Ovarian sex cord-stromal tumors in children and adolescents.

Ovarian sex cord-stromal tumors (OSCSTs) are a heterogeneous group of tumors that develop from the gonadal non-germ-cell component. Despite recent advances in the clinical and histopathologic diagnosis of OSCSTs, a high degree of uncertainty remains with regard to adequate therapy, particularly in patients presenting with microscopic or macroscopic tumor spread. We review the currently available data on the biology and histology of OSCST in children and adolescents. In addition, we summarize the data from our clinical, histopathologic and genetic analyses of patients that were prospectively reported to the German MAKEI protocols for treatment of nontesticular malignant germ cell tumors. Among these patients, juvenile granulosa cell tumors (JGCTs) constitute the most frequent histologic subtype, followed by Sertoli-Leydig cell tumors (SLCTs) and sclerosing stromal tumors. Patients with JGCT and SLCT show greater mitotic activity than do all those with other histologic types. Furthermore, high mitotic activity is associated with adverse outcome. In addition, prognosis correlates with tumor stage according to the International Federation of Obstetrics and Gynecology. Nevertheless, we observed a favorable response to cisplatin-based chemotherapy in the majority of stage II and III tumors. For the whole cohort of 62 patients, event-free survival was 0.87 +/- 0.05 months and overall survival 0.88 +/- 0.05. Genetic analysis of 27 tumors available for comparative genomic hybridization analysis revealed normal profiles in the majority of tumors and whole chromosomal gain, such as a gain of 12 in single tumors, with no consistent pattern with regard to histology or clinical outcome. This analysis confirmed that most OSCSTs present at a low tumor stage and that prognosis in these patients is excellent. Most important, patients at high risk can be identified through clinical and histopathologic analysis, and the majority can be treated successfully with adjuvant cisplatinum-based chemotherapy. Based on this analysis, a prospective study on OSCST in children and adolescents began recruiting cases in 2005.