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High-grade endometrioid carcinomas with pilomatrix-like features lacking CTNNB1 Mutations: Clinicopathologic
Lei Qin1, Wanrun Lin2, Suming Huang1
1Departments of Pathology, The International Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, 200030, China.
Context:
Pilomatrix-like high-grade endometrioid carcinoma (PiMHEC) represents a recently described, aggressive variant of endometrial carcinoma. Prior reports have linked PiMHEC with CTNNB1 exon 3 mutations and abnormal nuclear β-catenin expression.
Objective:
We aimed to expand the understanding a potential subclassification of PiMHEC by analyzing three new cases that lack CTNNB1 mutations and β-catenin nuclear accumulation.
Design:
Three cases of high-grade endometrioid carcinomas with pilomatrix-like features were identified and their clinical presentations and pathologic features reviewed. Immunohistochemistry (IHC) and targeted next-generation sequencing (NGS) were performed.
Results:
All tumors demonstrated two components: a high-grade basaloid component with solid sheets of atypical basaloid cells, geographic necrosis, and focal "ghost" cells, and an associated low-grade FIGO grade 1 endometrioid carcinoma component. Notably, none of the three cases showed nuclear β-catenin expression by IHC, and all lacked CTNNB1 exon 3 mutations. Despite this, the tumors fulfilled the morphologic criteria for PiMHEC described in prior studies and displayed aggressive clinical behavior. All the patients presented with advanced-stage disease (stages IIC-IVB), and two patients had a recurrence within 12 months. NGS revealed no CTNNB1 mutations in any case, but identified alternative likely oncogenic alterations: one tumor harbored an FGFR4 p. T259A mutation, two tumors had pathogenic TSC2 mutations, one had a KRAS p.G12D mutation, and two showed MYC amplification, among other genetic changes.
Conclusions:
High-grade endometrioid carcinomas with pilomatrix-like features lacking CTNNB1 mutations may represent a potential subclassification of PiMHEC, which exhibit aggressive behavior. CTNNB1-wildtype cases appear to rely on alternative oncogenic drivers, indicating that CTNNB1 mutation maybe not an absolute requirement for the PiMHEC phenotype.
