Renal Cell Carcinoma for USMLE Step 2
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Renal Cell Carcinoma for the USMLE Step 2 Exam
- Definition:
- Renal cell carcinoma (RCC) is the most common primary malignancy of the kidney, originating from the renal tubular epithelium. It comprises several histologic subtypes, with clear cell RCC being the most common.
- Epidemiology:
- RCC typically occurs in adults aged 60-70 years and is more common in men. Key risk factors include:
- Smoking: Strong association with increased RCC risk.
- Obesity: Particularly significant in women.
- Hypertension: Both treated and untreated hypertension increase the risk.
- Genetic Conditions:
- Von Hippel-Lindau (VHL) disease: Linked to clear cell RCC due to mutations in the VHL gene.
- Chronic Kidney Disease (CKD): Patients on long-term dialysis are at increased risk due to acquired cystic kidney disease.
- Pathophysiology:
- RCC arises from the proximal tubular epithelium and is classified into subtypes:
- Clear Cell RCC: Most common, accounting for 75-85% of cases, characterized by lipid and glycogen-rich clear cells.
- Papillary RCC: About 10-15% of cases, further divided into types 1 and 2.
- Chromophobe RCC: A rarer subtype with pale eosinophilic cells, generally associated with a better prognosis.
- RCC often invades local structures, such as the renal vein, and may extend into the inferior vena cava (IVC), contributing to hematogenous spread to the lungs, bones, liver, and brain.
- Clinical Presentation:
- RCC is frequently asymptomatic in early stages and often incidentally found on imaging. The classic triad of symptoms includes:
- Hematuria: Most common presenting symptom, either gross or microscopic.
- Flank Pain: Results from tumor growth and capsular distension.
- Palpable Abdominal Mass: Typically seen in advanced disease.
- Paraneoplastic Syndromes:
- RCC is associated with several paraneoplastic syndromes, including:
- Hypercalcemia: Due to parathyroid hormone-related peptide (PTHrP) production.
- Polycythemia: From increased erythropoietin production.
- Hypertension: Linked to excess renin secretion.
- Diagnosis:
- Imaging:
- CT Scan: The gold standard for diagnosis and staging, assessing tumor size, local invasion, and metastatic spread.
- MRI: Useful for evaluating venous involvement (e.g., tumor thrombus in the IVC).
- Urinalysis: Detects hematuria but is nonspecific.
- Biopsy: Generally not required for clear radiologic presentations but may be considered for indeterminate lesions or metastasis without an identifiable renal mass.
- Staging:
- RCC is staged using the TNM system:
- Stage I: Tumor confined to the kidney, ≤7 cm.
- Stage II: Tumor >7 cm but still confined to the kidney.
- Stage III: Tumor invades local structures (e.g., renal vein, perinephric tissues).
- Stage IV: Tumor invades adjacent organs or has distant metastasis.
- Management:
- Surgical Treatment:
- Radical Nephrectomy: Standard treatment for localized RCC, involving removal of the kidney, adrenal gland, and surrounding fat.
- Partial Nephrectomy: Preferred for small tumors (<4 cm) or patients with a solitary kidney to preserve renal function.
- Systemic Therapy:
- For advanced or metastatic RCC, targeted therapies such as tyrosine kinase inhibitors (e.g., sunitinib, pazopanib) are used to inhibit angiogenesis and tumor growth.
- Immune Checkpoint Inhibitors: Nivolumab and pembrolizumab (PD-1 inhibitors) are increasingly used for metastatic RCC, often in combination with targeted therapies.
- Ablative Therapies:
- Radiofrequency ablation (RFA) and cryoablation are options for small tumors in patients who are poor surgical candidates.
- Prognosis:
- Prognosis is highly dependent on the stage at diagnosis:
- Localized disease: Five-year survival exceeds 90%.
- Advanced/metastatic disease: Five-year survival is approximately 10-20%.
Key Points
- Renal cell carcinoma (RCC) is the most common kidney cancer, with clear cell RCC being the predominant subtype.
- Risk factors include smoking, obesity, hypertension, and genetic syndromes like Von Hippel-Lindau disease.
- RCC typically presents with hematuria, flank pain, and paraneoplastic syndromes like hypercalcemia and polycythemia.
- Imaging (CT or MRI) is crucial for diagnosis and staging, while biopsy is reserved for indeterminate cases.
- Surgical resection is the main treatment for localized RCC. Advanced disease is treated with targeted therapies and immune checkpoint inhibitors.
- Prognosis depends on disease stage, with early-stage RCC having a favorable outcome.