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A 30-year-old woman presented with increased body and facial hair, deepening of the voice, acne and menstrual abnormalities. An ultrasound showed a unilateral solid right ovarian mass. At surgery, the left ovary, uterus and abdominal cavity appeared normal. A unilateral salpingo-oophorectomy was performed. On gross examination, the ovary contained a well circumscribed 6.0 cm solid yellow, somewhat lobulated, mass without surface involvement. Tumor cells were positive for inhibin and calretinin, but were negative for cytokeratin 7.
Archive Case and Diagnosis:
This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2010, case 09, and is a steroid cell tumor, not otherwise specified.
Criteria for Diagnosis and Comments:
This tumor, composed of cells with moderate granular and eosinophilic to clear and vacuolated cytoplasm and round to oval typically centrally located nuclei with conspicuous nucleoli, represents a steroid cell tumor, not otherwise specified (NOS), of the ovary.
Steroid cell tumors of the ovary, which are composed of hormone producing cells, are divided into three groups: 1) stromal luteoma, 2) Leydig cell tumor and 3) steroid cell tumor, NOS. Steroid cell tumors in general are uncommon, representing only 0.1% of all ovarian neoplasms; however, within this category of tumors, steroid cell tumor, NOS is most frequent, representing approximately 60% of all ovarian steroid cell tumors.
Steroid cell tumor, NOS can occur over a wide age range; however most patients tend to be younger than those with the other types of ovarian steroid cell tumors with an average age of 43 years at presentation. Approximately 50% of patients present with virilization and hirsutism as was the case with this patient. A minority will present with estrogenic manifestations or occasionally Cushing syndrome due to cortisol production by tumor cells. The vast majority of tumors are unilateral and they are typically well circumscribed, lobulated or multinodular solid yellow to orange to brown tumors that may occasionally exhibit hemorrhage and/or necrosis. These tumors can be quite large (range up to 45 cm), but have an average size of 8.4 cm. Histologically, most show a diffuse pattern of growth, but they may also have a clustered or corded growth pattern as evident in this case. There is typically little intervening stroma, but there is often a rich vascular network of thin compressed capillaries. The tumor cells have moderate amounts of granular eosinophilic or vacuolated cytoplasm with distinct cell borders and centrally placed round and regular nuclei with conspicuous nucleoli. Cytologic atypia is uncommon and mitotic activity is usually low (<2 per 10 high power fields). Occasionally, hemorrhage and necrosis can be present. Tumor cells are positive for inhibin and calretinin, but are usually negative for keratin. Approximately 20% of patients with steroid cell tumor, NOS will have advanced stage disease at presentation and overall approximately 40% will be clinically malignant.
Features associated with poor outcome include: 1) > 2 mitoses per 10 high power fields (92% malignant), 2) necrosis (86% malignant), 3) size > 7 cm (78% malignant), hemorrhage (77% malignant), and high grade nuclear atypia (64% malignant).
Leydig cell tumor is distinguished from steroid cell tumor, NOS by 1) its more frequent location in the hilar region of the ovary, 2) its usually smaller size (most are < 3 cm), 3) the presence of Reinke crystals within the cytoplasm and 4) more commonly occurring at an older age (average age 58 years, although they can be seen in reproductive women).
Sertoli cell tumor is distinguished from steroid cell tumor, NOS by 1) more commonly being associated with estrogenic manifestations (tumors only occasionally produce androgens) and 2) its histologic appearance. Sertoli cell tumors have a characteristic growth pattern being composed of typically well formed hollow or solid tubules lined by cuboidal to columnar cells with abundant cytoplasm. The cytoplasm is usually eosinophilic, but may be filled with lipid and appear vacuolated (so called lipid rich variant or “folliculome lipidique”). The nuclei are round and regular and frequently contain nuclear grooves. Sertoli cells are also typically positive for inhibin and keratin (but negative for cytokeratin 7) and may be positive for calretinin.
Stromal luteoma more commonly occurs in postmenopausal patients (80%) and is more commonly associated with estrogenic manifestations. It typically is centered within the ovarian parenchyma and is associated with stromal hyperthecosis.
Clear cell carcinoma of the ovary typically exhibits other architectural patterns characteristic of the tumor type (particularly tubulocystic and papillary growth patterns) as well as hobnail cells. In addition, tumor cells are diffusely positive for cytokeratin 7.
Features that would favor metastatic renal cell carcinoma (which are lacking in this case) include 1) bilateral ovarian involvement, 2) other gross features of metastatic disease to the ovary including surface involvement, nodularity and lymphatic/vascular invasion, 3) presence of an adrenal or kidney mass compatible with a primary tumor
4) abundant glycogen within tumor cells and 5) diffuse positivity for pancytokeratin and CD10.