Steroid Cell Tumors of the Ovary

Background

This is a rare catgeory of ovarian neoplasms. Most tumors are classified into several categories listed below. By definition, tumors which do not neatly fall into the categories are termed steroid cell tumors, not otherwise specified (NOS). All of the tumors have malignant potential and the majority of these tumors produce steroids with testosterone being the most common hormonal manifestation.

Granulosa cell tumor
Juvenile Granulosa cell tumor
Sertoli-Leydig Cell tumor

OUTLINE

Disease Associations

Pathogenesis

Laboratory/Radiologic/Other Diagnostic Testing

Gross Appearance and Clinical Variants

Histopathological Features and Variants

Special Stains/Immunohistochemistry/Electron Microscopy

Prognosis

Treatment

Commonly Used Terms

Internet Links

DISEASE ASSOCIATIONS CHARACTERIZATION

CONGENITAL ADRENAL HYPERPLASIA

Bilateral ovarian steroid cell tumor in congenital adrenal hyperplasia due to classic 11beta-hydroxylase deficiency.

Bas F, Saka N, Darendeliler F, Tuzlali S, Ilhan R, Bundak R, Gunoz H.

Department of of Pediatrics, Faculty of Medicine, Istanbul University, Turkey.

J Pediatr Endocrinol Metab 2000 Jun;13(6):663-7 Abstract quote
An 8.7 year-old patient, raised as a boy, presented with premature appearance of pubic hair and accelerated growth since 2 years of age and ambiguous genitalia noted at birth. There was first degree consanguinity between his parents. A similar problem was reported in a cousin.

Examination of the external genitalia revealed complete scrotal fusion, a 5 cm long phallus, urogenital sinus at base of phallus with no gonads palpable. Pigmentation was increased. His blood pressure was 150/100 mm Hg. Pubic and axillary hair were at stage 3. Bone age was 17 years. Adrenal ultrasound was normal. Pelvic ultrasound showed relatively enlarged uterus and ovaries with normal echogenicity. Karyotype was 46,XX. Hormone profile was compatible with congenital adrenal hyperplasia (CAH) due to 11beta-hydroxylase deficiency (11-deoxycortisol: 11.5 nmol/l [400 ng/dl] [normal: 0.6-4.5 nmol/l [20-155 ng/ml]], androstenedione: 17.4 nmol/l [5 ng/ml] [normal: 0.1-1.2 nmol/l [0.03-0.35 ng/ml]]). Prednisolone and antihypertensive drugs were started. The patient underwent bilateral salpingo-oophorectomy and hysterectomy at 9.1 years.

Histopathological examination of both ovaries revealed steroid cell tumor. The type of the tumor was "not otherwise specified" (NOS). Basal hormone levels and ACTH test performed 10 months after the operation and 7 days off treatment reconfirmed the diagnosis of 11beta-hydroxylase deficiency. Steroid cell tumors are extremely rare forms of steroid hormone-reducing ovarian neoplasms in childhood and may coexist with or imitate virilizing CAH.

CUSHING'S SYNDROME

Ovarian steroid cell tumors associated with Cushing's syndrome: a report of three cases.

Young RH, Scully RE.
Int J Gynecol Pathol 1987;6(1):40-8 Abstract quote
Three ovarian tumors occurring in patients 35-52 years of age resulted in clinically typical and biochemically documented Cushing's syndrome. All three tumors were of steroid cell (lipid cell) type and had metastasized within the abdomen by the time of presentation.

PATHOGENESIS CHARACTERIZATION

GENERAL

Origin of an ovarian steroid cell tumor causing isosexual pseudoprecocious puberty demonstrated by the expression of adrenal steroidogenic enzymes and adrenocorticotropin receptor.

Lin CJ, Jorge AA, Latronico AC, Marui S, Fragoso MC, Martin RM, Carvalho FM, Arnhold IJ, Mendonca BB.

Laboratorio de Hormonios e Genetica Molecular LIM/42, Disciplina de Endocrinologia, Hospital das Clinicas, Sao Paulo, Brazil.

J Clin Endocrinol Metab 2000 Mar;85(3):1211-4 Abstract quote
Ovarian steroid cell tumors are rare neoplasms composed of typical steroid hormone-secreting cells. Most ovarian steroid cell tumors, however, cannot be appropriately classified on a morphological basis, because the neoplastic cells closely resemble adrenal cortical cells. Nevertheless, the true adrenal origin of such tumors has been difficult to demonstrate.

Here we report a 3-yr-old girl with isosexual pseudoprecocious puberty due to an ovarian steroid tumor whose adrenal cell origin was determined by the presence of messenger ribonucleic acid (mRNA) of adrenal-specific steroidogenic P450 enzymes (P450c11 and P450c21) and ACTH receptor (ACTHR). Her height was +2.3 SD, and she had Tanner stage III breast development, Tanner stage II pubic hair, and a normal clitoris. Bone age was 5 yr. Basal gonadotropin levels were undetectable (<0.6 U/L for LH and <1.0 U/L for FSH) and remained undetectable after stimulation with 100 microg GnRH, i.v. Basal serum testosterone and 17-hydroxyprogesterone levels were slightly elevated, whereas basal serum androstenedione, estradiol, and dehydroepiandrosterone sulfate levels were clearly elevated.

Pelvic ultrasound disclosed an enlarged uterus and an adnexal multicystic mass in the right ovary, and pathological studies disclosed an ovarian steroid cell tumor. To establish the cellular origin of the tumor we determined the presence of mRNA for P450c11, P450c21, and ACTHR in tumor tissue and normal adrenal and ovarian tissue. Detection of ACTHR, P450c21, and P450c11 mRNAs isoforms was achieved in tumoral and adrenal control tissue, but not in the ovary control tissue. The RT-PCR products of P450c11 from adrenal control tissue were composed by both BglI-sensitive and -resistant complementary DNAs, indicating the presence of both P450c11AS and P450c11beta, whereas RT-PCR product from the tumor was resistant to BglI digestion, indicating only the presence of P450c11beta.

We conclude that the histological origin of so-called adrenal rest tumor could be reliably determined by assessing the expression of specific genes in the tumor as P450c11beta and P450c21. The use ofthese molecular tools will allow a more precise classification of an important subset of the ovarian steroid cell tumors and can help to identify ectopic adrenal tissue in ovary and testis.

GONADOTROPINS

Role of gonadotropins in malignant progression of sex cord stromal tumors produced by sequential auto- and isogenic transplantation of ovarian tissue in ovariectomized rats.

Dittrich R, Recabarren S, Mitze M, Jaeger W.

Department of Obstetrics and Gynecology, University of Erlangen-Nuremberg, Erlangen, Germany.
J Cancer Res Clin Oncol 2001 Aug;127(8):495-501 Abstract quote
PURPOSE: In this study the effect of continuous stimulation of gonadotropins on sex cord stromal tumors in the rat was examined.

METHODS: Sex cord stromal tumors were induced by transplantation of ovaries under the splenic capsule of ovariectomized rats. Beginning 180 days after transplantation, these tumors were taken out and cut into several pieces, which were then retransplanted (by isotransplantation) under the splenic capsule of 80 either intact or ovariectomized rats.

RESULTS: Most of the tumor grafts grew up to a median size of 0.7 cm in ovariectomized rats. However, some of the tumors recovered from recipient rats that were retransplanted with donor tumors differed significantly from the others. Characterized by a high mitotic rate, nuclear atypia, size (up to 3.8 cm) as well as growth in intact animals, these tumors were defined as malignant. They could be kept in culture and always led to the development of metastases after retransplantation into other rats.

CONCLUSION: Benign sex cord stromal tumors can show malignant growth after transplantation. This study for the first time demonstrates that gonadotropins are involved in the induction of ovarian malignancies.

LABORATORY/RADIOLOGIC/
OTHER TESTS
CHARACTERIZATION

RADIOLOGIC

Steroid cell tumors of the ovary: clinical, ultrasonic, and MRI diagnosis--a case report.

Wang PH, Chao HT, Lee RC, Lai CR, Lee WL, Kwok CF, Yuan CC, Ng HT.

Department of Obstetrics and Gynecology, Veterans General Hospital-Taipei, Taiwan, ROC

Eur J Radiol 1998 Feb;26(3):269-73 Abstract quote
Steroid cell tumors of the ovary are rare sex-cord neoplasms which account for less than 0.1% of all ovarian tumors.

They have been divided into two subtypes according to their cell of origin as follows: stromal luteoma, and Leydig cell tumors, and a third subtype with lineage unknown is a steroid cell tumor, not otherwise specified (NOS).

The clinical presentation may take many forms, including pain, abdominal distention and bloating, but perhaps the most interesting and noticeable presentations are those related to the hormonal activity and virilizing properties of the tumor. No radiological features of the steroid cell tumor, NOS have been presented in the literature.

This report presents the MRI and ultrasonographic findings of a patient having steroid cell tumor, NOS, of the right ovary with metastasis to the uterus.

LABORATORY MARKERS

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

GENERAL

Ovarian steroid cell tumors, not otherwise specified: a case report and literature review.

Reedy MB, Richards WE, Ueland F, Uy K, Lee EY, Bryant C, van Nagell JR Jr.

Department of Obstetrics and Gynecology, The University of Kentucky Chandler Medical Center, Lexington, Kentucky 40536-0298, USA.
Gynecol Oncol 1999 Nov;75(2):293-7 Abstract quote
Steroid cell tumors, not otherwise specified, are rare ovarian sex cord-stromal tumors with malignant potential.

The majority of these tumors produce steroids with testosterone being the most common. A case of a 46-year-old woman who presented with sudden onset of virilization and a pelvic mass is reported.

Various aspects of the presentation, diagnosis, and treatment of these tumors are discussed.

VARIANTS

EXTRA-OVARIAN

Extraovarian steroid cell tumor 'not otherwise specified' as a rare cause of virilization in twelve-year-old girl.

Dumic M, Simunic V, Ilic-Forko J, Cvitanovic M, Plavsic V, Janjanin N, Ille J.

Department of Pediatrics, University Hospital Zagreb-Rebro, Zagreb, Croatia.
Horm Res 2001;55(5):254-7 Abstract quote
BACKGROUND: We present a 12-year-old girl with a 5-year history of progressive virilization.

RESULTS: Regarding elevated plasma levels of 17-hydroxyprogesterone (17-OHP) and androgens, normal ultrasound and CT scan of ovaries and adrenal glands, the nonclassic form of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency was presumed the cause of virilization. As the glucocorticoid therapy did not normalize high levels of 17-OHP and androgens, and the DNA analysis did not demonstrate a mutation causing CAH, a laparotomy was performed. Near the right ovary a tumor was found and extirpated. Pathohistological studies determined it to be a rare steroid cell tumor, 'not otherwise specified'. Within the next months the signs of virilization resolved and menarche occurred.

CONCLUSIONS: Steroid cell tumor should be considered in differential diagnosis of virilization in childhood. Regarding the age of our patient and pathohistological findings of the tumor, her prognosis is favorable.

Extraovarian sex cord-stromal tumor: case report and review of the literature.

Keitoku M, Konishi I, Nanbu K, Yamamoto S, Mandai M, Kataoka N, Oishi T, Mori T.

Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoto University, Japan.
Int J Gynecol Pathol 1997 Apr;16(2):180-5 Abstract quote
A 45-year-old woman was found at laparotomy to have a multinodular solid tumor within the broad ligament, which was removed by total hysterectomy and bilateral salpingo-oophorectomy. Both ovaries were unremarkable.

Three years after the operation, retroperitoneal tumor was detected, which was associated with clinical evidence of estrogen production. Histological examination of the primary and retroperitoneal tumors showed histological features that resembled those of granulosa cell tumors.

Previously reported sex cord-stromal tumors arising in extraovarian sites were reviewed with respect to the histogenesis of these tumors.

PEDIATRIC

Steroid cell tumor of the ovary in a child.

Harris AC, Wakely PE Jr, Kaplowitz PB, Lovinger RD.

Department of Pathology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Arch Pathol Lab Med 1991 Feb;115(2):150-4 Abstract quote
An 8-year-old girl exhibited severe, progressive virilization of 2 years' duration associated with markedly elevated circulating testosterone concentrations.

Based on her initial clinical presentation and results of a chemical evaluation, she was originally thought to have non-classic 21-hydroxylase deficiency, but her condition did not respond to corticosteroid therapy. Further evaluation confirmed the presence of an ovarian neoplasm. The excised ovary contained an attached gray-brown mass. Light microscopic and ultrastructural examination revealed the mass to be a steroid cell tumor. Because Reinke's crystals were not present, it was designated to be a steroid cell tumor not otherwise specified.

This case represents one of 22 reported cases of steroid cell tumor occurring in children described in the literature, most of which have been associated with heterosexual precocity. To our knowledge, steroid cell tumors are benign when they occur in prepubertal children. Although they are rare, steroid cell tumors of the ovary should be considered in cases of childhood virilization.

VIRILIZATION

Ovarian steroid cell tumor and a contralateral ovarian thecoma in a postmenopausal woman with severe hyperandrogenism.

Cserepes E, Szucs N, Patkos P, Csapo Z, Molnar F, Toth M, Dabasi G, Esik O, Racz K.

Department of Radiology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary.

Gynecol Endocrinol 2002 Jun;16(3):213-6 Abstract quote
A 49-year-old woman presented with rapidly progressing hirsutism, receding hairline, male-pattern baldness and deepening of voice, which had developed over the past 2 years. Hormonal evaluation showed a markedly elevated serum testosterone level (418 ng/dl) and no evidence of increased production of cortisol, dehydroepiandrosterone, dehydroepiadrosterone-sulfate, androstenedione, or 17-hydroxyprogesterone.

Transvaginal ultrasound examination suggested the presence of a small mass within the left ovary, but all other radiological studies, including adrenal and ovarian computed tomography, magnetic resonance imaging, radio-labelled cholesterol scintigraphy and positron emission tomography, were negative. Subsequently, bilateral selective venous sampling showed a marked testosterone gradient in the right ovarian vein. Bilateral salpingo-oophorectomy was performed (the patient had had a previous vaginal hysterectomy), and histopathological examination revealed a 10-mm steroid cell tumor within the right ovary and a 15-mm thecal cell tumor within the left ovary. The postoperative serum testosterone level returned to normal and the patient showed a slow regression of clinical symptoms.

The simultaneous occurrence of a virilizing ovarian steroid cell tumor and an apparently non-functioning thecoma within the contralateral ovary emphasizes the potential pitfalls that may exist in the preoperative evaluation of patients with markedly increased testosterone production.

Androgen-secreting steroid cell tumor of the ovary.

Powell JL, Dulaney DP, Shiro BC.

Department of Obstetrics and Gynecology, New Hanover Regional Medical Center, University of North Carolina School of Medicine, Wilmington 28402-9025, USA.

South Med J 2000 Dec;93(12):1201-4 Abstract quote
We present the case of a 93-year-old virilized woman with an androgen-secreting ovarian tumor. This rare ovarian sex cord stromal tumor behaved in a malignant fashion.

Various aspects of the presentation, diagnosis, and treatment of these tumors are discussed.

Androgen-producing ovarian tumors: a clinicopathological study of 3 cases.

Arai M, Jobo T, Iwaya H, Sato R, Watanabe J, Ohno E, Kuramoto H.

Department of Obstetrics and Gynecology, School of Medicine, Kitasato University, Kanagawa, Japan.
J Obstet Gynaecol Res 1999 Dec;25(6):411-8 Abstract quote
The clinical course and pathological findings of 3 rare cases of androgen-producing ovarian tumors are presented. The ages of the 3 patients (Cases 1, 2, and 3, respectively) were 43, 34, and 57 years, respectively. Their preoperative serum testosterone levels were 506, 491, and 231 ng/dl, respectively.

The pathological diagnoses of Cases 1, 2, and 3 were a Sertoli-stromal cell tumor of intermediate differentiation, a stromal tumor containing Leydig cells, and a stromal tumor with minor sex cord elements, respectively.

Patient 1 experienced a recurrence, of a lesion at the vaginal stump 1 year and 2 months after the initial surgery. The clinical courses of Cases 2 and 3 have been non-contributory.

Virilizing ovarian tumor of cell tumor type not otherwise specified: a case report.

Faraj G, Di Gregorio S, Misiunas A, Faure EN, Villabrile P, Stringa I, Petroff N, Bur G.

Endocrinology, Service of Hospital Churruca-Visca, Buenos Aires, Argentina.

Gynecol Endocrinol 1998 Oct;12(5):347-52 Abstract quote
Whereas ovarian tumors with overt endocrine manifestations account for less than 5% of all ovarian neoplasms, the incidence of virilizing type tumors in postmenopausal women is even lower since the average age of occurrence is 43 years. Steroid cell tumors not otherwise specified (NOS) are even more rare.

We report the case of a 56-year-old woman (age of onset of menopause 43 years) who consulted our service due to a hyperandrogenic syndrome: deepening of the voice, temporal balding, hirsutism and cliteromegaly. Laboratory findings indicated hyperandrogenism in male range. The dexamethasone suppression test did not modify basal values, indicating that adrenal origin was unlikely. Transvaginal ultrasound disclosed multiple microcysts in the left ovary. Abdominal tomography was normal. Suspecting an ovarian tumor, bilateral oophorectomy was performed and a pediculate, 3 cm in diameter, was encountered in the left ovary. Histopathological studies determined it to be a virilizing ovarian tumor NOS.

Postoperative recovery was fast; normal hormonal values were reached together with visible clinical improvement. This case is reported because this type of tumor is very infrequent in postmenopausal women, and because in this case it was the functional hormonal test that allowed tumor localization.

HISTOLOGICAL TYPES CHARACTERIZATION

GENERAL

Unclassified sex cord-stromal tumors of the ovary: a report of eight cases.

Simpson JL, Michael H, Roth LM.

Department of Pathology, Indiana University Medical Center, Indiana University, Indianapolis 46202-5280, USA.
Arch Pathol Lab Med 1998 Jan;122(1):52-5 Abstract quote
OBJECTIVE: To evaluate the histologic features and biologic behavior of unclassified sex cord-stromal tumors.

PATIENTS: The eight patients' ages at presentation ranged from 14 to 83 years. Presenting symptoms and physical findings included abdominal pain, abnormal uterine bleeding, ascites, and abdominal and pelvic masses. One patient also had bilateral sex cord tumors with annual tubules and probable Peutz-Jeghers syndrome.

RESULTS: The tumors ranged from 4 to 27 cm in diameter and were described as partially encapsulated, solid, and cystic. Histologically, the tumors were composed of diffuse proliferations of sex cord cells, with cords, tubules, and follicle-like structures. The stromal cells were spindle-shaped, with scanty cytoplasm. The neoplasms were vimentin-positive and, sometimes, cytokeratin CAM 5.2- and AE1/3-positive and epithelial membrane antigen-negative. Six patients were disease-free from 2 months to 6 years after operation. One patient was lost to follow-up. The patient with probable Peutz-Jeghers syndrome had a tumor with unusual morphology and died of the neoplasm 4 years after the diagnosis. Three of 32 other cases with clinical follow-up mentioned in the pathology literature have been associated with a malignant behavior.

CONCLUSION: The biologic behavior of unclassified sex cord-stromal tumors resembles that of Sertoli-Leydig cell tumors of intermediate differentiation rather than poorly differentiated tumors, which might have been expected in view of the lack of specific differentiation. This finding is important with regard to postoperative management.

SPECIAL STAINS/IMMUNOPEROXIDASE/
OTHER CHARACTERIZATION

SPECIAL STAINS

IMMUNOPEROXIDASE

GENERAL

Ovarian sex cord-stromal tumors: an immunohistochemical study including a comparison of calretinin and inhibin.

Deavers MT, Malpica A, Liu J, Broaddus R, Silva EG.

Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Mod Pathol. 2003 Jun;16(6):584-90. Abstract quote
Because ovarian sex cord-stromal tumors (SCST) are morphologically heterogeneous neoplasms that are relatively infrequently encountered, their diagnosis can be difficult. Immunohistochemical staining may be useful for establishing the diagnosis in problematic cases.

We studied 53 ovarian SCSTs to characterize their immunohistochemical staining pattern: 17 adult granulosa cell tumors (AGCTs), 4 juvenile granulosa cell tumors (JGCTs), 3 sex cord tumors with annular tubules (SCTATs), 9 Sertoli-Leydig cell tumors (SLCTs), 10 fibromas, 5 fibrothecomas (FTs), and 5 thecomas. In 8 of the 53 cases, the tissue studied was from a metastatic site. The immunopanel included calretinin, inhibin, WT1, cytokeratin cocktail, epithelial membrane antigen (EMA), and cytokeratin 5/6 (CK5/6). The fibromas and FTs were also tested with CD10. The extent of staining was assessed in a semiquantitative fashion and ranked on a scale of 0 through 4+. All of the tumors, except for 1 metastatic SLCT, were positive for calretinin. Forty-five of the cases (85%) stained for inhibin; 1 metastatic AGCT, 3 fibromas, and 4 FTs were negative. WT1 was present in 39 tumors (74%), with expression most prominent in the SLCTs. The cytokeratin cocktail stained 23 of the 53 tumors (43%), whereas just 1 tumor was positive for EMA (1+ in a JGCT). All tumors were negative for CK5/6, and the 15 fibromas and FTs were negative for CD10.

We conclude that because cytokeratin is frequently expressed by SCSTs, in particular by granulosa cell tumors, SLCTs, and SCTATs, the inclusion of EMA in a panel may help to exclude epithelial neoplasms. In addition, WT1, present in normal granulosa cells, is expressed by a majority of SCSTs. Finally, these results demonstrate that calretinin is at least as sensitive as inhibin for ovarian SCSTs overall and that it is more sensitive than inhibin for fibromas and FTs.

Ovarian steroid cell tumors: an immunohistochemical study including a comparison of calretinin with inhibin.

Deavers MT, Malpica A, Ordonez NG, Silva EG.
Int J Gynecol Pathol 2003 Apr;22(2):162-7 Abstract quote
Ovarian steroid cell tumors, not otherwise specified (SCTs, NOS) are uncommon sex cord-stromal tumors that may be difficult to distinguish from other oxyphilic or clear-cell neoplasms. Immunohistochemical staining for inhibin, although generally useful in the diagnosis of SCTs, NOS, is not positive in every case and not all laboratories have this marker available. Recently, it has been reported that calretinin is expressed by sex cord-stromal tumors.

We studied six SCTs, NOS for both calretinin and inhibin expression to evaluate the sensitivity of calretinin in comparison to inhibin. We also tested for CD99, Melan-A (A103), and S-100, other markers reported to be positive in these tumors. HMB-45 and MART-1 (Ab3) completed our panel of markers. All six tumors were positive for both calretinin and inhibin. Calretinin positivity was present in 60% to >90% of tumor cells, whereas inhibin reactivity ranged from <5% to >90% of tumor cells. Membranous staining for CD99 was present in one tumor. S-100-positive cells were seen in two tumors, whereas four tumors were immunoreactive for HMB-45. All six tumors were positive for Melan-A (A103), but in general the staining was less diffuse than with calretinin. All of the tumors were essentially negative for MART-1 (Ab3).

The consistent diffuse staining of the tumors in this study for calretinin, in comparison to inhibin and Melan-A (A103), suggests that it is a sensitive marker for SCTs, NOS. MART-1 (Ab3) immunostaining may be useful for cases in which melanoma is considered in the differential diagnosis.

ELECTRON MICROSCOPY

PROGNOSIS CHARACTERIZATION

GENERAL Dependent upon the stage

TREATMENT CHARACTERIZATION

GENERAL Dependent upon the stage

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Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

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Last Updated 7/3/2003

Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/Immunohistochemistry/Electron Microscopy
Prognosis
Treatment
Commonly Used Terms
Internet Links

DISEASE ASSOCIATIONS	CHARACTERIZATION
CONGENITAL ADRENAL HYPERPLASIA
Bilateral ovarian steroid cell tumor in congenital adrenal hyperplasia due to classic 11beta-hydroxylase deficiency. Bas F, Saka N, Darendeliler F, Tuzlali S, Ilhan R, Bundak R, Gunoz H. Department of of Pediatrics, Faculty of Medicine, Istanbul University, Turkey.	J Pediatr Endocrinol Metab 2000 Jun;13(6):663-7 Abstract quote An 8.7 year-old patient, raised as a boy, presented with premature appearance of pubic hair and accelerated growth since 2 years of age and ambiguous genitalia noted at birth. There was first degree consanguinity between his parents. A similar problem was reported in a cousin. Examination of the external genitalia revealed complete scrotal fusion, a 5 cm long phallus, urogenital sinus at base of phallus with no gonads palpable. Pigmentation was increased. His blood pressure was 150/100 mm Hg. Pubic and axillary hair were at stage 3. Bone age was 17 years. Adrenal ultrasound was normal. Pelvic ultrasound showed relatively enlarged uterus and ovaries with normal echogenicity. Karyotype was 46,XX. Hormone profile was compatible with congenital adrenal hyperplasia (CAH) due to 11beta-hydroxylase deficiency (11-deoxycortisol: 11.5 nmol/l [400 ng/dl] [normal: 0.6-4.5 nmol/l [20-155 ng/ml]], androstenedione: 17.4 nmol/l [5 ng/ml] [normal: 0.1-1.2 nmol/l [0.03-0.35 ng/ml]]). Prednisolone and antihypertensive drugs were started. The patient underwent bilateral salpingo-oophorectomy and hysterectomy at 9.1 years. Histopathological examination of both ovaries revealed steroid cell tumor. The type of the tumor was "not otherwise specified" (NOS). Basal hormone levels and ACTH test performed 10 months after the operation and 7 days off treatment reconfirmed the diagnosis of 11beta-hydroxylase deficiency. Steroid cell tumors are extremely rare forms of steroid hormone-reducing ovarian neoplasms in childhood and may coexist with or imitate virilizing CAH.
CUSHING'S SYNDROME
Ovarian steroid cell tumors associated with Cushing's syndrome: a report of three cases. Young RH, Scully RE.	Int J Gynecol Pathol 1987;6(1):40-8 Abstract quote Three ovarian tumors occurring in patients 35-52 years of age resulted in clinically typical and biochemically documented Cushing's syndrome. All three tumors were of steroid cell (lipid cell) type and had metastasized within the abdomen by the time of presentation.

PATHOGENESIS	CHARACTERIZATION
GENERAL
Origin of an ovarian steroid cell tumor causing isosexual pseudoprecocious puberty demonstrated by the expression of adrenal steroidogenic enzymes and adrenocorticotropin receptor. Lin CJ, Jorge AA, Latronico AC, Marui S, Fragoso MC, Martin RM, Carvalho FM, Arnhold IJ, Mendonca BB. Laboratorio de Hormonios e Genetica Molecular LIM/42, Disciplina de Endocrinologia, Hospital das Clinicas, Sao Paulo, Brazil.	J Clin Endocrinol Metab 2000 Mar;85(3):1211-4 Abstract quote Ovarian steroid cell tumors are rare neoplasms composed of typical steroid hormone-secreting cells. Most ovarian steroid cell tumors, however, cannot be appropriately classified on a morphological basis, because the neoplastic cells closely resemble adrenal cortical cells. Nevertheless, the true adrenal origin of such tumors has been difficult to demonstrate. Here we report a 3-yr-old girl with isosexual pseudoprecocious puberty due to an ovarian steroid tumor whose adrenal cell origin was determined by the presence of messenger ribonucleic acid (mRNA) of adrenal-specific steroidogenic P450 enzymes (P450c11 and P450c21) and ACTH receptor (ACTHR). Her height was +2.3 SD, and she had Tanner stage III breast development, Tanner stage II pubic hair, and a normal clitoris. Bone age was 5 yr. Basal gonadotropin levels were undetectable (<0.6 U/L for LH and <1.0 U/L for FSH) and remained undetectable after stimulation with 100 microg GnRH, i.v. Basal serum testosterone and 17-hydroxyprogesterone levels were slightly elevated, whereas basal serum androstenedione, estradiol, and dehydroepiandrosterone sulfate levels were clearly elevated. Pelvic ultrasound disclosed an enlarged uterus and an adnexal multicystic mass in the right ovary, and pathological studies disclosed an ovarian steroid cell tumor. To establish the cellular origin of the tumor we determined the presence of mRNA for P450c11, P450c21, and ACTHR in tumor tissue and normal adrenal and ovarian tissue. Detection of ACTHR, P450c21, and P450c11 mRNAs isoforms was achieved in tumoral and adrenal control tissue, but not in the ovary control tissue. The RT-PCR products of P450c11 from adrenal control tissue were composed by both BglI-sensitive and -resistant complementary DNAs, indicating the presence of both P450c11AS and P450c11beta, whereas RT-PCR product from the tumor was resistant to BglI digestion, indicating only the presence of P450c11beta. We conclude that the histological origin of so-called adrenal rest tumor could be reliably determined by assessing the expression of specific genes in the tumor as P450c11beta and P450c21. The use ofthese molecular tools will allow a more precise classification of an important subset of the ovarian steroid cell tumors and can help to identify ectopic adrenal tissue in ovary and testis.
GONADOTROPINS
Role of gonadotropins in malignant progression of sex cord stromal tumors produced by sequential auto- and isogenic transplantation of ovarian tissue in ovariectomized rats. Dittrich R, Recabarren S, Mitze M, Jaeger W. Department of Obstetrics and Gynecology, University of Erlangen-Nuremberg, Erlangen, Germany.	J Cancer Res Clin Oncol 2001 Aug;127(8):495-501 Abstract quote PURPOSE: In this study the effect of continuous stimulation of gonadotropins on sex cord stromal tumors in the rat was examined. METHODS: Sex cord stromal tumors were induced by transplantation of ovaries under the splenic capsule of ovariectomized rats. Beginning 180 days after transplantation, these tumors were taken out and cut into several pieces, which were then retransplanted (by isotransplantation) under the splenic capsule of 80 either intact or ovariectomized rats. RESULTS: Most of the tumor grafts grew up to a median size of 0.7 cm in ovariectomized rats. However, some of the tumors recovered from recipient rats that were retransplanted with donor tumors differed significantly from the others. Characterized by a high mitotic rate, nuclear atypia, size (up to 3.8 cm) as well as growth in intact animals, these tumors were defined as malignant. They could be kept in culture and always led to the development of metastases after retransplantation into other rats. CONCLUSION: Benign sex cord stromal tumors can show malignant growth after transplantation. This study for the first time demonstrates that gonadotropins are involved in the induction of ovarian malignancies.

LABORATORY/RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
RADIOLOGIC
Steroid cell tumors of the ovary: clinical, ultrasonic, and MRI diagnosis--a case report. Wang PH, Chao HT, Lee RC, Lai CR, Lee WL, Kwok CF, Yuan CC, Ng HT. Department of Obstetrics and Gynecology, Veterans General Hospital-Taipei, Taiwan, ROC	Eur J Radiol 1998 Feb;26(3):269-73 Abstract quote Steroid cell tumors of the ovary are rare sex-cord neoplasms which account for less than 0.1% of all ovarian tumors. They have been divided into two subtypes according to their cell of origin as follows: stromal luteoma, and Leydig cell tumors, and a third subtype with lineage unknown is a steroid cell tumor, not otherwise specified (NOS). The clinical presentation may take many forms, including pain, abdominal distention and bloating, but perhaps the most interesting and noticeable presentations are those related to the hormonal activity and virilizing properties of the tumor. No radiological features of the steroid cell tumor, NOS have been presented in the literature. This report presents the MRI and ultrasonographic findings of a patient having steroid cell tumor, NOS, of the right ovary with metastasis to the uterus.
LABORATORY MARKERS

SPECIAL STAINS/IMMUNOPEROXIDASE/ OTHER	CHARACTERIZATION
SPECIAL STAINS
IMMUNOPEROXIDASE
GENERAL
Ovarian sex cord-stromal tumors: an immunohistochemical study including a comparison of calretinin and inhibin. Deavers MT, Malpica A, Liu J, Broaddus R, Silva EG. Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.	Mod Pathol. 2003 Jun;16(6):584-90. Abstract quote Because ovarian sex cord-stromal tumors (SCST) are morphologically heterogeneous neoplasms that are relatively infrequently encountered, their diagnosis can be difficult. Immunohistochemical staining may be useful for establishing the diagnosis in problematic cases. We studied 53 ovarian SCSTs to characterize their immunohistochemical staining pattern: 17 adult granulosa cell tumors (AGCTs), 4 juvenile granulosa cell tumors (JGCTs), 3 sex cord tumors with annular tubules (SCTATs), 9 Sertoli-Leydig cell tumors (SLCTs), 10 fibromas, 5 fibrothecomas (FTs), and 5 thecomas. In 8 of the 53 cases, the tissue studied was from a metastatic site. The immunopanel included calretinin, inhibin, WT1, cytokeratin cocktail, epithelial membrane antigen (EMA), and cytokeratin 5/6 (CK5/6). The fibromas and FTs were also tested with CD10. The extent of staining was assessed in a semiquantitative fashion and ranked on a scale of 0 through 4+. All of the tumors, except for 1 metastatic SLCT, were positive for calretinin. Forty-five of the cases (85%) stained for inhibin; 1 metastatic AGCT, 3 fibromas, and 4 FTs were negative. WT1 was present in 39 tumors (74%), with expression most prominent in the SLCTs. The cytokeratin cocktail stained 23 of the 53 tumors (43%), whereas just 1 tumor was positive for EMA (1+ in a JGCT). All tumors were negative for CK5/6, and the 15 fibromas and FTs were negative for CD10. We conclude that because cytokeratin is frequently expressed by SCSTs, in particular by granulosa cell tumors, SLCTs, and SCTATs, the inclusion of EMA in a panel may help to exclude epithelial neoplasms. In addition, WT1, present in normal granulosa cells, is expressed by a majority of SCSTs. Finally, these results demonstrate that calretinin is at least as sensitive as inhibin for ovarian SCSTs overall and that it is more sensitive than inhibin for fibromas and FTs.
Ovarian steroid cell tumors: an immunohistochemical study including a comparison of calretinin with inhibin. Deavers MT, Malpica A, Ordonez NG, Silva EG.	Int J Gynecol Pathol 2003 Apr;22(2):162-7 Abstract quote Ovarian steroid cell tumors, not otherwise specified (SCTs, NOS) are uncommon sex cord-stromal tumors that may be difficult to distinguish from other oxyphilic or clear-cell neoplasms. Immunohistochemical staining for inhibin, although generally useful in the diagnosis of SCTs, NOS, is not positive in every case and not all laboratories have this marker available. Recently, it has been reported that calretinin is expressed by sex cord-stromal tumors. We studied six SCTs, NOS for both calretinin and inhibin expression to evaluate the sensitivity of calretinin in comparison to inhibin. We also tested for CD99, Melan-A (A103), and S-100, other markers reported to be positive in these tumors. HMB-45 and MART-1 (Ab3) completed our panel of markers. All six tumors were positive for both calretinin and inhibin. Calretinin positivity was present in 60% to >90% of tumor cells, whereas inhibin reactivity ranged from <5% to >90% of tumor cells. Membranous staining for CD99 was present in one tumor. S-100-positive cells were seen in two tumors, whereas four tumors were immunoreactive for HMB-45. All six tumors were positive for Melan-A (A103), but in general the staining was less diffuse than with calretinin. All of the tumors were essentially negative for MART-1 (Ab3). The consistent diffuse staining of the tumors in this study for calretinin, in comparison to inhibin and Melan-A (A103), suggests that it is a sensitive marker for SCTs, NOS. MART-1 (Ab3) immunostaining may be useful for cases in which melanoma is considered in the differential diagnosis.
ELECTRON MICROSCOPY