Pilomatrix-like High-grade Endometrial Carcinoma: An Underdiagnosed Entity With Aggressive Clinicopathologic Features

Area of Science:

• Gynecologic Pathology
• Oncology
• Molecular Pathology

Background:

• Pilomatrix-like high-grade endometrial carcinoma (PiMHEC) is a rare and aggressive endometrial cancer variant.
• It is frequently misdiagnosed due to overlapping features with other high-grade malignancies.
• Standardized diagnostic criteria and terminology are lacking.

Purpose of the Study:

• To characterize the clinicopathologic, immunophenotypic, and molecular features of PiMHEC.
• To establish key diagnostic criteria for PiMHEC.
• To propose standardized terminology for PiMHEC.

Main Methods:

• Histopathologic examination of 10 tumors.
• Immunohistochemistry for key markers.
• Next-generation sequencing for molecular profiling.

Main Results:

• PiMHEC exhibits distinct low-grade endometrioid and high-grade basaloid components, often with shadow cells and necrosis.
• High-grade areas are ER/PR negative with nuclear beta-catenin staining, linked to CTNNB1 mutations.
• Aggressive clinical behavior observed, with high recurrence rates and early mortality; potential therapeutic targets include PD-L1 and HER2.

Conclusions:

• PiMHEC is a distinct, highly aggressive endometrial carcinoma with unique histopathologic and molecular features.
• Key diagnostic features include basaloid cells, shadow cells, necrosis, and nuclear beta-catenin staining.
• The proposed term 'pilomatrix-like high-grade endometrial carcinoma' aims to improve diagnostic accuracy.