11.3 Renal Cell Carcinoma

Renal Cell Carcinoma (RCC)

• RCC is a malignancy originating in the renal tubules, comprising 80% of kidney cancers.
• Clear cell carcinoma is the most prevalent histological subtype (80% of RCC cases).
• Paraneoplastic syndromes, like hypercalcemia and erythrocytosis, may present with RCC.
• Staging (TNM) categorizes tumor (T), lymph node (N), and metastasis (M) extent.
• Key risk factors are smoking, obesity, and hypertension.
• Clinical presentation often includes flank pain, hematuria, and a palpable abdominal mass (in 6-10% of cases).
• Diagnostic approach includes ultrasound, CT scan (gold standard), and MRI, followed by potential biopsy.
• T1/T2 tumors are confined to the kidney, whereas T3/T4 tumors involve local or distant spread.
• Treatment for localized RCC centers around radical nephrectomy.
• Metastatic RCC utilizes targeted therapies (e.g., tyrosine kinase inhibitors) and immunotherapies.

Learning Objectives

• Define the epidemiology and risk factors for renal cancer.
• Describe the clinical presentation and diagnostic evaluation of patients with suspected renal cancer.
• Explain the staging system for renal cell carcinoma.
• Describe management strategies for RCC, including surgical and non-surgical approaches.

Key Concepts

• Renal Cell Carcinoma (RCC): A malignant tumor originating in the renal tubules; accounts for 80% of all kidney cancers.
• Clear Cell Carcinoma: The most common histological subtype of RCC (80%).
• Paraneoplastic Syndrome: Symptoms resulting from the immune response to cancer.
• TNM Staging: A system for classifying tumor, lymph node, and metastasis extent in cancer staging.

Clinical Applications

• Case Study: A 65-year-old male with gross hematuria, right flank pain, and a palpable mass.
• Diagnostic approach involves urgent ultrasound and contrast-enhanced CT for tumor evaluation, lymph node assessment and metastasis status.
• Treatment for stage T2 tumors (less than 7 cm and confined to the kidney) often involves radical nephrectomy.
• Metastatic disease management utilizes systemic therapies, including immunotherapies and targeted therapies.

Pathophysiology

• Tumor Development: Mutations in tumor suppressor genes (e.g., VHL gene) underlie abnormal cell proliferation.
• Paraneoplastic Effects: RCC can induce syndromes like hypercalcemia (through PTH-related protein), erythrocytosis (due to excess erythropoietin), and Stauffer's syndrome (non-metastatic hepatic dysfunction).

Pharmacology

• Systemic Therapy: Targeted therapies (e.g., tyrosine kinase inhibitors like sunitinib) and immunotherapies are utilized for metastatic RCC.

Differential Diagnosis

• Crucial to differentiate RCC from other conditions such as oncocytoma, angiomyolipoma, renal abscess, and urothelial carcinoma. Images and markers may help.

Investigations

• Essential blood tests (CBC, renal function tests, serum calcium) screen for paraneoplastic syndromes.
• Initial diagnostic approaches includes imaging (ultrasound), followed by contrast-enhanced CT and MRI, if needed.
• Biopsy is used for definitive histologic diagnosis, particularly if non-surgical options are being considered.

Summary & Key Takeaways

• RCC is a significant kidney malignancy, with clear cell carcinoma being the most prevalent subtype.
• Risk factors include smoking, obesity, and hypertension.
• Clinical presentation is variable, with a minority presenting with the classical triad.
• TNM staging is key for treatment planning.
• Local disease management predominantly relies on surgery, whereas metastatic disease mandates systemic therapies.