fibrous stroma in periphery are seen at right side adjacent to capillary with red blood cells. On left side are Leydig cells between dense fibrous bands. Arrow shows crystals of Reinke. Reduced from X20. B, predominant pattern was Sertoli cells in trabecular arrangement with rows of Sertoli cells between scanty fibrous stroma. Reduced from XlO.
Fm. 3. Crystals of Reinke in Leydig cells appear as sharply truncated, slender cylinders that stain with eosin. Reduced from X40.
aforementioned cell populations.8·9 This theory has been supported through studies showing ultrastructural similarities in immature stromal cells found in mixed cell tumors, and epithelial cells of pure Sertoli and pure Leydig cell tumors. 10 Also, in immunohistochemical studies researchers demonstrated testosterone and estradiol in Sertoli, Leydig and less differentiated stromal cells resembling those found in the embryonic gonad.11 The existence of mixed tumors containing well differentiated
and incompletely differentiated components favors the common stem cell hypothesis. Regardless, it is the indifferent gonad from which all cell lines of sex cord/gonadal stromal tumors evolve. Several synonyms have been used to describe tumors arising from the indifferent fetal gonad, including androblastomas, 12 gonadal stromal tumors 8 and Sertoli cell tumors. 13 Broad classification is no longer based on function or predominant histological findings. The name sex cord/gonadal stromal tumors evolved to represent the similar embryological pathways from which each divergent tumor has originated. Sex cord/gonadal stromal tumors of the gonads comprise tumors of Leydig, Sertoli, granulosa and thecal cell origins. In any individual tumor the cell grouping can be mixed, incompletely differentiated and resemble any of the specialized supportive structures of the male and female gonad. Expectantly, cells within the ovary have similar oncogenic potentialities. Homologous ovarian and testicular tumors have been recognized since 1946. Teilum called them androblastomas and described testicular tumors derived from the undifferentiated gonadal mesenchyme. 14 Since then many tumors arising from the gonadal ridge have been identified. The development of these types of tumors illustrates the competency of the testis and ovary to elaborate identical neoplasms. Sertoli-Leydig cell tumors in female patients (arrhenoblastomas) are common among the sex cord tumors. They arise from the same female sex cord stromal cells as granulosa-theca cell tumors and consistently contain female sex chromatin. 15 An identical tumor in the male patient containing mature, pure Sertoli and Leydig cell components has been illustrated previously.1 However, to our knowledge this tumor has never been formally described in the urological literature. Although mixed sex cord/gonadal stromal tumors have been reported, 16-18 the number of cases is small and all of the tumors described had immature cell populations resembling 1 or all of the cell groups (Sertoli, Leydig, granulosa and thecal). The existence of a male homologue to the female arrhenoblastoma containing mature populations of Sertoli and Leydig cells again supports the current hypothesis of gonadal development, and the common steps found in the male and female pathways. Tumors that arise from embryonic sex cords produce the full range of ovarian and testicular steroids. Many tumors secrete steroid hormones that can be detected in serum or urine, especially well differentiated Leydig cell neoplasms. 19 Most Sertoli-Leydig cell tumors in female patients produce androgens and masculinize the patient. 2°Conversely, in male patients with Leydig cell or Sertoli cell tumors the prevalence of feminizing endocrine manifestations is 20 to 40% 21 and 20 to 30%, 22 respectively. In our patient serum hormonal values were normal. Embryological and pathological similarities between SertoliLeydig cell tumors (arrhenoblastoma) and other sex cord/ gonadal stromal tumors may certainly aid in the treatment of our patient. Sertoli-Leydig cell tumors in female patients have metastatic rates of 15 to 20% and tend to grow locally. 16 Metastatic rates for pure Sertoli or pure Leydig cell tumors are similarly 10 to 20% 23 and 10 to 15%, 24 respectively, and both tend to expand locally. Most mixed/undifferentiated sex cord tumors are benign but occasional examples of malignancy have been recorded. 16 Malignant behavior has been loosely associated with mitotic figures and little else in all of the aforementioned tumor types. 23-25 Subsequently, all sex cord/gonadal stromal tumors, including granulosa cell tumors of the testis and granulosa-theca cell tumors of the ovary, have similar treatment recommendations for localized disease. Surgical resection of the tumor is necessary with prolonged followup for distant metastasis. Testicular tumors are rare, yet they have attracted disproportionate amounts of research from clinicians and laboratory scientists alike. The classification of testicular tumors is elab-
""
..
~'
."."
---·,··- --·
SERTOLI·LEYDIG CELL TUMOR
orate and ever changing. the success of treatment regimens in germ cell tumors may prompt a restructuring of their classification into 2 basic types of germ cell tumors: 1) seminomatous and 2) nonseminomatous germ cell tumors. Similarly, sex cord/gonadal stromal tumors may be classed together based on embryonic origin and response to surgical treatment. With greater use of testicular ultrasound we may see more nonpalpable Sertoli-Leydig cell tumors in the future. A working knowledge of gonadal development and tumor homology should allow us to understand better the presentation and treatment of sex cord/gonadal stromal tumors.
14.
REFERENCES
15.
1. Mostofi, F. K. and Sobin, L. H.: Histological Typing of Testis
Tumours (No. 16). Geneva: World Health Organization, 1977. 2. 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, pp. 85-114, 1973. 3. Lawrence, W. D., Young, R.H. and Scully, R. E.: Sex cord-stromal tumors. Contemp. Issues Surg. Path., 7: 67, 1986. 4. Mount, B. M., Huvos, A.G. and Whitmore, W. F., Jr.: Leydig cell tumors of testis including cryptorchid testis. N. Y. State J. Med., 72: 601, 1972. 5. Chen, K. T. K., Spaulding, R. W., Flam, M. S. and Brittin, G. M.: Malignant interstitial cell tumor of the testis. Cancer, 49: 547, 1982. 6. Damjanov, I.: Spontaneous and experimental testicular tumors in animals. In: Pathology of the Testis and Its Adnexa. Edited by A. Talerman and L. M. Roth. New York: Churchill-Livingstone, chapt. 10,p. 193, 1986. 7. Moore, K. L.: The Developing Human, 3rd ed. Phiiadelphia: W. B. Saunders Co., pp. 271-276, 1982. 8. Mostofi, F. K., Theiss, E. A. and Ashley, D. J. B.: Tumors of specialized gonadal stroma in human male patients. Cancer, 12: 944, 1959. 9. Gillman, J.: Development of gonads in man, with consideration of role of fetal endocrines and histogenesis of ovarian tumors. Contrib. Embryo!., 32: 81, 1948. 10. Wiederhold, M. D., Gonzalez-Crussi, F., Ou, D. W. and Yokoyama,
11.
12. 13.
16. 17. 18. 19. 20.
21. 22. 23. 24. 25.
885.
M. M.: Ultrastructure of an undifferentiated Sertoii cell tumor of the testicie. UroL 37: 297, 1982. Kurman, R. J., Andrade, Goebelsmann, U. and Taylor, C. R.: An immunohistological study of steroid localization in SertoliLeydig celi tumors of the ovary and testis. Cancer, 43: 1772, 1978. Teilum, G.: Estrogen-producing Bertoli cell tumors (androblastoma tubulare lipoides) of the human testis and ovary; homologous ovarian and testicular tumors. III. J. Clin. Endocr., 9: 301, 1949. Collins, D. H. and Symington, T.: Bertoli cell tumor. Brit. J. Urol., suppl., 36: 52, 1964. Teilum, G.: Arrhenoblastoma-androblastoma, homologous ovarian and testicular tumors; including the so-called "luteomas" and "adrenal tumors" of ovary and interstitial cell tumors of testis. Acta Path. Microbiol. Scand., 23: 252, 1946. O'Hern, T. M. and Neubecker, R. D.: Arrhenoblastoma. Obst. Gynec., 19: 758, 1962. Eble, J. N., Hull, M. T., Warfel, K. A. and Donohue, J. P.: Malignant sex cord-stromal tumor of testis. J. Urol., 131: 546, 1984. Masterson, J. S. T., McCullough, A. R., Smith, R.R. L. and Jeffs, R. D.: Neonatal gonadal stromal tumor of the testis: limitations of tumor markers. J. Urol., 134: 558, 1985. White, J. M. and McCarthy, M. P.: Testicular gonadal stromal tumors in newborns. Urology, 20: 121, 1982. Damjanov, I., Katz, S. M. and Jewett, M. A. S.: Leydig cell tumors of the testis. Ann. Clin. Lab. Sci., 9: 157, 1979. DiSaia, P. J.: Ovarian disorders. In: Obstetrics and Gynecology, 6th ed. Edited by J. R. Scott, P. J. DiSaia, C. B. Hammond and W. N. Spellacy. Philadelphia: J.B. Lippincott Co., chapt. 52, pp. 1067-1120, 1990. Gabrilove, J. L., Nicolis, G. L., Mitty, M. A. and Sohval, A. R.: Feminizing interstitial cell tumor of the testis: personal observations and a review of the literature. Cancer, 35: 1184, 1975. Gabrilove, J. L., Freiberg, E. K., Leiter, E. and Nicolis, G. L.: Feminizing and non-feminizing Sertoli cell tumors. J. Urol., 124: 757, 1980. Dilworth, J.P., Farrow, G. M. and Oesterling, J.E.: Non-germ cell tumors of testis. Urology, 37: 399, 1991. Grem, J. L., Robins, H. I., Wilson, K. S., Gilchrist, K. and Trump, D. L.: Metastatic Leydig cell tumor of the testis. Report of three cases and review of the literature. Cancer, 58: 2116, 1986. Young, R.H. and Scully, R. E.: Ovarian sex cord-stromal tumors: recent progress. Int. J. Gynec. Path., 1: 101, 1982.
Vol. 148, 883-885, September 1992
Printed in U.S.A.
SERTOLI-LEYDIG CELL TESTICULAR TUMOR: CASE REPORT AND REVIEW OF SEX CORD/GONADAL STROMAL TUMOR HISTOGENESIS PAULE. PERITO, GAETANO CIANCIO, FRANCISCO CIVANTOS
AND
V. A. POLITANO
From the Departments of Urology and Pathology, University of Miami School of Medicine and Jackson Memorial Hospital, Miami, Florida
ABSTRACT
We describe a case of well differentiated Sertoli-Leydig cell tumor in a testicle. Previously, this tumor has only been illustrated histologically. The existence of a male homologue to the female arrhenoblastoma containing Sertoli and Leydig cells again supports the current hypothesis of gonadal development, and the common steps found in the male and female pathways. KEY WORDS: testicular neoplasms, Leydig cell tumor, Sertoli cell tumor
Testicular tumors are currently subdivided according to microscopic appearance into germ cell and nongerm cell tumors in the World Health Organization classification. 1 Because testicular tumors are heterogeneous, histological subtypes vary from study to study. Nongerm cell tumors represent only 5 to 10% of all testicular tumors. 2 Sex cord/gonadal stromal tumors are included in this group, most being differentiated toward Leydig or Sertoli cell components. Only 4 to 5% of all testicular tumors in adults are sex cord/gonadal stromal tumors. 3 Little is understood concerning the etiology and pathogenesis of these tumors. Sex cord/gonadal stromal tumors have been discovered in cryptorchid testes but no causal relationship has been found in maldescended testes. 4 • 5 Interestingly, the tumor is common in domestic dogs, laboratory rodents and wild animals but the application of knowledge gained from animal sex cord/gonadal stromal tumors is not yet established. 6 We describe a case of well differentiated Sertoli-Leydig cell tumor in a testicle. Previously, this tumor has only been illustrated histologically. 1 To our knowledge the tumor has never been formally described and discussed. We also discuss its controversial embryonic origin and relationship to the female homologue, previously known as arrhenoblastoma.
CASE REPORT
H. E., a 66-year-old healthy white man, presented with complaints of a full feeling in the left testicle. Physical examination revealed a normal left testicle and spermatic cord, and a 1 X 1 cm. area of barely palpable induration in the posterior aspect of the right testicle. No lymphadenopathy, abdominal masses, signs of virilization or gynecomastia was noted. Bilateral testicular ultrasound revealed simple cysts in the left testicle and a discrete lesion with high density internal structures within the posterior portion of the right testicle, opposite the side of the symptoms. The serum (3-human chorionic gonadotropin level was within the normal adult range (less than 5 mIU/ml.), a-fetoprotein was 9.1 ng./ml. (normal adult less than 15) and testosterone was 414 ng./dl. (normal adult 270 to 1,070). Right scrotal exploration revealed a 1.8 x 1 x 1 cm. ovoid mass within the parenchyma of the testicle. Frozen section of the mass was reported as a testicular tumor. At this point right radical orchiectomy was performed. Postoperatively, abdominal computerized tomography was negative. The patient had no signs of metastases or recurrence at 1 year postoperatively. Pathology data. The specimen was a 5 x 4 x 3 cm. testis containing an ovoid 1.8 x 1 x 1 cm. mass (fig. 1). Cross sections revealed white fibrous tissue between pink soft nodules. There Accepted for publication February 21, 1992. 883
FIG. 1. Well circumscribed nodule, partially resected, shows nodular pattern on cut surface.
was no gross extension into the rete testis or spermatic cord. The tumor was well circumscribed and well demarcated from the adjacent testicular parenchyma. Microscopic findings revealed mature Sertoli and Leydig cell components intermixed with fibrous stroma (fig. 2, A). The Sertoli cell component was the predominant cell population in the tumor (fig. 2, B). In areas the Sertoli cells were focally arranged in solid tubules that resembled immature seminiferous tubules (tubular adenoma pattern). Sparse connective tissue stroma surrounded the tubules. No annular tubules similar to those reported in the Peutz-Jeghers syndrome were noted in the Sertoli cell component. The tubules were narrowed and became a single cell row (trabecular pattern), which was the predominant arrangement. The Leydig cell component was arranged into nests of polygonal acidophilic cells. Pathognomonic Reinke crystals were present (fig. 3). No foci of necrosis, nuclear atypia, vascular or lymphatic invasion were present in the tumor. Mitoses were rare. DISCUSSION
The fetal gonad is derived from 3 sources: 1) coelomic epithelium, 2) mesenchyme and 3) primordial germ cells. 7 Thickening of coelomic epithelium and mesenchyme produces a bulge in the medial side of the mesonephros known as the gonadal ridge. This is the indifferent gonad from which the supportive structures of the testis and ovary arise before germ cell migration into the gonadal ridges. It has been postulated that the supportive cells of the gonadal ridge develop from a common stem cell rather than 2 of the 3
884
PERITO AND ASSOCIATES
Fm. 2. A, Sertoli cells in solid tubules with scanty fibrous stroma in periphery are seen at right side adjacent to capillary with red blood cells. On left side are Leydig cells between dense fibrous bands. Arrow shows crystals of Reinke. Reduced from X20. B, predominant pattern was Sertoli cells in trabecular arrangement with rows of Sertoli cells between scanty fibrous stroma. Reduced from XlO.
Fm. 3. Crystals of Reinke in Leydig cells appear as sharply truncated, slender cylinders that stain with eosin. Reduced from X40.
aforementioned cell populations.8·9 This theory has been supported through studies showing ultrastructural similarities in immature stromal cells found in mixed cell tumors, and epithelial cells of pure Sertoli and pure Leydig cell tumors. 10 Also, in immunohistochemical studies researchers demonstrated testosterone and estradiol in Sertoli, Leydig and less differentiated stromal cells resembling those found in the embryonic gonad.11 The existence of mixed tumors containing well differentiated
and incompletely differentiated components favors the common stem cell hypothesis. Regardless, it is the indifferent gonad from which all cell lines of sex cord/gonadal stromal tumors evolve. Several synonyms have been used to describe tumors arising from the indifferent fetal gonad, including androblastomas, 12 gonadal stromal tumors 8 and Sertoli cell tumors. 13 Broad classification is no longer based on function or predominant histological findings. The name sex cord/gonadal stromal tumors evolved to represent the similar embryological pathways from which each divergent tumor has originated. Sex cord/gonadal stromal tumors of the gonads comprise tumors of Leydig, Sertoli, granulosa and thecal cell origins. In any individual tumor the cell grouping can be mixed, incompletely differentiated and resemble any of the specialized supportive structures of the male and female gonad. Expectantly, cells within the ovary have similar oncogenic potentialities. Homologous ovarian and testicular tumors have been recognized since 1946. Teilum called them androblastomas and described testicular tumors derived from the undifferentiated gonadal mesenchyme. 14 Since then many tumors arising from the gonadal ridge have been identified. The development of these types of tumors illustrates the competency of the testis and ovary to elaborate identical neoplasms. Sertoli-Leydig cell tumors in female patients (arrhenoblastomas) are common among the sex cord tumors. They arise from the same female sex cord stromal cells as granulosa-theca cell tumors and consistently contain female sex chromatin. 15 An identical tumor in the male patient containing mature, pure Sertoli and Leydig cell components has been illustrated previously.1 However, to our knowledge this tumor has never been formally described in the urological literature. Although mixed sex cord/gonadal stromal tumors have been reported, 16-18 the number of cases is small and all of the tumors described had immature cell populations resembling 1 or all of the cell groups (Sertoli, Leydig, granulosa and thecal). The existence of a male homologue to the female arrhenoblastoma containing mature populations of Sertoli and Leydig cells again supports the current hypothesis of gonadal development, and the common steps found in the male and female pathways. Tumors that arise from embryonic sex cords produce the full range of ovarian and testicular steroids. Many tumors secrete steroid hormones that can be detected in serum or urine, especially well differentiated Leydig cell neoplasms. 19 Most Sertoli-Leydig cell tumors in female patients produce androgens and masculinize the patient. 2°Conversely, in male patients with Leydig cell or Sertoli cell tumors the prevalence of feminizing endocrine manifestations is 20 to 40% 21 and 20 to 30%, 22 respectively. In our patient serum hormonal values were normal. Embryological and pathological similarities between SertoliLeydig cell tumors (arrhenoblastoma) and other sex cord/ gonadal stromal tumors may certainly aid in the treatment of our patient. Sertoli-Leydig cell tumors in female patients have metastatic rates of 15 to 20% and tend to grow locally. 16 Metastatic rates for pure Sertoli or pure Leydig cell tumors are similarly 10 to 20% 23 and 10 to 15%, 24 respectively, and both tend to expand locally. Most mixed/undifferentiated sex cord tumors are benign but occasional examples of malignancy have been recorded. 16 Malignant behavior has been loosely associated with mitotic figures and little else in all of the aforementioned tumor types. 23-25 Subsequently, all sex cord/gonadal stromal tumors, including granulosa cell tumors of the testis and granulosa-theca cell tumors of the ovary, have similar treatment recommendations for localized disease. Surgical resection of the tumor is necessary with prolonged followup for distant metastasis. Testicular tumors are rare, yet they have attracted disproportionate amounts of research from clinicians and laboratory scientists alike. The classification of testicular tumors is elab-
""
..
~'
."."
---·,··- --·
SERTOLI·LEYDIG CELL TUMOR
orate and ever changing. the success of treatment regimens in germ cell tumors may prompt a restructuring of their classification into 2 basic types of germ cell tumors: 1) seminomatous and 2) nonseminomatous germ cell tumors. Similarly, sex cord/gonadal stromal tumors may be classed together based on embryonic origin and response to surgical treatment. With greater use of testicular ultrasound we may see more nonpalpable Sertoli-Leydig cell tumors in the future. A working knowledge of gonadal development and tumor homology should allow us to understand better the presentation and treatment of sex cord/gonadal stromal tumors.
14.
REFERENCES
15.
1. Mostofi, F. K. and Sobin, L. H.: Histological Typing of Testis
Tumours (No. 16). Geneva: World Health Organization, 1977. 2. 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, pp. 85-114, 1973. 3. Lawrence, W. D., Young, R.H. and Scully, R. E.: Sex cord-stromal tumors. Contemp. Issues Surg. Path., 7: 67, 1986. 4. Mount, B. M., Huvos, A.G. and Whitmore, W. F., Jr.: Leydig cell tumors of testis including cryptorchid testis. N. Y. State J. Med., 72: 601, 1972. 5. Chen, K. T. K., Spaulding, R. W., Flam, M. S. and Brittin, G. M.: Malignant interstitial cell tumor of the testis. Cancer, 49: 547, 1982. 6. Damjanov, I.: Spontaneous and experimental testicular tumors in animals. In: Pathology of the Testis and Its Adnexa. Edited by A. Talerman and L. M. Roth. New York: Churchill-Livingstone, chapt. 10,p. 193, 1986. 7. Moore, K. L.: The Developing Human, 3rd ed. Phiiadelphia: W. B. Saunders Co., pp. 271-276, 1982. 8. Mostofi, F. K., Theiss, E. A. and Ashley, D. J. B.: Tumors of specialized gonadal stroma in human male patients. Cancer, 12: 944, 1959. 9. Gillman, J.: Development of gonads in man, with consideration of role of fetal endocrines and histogenesis of ovarian tumors. Contrib. Embryo!., 32: 81, 1948. 10. Wiederhold, M. D., Gonzalez-Crussi, F., Ou, D. W. and Yokoyama,
11.
12. 13.
16. 17. 18. 19. 20.
21. 22. 23. 24. 25.
885.
M. M.: Ultrastructure of an undifferentiated Sertoii cell tumor of the testicie. UroL 37: 297, 1982. Kurman, R. J., Andrade, Goebelsmann, U. and Taylor, C. R.: An immunohistological study of steroid localization in SertoliLeydig celi tumors of the ovary and testis. Cancer, 43: 1772, 1978. Teilum, G.: Estrogen-producing Bertoli cell tumors (androblastoma tubulare lipoides) of the human testis and ovary; homologous ovarian and testicular tumors. III. J. Clin. Endocr., 9: 301, 1949. Collins, D. H. and Symington, T.: Bertoli cell tumor. Brit. J. Urol., suppl., 36: 52, 1964. Teilum, G.: Arrhenoblastoma-androblastoma, homologous ovarian and testicular tumors; including the so-called "luteomas" and "adrenal tumors" of ovary and interstitial cell tumors of testis. Acta Path. Microbiol. Scand., 23: 252, 1946. O'Hern, T. M. and Neubecker, R. D.: Arrhenoblastoma. Obst. Gynec., 19: 758, 1962. Eble, J. N., Hull, M. T., Warfel, K. A. and Donohue, J. P.: Malignant sex cord-stromal tumor of testis. J. Urol., 131: 546, 1984. Masterson, J. S. T., McCullough, A. R., Smith, R.R. L. and Jeffs, R. D.: Neonatal gonadal stromal tumor of the testis: limitations of tumor markers. J. Urol., 134: 558, 1985. White, J. M. and McCarthy, M. P.: Testicular gonadal stromal tumors in newborns. Urology, 20: 121, 1982. Damjanov, I., Katz, S. M. and Jewett, M. A. S.: Leydig cell tumors of the testis. Ann. Clin. Lab. Sci., 9: 157, 1979. DiSaia, P. J.: Ovarian disorders. In: Obstetrics and Gynecology, 6th ed. Edited by J. R. Scott, P. J. DiSaia, C. B. Hammond and W. N. Spellacy. Philadelphia: J.B. Lippincott Co., chapt. 52, pp. 1067-1120, 1990. Gabrilove, J. L., Nicolis, G. L., Mitty, M. A. and Sohval, A. R.: Feminizing interstitial cell tumor of the testis: personal observations and a review of the literature. Cancer, 35: 1184, 1975. Gabrilove, J. L., Freiberg, E. K., Leiter, E. and Nicolis, G. L.: Feminizing and non-feminizing Sertoli cell tumors. J. Urol., 124: 757, 1980. Dilworth, J.P., Farrow, G. M. and Oesterling, J.E.: Non-germ cell tumors of testis. Urology, 37: 399, 1991. Grem, J. L., Robins, H. I., Wilson, K. S., Gilchrist, K. and Trump, D. L.: Metastatic Leydig cell tumor of the testis. Report of three cases and review of the literature. Cancer, 58: 2116, 1986. Young, R.H. and Scully, R. E.: Ovarian sex cord-stromal tumors: recent progress. Int. J. Gynec. Path., 1: 101, 1982.
