Endometrial carcinomas – Challenges and updates on selected topics

Abstract

Endometrial carcinoma comprises a heterogeneous group of tumors with distinct histologic, immunophenotypic, and molecular profiles that have important diagnostic and clinical implications. This review focuses on selected subtypes of endometrial carcinomas with the most update. Endometrial serous carcinoma, though representing ∼10 % of endometrial cancers, accounts for a disproportionate number of endometrial cancer deaths; its early forms - serous endometrial intraepithelial carcinoma and superficial serous carcinoma, collectively termed minimal uterine serous carcinoma (MUSC) - predominantly arise in an endometrial polyp and demonstrate a paradoxically high rate of extrauterine spread despite minimal tumor volume, mandating comprehensive staging. Corded and hyalinized endometrioid carcinoma (CHEC) and pilomatrix-like high-grade endometrial carcinoma (PiMHEC) are CTNNB1/β-catenin–driven variants of endometrioid carcinoma with biphasic or basaloid morphology that may mimic carcinosarcoma, serous, or squamous carcinoma and show variable, sometimes aggressive behavior. Mesonephric-like adenocarcinoma (MLA) is an ER/PR-negative, KRAS-mutated carcinoma with mesonephric-type morphology, frequent deep myometrial and lymphovascular invasion, and a predilection for pulmonary metastasis. Primary endometrial squamous cell carcinoma (PESCC) and endometrial gastric (gastrointestinal)-type mucinous carcinoma (EmGA) are exceptionally rare entities that require stringent exclusion of cervical or metastatic primaries and are typically associated with p53-abnormal and/or gastrointestinal-type molecular signatures and poor outcomes. Across these variants, integration of morphology with immunohistochemistry and molecular testing (including p53, MMR status, POLE) is essential for accurate classification and risk stratification. HER2 overexpression and/or amplification occurs in 25–30 % endometrial serous carcinoma and HER2 testing has become a standard biomarker for selecting patients with recurrent or advanced disease for trastuzumab, and more recently trastuzumab-deruxtecan therapy.