Squamous morphology in endometrial tumours: two challenging cases including a rare pilomatrix-like variant

Endometrial carcinoma with predominant squamous differentiation is rare and poses diagnostic difficulties. Pilomatrix-like high-grade endometrioid carcinoma (PiMHEC) is a recently described aggressive variant, while primary squamous cell carcinoma (PSCC) of the endometrium is also very uncommon. We present two challenging cases comparing their clinicopathological and immunohistochemical features. Two postmenopausal women presenting with vaginal bleeding underwent endometrial sampling followed by total hysterectomy with bilateral salpingo-oophorectomy and sentinel lymph node evaluation. Histopathology and immunohistochemistry were performed, including ER, PR, p53, p16, p40, beta-catenin, and MMR proteins. Case 1 was diagnosed as a PiMHEC, characterized by basaloid nests, ghost cell keratinization, lower-grade glandular components, diffuse nuclear/cytoplasmic beta-catenin expression and MMR proficiency. Focal lymphovascular invasion was observed and nodes were negative. Case 2 was a PSCC showing nests of keratinizing squamoid cells, strong p40 positivity, membranous beta-catenin, negative ER/p16, and extensive lymphovascular invasion with isolated nodal tumour cells. No glandular or pilomatrix differentiation was present and there was no background cervical intraepithelial neoplasia. PiMHEC and PSCC are rare endometrial malignancies that may appear morphologically similar but demonstrate distinct immunophenotypic profiles. Accurate diagnosis requires careful histological assessment, appropriate immunohistochemistry, and exclusion of cervical or metastatic disease. PiMHEC characteristically shows aberrant nuclear and cytoplasmic β-catenin expression, reflecting frequent CTNNB1 mutations, a useful feature for guiding optimal management. Tumours with CTNNB-1 mutation are currently classified in the subset of “no specific molecular profile” category of endometrial carcinomas. Early recognition is essential due to the aggressive clinical behaviour of these tumours.