These include tumors arising from the sex cords; granulosa cells; Sertoli cells; and the specialized stroma of the genital ridge, theca, and Leydig cells. They comprise fewer than 5% of all ovarian tumors.
Although granulosa cell tumors are malignant and Sertoli-Leydig cell tumors less so, they behave in a much less malignant fashion than EOC. Benign tumors in the group include thecoma and fibroma. Granulosa cell tumors and pure Sertoli cell tumors commonly secrete estrogen, while Leydig cell tumors and combined Sertoli-Leydig tumors often secrete androgens.
Granulosa cell tumor
This is the most common malignant sex-cord stromal tumor. It can occur at any age, with a mean age of the early fifties. Because of the secretion of estrogen, the presenting features depend on the patient's age. Prepubertal girls typically present with precocious sexual development, women of reproductive age have heavy or irregular periods, and postmenopausal women may have postmenopausal bleeding. At all ages, the tumor may present with acute abdominal pain due to rupture or hemorrhage.
The tumors vary in size and may be solid or partially cystic. The cut surface may be grey-white or yellow, depending on lipid content. Necrosis and hemorrhage often are present, with cystic compartments filled with fluid or clotted blood. The microscopic features are granulosa cells in a wide variety of patterns, and characteristic Call-Exner bodies may be present.
Juvenile granulosa cell tumor is a variant of granulosa cell tumor that is rarely malignant. It most often presents in young girls with isosexual precocious puberty. The tumor usually is unilateral and confined to the ovary and can be managed with surgery alone.
Ultrasound is the most useful preoperative investigation in a patient found to have a pelvic mass. Ultrasound studies may show the presence of ascites and may help define the morphology of the pelvic tumor. In addition, it can determine whether large masses are present in other parts of the abdomen, including the liver, and it can help evaluate the kidneys for evidence of ureteric obstruction. CT scan can detect enlarged pelvic masses and other evidence of intra-abdominal metastasis and disease within the chest.
Ninety percent of granulosa cell tumors are stage I at the time of diagnosis. Surgery is performed as described in Surgery for ovarian cancer. Because bilateral involvement of the ovaries is observed in only 2% of cases, the opposite ovary can be conserved in younger women. If the uterus is to be left behind, endometrium biopsy should be performed because of the synchronous occurrence of endometrial adenocarcinoma associated with estrogen secretion.
No adjuvant therapy is available for early-stage disease that is completely excised. Patients with recurrent disease or residual disease after surgery should be treated with BEP. No evidence demonstrates that treatment with progesterone is beneficial. Radiation has a definite role, especially for palliation in recurrent disease in the pelvis.
Granulosa cell tumors typically recur a long time after primary treatment. Factors reported to be associated with outcome include stage at presentation, age older than 40 years, tumor size, tumor rupture, histologic pattern, high mitotic count, and nuclear atypicality.
The 5-year survival rate for stage I is 86-96%, and for all other stages, it is 26-46%.
Inhibin
Inhibin is a glycoprotein produced by granulosa cells that can be used as a tumor marker. It is undetectable in the serum of postmenopausal women without ovaries and returns to normal 1 week after removal of a granulosa cell tumor. The best discrimination is made with assays detecting the alpha subunit of inhibin. Inhibin also may be elevated in postmenopausal women with mucinous carcinomas.
Recurrence
Granulosa cell tumors can recur a long time after initial treatment, with an average time interval of 5-10 years. The longest reported interval is 37 years, and lifelong follow-up care, therefore, is necessary. Recurrences can be treated with surgery and/or chemotherapy and radiation. The combination of BEP is the most active chemotherapy regimen.
Sertoli-Leydig cell tumors
These tumors are rare. They are a form of low-grade malignancy that typically produces androgens and rarely estrogens.
The surgery is unilateral oophorectomy, and, if patients' childbearing has been completed, total hysterectomy and bilateral oophorectomy is performed. The overall 5-year survival rate is 70-90%.
Other rare tumors
Small-cell carcinoma: This is a rare type of carcinoma that occurs in females aged 2-46 years. It often is associated with hypercalcemia. Treatment is with surgery and chemotherapy, but the prognosis is poor.
Sarcoma: The most common form of this rare tumor in the ovary is the mixed mesodermal sarcoma or carcinosarcoma. Patients should be treated with surgery as described in Surgery for ovarian cancer, followed by platinum-containing chemotherapy. Prognosis is poor.
Metastatic: Metastatic tumors of the ovary arise from direct extension and spread within the bloodstream or lymphatic system or within the peritoneal cavity. Sites of origin include the endometrium; cervix; and nongynecologic sites such as breast, colon, and stomach. The classic Krukenberg tumor refers to bilateral enlargement of the ovaries from metastases from a signet-ring carcinoma of the stomach. Treatment of metastatic disease relates to the primary site.
Effects of chemotherapy on ovarian function, fertility, and the fetus
Many women experience symptoms of ovarian dysfunction, ie, amenorrhea and hot flashes, during treatment with chemotherapy. The younger the woman at the time of treatment, the more likely the return of normal ovarian function and the more tolerant the ovaries are to higher doses of alkylating agents.
An increase in congenital anomalies in babies conceived following treatment with chemotherapy does not seem to occur. The necessity for chemotherapy during a preexisting pregnancy fortunately is rare, but antifolate drugs such as methotrexate probably should be avoided during the first trimester.