Controversies in the management of ovarian granulosa cell and Sertoli-Leydig cell tumors

Ovarian sex cord-stromal tumors are rare and include adult granulosa cell tumors, juvenile granulosa cell tumors, and Sertoli-Leydig cell tumors. Adult granulosa cell tumors the most prevalent malignant ovarian sex cord stromal tumors are the focus of the review which synthesizes published data to highlight the diagnostic challenges and the controversies surrounding the management of adult granulosa cell tumors, juvenile granulosa cell tumors, and Sertoli-Leydig cell tumors. Adult granulosa cell tumors have frequently been misdiagnosed, with up to 30% of cases reassigned after a contemporary review of historical cases, which could affect the interpretation of older studies. Diagnostic accuracy improved in 2009 following the identification of a somatic FOXL2 c.402C>G missense point in almost all adult granulosa cell tumors. Surgery is the mainstay of treatment at diagnosis and recurrence, and fertility-sparing surgery is recommended for younger patients with stage 1 ovarian sex cord-stromal tumors. The role of adjuvant chemotherapy in stage I high-risk adult granulosa and Sertoli-Leydig cell tumors remains controversial, with guidelines providing varied and conflicting recommendations based on limited evidence. Surveillance strategies, including the frequency of follow-up, duration of surveillance, sensitivity, and specificity of tumor markers, and the timing and nature of imaging, are debatable. We reviewed the evolution of systemic therapy for ovarian sex cord-stromal tumors over the last 4 decades and raised questions regarding the choice of chemotherapy regimens and evidence to support adjuvant chemotherapy. The efficacy of endocrine therapy in adult granulosa cell tumors is contentious, and most studies are retrospective with variable criteria to define response and clinical benefit. The available data are discussed, including trials in progress. In conclusion, the management of ovarian sex cord-stromal tumors requires a nuanced understanding of their unique pathologic and biological characteristics and an appreciation of the limitations of the existing evidence. There is a high priority to encourage international collaboration through prospective data collection and randomized trials to provide the required evidence to support treatment guidelines and ultimately improve patient outcomes.