This category of ovarian neoplasms includes all those that contain granulosa cells, theca cells and their luteinized derivatives, Sertoli cells, Leydig cells, and fibroblasts of gonadal stromal origin, singly or in various combinations, and in varying degrees of differentiation.247–250,311,316,320 The generic terms that have been most widely applied to these tumors reflect differing views of gonadal embryology. Those investigators who are convinced that all the cell types listed above are derived from the mesenchyme, or specialized stroma, of the genital ridge have proposed the terms mesenchymomas 44 and gonadal stromal tumors for these neoplasms.197,198,204 In contrast, other investigators, recognizing that many embryologists favor the participation of coelomic and mesonephric epithelium in the formation of the sex cords, which are the proximal precursors of granulosa and Sertoli cells, have preferred the terms sex cord-mesenchyme tumors 187,244 and sex cord-stromal tumors. 257

Sex Cord-Stromal, Steroid Cell, and Other Ovarian Tumors with Endocrine, Paraendocrine, and Paraneoplastic Manifestations

Five cases of ovarian carcinoma with hepatoid features, three of them primary and two probably primary, are described. The tumor cells were arranged predominantly in sheets and contained moderate to abundant amounts of eosinophilic cytoplasm; varying numbers of tumor cells stained immunohistochemically for alpha fetoprotein. In contrast to the much younger age range of patients with ovarian hepatoid yolk sac tumors, the ages of the five patients with hepatoid carcinomas ranged from 42 to 78 (average, 63 years), and none of them had gonadal dysgenesis or recognizable germ cell components within their tumors. All the tumors presented as adnexal masses; in four cases they were Stage III and in one case, Stage IIB; this last tumor spread to the upper abdomen within 4 years. In three cases the clinical course and pathology findings indicated that the tumor had originated in the ovary; in the remaining two cases the tumors were interpreted as only probably primary in the ovary. Hepatoid carcinomas must be distinguished from other ovarian neoplasms, especially from hepatoid yolk sac tumors.

Hepatoid carcinoma of the ovary. A newly described tumor

Ovarian malignant melanoma (MM), primary or metastatic, is an extremely rare tumor and in the absence of a previous diagnosis can represent a diagnostic challenge. We present the clinicopathologic and immunohistochemical features of 23 cases seen in our institution over a period of 40 years (1962-2001). The patients' age ranged from 14 to 53 years (mean 35.7 years). Ethnicity was known in 19 patients: 14 white, 4 Hispanic, and 1 black. A previous history of MM was definitively obtained in 14 patients; in these cases, the interval between the primary MM and the ovarian metastasis ranged from 15 to 228 months (mean 77.7 months). The tumor was unilateral in 19 and bilateral in 4 cases. The tumor size ranged from 4.5 to 23 cm (average 10 cm); the melanoma arising in a cystic teratoma was 0.2 mm in thickness. The tumor was grossly pigmented in 8 cases (35%). The architectural pattern was nodular (8 cases), diffuse (6 cases), nodular and diffuse (5 cases), nested (3 cases), and lentiginous arising in a teratoma (1 case). Follicle-like spaces were seen in 8 cases, pseudo-glandular areas in 1 case, pseudo-myxoid areas in 1 case, and cords in 1 case. The tumor cell type was epithelioid in 19 cases, spindled in 2 cases, mixed epithelioid and spindled in 1 case, and small cell in 1 case. Nucleoli were prominent in 18 cases, and nuclear inclusions were present but rare in the majority of cases. Nuclear grooves were seen in 3 cases. Necrosis was extensive in 8 cases, focal in 10 cases, and was absent in 5 cases. In 8 cases, initial diagnoses included sex cord stromal tumor, germ cell tumor, sarcoma, or undifferentiated carcinoma. S-100 was positive in 18 of 19 cases, HMB-45 in 17 of 20 cases, MART-1 in 13 of 15 cases, tyrosinase in 10 of 15 cases, and Mitf in 8 of 14 cases. Inhibin was positive in 3 of 14 cases. Calretinin was focally positive in 1 of 12 cases. Treatment performed in 18 of the cases are as follows: oophorectomy with/without chemotherapy (10); total abdominal hysterectomy with bilateral salpingo-oophorectomy with/without chemotherapy (6); vaginal hysterectomy, bilateral salpingo-oophorectomy, and chemotherapy (1); and total abdominal hysterectomy with salpingo-oophorectomy (1). Follow-up ranging from 2 to 96 months was available in 18 patients. All but one had metastases in other organs, most often in the lungs. Thirteen patients died of disease (range 2-76 months), 3 are alive with disease (6-18 months), and 2 have no evidence of disease at 24 and 96 months; one was the patient with melanoma arising within a teratoma. In conclusion, MM involving the ovary is a rare disease, predominantly seen in women of reproductive age, and is associated with a poor prognosis. The tumor is most often metastatic from another site and is unilateral in most cases. Nodular or diffuse pattern and epithelioid cell type are most frequently seen, and the tumor can be mistaken for germ cell and sex cord stromal tumors. S-100 is the most sensitive marker. MART-1 was positive in the few cases that were negative with HMB-45. Inhibin can be focally positive in some cases.

Malignant melanoma involving the ovary: a clinicopathologic and immunohistochemical study of 23 cases.

In recent years, our knowledge of ovarian sex cord-stromal tumors has increased, and their classification has evolved. In this review, recent advances in the classification and pathology of ovarian sex cord-stromal tumors are discussed, and the controversy regarding the classification of sex cord tumor with annular tubules is addressed. The current classification is built on those of the past, and future classifications should improve on what is now in place incorporating new knowledge from more sophisticated clinicopathologic studies and advanced molecular techniques. This review emphasizes articles written in the 21st century as well as those that have significantly advanced our knowledge of sex cord-stromal tumors in past decades. The tumors in this group occur over a wide age range and are often unilateral. In difficult cases, immunocytochemistry provides improved diagnostic accuracy. The most useful immunohistochemical marker for their identification is alpha-inhibin, which is positive in most neoplasms in the sex cord-stromal group. The article concludes with a section discussing the pathogenesis of sex cord-stromal tumors.

Recent advances in the pathology and classification of ovarian sex cord-stromal tumors.

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

:The clinical and pathological features of 63 steroid cell tumors, not otherwise specified, were reviewed. The patients ranged in age from 2'A to 80 years. The most common initial manifestation was virilization (41%); four patients had estrogenic manifestations, and four had hypercortisolemi

Ovarian steroid cell tumors (not otherwise specified). A clinicopathological analysis of 63 cases.

Ovarian Steroid Cell Tumors (Not Otherwise Specified): A Clinicopathological Analysis of 63 Cases

The clinical and pathological features of 25 stromal luteomas were reviewed. The patients ranged in age from 28-74 (average 58.4) years. The most common initial manifestation (60%) was abnormal vaginal bleeding; three patients (12%) were virilized. The tumors, only one of which was bilateral, ranged from 0.25-2.9 (average 1.3) cm in greatest diameter. They were all well circumscribed. Microscopic examination revealed unencapsulated nodules composed of rounded polyhedral cells that were arranged either diffusely or in nests and cords. Twenty percent showed degeneration within aggregates of cell resulting in the formation of pseudoacinar structures. The cytoplasm of the neoplastic cells was generally eosinophilic and granular, and lipochrome granules were present in over half the tumors. In 92% of the cases hyperthecosis was present in the adjacent ovarian stroma. Follow-up of 6 months to 17 years was available for 19 patients. Sixteen of them were alive and free of disease; the remaining three died of other causes. The benign course in all the cases in which follow-up data were available was expected in view of the small size of the tumors and their benign microscopic appearance.

Mary C. Hayes

Papers

Ovarian steroid cell tumors (not otherwise specified). A clinicopathological analysis of 63 cases.

Ovarian Steroid Cell Tumors (Not Otherwise Specified): A Clinicopathological Analysis of 63 Cases

Stromal luteoma of the ovary: a clinicopathological analysis of 25 cases.