Molecular basis of uterine mesenchymal tumours

Abstract

Uterine mesenchymal tumours present significant management challenges due to their varied histological subtypes and clinical behaviours. This review explores the recent advances in the molecular pathology of uterine mesenchymal tumours. Leiomyosarcoma, the most common malignant uterine mesenchymal tumour, exhibits complex genomic alterations, with subtypes including spindled, myxoid, epithelioid and the emerging lipoleiomyosarcoma. Smooth Muscle Tumours of Uncertain Malignant Potential (STUMP) and low-grade endometrial stromal sarcomas (LGESS) show diverse morphologies and molecular profiles. High-grade endometrial stromal sarcomas (HGESS) are distinguished by molecular subtypes like YWHAE:: NUTM2, BCOR rearrangements and BCOR internal tandem duplications (ITDs). Rarer tumours, including inflammatory myofibroblastic tumours (IMT) with ALK rearrangements, NTRK-rearranged spindle cell tumours, and perivascular epithelioid cell tumours with TSC1/TSC2 alterations and TFE3 rearrangements, expand the spectrum of uterine mesenchymal neoplasms. Newer fusion sarcomas, such as MEIS1::NCOA2/1, COL1A1::PDGFB, KAT6B/A::KANSL1 and RAD51B fusion sarcoma further our understanding of the various tumour types. Molecular diagnostics are crucial for identifying targetable pathways, accurate tumour classification, and guiding treatment decisions. Understanding these molecular alterations is essential for advancing therapeutic strategies and improving prognosis for patients with uterine mesenchymal tumours.