A 45-year-old woman has an ovarian tumor with serum CA-125 of 980 U/mL and peritoneal implants. Histology shows psammoma bodies with papillary fronds lined by high-grade columnar cells. Which carcinogenesis pathway does this tumor follow?

• A Type I pathway: stepwise mutation via K-RAS and BRAF
• B Microsatellite instability pathway via MLH1 promoter methylation
• C Wnt/beta-catenin pathway via APC mutation
• D Type II pathway: genomic instability via TP53 and BRCA mutations ✓

Explanation

High-grade serous carcinoma of the ovary follows the Type II pathway characterised by TP53 mutations in virtually all cases and frequent BRCA1/2 germline or somatic mutations. These tumors arise de novo with genomic instability rather than through an identifiable precursor lesion. Type I pathway tumors (endometrioid, mucinous, low-grade serous) are indolent, have K-RAS, BRAF, or PTEN mutations, and arise from benign borderline tumors. Psammoma bodies and high-grade cytology with peritoneal spread strongly favour high-grade 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.