Pathology of Renal Cell Carcinoma

Overview

• Study of renal cell carcinoma (RCC) includes its origin, risk factors, types, pathogenesis, and morphology.

Origin

• RCC originates from renal tubular epithelium.

Risk Factors

1. Smoking
2. Obesity
3. Hypertension (vascular disorder associated as a risk factor)
4. Exposure to cadmium
5. Acquired polycystic kidney disease (common in chronic dialysis patients)

Types of Renal Cell Carcinomas

1. Clear Cell Carcinoma
   • Most common type
2. Papillary Cell Carcinoma
3. Chromophobe Cell Carcinoma
   • Least common type

Clear Cell Carcinoma

Pathogenesis

• Mutations in VHL gene on chromosome 3.
• VHL gene is a tumor suppressor gene.
• Loss of VHL results in increased production of HIF (hypoxia-inducible factor).
• HIF increases transcription of growth factors (e.g., vascular endothelial growth factor).
• Results in uncontrolled cell division.
• Related to von Hippel-Lindau disease (autosomal dominant trait).

Morphology

Gross Features

• Solitary mass with cystic areas or hemorrhage.
• Tendency to invade renal veins, growing into the inferior vena cava.

Microscopic Features

• Clear cells with empty cytoplasm.
• Cells arranged in tubules or cords.
• Scanty but vascular stroma.

Papillary Renal Cell Carcinoma

Pathogenesis

• Activating mutations in MET proto-oncogene on chromosome 7.
• Increased receptor tyrosine kinase activity.

Morphology

Gross Features

• Bilateral or multiple masses.
• Cysts and hemorrhages similar to clear cell carcinoma.

Microscopic Features

• Papillary structures (finger-like projections) lined by neoplastic epithelial cells.

Chromophobe Renal Cell Carcinoma

Pathogenesis

• Arises from intercalated cells of collecting ducts.
• Characterized by extreme hypoploidy (loss of entire chromosomes).

Morphology

Gross Features

• Tan brown masses.

Microscopic Features

• PPP mnemonic: Pale-staining cytoplasm, Perinuclear clearing, Prominent cell membranes.

Clinical Features

Renal Manifestations

• Classical triad: palpable mass, flank pain, hematuria.

Extra Renal Manifestations

• Paraneoplastic syndromes: polycythemia, Cushing's syndrome, hypercalcemia.

Metastasis

• Common sites: lungs and bones.

This concludes the study on renal cell carcinomas.