The other symptoms and signs of granulosa cell tumors are nonspecific and the same as most ovarian malignancies. Ascites is present in about 10% of cases, and, rarely, a pleural effusion is present (419–422). Granulosa tumors tend to be hemorrhagic; occasionally, they rupture and produce a hemoperitoneum.
Adult granulosa cell tumors are usually stage I at diagnosis, but may recur 5 to 30 years after initial diagnosis (421). Most juvenile granulosa cell tumors are clinically benign; only about 10% recur and when they do so, it is generally within 5 years of the initial diagnosis. The tumors may spread hematogenously, and metastases can develop in the lungs, liver, and brain years after initial diagnosis. When adult granulosa cell tumors do recur, they can progress rapidly. Malignant thecomas are extremely rare, and their signs and symptoms, management, and outcome are similar to those of the granulosa cell tumors (419). Inhibin is secreted by some granulosa cell tumors and is a useful marker for the disease (427–431). An elevated serum inhibin level in a premenopausal woman presenting with amenorrhea and infertility is suggestive of a granulosa cell tumor (432).
The treatment of granulosa cell tumors depends on the age of the patient and the extent of disease. For most patients, surgery alone is sufficient primary therapy; radiation and chemotherapy are reserved for the treatment of recurrent or metastatic disease (422–429,433–436).
Surgery Because granulosa cell tumors are bilateral in only about 2% of patients, a unilateral salpingo-oophorectomy is appropriate therapy for stage IA tumors in children or in women of reproductive age (420). At the time of laparotomy, if a granulosa cell tumor is identified by frozen section, a staging operation is performed, including an assessment of the contralateral ovary. If the opposite ovary appears enlarged, it should be sampled for biopsy. For perimenopausal and postmenopausal women for whom ovarian preservation is not important, a hysterectomy and bilateral salpingo-oophorectomy should be performed. For premenopausal patients in whom the uterus is left in situ, an endometrial biopsy should be performed because of the possibility of a coexistent adenocarcinoma of the endometrium (422).
Radiation Therapy There is no evidence to support the use of adjuvant radiation therapy for granulosa cell tumors, although pelvic irradiation may help to palliate isolated pelvic recurrences (422,434).