Renal cell carcinoma ✅

Related Subjects: |Urothelial tumour s |Haematuria |Acute Urinary Retention |Anuria and Oliguria |Bladder cancer |Renal cell carcinoma |Benign Prostatic Hyperplasia |IgA nephropathy |Prostate Cancer |Henoch-Schonlein purpura |Glomerulonephritis

🔎 About Renal Cell Carcinoma (RCC)

• 🧬 Renal cell carcinoma (RCC) is the most common primary kidney cancer in adults, accounting for ~90% of renal malignancies.
• 👨‍🦳 Typically occurs in people aged 50–70 years and is around 2–3× more common in males.
• 🩺 Many cases are now detected incidentally on imaging performed for unrelated reasons.
• 📈 Incidence has increased with widespread use of abdominal CT and ultrasound.

🧬 Aetiology

• Genetic Syndromes
  • 🧩 Von Hippel–Lindau (VHL) syndrome – mutation of the VHL tumour suppressor gene → predisposition to clear cell RCC.
  • 🧬 Hereditary papillary RCC – autosomal dominant mutation affecting MET proto-oncogene.
  • 🧬 Birt-Hogg-Dubé syndrome – folliculin gene mutation.
  • 🧬 Hereditary leiomyomatosis and RCC – fumarate hydratase mutation.
• Lifestyle Factors
  • 🚬 Smoking – strongest modifiable risk factor.
  • ⚖️ Obesity – increased risk due to metabolic and hormonal effects.
• Medical Conditions
  • 📈 Hypertension
  • 🩺 Chronic kidney disease
  • 🩸 Long-term dialysis and acquired cystic kidney disease
• Occupational Exposures
  • 🏭 Heavy metals (e.g. cadmium)
  • 🏭 Industrial solvents and dyes

🧫 Histology

• RCC arises from the renal tubular epithelium.
• 📊 Major subtypes:
• Clear cell RCC (~75–80%) – most common and often associated with VHL mutation.
• Papillary RCC (~10–15%).
• Chromophobe RCC (~5%).
• 🧬 Tumours may invade renal veins and the inferior vena cava.

⚠️ Risk Factors

• 👨 Male sex
• 🚬 Smoking
• ⚖️ Obesity
• 📈 Hypertension
• 🩺 CKD and long-term dialysis
• 🧬 Genetic syndromes
• 🩸 Acquired cystic kidney disease

🩺 Clinical Features

• Classic triad (rare): 🩸 haematuria, flank pain, palpable abdominal mass.
• 📉 Constitutional symptoms: weight loss, fatigue, fever.
• 🍇 Left-sided varicocele (compression of left testicular vein).
• 🩸 Paraneoplastic syndromes:
• Polycythaemia (↑ erythropoietin)
• Hypercalcaemia (PTH-related peptide)
• Hypertension (renin secretion)
• Non-metastatic hepatic dysfunction (Stauffer syndrome)
• 🌍 Metastatic spread commonly to lungs, bones, liver, brain.
• 🫀 Tumour may extend into renal vein → inferior vena cava → right atrium.

🔍 Investigations

• 💉 Urinalysis: haematuria
• 📊 Blood tests: FBC, U&E, calcium, LFTs
• Imaging
  • 🖥️ Ultrasound – may detect a renal mass.
  • 🖼️ Contrast CT (renal protocol) – main diagnostic and staging investigation.
  • 🧲 MRI – useful if venous invasion suspected or CT contraindicated.
• 🫁 CT chest for metastatic staging.
• 🧪 Renal tumour biopsy may be performed if systemic therapy is planned or diagnosis uncertain.

💡 Key concept: Many RCCs are now discovered incidentally on CT scans. Early-stage tumours are often asymptomatic and potentially curable with surgery.

🛠️ Management (UK Practice)

• General Measures
  • 🚭 Smoking cessation
  • ⚖️ Weight management
  • 🩺 Optimisation of cardiovascular risk factors
• Surgical Treatment (Preferred for Localised Disease)
  • 🔪 Partial nephrectomy – nephron-sparing surgery for small tumours (T1).
  • ⚡ Radical nephrectomy – removal of kidney ± adrenal ± lymph nodes if larger or invasive tumour.
• Ablative Therapies
  • 🔥 Radiofrequency ablation
  • ❄️ Cryoablation
  • Used for small tumours in patients unsuitable for surgery.
• Systemic Therapy (Metastatic Disease)
  • 🛡️ Immune checkpoint inhibitors (e.g. nivolumab, pembrolizumab, ipilimumab)
  • 🎯 Tyrosine kinase inhibitors (VEGF inhibitors) (e.g. sunitinib, pazopanib, cabozantinib)
  • ⚡ Combination therapy often used first-line (e.g. immunotherapy + TKI).
• Radiotherapy
  • 🎯 Primarily palliative for bone or brain metastases.

📊 Prognosis

• 📍 Localised disease → ~60–75% 5-year survival.
• 🌍 Metastatic disease → significantly lower survival.
• Outcome depends strongly on stage at diagnosis.

🩺 Case 1 – Localised RCC

A 58-year-old smoker presents with intermittent painless haematuria. CT scan shows a 5.2 cm enhancing upper-pole renal mass without metastases. Management: nephron-sparing partial nephrectomy. Post-operative follow-up includes surveillance CT imaging and renal function monitoring.

🩺 Case 2 – Metastatic RCC

A 72-year-old patient presents with weight loss, bone pain and hypercalcaemia. CT demonstrates an 8 cm renal mass with lung metastases. Management: systemic therapy with immune checkpoint inhibitor + VEGF-targeted therapy. Palliative radiotherapy may be used for symptomatic bone metastases.

📚 References

• NICE Kidney Cancer Guidance
• European Association of Urology (EAU) Guidelines
• American Cancer Society Kidney Cancer Resources