New insights into testicular granulosa cell tumors (Review)

Abstract

Testicular granulosa cell tumors (TGCTs) are rare tumors of sex cord‑stromal origin. TGCTs are mostly benign and can be classified into the adult type and the juvenile type. Due to the rarity of clinical cases and limited research efforts, the mechanism underpinning the development of TGCTs remains poorly understood. A landmark study has identified a forkhead box L2 mutation (C134W) in nearly all adult ovarian GCTs, but its implications in TGCTs are unclear. The present study focuses on reviewing the major signaling pathways (e.g., the transforming growth factor β signaling pathway) critical for the development of TGCTs, as revealed by genetically modified mouse models, with a goal of providing new insights into the pathogenesis of TGCTs and offering directions for future studies in this area. We posit that a comparative approach between testicular and ovarian GCTs is valuable, as granulosa cells and Sertoli cells arise from the same progenitor cells during gonadal development. Developing pre‑clinical mouse models that recapitulate TGCTs will help answer the remaining questions around this type of rare tumor.