Ovarian sex cord-stromal tumours: an update in recent molecular advances

Sex cord-stromal tumours (SCSTs) consist of a heterogeneous group of neoplasms with diverse clinicopathological features and biological behaviour. They often present as a diagnostic challenge as they have varied and occasionally overlapping histomorphology and some may even mimic non-SCSTs. An accurate diagnosis is important for therapeutic and prognostic purposes. The use of a panel of immunohistochemical markers which are sensitive and specific for sex cord-stromal differentiation such as α-inhibin, calretinin, SF-1 and FOXL2, may be helpful in confirming the cellular lineage of these tumours, but is of limited utility in distinguishing between the different tumour types within this category. Additionally, the development of new therapeutic strategies in patients with SCSTs is also hampered by the infrequent occurrence of these neoplasms. Recent molecular analyses of some SCSTs has led to the discovery of novel molecular events, which may have important diagnostic, prognostic and therapeutic implications. The salient pathological features, management issues and recently described genetic aberrations in adult and juvenile granulosa cell tumours as well as Sertoli-Leydig cell tumours are discussed in this review, with particular emphasis on the clinical significance of FOXL2 and DICER1 mutations. An in-depth understanding of the molecular pathogenesis underlying SCSTs may aid in improving tumour classification and disease prognostication and also potentially lead to the discovery of more effective treatment strategies.