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Estrogen-producing Sertoli cell tumor of the ovary—A case report
GYNECOLOGIC
ONCOLOGY
19, 348-354 (1984)
CASE REPORTS Estrogen-Producing Sertoli Cell Tumor of the Ovary-A Case Report ELIEZER SHALEV, M.D., *J HENRYK ZUCKERMAN, AND IOSEFINA RISESCU, M.D.? *Department
of Obstetrics and Gynecology Central Emek Hospital,
and fDepartment
M.D.,* of Pathology,
Afula, Israel
Received April 18, 1983 Estrogen-secreting Sertoli cell tumor of the ovary is rare. The few cases reported were characterized by metrorrhagia suggesting the hyperestrogenic state. An additional case of Sertoli cell tumor is reported in which the clinical picture is of secondary ammenorrhea followed by metrorrhagia. The endocrinological status was investigated by hormonal assays showing a high level of estradiol, which was consistent with endometrial biopsy. A review of the literature together with a discussion on the histogenesis and diagnosis of the tumor 0 1984 Academic Press, Inc. iS presented.
The “Sertoli cell” was described in 1865 by Enrico Sertoli as a supportive and nutritive cell in the testis. Studies of Sertoli cell tumors of the testis in feminized dogs showed evidence of endocrine function connected with production of estrogen in such tumors [l]. In human tumor pathology, the “Sertoli cell” was introduced as a hormone-producing cell with Teilum’s [2] description of “estrogen-producing testicular androblastoma.” Morphological congruence was demonstrated by Teilum [3] between the “feminizing androblastoma testis” and feminizing ovarian tumors which had previously been described as “folliculom lipidique” [4] or “granulosa cell tumor” of “tubular” or “adenomatous” type [5,6]. Such ovarian tumors were thus classified as “androblastoma” or “Sertoli cell tumor of the ovary.” There is no estimation of the occurrence rate of the estrogen-producing Sertoli cell tumor, but it seems to be very low. Apart from Teilum’s [3] description in 1949 of 10 cases, we found only 10 other cases which were added to the literature [7-141. An additional case of Sertoli cell tumor and a review of the literature ae reported here. CASE REPORT
A 30-year-old, para l-0-2-1, was referred to the Central Emek Hospital because of vaginal bleeding which had started 3 weeks prior to admission. Menarche had occurred at the age of 16, followed by regular menstrual intervals of 28 days, ’ To whom reprint requests should be addressed. 348 0090-8258/84$1.50 Copyright All rights
0 1984 by Academic Press, Inc. of reproduction in any form reserved.
349
CASE REPORTS
with a menses duration of 5 days. At the age of 24 and after two spontaneous abortions, she delivered a healthy child by cesarean section owing to premature rupture of membranes. Menstruation continued to be spontaneous and regular until 2 years before admission, when she became amenorrheic. She was treated with progestational medication by her gynecologist who noted “enlargement of the left ovary.” The patient noticed the appearance of brown spots on her face and engorgement of the breasts. One year later she decided to stop medication and 4 months later continuous vaginal bleeding occurred which necessitated hospitalization. Physical examination revealed a slender woman, 151 cm tall, and weighing 43 kg. Vital signs were within the normal range; body hair distribution was normaily feminine. She had brownish patches on her face resembling the “mask of pregnancy.” Breasts were normally developed, tender, but with no galactorhea. External genitalia were normal. Pelvic examination revealed slightly enlarged hard uterus, and tender left adnexal mass measuring 5 cm in diameter. Results of laboratory studies were as follows: Hb-I 1.8 g/dl, Hct-37.5%, WBC, routine urinalysis, and blood chemistry all within the normal range. Table 1 shows the hormone profile of this case. The patient was found to be normoprolactinemic. Gonadotropins and androgenic hormones were not elevated. The estradiol value was significantly higher than normal. The thyroxin value was found to be high, probably in part because of the hyperestrogenic state. Thus normalized T4 was found to be normal. The hyperestrogenic activity was also confirmed by diagnostic curettage which revealed the endometrium to be in state of “cystic hyperplasia,” the endometrial glands were large and cystic showing marked disparity and lined by a single layer of epithelium (Fig. 1). Additional investigation included barium enema, IVP, isotopic scanning of the liver, spleen, and thyroid gland, and all were found to be normal. On the 5th day of hospitalization a laparotomy was performed. The uterus was found to be enlarged to 6-weeks gestation size, in addition there were two moderate-size intramural leiomyomas, 3 cm in diameter each. One myoma was TABLE 1 HORMONE “PROFILE”
Test Serum prolactin FSH ;-:G Estradiol” Progesterone Testosterone Urine 17 KS Serum T, NTV
Measured value 6 8 6 @/ml 1.4 mu/ml 5.3 mu/ml 7.45 pU/ml 7 1 4 pgiml 3.1 ngiml 0.4 rig/ml 3.9 mg/24 hr 13.9 /.&dl 1.01
Normal vaiue” 25 mu/ml) 3-20 mu/ml (ovulation > 30 mu/ml) pregnancy > 50 pU/ml 40-100 (ovulation > 200 pgiml) ovulation > 12 rig/ml
Note. All samples were taken from an arm vein. a Normal values in our laboratory. ’ Estradiol was assayed with a radioimmunoassay kit (Cis, Sorin, France).
350
SHALEV,
ZUCKERMAN,
AND
RISESCU
FIG. 1. Endometrial biopsy, the enlarged cystic glands showing marked disparity. (Hematoxylin and eosin, x 40.)
in the uterine fundus and the other in the posterior uterine wall. On the left ovary a solid, capsulated, moderate-size tumor, 3.5 cm in diameter, was found. Left oophorectomy was performed. PATHOLOGY Gross. The tumor was of moderate size, 3.5 cm in diameter, solid, lobulated with a smooth external capsule, and had a cut surface, white with yellowish hue. Microscopic. The tumor shows a tubular structure or branching solid cords lined by tall columnar Sertoli cells. The cords are surrounded by a distinct basement membrane and separated by a scanty fibrous ovarian stroma. There are areas composed essentially of Sertoli cells arranged in solid cords forming solid winding tubules (Fig. 2). Scanty clusters of typical Leydig cells were present in other sections of the tumor (Fig. 3). The tumor contains large amount of lipid with typical Sertoli cells distended by their cytoplasmic content of lipid with a positive reaction for fat (osmic acid-frozen section) (Fig. 4). Examination under high-power field did not demonstrate any malignant features and no mitotic activity was observed. The postoperative course was uneventful; follow-up of estradiol levels showed a decrease to 57 pg/ml on the sixth day after the operation. The first spontaneous menstruation occurred 32 days after that time. Three months after her discharge from hospital, the patient became pregnant, and 9 months later she was delivered by cesarean section of a healthy boy.
CASE
REPORTS
351
FIG. 2. Sertoli cell tumor showing branching solid cords and trabeculae of neoplastic cells reminiscent of Sertoli cells in testicular feminization. The cords are surrounded by distinct basement membrane and separated by a scanty fibrous ovarian stroma. (Hematoxylin and eosin, x 40.)
FIG.
3. Area with clusters of Leydig cells. (Hematoxylin and eosin, x 400.)
352
SHALEV, ZUCKERMAN, AND RISESCU
FIG. 4. Tubules in cross section lined by Sertoli cells with storage of lipoid material (osmic acid stain) surrounded by fibrous ovarian stroma.
Wedge resection of the contralateral ovary was performed at operation, and pathological examination revealed no tumor cell. DISCUSSION Pick [ 151in 1905 was the first to describe an ovarian tumor with morphological resemblance to the benign adenoma of the testis and he therefore called this tumor “adenoma testicular ovary.” Meyer [16] in 1930 coined the term “arrhenoblastoma” for a group of tumors with a virilizing nature and classified them into three types according to their differentiation. The “tubular adenoma” of Pick was designated as the highly differentiated tubular form of arrhenoblastoma, although the patient was presented with metrorrhagia and had no masculinizing signs. Teilum [2,3] classified the same group of tumors on a morphological basis, reflecting the various phases in the development of the testicular structure. He termed the tumors in either sex as “androblastoma.” Depending on the type of functioning cells, the androblastoma may be feminizing or virilizing or may exhibit no endocrine effect. According to Teilum [3], the tubular epithelial elements of the feminizing ovarian tumor are analogous to Sertoli cells, and because of their hormonal effect, such tumors have been misinterpreted and classified under various names. Ten such tumors had been collected by him; all of them showed a tubular structure with high lipid content within the Sertoli cells. The patients were mostly in their thirties and clinically they presented with metrorrhagia. An additional six cases of feminizing Sertoli cell tumors were reported later
CASE REPORTS
353
[7-l 11;all of these cases were young, women and had the characteristic estrogenic manifestation of endometrial hyperplasia and metrorrhagia. A peculiar clinical picture of aldosteronism and precocious puberty in association with Sertoli cell tumor was described by Ehrlich et al in 1963 [12], and an additional case of Sertoli cell tumor with precocious puberty was reported by Bastidas et al. [13] in 1977. The origin of the Sertoli cell tumor is still being debated. Pick in 1905 [15] considered it as the testicular component of an ovotestis. The characteristic medullary localization of the tumor as shown in the cases of Dougal [6] and Shui-Nien [lo] can be considered as evidence for the origin of the tumor from male elements within the hilus of the ovary. Such a theory is supported by the similarity between the tumor cell and the testicular Sertoli cell demonstrated by Ramzy and Box [14], in an ultrastructural study on two additional cases of pure Sertoli cell tumor. Classification of the tumor is a source of controversy and confusion. Novak et al. [17] adopted Sandberg’s [ 181idea that histologic morphology is inadequate for diagnosis and morphologically typical tumors can show an endocrine effect exactly opposite to the histological pattern. Therefore, the endocrine effect should be the decisive diagnostic feature. For almost the same reasons Teilum [19] claimed that classification of gonadal tumors should be based on morphological features rather than on function. Considering treatment it was difficult for us to decide on the proper treatment, mainly because of the fact that so few cases have been documented. As no tumor-related death was observed and the tumor seemed to be of low-grade malignancy, we think simple adnexectomy to be the recommended treatment for the young patient with a well-circumscribed tumor, who still desires further pregnancies. The total abdominal hysterectomy with bilateral adnexectomy is reserved for the older, parous women or for the more advanced tumor. ACKNOWLEDGMENT The authors are grateful to Dr. S. Harpaz-Kerpel for performing the hormone assays.
REFERENCES 1. Huggins, C., and Moulder, P. V. Estrogen producing by Sertoli cell tumors of testis, Cancer Res. 5, 510-514 (1945). 2. Teilum, G. Arrhenoblastoma-androblastoma, homologous ovarian and testicular tumors II, Acta Pathol. Microbial. Stand. 23, 252-264 (1946). 3. Teilum, G. Estrogen-producing Sertoli cell tumors (androblastoma tubular lipoides) of human testis and ovary. Homologous ovarian and testicular tumors III, 1. Clin. Endocrinol. 9, 301318 (1949). 4. Christian, E. Un Cas d’Epithelioma a granulations de luteine, d’origine probablement ovarienne, Sot. Anat. Ann. 85, 6, 12, 639-641 (1910), as quoted by Teilum (3). 5. Traut, H. F., and Butterworth, J. S. The theta, granulosa, lutein cell tumors of the human ovary and similar tumors of the mouse’s ovary, Amer. J. Obstet. Gynecol. 34, 987-1006 (1937). 6. Dougal, D. A. Granulosa cell tumor of tubular adenomatous type, J. Obstet. Gynaecol. Bit. Emp. 52, 370-371 (1945). 7. Langley, F. A. Sertoh and Leydig cells in relation to ovarian tumors, 1. C/in. Puthof. 7, IO-17 (1954).
354
SHALEV,
ZUCKERMAN,
AND RISESCU
8. Schiller, W. Female genitalia, in Pathology (W. A. D. Anderson, Ed.), Mosby, St. Louis, pp. 1044-1101 (1953). 9. Von Numers, C., and Gylling, T. Sertoli cell tumors of ovary (androblastoma tubular lipoides Teilum): Report of 3 cases, Ann. Chir. Gynaecol. Fem. 42, 161-167 (1953). 10. Shui-Nien, W. Androblastoma tubular lipoides (Sertoli cell tumor or testicular tubular adenoma) of ovary: Report of case and review of literature, Chin. Med. .I. (Pelein, Engl. Ed.) 73, 5565 (1955). 11. Fuglsang, F., and Ohlsen, A. S. Androblastoma predominantly feminizing with report of a case, Acra Chir. Stand. 112, 405-410 (1956). 12. Ehrlich, E. N., Dominquez, 0. V., Samuels, L. T., Lynch, D., Oberhelman, H., and Warner, N. E. Aldosteronism and precocious puberty due to an ovarian androblastoma (Sertoli cell tumor), J. C/in. Endocrinol. Metabol. 23, 358-367 (1963). 13. Bastidas, B. S., Chavez, N. C., and Villasenor, M. J. Tumor ovarico de celulas de Sertoli, reportre de un case, Ginecol. Obstet. Mex. 42, 269-274 (1977). 14. Ramzy, I., and Bos, C. Sertoli cell tumors of ovary. Light microscopic and ultrastructural study with histogenetic consideration, Cancer 38, 2447-2456 (1976). 15. Pick, L. Ueber Neubildungen am Genitale bei Zwittern nebst Beitraegen zur Lehre von den Adenomen des Hodens und Eierstockes. Arch. Gynaekof. 76,191-281(1905), quoted by Teilum (3). 16. Meyer, R. Tubulare (testiculare) und solide Formen des Andreioblastoma ovarii und ihre Beziehung zur Vermaennlichung, Beirr. Pathof. Amt. Alla. Parhof. 84, 485-520 (1930). 17. Novak, E. R., Jones, G. S., and Jones, H. W. Functioning ovarian tumors, in Novnk’s textbook of gynecology, Williams & Wilkins, Baltimore, pp. 536-537 (1975). 18. Sandberg, E. C. The virilizing ovary, Obstet. Gynecol. Sum. 17, 165 (1962). 19. Teilum, G. Special tumors of ovary and testis and related extragonadal lesions, in Comparative pathofogy and histological identifcarion, Lippincott, Philadelphia, 79-98 (1971).
ONCOLOGY
19, 348-354 (1984)
CASE REPORTS Estrogen-Producing Sertoli Cell Tumor of the Ovary-A Case Report ELIEZER SHALEV, M.D., *J HENRYK ZUCKERMAN, AND IOSEFINA RISESCU, M.D.? *Department
of Obstetrics and Gynecology Central Emek Hospital,
and fDepartment
M.D.,* of Pathology,
Afula, Israel
Received April 18, 1983 Estrogen-secreting Sertoli cell tumor of the ovary is rare. The few cases reported were characterized by metrorrhagia suggesting the hyperestrogenic state. An additional case of Sertoli cell tumor is reported in which the clinical picture is of secondary ammenorrhea followed by metrorrhagia. The endocrinological status was investigated by hormonal assays showing a high level of estradiol, which was consistent with endometrial biopsy. A review of the literature together with a discussion on the histogenesis and diagnosis of the tumor 0 1984 Academic Press, Inc. iS presented.
The “Sertoli cell” was described in 1865 by Enrico Sertoli as a supportive and nutritive cell in the testis. Studies of Sertoli cell tumors of the testis in feminized dogs showed evidence of endocrine function connected with production of estrogen in such tumors [l]. In human tumor pathology, the “Sertoli cell” was introduced as a hormone-producing cell with Teilum’s [2] description of “estrogen-producing testicular androblastoma.” Morphological congruence was demonstrated by Teilum [3] between the “feminizing androblastoma testis” and feminizing ovarian tumors which had previously been described as “folliculom lipidique” [4] or “granulosa cell tumor” of “tubular” or “adenomatous” type [5,6]. Such ovarian tumors were thus classified as “androblastoma” or “Sertoli cell tumor of the ovary.” There is no estimation of the occurrence rate of the estrogen-producing Sertoli cell tumor, but it seems to be very low. Apart from Teilum’s [3] description in 1949 of 10 cases, we found only 10 other cases which were added to the literature [7-141. An additional case of Sertoli cell tumor and a review of the literature ae reported here. CASE REPORT
A 30-year-old, para l-0-2-1, was referred to the Central Emek Hospital because of vaginal bleeding which had started 3 weeks prior to admission. Menarche had occurred at the age of 16, followed by regular menstrual intervals of 28 days, ’ To whom reprint requests should be addressed. 348 0090-8258/84$1.50 Copyright All rights
0 1984 by Academic Press, Inc. of reproduction in any form reserved.
349
CASE REPORTS
with a menses duration of 5 days. At the age of 24 and after two spontaneous abortions, she delivered a healthy child by cesarean section owing to premature rupture of membranes. Menstruation continued to be spontaneous and regular until 2 years before admission, when she became amenorrheic. She was treated with progestational medication by her gynecologist who noted “enlargement of the left ovary.” The patient noticed the appearance of brown spots on her face and engorgement of the breasts. One year later she decided to stop medication and 4 months later continuous vaginal bleeding occurred which necessitated hospitalization. Physical examination revealed a slender woman, 151 cm tall, and weighing 43 kg. Vital signs were within the normal range; body hair distribution was normaily feminine. She had brownish patches on her face resembling the “mask of pregnancy.” Breasts were normally developed, tender, but with no galactorhea. External genitalia were normal. Pelvic examination revealed slightly enlarged hard uterus, and tender left adnexal mass measuring 5 cm in diameter. Results of laboratory studies were as follows: Hb-I 1.8 g/dl, Hct-37.5%, WBC, routine urinalysis, and blood chemistry all within the normal range. Table 1 shows the hormone profile of this case. The patient was found to be normoprolactinemic. Gonadotropins and androgenic hormones were not elevated. The estradiol value was significantly higher than normal. The thyroxin value was found to be high, probably in part because of the hyperestrogenic state. Thus normalized T4 was found to be normal. The hyperestrogenic activity was also confirmed by diagnostic curettage which revealed the endometrium to be in state of “cystic hyperplasia,” the endometrial glands were large and cystic showing marked disparity and lined by a single layer of epithelium (Fig. 1). Additional investigation included barium enema, IVP, isotopic scanning of the liver, spleen, and thyroid gland, and all were found to be normal. On the 5th day of hospitalization a laparotomy was performed. The uterus was found to be enlarged to 6-weeks gestation size, in addition there were two moderate-size intramural leiomyomas, 3 cm in diameter each. One myoma was TABLE 1 HORMONE “PROFILE”
Test Serum prolactin FSH ;-:G Estradiol” Progesterone Testosterone Urine 17 KS Serum T, NTV
Measured value 6 8 6 @/ml 1.4 mu/ml 5.3 mu/ml 7.45 pU/ml 7 1 4 pgiml 3.1 ngiml 0.4 rig/ml 3.9 mg/24 hr 13.9 /.&dl 1.01
Normal vaiue”
Note. All samples were taken from an arm vein. a Normal values in our laboratory. ’ Estradiol was assayed with a radioimmunoassay kit (Cis, Sorin, France).
350
SHALEV,
ZUCKERMAN,
AND
RISESCU
FIG. 1. Endometrial biopsy, the enlarged cystic glands showing marked disparity. (Hematoxylin and eosin, x 40.)
in the uterine fundus and the other in the posterior uterine wall. On the left ovary a solid, capsulated, moderate-size tumor, 3.5 cm in diameter, was found. Left oophorectomy was performed. PATHOLOGY Gross. The tumor was of moderate size, 3.5 cm in diameter, solid, lobulated with a smooth external capsule, and had a cut surface, white with yellowish hue. Microscopic. The tumor shows a tubular structure or branching solid cords lined by tall columnar Sertoli cells. The cords are surrounded by a distinct basement membrane and separated by a scanty fibrous ovarian stroma. There are areas composed essentially of Sertoli cells arranged in solid cords forming solid winding tubules (Fig. 2). Scanty clusters of typical Leydig cells were present in other sections of the tumor (Fig. 3). The tumor contains large amount of lipid with typical Sertoli cells distended by their cytoplasmic content of lipid with a positive reaction for fat (osmic acid-frozen section) (Fig. 4). Examination under high-power field did not demonstrate any malignant features and no mitotic activity was observed. The postoperative course was uneventful; follow-up of estradiol levels showed a decrease to 57 pg/ml on the sixth day after the operation. The first spontaneous menstruation occurred 32 days after that time. Three months after her discharge from hospital, the patient became pregnant, and 9 months later she was delivered by cesarean section of a healthy boy.
CASE
REPORTS
351
FIG. 2. Sertoli cell tumor showing branching solid cords and trabeculae of neoplastic cells reminiscent of Sertoli cells in testicular feminization. The cords are surrounded by distinct basement membrane and separated by a scanty fibrous ovarian stroma. (Hematoxylin and eosin, x 40.)
FIG.
3. Area with clusters of Leydig cells. (Hematoxylin and eosin, x 400.)
352
SHALEV, ZUCKERMAN, AND RISESCU
FIG. 4. Tubules in cross section lined by Sertoli cells with storage of lipoid material (osmic acid stain) surrounded by fibrous ovarian stroma.
Wedge resection of the contralateral ovary was performed at operation, and pathological examination revealed no tumor cell. DISCUSSION Pick [ 151in 1905 was the first to describe an ovarian tumor with morphological resemblance to the benign adenoma of the testis and he therefore called this tumor “adenoma testicular ovary.” Meyer [16] in 1930 coined the term “arrhenoblastoma” for a group of tumors with a virilizing nature and classified them into three types according to their differentiation. The “tubular adenoma” of Pick was designated as the highly differentiated tubular form of arrhenoblastoma, although the patient was presented with metrorrhagia and had no masculinizing signs. Teilum [2,3] classified the same group of tumors on a morphological basis, reflecting the various phases in the development of the testicular structure. He termed the tumors in either sex as “androblastoma.” Depending on the type of functioning cells, the androblastoma may be feminizing or virilizing or may exhibit no endocrine effect. According to Teilum [3], the tubular epithelial elements of the feminizing ovarian tumor are analogous to Sertoli cells, and because of their hormonal effect, such tumors have been misinterpreted and classified under various names. Ten such tumors had been collected by him; all of them showed a tubular structure with high lipid content within the Sertoli cells. The patients were mostly in their thirties and clinically they presented with metrorrhagia. An additional six cases of feminizing Sertoli cell tumors were reported later
CASE REPORTS
353
[7-l 11;all of these cases were young, women and had the characteristic estrogenic manifestation of endometrial hyperplasia and metrorrhagia. A peculiar clinical picture of aldosteronism and precocious puberty in association with Sertoli cell tumor was described by Ehrlich et al in 1963 [12], and an additional case of Sertoli cell tumor with precocious puberty was reported by Bastidas et al. [13] in 1977. The origin of the Sertoli cell tumor is still being debated. Pick in 1905 [15] considered it as the testicular component of an ovotestis. The characteristic medullary localization of the tumor as shown in the cases of Dougal [6] and Shui-Nien [lo] can be considered as evidence for the origin of the tumor from male elements within the hilus of the ovary. Such a theory is supported by the similarity between the tumor cell and the testicular Sertoli cell demonstrated by Ramzy and Box [14], in an ultrastructural study on two additional cases of pure Sertoli cell tumor. Classification of the tumor is a source of controversy and confusion. Novak et al. [17] adopted Sandberg’s [ 181idea that histologic morphology is inadequate for diagnosis and morphologically typical tumors can show an endocrine effect exactly opposite to the histological pattern. Therefore, the endocrine effect should be the decisive diagnostic feature. For almost the same reasons Teilum [19] claimed that classification of gonadal tumors should be based on morphological features rather than on function. Considering treatment it was difficult for us to decide on the proper treatment, mainly because of the fact that so few cases have been documented. As no tumor-related death was observed and the tumor seemed to be of low-grade malignancy, we think simple adnexectomy to be the recommended treatment for the young patient with a well-circumscribed tumor, who still desires further pregnancies. The total abdominal hysterectomy with bilateral adnexectomy is reserved for the older, parous women or for the more advanced tumor. ACKNOWLEDGMENT The authors are grateful to Dr. S. Harpaz-Kerpel for performing the hormone assays.
REFERENCES 1. Huggins, C., and Moulder, P. V. Estrogen producing by Sertoli cell tumors of testis, Cancer Res. 5, 510-514 (1945). 2. Teilum, G. Arrhenoblastoma-androblastoma, homologous ovarian and testicular tumors II, Acta Pathol. Microbial. Stand. 23, 252-264 (1946). 3. Teilum, G. Estrogen-producing Sertoli cell tumors (androblastoma tubular lipoides) of human testis and ovary. Homologous ovarian and testicular tumors III, 1. Clin. Endocrinol. 9, 301318 (1949). 4. Christian, E. Un Cas d’Epithelioma a granulations de luteine, d’origine probablement ovarienne, Sot. Anat. Ann. 85, 6, 12, 639-641 (1910), as quoted by Teilum (3). 5. Traut, H. F., and Butterworth, J. S. The theta, granulosa, lutein cell tumors of the human ovary and similar tumors of the mouse’s ovary, Amer. J. Obstet. Gynecol. 34, 987-1006 (1937). 6. Dougal, D. A. Granulosa cell tumor of tubular adenomatous type, J. Obstet. Gynaecol. Bit. Emp. 52, 370-371 (1945). 7. Langley, F. A. Sertoh and Leydig cells in relation to ovarian tumors, 1. C/in. Puthof. 7, IO-17 (1954).
354
SHALEV,
ZUCKERMAN,
AND RISESCU
8. Schiller, W. Female genitalia, in Pathology (W. A. D. Anderson, Ed.), Mosby, St. Louis, pp. 1044-1101 (1953). 9. Von Numers, C., and Gylling, T. Sertoli cell tumors of ovary (androblastoma tubular lipoides Teilum): Report of 3 cases, Ann. Chir. Gynaecol. Fem. 42, 161-167 (1953). 10. Shui-Nien, W. Androblastoma tubular lipoides (Sertoli cell tumor or testicular tubular adenoma) of ovary: Report of case and review of literature, Chin. Med. .I. (Pelein, Engl. Ed.) 73, 5565 (1955). 11. Fuglsang, F., and Ohlsen, A. S. Androblastoma predominantly feminizing with report of a case, Acra Chir. Stand. 112, 405-410 (1956). 12. Ehrlich, E. N., Dominquez, 0. V., Samuels, L. T., Lynch, D., Oberhelman, H., and Warner, N. E. Aldosteronism and precocious puberty due to an ovarian androblastoma (Sertoli cell tumor), J. C/in. Endocrinol. Metabol. 23, 358-367 (1963). 13. Bastidas, B. S., Chavez, N. C., and Villasenor, M. J. Tumor ovarico de celulas de Sertoli, reportre de un case, Ginecol. Obstet. Mex. 42, 269-274 (1977). 14. Ramzy, I., and Bos, C. Sertoli cell tumors of ovary. Light microscopic and ultrastructural study with histogenetic consideration, Cancer 38, 2447-2456 (1976). 15. Pick, L. Ueber Neubildungen am Genitale bei Zwittern nebst Beitraegen zur Lehre von den Adenomen des Hodens und Eierstockes. Arch. Gynaekof. 76,191-281(1905), quoted by Teilum (3). 16. Meyer, R. Tubulare (testiculare) und solide Formen des Andreioblastoma ovarii und ihre Beziehung zur Vermaennlichung, Beirr. Pathof. Amt. Alla. Parhof. 84, 485-520 (1930). 17. Novak, E. R., Jones, G. S., and Jones, H. W. Functioning ovarian tumors, in Novnk’s textbook of gynecology, Williams & Wilkins, Baltimore, pp. 536-537 (1975). 18. Sandberg, E. C. The virilizing ovary, Obstet. Gynecol. Sum. 17, 165 (1962). 19. Teilum, G. Special tumors of ovary and testis and related extragonadal lesions, in Comparative pathofogy and histological identifcarion, Lippincott, Philadelphia, 79-98 (1971).