Chemotherapy There is no evidence that adjuvant chemotherapy will prevent recurrence of disease (436–439). Metastatic lesions and recurrences were treated with a variety of antineoplastic drugs. Although the data are inconclusive, BEP or carboplatin and paclitaxel are used in selected patients with stage III or IV tumors or recurrent disease (433). In a GOG study, 37% (14 of 30) patients treated with BEP had a negative second-look laparotomy, and these patients had a median time to progression of 24.4 months (440). Granulosa cell tumors are potentially hormonally responsive, with about 30% of granulosa tumors expressing estrogen receptors and almost 100% expressing progesterone receptors. Hormonal agents such as progestins or luteinizing hormone-releasing hormone agonists are used to treat these patients because they are often elderly (441–445). There are case reports of durable response to aromatase inhibitors in patients with metastatic granulosa cell tumors who received multiple prior treatment (443). Small clinical series and case reports indicated that luteinizing hormone-releasing hormone agonists had a 50% response rate in 13 patients, while 4 of 5 patients in the literature responded to a progestational agent. Two case series reported durable responses in a total of six patients receiving aromatase inhibitors among those who progressed on or were intolerant of chemotherapy (442–445).
Adult granulosa cell tumors have a prolonged natural history and a tendency toward late relapse, reﬂecting their low-grade biology. Ten-year survival rates of about 90% are reported, with 20-year survival rates dropping to 75% (420–422,432,433). Most histologic types have the same prognosis, but patients with the more poorly differentiated diffuse or sarcomatoid type tend to do worse (419).
The DNA ploidy of the tumors is correlated with survival. Holland et al. reported DNA aneuploidy in 13 of 37 patients (35%) with primary adult granulosa cell tumors (437). The presence of residual disease is the most important predictor of progression-free survival, but DNA ploidy is an independent prognostic factor. Patients with residual-negative DNA diploid tumors had a 10-year progression-free survival of 96%.
Juvenile granulosa cell tumors of the ovary are rare and constitute less than 5% of ovarian tumors in childhood and adolescence (446). About 90% are diagnosed in stage I, and they have a favorable prognosis. The juvenile subtype behaves less aggressively than the adult type. Only about 10% of juvenile granulosa cell tumors are malignant and late relapse is unusual. Advanced-stage tumors are successfully treated with platinum-based combination chemotherapy (e.g., BEP) (433,440).
Sertoli-Leydig Tumors Sertoli-Leydig tumors occur most frequently in the third and fourth decades of life; 75% of these tumors are seen in women younger than 40 years. These neoplasms are extremely rare and account for less than 0.2% of ovarian cancers (2,447,448). Sertoli-Leydig cell tumors are most frequently low-grade malignancies; a poorly differentiated variety may behave more aggressively (Fig. 37.24) (447–449).