Wentao Yang

Endometrial carcinomas with solid basaloid morphology and geographic necrosis: clinicopathological and molecular features of 18 cases

Pilomatrix-like high-grade endometrioid carcinoma (PiMHEC) is characterized by solid basaloid morphology, geographic necrosis, and shadow cells, often associated with CTNNB1 mutations and aberrant β-catenin expression, exhibiting aggressive behavior. However, high-grade endometrial carcinomas with similar solid basaloid/geographic necrosis (SB-GN) features may overlap diagnostically with PiMHEC. This study aimed to investigate the clinicopathological and molecular characteristics of endometrial carcinomas with SB-GN and compare them with PiMHEC. Eighteen endometrial carcinomas with SB-GN (including 6 PiMHECs) were diagnosed in Fudan University Shanghai Cancer Center. Histopathological, immunohistochemical, and molecular features based on next-generation sequencing were reviewed. In our cohort, recurrence/metastasis occurred early (median: 5 months; range: 0-21). Most cases had classic basaloid tumor cells with solid growth pattern. Spindle-shaped cells or tumor cells with more cytoplasm were occasionally observed. Twenty-eight percent of patients had squamous differentiation and 33% had shadow cells. In solid components, aberrant β-catenin expression was observed in 77.8% of cases. Eighty-three percent harbored CTNNB1 exon 3 mutations (frequent co-mutations: PTEN, ARID1A, PIK3CA). Molecular classification revealed 28% MMR-deficient, 22% POLE-mutated, 6% p53-abnormal, and 44% no specific molecular profile (NSMP). Endometrial carcinomas with SB-GN showed no significant differences compared to PiMHECs, except for higher PR positivity in solid components (58.3% vs. 0%, p = 0.046). Endometrial carcinomas with SB-GN represent a distinct and aggressive tumor group characterized by solid growth pattern, prominent necrosis, frequent basaloid morphology, high rates of CTNNB1 mutations, and aberrant β-catenin staining. Our results demonstrate that endometrial carcinomas with SB-GN and PiMHECs share similar clinicopathologic and molecular profiles, supporting a unified biological spectrum.