Abstract
Endometrial stromal tumors (ESTs) are uncommon mesenchymal tumors of the reproductive system associated with heterogeneous histomolecular features. According to the World Health Organization (WHO), ESTs are classified into benign endometrial stromal nodules (BESN) and endometrial stromal sarcomas (ESSs), which are further divided into low-grade and high-grade subtypes. High-grade ESS is frequently associated with YWHAE-NUTM2 gene fusions, while a newly recognized subtype with BCOR rearrangements, including fusions, alterations, and internal tandem duplications (ITDs), has recently been incorporated into the molecular classification of ESS. BCOR, a transcriptional corepressor of BCL-6, contributes to tumor progression through its role in polycomb repressive complex 1 (PRC1), underscoring its importance in oncogenesis and potential as a therapeutic target. Advances in molecular diagnostics, such as next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH), have improved the precision of diagnosing BCOR-altered ESS, enabling better prognostic stratification. These findings also support the development of targeted therapies, including CDK4/6 inhibitors and immunotherapies targeting PD-1 and CTLA-4 pathways. Despite these advancements, barriers such as limited access to molecular diagnostics and the high cost of novel therapies remain significant challenges. This review bridges molecular and clinical insights into ESS, emphasizing the diagnostic, prognostic, and therapeutic implications of BCOR rearrangements. By integrating these advances into clinical practice, it aims to improve outcomes for patients with this rare and aggressive malignancy.