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%).
- 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
3: A mutation in the VHL (von Hippel-Lindau) gene on chromosome 3 causes RCC (renal cell carcinoma).
Rule of
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
- 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
- Clear cells
Differential diagnosis
Benign renal masses
Oncocytoma
- Definition: benign epithelial tumor arising from the intercalated tubular cells in the collecting duct
Mnemonic
**collecting ducts, well-c**ircumscribed mass with central scar
- 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)
- Large eosinophilic cells with abundant mitochondria without perinuclear clearing (Compared with chromophobe renal cell carcinoma)
- Macroscopy: smooth, clearly defined brown tumor with central radial scar
- 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