High-grade Endometrial Carcinomas With Solid Basaloid Morphology and Geographic Necrosis Lacking Definitive...

Area of Science:

• Gynecologic Oncology
• Pathology
• Molecular Oncology

Background:

• High-grade endometrioid carcinomas can exhibit solid basaloid morphology with geographic necrosis (SB-GN).
• Pilomatrix-like high-grade endometrioid carcinoma (PiMHEC) is a recently defined subtype with SB-GN, shadow cells, CTNNB1 mutations, CDX2 expression, and poor outcomes.
• The clinicopathologic spectrum and molecular landscape of SB-GN in endometrial carcinomas beyond PiMHEC are not well-established.

Purpose of the Study:

• To investigate the clinicopathologic features, molecular alterations, and outcomes of endometrial carcinomas displaying SB-GN.
• To determine the overlap between SB-GN histology and pilomatrix-like high-grade endometrioid carcinoma (PiMHEC).
• To identify potential therapeutic implications of novel molecular findings in SB-GN endometrial carcinomas.

Main Methods:

• Screening of 300 endometrial carcinomas for SB-GN histology using tissue microarrays.
• Detailed whole-section morphologic review, immunohistochemical analysis (including CDX2), and next-generation sequencing on identified SB-GN cases.
• Clinical follow-up data review for outcome assessment.

Main Results:

• Four cases (1.3%) exhibited SB-GN histology.
• All three cases with follow-up showed aggressive behavior, even when mismatch repair-deficient (MMR-D), contrasting with other MMR-D high-grade carcinomas.
• Molecular analysis revealed diverse alterations including CTNNB1, KRAS, FGFR2, and Notch pathway variants, with absence of shadow cells in most cases. One case with CTNNB1 mutation responded to immunotherapy.

Conclusions:

• The SB-GN pattern in high-grade endometrioid carcinoma may indicate a poor prognosis, irrespective of overt pilomatrix-like differentiation.
• Novel molecular events, including FGFR2 and Notch pathway alterations, are implicated in SB-GN endometrial carcinomas.
• These molecular findings may offer new therapeutic targets and strategies for managing these aggressive tumors.