| Abstract|| |
Steroid cell tumors (SCTs), not otherwise specified of the ovary are rare subgroup of sex cord tumors, which account for less than 0.1% of all ovarian tumors and also that will present at any age. The majority of these tumors produce steroids with testosterone being the most common. A case of a 28-year-old woman who presented with symptoms of virilization is reported. Although SCTs are generally benign, there is a risk for malignant transformation. Surgery is the most important and hallmark treatment.
Keywords: Cystectomy, ovary, Steroid cell tumor, virilization
|How to cite this article:|
Udhreja PR, Banerji A, Desai DP, Vaishnani JB. Androgen - secreting steroid cell tumor of the ovary. Indian J Pathol Microbiol 2014;57:94-7
| Introduction|| |
The term steroid cell tumor was proposed in the late 1970's by Scully,  to more accurately describe both the morphological features of the tumor cells and their intrinsic property of synthesizing steroid hormones. , Steroid cell tumors (SCTs) of the ovary are rare subgroup of sex cord tumors, account for less than 0.1% of all ovarian tumors and also that will present at any age.  In the most recent World Health Organization classification, these tumors are called steroid cell tumors and they are sub-classified as (1) stromal luteoma arising from ovarian stroma (2) leydig cell tumors (hilus cell tumor and leydig cell tumor, non-hilar type) arising from leydig cell (3) steroid cell tumors not otherwise specified (NOS) when the lineage of tumor is unknown.  A minor proportion of the tumors in the last subgroup show clinically malignant behavior, whereas those in the first two categories are invariably benign.  Steroid cell tumors NOS account for over 60% of all SCTs of the ovary. , They occur at any age but the patients are typically younger (mean 43 years) than those with the other types of SCTs. , Patients with clinically malignant tumors were shown to be significantly (more than 15 years) older than patients with benign tumors.  So far, no malignant SCTs NOS have been reported in women under 30 years of age. , In a series of 63 cases from Massachusetts General Hospital, 94% of the tumors were found to be unilateral and 28.6% were malignant.  In the earlier literature, ovarian tumors composed of cells resembling typical steroid hormone-secreting cells (i.e. lutein cells, leydig cells, or adrenal cortical cells) have been called with a variety of names, including the following: (1) adrenal rest tumors, (2) adrenal-like tumors, (3) masculinovoblastomas, (4) lipoid cell tumors and (5) lipid cell tumors. , These tumors can produce steroids, especially testosterone and may give symptoms such as hirsutism, hair loss, amenorrhea or oligomenorrhea. 
| Case Report|| |
This was a case report of a 28-year-old woman, presented to skin out-patient department (OPD) with excessive hair growth over face, change in voice, weight gain and scanty menses. Physical examination revealed a male pattern of coarse hair distribution in the beard region [Figure 1], anterior chest wall and arms. Abdominal examination showed no abnormality and vaginal examination disclosed clitoromegaly. Computed tomography of the abdomen revealed a round solid heterogenously enhancing hyperdense mass measuring 31 mm × 28 mm × 33 mm arising from right ovary. There was no free fluid, significant lymphadenopathy, or adrenal gland enlargement.
|Figure 1: 28-year-old woman presented to skin out-patient department with excessive hair growth over face|
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Her laboratory findings showed normal hemogram, electrolyte, creatinine liver enzyme levels, sex hormone binding globulin, thyroid function test, follicle-stimulating hormone, luteinizing hormone, prolactin and dehydroepiandrosterone sulfate. The testosterone level was 13.53 ng/ml. Estradiol level was not measured. The patient underwent an exploratory laparotomy, due to the possibility of malignancy; right ovarian oopherectomy was performed and frozen section revealed a SCT. The other ovary was normal.
Macroscopic examination showed a well-circumscribed tumoral mass measured as 3.4 cm × 2.5 cm × 2 cm. The neoplasm had a lobulated, solid, homogeneous, yellow cut surface without area of hemorrhage and necrosis [Figure 2].
Imprint cytology showed scattered single polygonal cells with centrally placed nucleus and vacuolated clear cytoplasm [Figure 3].
Microscopic examination showed diffuse sheets of large polygonal to round tumor cells with distinct cell border, centrally placed nuclei and moderate to abundant cytoplasm. Cytoplasm is vacuolated to eosinophilic and granular with vesicular nuclei along with presence of prominent nucleoli. Crystals of Reinke, which are usually seen in hilus tumors, were not seen. No evidence of atypia or mitosis [Figure 4] and [Figure 5].
Her symptoms regressed at the post-operative 2 nd month and her menses period came back. The patient is followed up closely and regularly with measurement of hormone levels and pelvic ultrasound as markers of recurrence.
| Discussion|| |
Ovarian SCTs account for less than 0.1% of all ovarian tumors.  They are grouped under sex-cord stromal tumors and are usually benign, unilateral and characterized by a steroid cell proliferation. , They are further divided into three subtypes: Stromal leuteoma, leydig cell tumor and SCT NOS type, ,, the latter being the most common of the three subtypes accounting for approximately 60% of cases. Difference between subtypes of SCTs is shown in [Table 1].
|Table 1: Difference between subtypes of steroid cell tumor and related findings in this case|
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SCTs are associated with androgenic changes with variable frequency, ranging from 12% to over 50% ,, and they are usually of many years duration. , This case is unique because the patient first presented to skin OPD for complain of excessive hair growth on face.
Historically these tumors have been variously referred to as lipoid cell tumors, lipid cell tumors, adrenal-like tumors, masculinovoblastomas, leutomas, hypernephroid tumors and adrenal rest tumors, indicating the infidelity of their supposed lineage. ,,,
The majority of SCTs have a benign or low-grade behavior. Interestingly, pathologically-benign tumors can behave in a clinically malignant fashion.  About 20% patients develop metastatic lesions usually within the peritoneal cavity, and rarely at distant sites.  In a series of 63 cases from the Massachusetts General Hospital, 94% of the tumors were found to be unilateral and 28.6% cases had features suggestive of malignant nature. 
Hayes and Scully  have identified five pathologic features that are highly associated with malignancy: More than two mitoses per high-power field; necrosis; size of 7 cm or larger; hemorrhage; and Grade 2 or 3 nuclear atypia. The final pathologic diagnosis is based on the characteristic histological appearance, including polygonal to round cells with distinct cell borders and an abundant cytoplasm and the absence of Reinke's crystals, and a characteristic pattern of immunohistochemistry staining for inhibin and vimentin (75%), anti-human cytokeratin (46 %), and AE1/AE3 (37 %). 
There are no special features in their gross appearance that would enable the distinction of lipid cell tumors NOS from the other lipid cell tumors. The tumors are typically solid and well circumscribed, are occasionally lobulated, and have a mean diameter of 8.4 cm. The cut surfaces are typically yellow or orange if large amounts of lipid are present, red to brown if the cells are lipid-poor or dark brown to black if large quantities of cytoplasmic lipochrome pigment are present. Necrosis, hemorrhage and cystic degeneration are occasionally observed. Only 5% of these tumors have been bilateral. ,,
On microscopic examination, a characteristic steroid cell tumor NOS is presented with cells that are typically arranged diffusely.  Occasionally, the cells are found to grow in large aggregates, solid nests, clusters, cords, or even in columnar pattern. According to the description by Hayes and Scully,  the tumor cells are polygonal or rounded, with distinct cell borders, central nuclei, and moderate to abundant cytoplasm. Nuclei may contain prominent nucleoli, and the cytoplasm varies from eosinophilic and granular (in lipid-free or lipid poor tumors) to vacuolated and spongy (in lipid-rich lesions). 
The stroma is typically inconspicuous, but prominent in a minor proportion of cases. Sometimes the stroma may be edematous or even myxoid, with scattered tumor cells within. Stromal calcification and abundant psammoma bodies is an extreme occurrence. ,,
The discovery of a prominent fibromatous component in some of these tumors led the authors to speculate that some steroid cell tumors may be, indeed, completely luteinized thecomas. 
In tumors with significant cytological atypia, necrosis and hemorrhage may be a prominent feature. , In the largest series published so far, nuclear atypia of various grades (Grade 1-3) was associated with a concomitant increase in mitotic activity (up to 15 mitotic figures/10 high-power fields).  In the same series, the assessment of this mitotic activity was the best predictor of their malignant behavior.  Importantly, however, some steroid cell tumors NOS with cytologically benign appearance, may be clinically malignant. ,
The primary treatment is surgical extirpation of the primary lesion, and there are no reports of effective radiation or chemotherapy. In a young patient with stage IA disease, a unilateral salpingo-oophorectomy is adequate since the frequency of bilateral occurrence is only 6%. ,
The main reason for poor understanding of the therapeutic value of chemotherapy and radiotherapy in the treatment of these tumors is due to the rarity of this tumor. In recent years attempts have been made to describe the use of gonadotrophin releasing hormone analogues to induce a suppression of secretions and an apoptosis leading to a non-surgical cure. Further insight into the nature, biology and behavior of these tumors may change the gold standard of treatment from surgical extirpation to medical management over time.
| Conclusion|| |
SCTs grouped under sex-chord stromal tumors, account for less than 0.1% of all ovarian tumors and androgenic symptoms with increased testosterone levels are important suspicious signs for a functional ovarian tumor. They are usually benign, unilateral and are characterized by a steroid cell proliferation.  This case is unique because the patient first presented to skin OPD for complain of excessive hair growth on face. The primary treatment is surgical extirpation of the primary lesion and there are no reports of effective treatment with radiation or chemotherapy. In a young patient with stage IA disease, a unilateral salpingo-ophorectomy is adequate since the frequency of bilateralism is only 6%. , Malignancy is an important risk for SCTs and pathologic evaluation is essential for the diagnosis of malignancy.
| References|| |
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Paras Ratilal Udhreja
B-103, Jolly Avenue, Trikamnagar, Varachha, Surat - 395 006, Gujarat
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]