A 55-year-old male smoker presents with a 3 cm renal mass discovered incidentally on CT. Nephrectomy shows a golden-yellow tumor confined to the kidney with clear cells on histology. Cytogenetics reveals deletion of chromosome 3p. What is the molecular basis of carcinogenesis in this tumor?

• A WT1 tumor suppressor gene mutation
• B Inactivation of the VHL gene with HIF-1α accumulation ✓
• C MET proto-oncogene mutation
• D Translocation involving TFE3 gene

Explanation

Clear cell renal cell carcinoma (ccRCC) is the most common type, accounting for ~70% of RCCs, and is characterized by deletion of 3p25 where the VHL tumor suppressor gene resides. Loss of functional VHL protein prevents degradation of HIF-1α, leading to upregulation of VEGF and erythropoietin, driving angiogenesis and tumor growth. The classic gross appearance of a golden-yellow tumor reflects the intracellular lipid and glycogen accumulation in the clear cells.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.