A 55-year-old woman undergoes surgery for a pelvic mass. Histology shows an ovarian carcinoma with characteristic psammoma bodies, slit-like spaces, and papillary architecture with solid nests. The molecular signature most likely involves:

• A KRAS mutation with low chromosomal instability (Type I tumour)
• B CTNNB1 (beta-catenin) mutation with endometrioid differentiation
• C BRCA2 loss with mucinous phenotype
• D TP53 mutation with high-grade chromosomal instability (Type II tumour) ✓

Explanation

The described features — papillary architecture, psammoma bodies, and slit-like spaces — are characteristic of high-grade serous carcinoma (HGSC), which is the most common ovarian carcinoma. HGSC is a Type II tumour characterised by TP53 mutation (present in >96% of cases) and marked chromosomal instability (copy number alterations). Type I tumours (low-grade serous, mucinous, endometrioid, clear cell) harbour KRAS, BRAF, CTNNB1, or ARID1A mutations and have low chromosomal instability. BRCA1/2 germline mutations predispose to HGSC, not the mucinous type.

Reference: Shaw's Textbook of Gynaecology, 17th ed.

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Written and medically reviewed by the StethoPrep medical team.