An important cause of infertility in patients with ovarian germ cell tumors is unnecessary bilateral salpingo-oophorectomy and hysterectomy. Although temporary ovarian dysfunction or failure is common with platinum-based chemotherapy, most women will resume normal ovarian function, and childbearing is usually preserved (349,355). In one representative series of 47 patients treated with combination chemotherapy for germ cell malignancies, 91.5% resumed normal menstrual function, and there were 14 healthy live births and no birth defects (370). Factors such as older age at initiation of chemotherapy, greater cumulative drug dose, and longer duration of therapy all have an adverse effect on future gonadal function.
An important cause of late morbidity and mortality in patients receiving chemotherapy for germ cell tumors is the development of secondary tumors. Etoposide in particular was implicated in the development of treatment-related leukemias (417,418).
The chance of developing treatment-related leukemia following etoposide is dose related. The incidence of leukemia is approximately 0.4% to 0.5% (representing a 30-fold increased likelihood) in patients receiving a cumulative etoposide dose of less than 2,000 mg/m2, compared with as much as 5% (representing a 336-fold increased likelihood) in those receiving more than 2,000 mg/m2 (417). In a typical three-or four-cycle course of BEP, patients receive a cumulative etoposide dose of 1,500 or 2,000 mg/m2, respectively.
Despite the risk of secondary leukemia, risk-benefit analyses concluded that etoposidecontaining chemotherapy regimens are beneficial in advanced germ cell tumors; one case of treatment-induced leukemia would be expected for every 20 additionally cured patients who receive BEP as compared with platinum, vincristine, bleomycin (PVB). The risk–benefit balance for low-risk disease, or for high-dose etoposide in the salvage setting, is less clear (418).
Sex cord–stromal tumors of the ovary account for about 5% to 8% of all ovarian malignancies (2,3,342,343,419–425). This group of ovarian neoplasms is derived from the sex cords and the ovarian stroma or mesenchyme. The tumors usually are composed of various combinations of elements, including the “female” cells (i.e., granulosa and theca cells) and “male” cells (i.e., Sertoli and Leydig cells), and morphologically indifferent cells. A classification of this group of tumors is presented in Table 37.8.
Table 37.8 Sex Cord–Stromal and Steroid Cell Tumors 1.
A. Granulosa cell tumor
B. Tumors in thecoma-fibroma group 1.
2.
3.
2. Androblastomas; Sertoli-Leydig cell tumors
A. Well-differentiated 1.
2.
3.
B. Moderately differentiated
C. Poorly differentiated (sarcomatoid)
D. With heterologous elements 3.
4.
Sex cord tumor with annular tubules 5.
Sex cord-stromal tumors, unclassified 6.
A. Stromal luteoma
B. Leydig cell tumor
C. Steroid cell tumor, not otherwise classified
Granulosa-stromal cell tumors include granulosa cell tumors, thecomas, and fibromas. The granulosa cell tumor is a low-grade malignancy; rarely, thecomas and fibromas have morphologic features of malignancy and may be referred to as fibrosarcomas.