A 55-year-old post-menopausal woman has endometrial carcinoma with deep myometrial invasion and lymphovascular space invasion (LVSI). This is a Type I endometrial carcinoma. Its hallmark precursor lesion and associated molecular alteration are:

• A Endometrial intraepithelial carcinoma (EIC) with TP53 mutation
• B Atypical endometrial hyperplasia (endometrial intraepithelial neoplasia) with PTEN loss ✓
• C Endometrial glandular dysplasia with MSI-H from MLH1 methylation
• D Complex hyperplasia without atypia with CTNNB1 (beta-catenin) exon 3 mutation

Explanation

Type I endometrial carcinoma (endometrioid adenocarcinoma) arises in an oestrogen-rich background and is preceded by atypical endometrial hyperplasia (also called endometrial intraepithelial neoplasia, EIN) as a precursor. The molecular hallmark is PTEN loss (by mutation, deletion, or promoter methylation), occurring early in pathogenesis; KRAS, PIK3CA, and CTNNB1 mutations are also common, and microsatellite instability from MLH1 promoter hypermethylation is seen in approximately 30%. Endometrial intraepithelial carcinoma (EIC) with TP53 mutation is the precursor of Type II (serous) carcinoma.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.