Breast cancer susceptibility gene 2 (BRCA2) and neurofibromatosis type 2 (NF2) are key tumor suppressor genes involved in homologous recombination repair of DNA double-strand breaks and various signaling pathways, respectively. While BRCA2 and NF2 mutations are well-established in many solid tumors, their role in renal cell carcinoma (RCC) remains unclear. We describe a 60-year-old African American man with a radiologically confirmed right renal mass extending into the liver. Radical nephrectomy revealed a high-grade renal tumor with sarcomatoid and rhabdoid differentiation, extensive fibrosclerotic stroma, and prominent lymphoplasmacytic infiltrate. Immunohistochemistry confirmed renal epithelial differentiation, with the expression of KRT7, PAX8, AMACR, and CD10. Retained SMARCB1 and FH expression helped exclude SMARCB1 and FH-deficient RCC. Comprehensive genomic profiling identified a BRCA2 mutation and a concurrent NF2 mutation. Although rare, these tumors may represent a molecularly defined subset of RCC with potential therapeutic implications. BRCA2-mutated tumors have shown sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors in other malignancies, suggesting a possible role for targeted therapy in select RCC patients. As genomic profiling becomes more integrated into oncologic practice, recognizing this rare but emerging subset of BRCA2-NF2 altered RCC is essential to expand treatment options and improve patient outcomes.
Talafha et al. (Mon,) studied this question.