Renal Cell Cancer

Key points

• Renal cell carcinoma (RCC), especially clear-cell RCC, is the commonest adult primary renal malignancy; clear-cell RCC arises from proximal tubular epithelium. The old fixed statement that RCC accounts for exactly ~85% of all primary renal neoplasms is too rigid for MRCP notes.
• Clear-cell RCC is associated with von Hippel–Lindau (VHL) disease. Tuberous sclerosis is classically associated with renal angiomyolipomas rather than being a core RCC association; other hereditary RCC syndromes include hereditary leiomyomatosis and Birt–Hogg–Dubé syndrome.
• Classic triad: haematuria, loin/flank pain and an abdominal mass is characteristic but uncommon in modern presentation because many RCCs are detected incidentally.
• Other features: unexplained fever/constitutional symptoms can occur; a new left-sided varicocele can occur from renal-vein obstruction, although this is uncommon.
• Paraneoplastic/endocrine effects: RCC may produce erythropoietin causing polycythaemia, PTH-related peptide causing hypercalcaemia, renin causing hypertension and, rarely, ACTH or other hormone-like effects.
• Metastases are present in a substantial minority at diagnosis ; a fixed '~25%' figure is not sufficiently current or universal and should not be memorised.
• Stauffer syndrome is a paraneoplastic hepatic dysfunction associated with RCC, often with cholestatic liver-test abnormalities and sometimes hepatosplenomegaly, classically mediated by inflammatory cytokines such as IL-6.
• Localised RCC: management depends on lesion size, stage, renal function and patient factors. Current NICE 2026 guidance includes surgery, with partial nephrectomy preferred when renal preservation is appropriate; active surveillance, thermal ablation or SABR are options in selected patients, particularly when surgery is unsuitable.
• Advanced/metastatic RCC: modern treatment is predominantly immune-checkpoint inhibitor and/or targeted systemic therapy selected by risk and histology. Older TKI-only regimens such as sunitinib or sorafenib are no longer the preferred generic description of first-line metastatic RCC treatment; interferon-alpha/interleukin-2 are historical.
• MRCP discriminator: painless haematuria + flank mass/pain + polycythaemia or hypercalcaemia → RCC.
• Current treatment trap: do not answer metastatic RCC with 'interferon/IL-2' or a TKI alone as the generic modern first-line answer.