Etiology

• Risk factors for sporadic RCC
  • Smoking
  • Obesity
• Hereditary renal cell carcinomas
  • Von Hippel-Lindau syndrome: Approx. 40% of patients with VHL syndrome develop renal cell carcinomas (usually clear cell RCC).

Pathology

• Renal cell carcinomas are adenocarcinomas that usually arise from the epithelial cells of the proximal convoluted tubule (80%).
  • Because of high metabolic activity and exposure to toxins
• Clear cell renal cell carcinoma
  • Frequency: 70%
  • Etiology: Sporadic or inherited mutation of VHL gene on chromosome 3p
  • Microscopic appearance:
    • Polygonal cells arranged as cords or tubules (non-papillary growth)
    • Clear, glycogen and/or lipid-filled cytoplasm

Clinical features

• Constitutional symptoms
  • Weight loss, fatigue
  • Fever, night sweats
  • Anemia
• Symptoms caused by primary tumor
  • Hematuria
  • Flank pain
  • Palpable renal mass

Diagnostics

Pathology

Clear cell renal cell carcinoma

• Macroscopic appearance
  • Yellow or golden due to high intracellular lipid concentration
• Microscopic appearance
  • Clear cells
    • Polygonal cells arranged as cords or tubules (non-papillary growth)
    • Clear, glycogen and/or lipid-filled cytoplasm
      • Mutations in the VHL gene lead to accumulation of hypoxia-inducible factor (HIF).
      • The accumulation of HIF promotes a cellular environment that mimics hypoxia (low oxygen levels), even when oxygen is abundant. This state triggers several metabolic changes in the cell, notably an increase in glucose uptake and a shift towards glycolysis and lipid biosynthesis. Consequently, lipids accumulate within the cytoplasm, giving the cells their characteristic "clear" appearance.
  • Unifocal, unilateral growth

Differential diagnosis

Benign renal masses

Oncocytoma

• Definition: benign epithelial tumor arising from the intercalated tubular cells in the collecting duct

• Clinical features
  • Painless hematuria
  • Abdominal mass
  • Flank pain
• Pathology
  • Macroscopy: smooth, clearly defined brown tumor with central radial scar
  • Microscopy
    • Large eosinophilic cells with abundant mitochondria without perinuclear clearing (Compared with chromophobe renal cell carcinoma)
    • Excessive amount of mitochondria → acidophilic, granular cytoplasm without perinuclear clearing (unlike chromophobe RCC)
• Treatment
  • Often resected in order to exclude RCC
  • Surveillance

Treatment

Complications

Complications caused by paraneoplastic syndromes

• Secondary hypercortisolism: due to ectopic ACTH release
• Secondary polycythemia: due to ectopic erythropoietin (EPO) secretion
• Hypertension: due to the release of renin
• Hypercalcemia: due to the release of PTHrP (parathyroid hormone-related protein)

Complications caused by local spread

• Varicocele
  • Rare, classically associated with left-sided RCC
  • Malignant cells grow inside the left renal vein and occlude the ostium of the left gonadal vein.
• Budd-Chiari syndrome: caused by involvement of the IVC
  • Lower limb edema
  • Ascites
  • Hepatic dysfunction