Renal Cell Carcinoma (RCC)

1. Epidemiology and Risk Factors

  • Most common kidney cancer in adults (80-85% of cases).

  • Peak incidence: 60-70 years old.

  • Male-to-female ratio: 2:1.

  • Risk factors:

    • Smoking.

    • Obesity.

    • Hypertension.

    • Chronic kidney disease (especially dialysis-related cystic disease).

    • Genetic syndromes (e.g., von Hippel-Lindau disease, hereditary papillary RCC, Birt-Hogg-Dubé syndrome).

2. Pathophysiology

  • Originates from proximal tubular epithelial cells.

  • Clear cell RCC (70-80% of cases):

    • Associated with VHL gene mutations (chromosome 3p deletion).

    • Leads to overexpression of hypoxia-inducible factors (HIF) and angiogenesis (e.g., VEGF, PDGF).

  • Papillary RCC (10-15%):

    • Type 1: Associated with MET proto-oncogene mutations.

    • Type 2: More aggressive.

  • Chromophobe RCC (5%):

    • Better prognosis than clear cell and papillary types.

  • Oncocytoma:

    • Benign tumor, often incidental finding.

3. Clinical Presentation

  • Classic triad (seen in <10% of cases):

    • Flank pain.

    • Hematuria.

    • Palpable abdominal mass.

  • Most cases are asymptomatic and detected incidentally on imaging.

  • Paraneoplastic syndromes:

    • Erythrocytosis (due to erythropoietin production).

    • Hypercalcemia (PTH-related peptide secretion).

    • Non-metastatic liver dysfunction (Stauffer syndrome).

    • Hypertension (renin secretion).

    • Fever, cachexia, weight loss (cytokine release).

4. Diagnosis

  • Imaging:

    • CT abdomen with contrast: Gold standard for diagnosis and staging.

    • Ultrasound: Often used initially to detect renal masses.

    • MRI: Useful for evaluating venous involvement (e.g., renal vein or IVC thrombus).

  • Biopsy:

    • Not routinely required if imaging is diagnostic.

    • Reserved for atypical cases or before systemic therapy.

  • Laboratory findings:

    • Hematuria (microscopic or gross).

    • Elevated hematocrit (erythrocytosis).

    • Hypercalcemia, elevated alkaline phosphatase (paraneoplastic).

5. Staging (TNM System)

  • T1: Tumor ≤7 cm, limited to kidney.

  • T2: Tumor >7 cm, limited to kidney.

  • T3: Tumor extends into major veins or perinephric tissues.

  • T4: Tumor invades beyond Gerota’s fascia or into adrenal gland.

  • N1: Regional lymph node involvement.

  • M1: Distant metastasis (e.g., lung, bone, liver).

6. Treatment

  • Localized disease:

    • Partial nephrectomy: Preferred for small tumors (<4 cm) or when preserving renal function is critical.

    • Radical nephrectomy: For larger tumors or centrally located masses.

  • Metastatic disease:

    • Targeted therapy: Tyrosine kinase inhibitors (e.g., sunitinib, pazopanib) or mTOR inhibitors (e.g., everolimus).

    • Immunotherapy: Checkpoint inhibitors (e.g., nivolumab, ipilimumab).

    • Cytoreductive nephrectomy: In select patients with good performance status.

7. Prognosis

  • 5-year survival:

    • Localized disease: >90%.

    • Regional lymph node involvement: ~50%.

    • Distant metastasis: ~10%.

  • Poor prognostic factors:

    • High-grade tumor.

    • Sarcomatoid features.

    • Metastatic disease.

Sample MCCQE-Style Questions

Question 1

A 65-year-old man presents with intermittent gross hematuria and a 10-pound weight loss over the past 3 months. He has a history of hypertension and smoking. Physical examination reveals a palpable right flank mass. Laboratory tests show a hematocrit of 52% (elevated) and serum calcium of 2.8 mmol/L (elevated). What is the most likely diagnosis?

A) Renal cell carcinoma
B) Transitional cell carcinoma
C) Polycystic kidney disease
D) Renal tuberculosis

Answer: A) Renal cell carcinoma
Explanation: The patient’s presentation (hematuria, weight loss, palpable mass, erythrocytosis, and hypercalcemia) is classic for RCC with paraneoplastic syndromes.

Question 2

A 58-year-old woman is found to have a 6 cm renal mass on abdominal CT performed for unrelated reasons. She is asymptomatic, and her laboratory tests are normal. What is the next best step in management?

A) Renal biopsy
B) Partial nephrectomy
C) Radical nephrectomy
D) Observation with repeat imaging in 6 months

Answer: B) Partial nephrectomy
Explanation: For a localized renal mass <7 cm, partial nephrectomy is the preferred treatment to preserve renal function.

Question 3

A 70-year-old man with a history of renal cell carcinoma treated with nephrectomy 5 years ago presents with new-onset bone pain and fatigue. Imaging reveals multiple lytic lesions in the spine and pelvis. What is the most likely explanation for these findings?

A) Osteoporosis
B) Metastatic renal cell carcinoma
C) Multiple myeloma
D) Paget’s disease

Answer: B) Metastatic renal cell carcinoma
Explanation: RCC commonly metastasizes to the bones, lungs, and liver. Lytic bone lesions in a patient with a history of RCC suggest metastatic disease.

Question 4

Which of the following genetic syndromes is most strongly associated with clear cell renal cell carcinoma?

A) von Hippel-Lindau disease
B) Tuberous sclerosis
C) Lynch syndrome
D) Neurofibromatosis type 1

Answer: A) von Hippel-Lindau disease
Explanation: VHL disease is associated with clear cell RCC due to mutations in the VHL gene on chromosome 3p.

Question 5

A 62-year-old man with metastatic renal cell carcinoma is started on sunitinib. Which of the following is a common side effect of this medication?

A) Hypertension
B) Hypoglycemia
C) Hypothyroidism
D) Hyperkalemia

Answer: A) Hypertension
Explanation: Sunitinib, a tyrosine kinase inhibitor, commonly causes hypertension due to its anti-angiogenic effects.


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