Uterine smooth muscle tumors (USMTs) represent a diagnostically and clinically challenging subset of uterine mesenchymal neoplasms. Up to 5% of these tumors exhibit ambiguous histological features that preclude definitive classification as either benign leiomyomas or malignant leiomyosarcomas. This review provides a comprehensive synthesis of the evolving diagnostic criteria, histopathological variants, and recent advancements in immunohistochemical and molecular profiling of smooth muscle tumors with uncertain malignant potential (STUMPs). The review traces the historical development of diagnostic criteria, from the original mitotic thresholds to the "Stanford criteria," which incorporate mitotic index, cytological atypia, and tumor cell necrosis. Contemporary WHO guidelines largely uphold these principles, with nuanced refinements for spindle, myxoid, and epithelioid subtypes. However, recent studies suggest additional morphologic indicators, such as atypical mitoses, infiltrative margins, and vascular invasion, may provide prognostic insight. Notably, necrosis remains the most reliable histologic predictor of recurrence, while mitotic activity and atypia, though important, are less specific. In conclusion, STUMPs represent a heterogeneous group with unpredictable behavior that requires long-term clinical follow-up. While existing histological and molecular tools aid classification, definitive prognostic markers remain elusive. Further studies integrating histopathology, immunohistochemistry, and molecular biology are essential to refine diagnosis and improve therapeutic decision-making in this diagnostically ambiguous group of uterine tumors.
Satala et al. (2026) studied this question.