A 58-year-old man from rural India presents with haematuria and flank pain. Imaging reveals a 6 cm heterogeneous mass in the kidney. Histopathology shows polygonal cells with clear cytoplasm arranged in nests separated by a delicate vascular network. Which is the most common histological subtype of renal cell carcinoma in this patient?

Question

Accepted Answer

B. Clear cell renal cell carcinoma. ## Most Common Histological Subtype of RCC

**Key Point:** Clear cell RCC (ccRCC) accounts for 70–80% of all renal cell carcinomas, making it the most common subtype by a significant margin.

### Histopathological Features of Clear Cell RCC
- **Cytoplasm:** Abundant lipid and glycogen → clear appearance on H&E staining
- **Architecture:** Nests and sheets of polygonal cells separated by delicate capillary network
- **Nuclei:** Variable size and irregularity (Fuhrman grading)
- **Vascularity:** Highly vascular with prominent hemangiopericytoma-like pattern

### Molecular Basis
- **VHL gene mutation:** Present in ~80% of sporadic ccRCC [cite:Robbins 10e Ch 20]
- Loss of chromosome 3p (where VHL resides)
- Results in accumulation of HIF-1α → angiogenesis and tumour growth

### Comparative Frequency Table

| Subtype | Frequency | Key Feature | Prognosis |
|---------|-----------|-------------|----------|
| Clear cell | 70–80% | Clear cytoplasm, VHL mutation | Intermediate |
| Papillary | 10–15% | Papillary architecture, MET mutation | Generally better |
| Chromophobe | 5–10% | "Vegetable cells", binucleate, pale cytoplasm | Best |
| Collecting duct | <1% | Aggressive, tubulopapillary | Worst |

**Clinical Pearl:** Despite being the most common, clear cell RCC has intermediate prognosis. Chromophobe RCC, though rare, has the best 5-year survival (~90%), while collecting duct carcinoma is highly aggressive.

**High-Yield:** The clear cytoplasm in ccRCC is due to lipid and glycogen content, not fat infiltration. This is a critical distinction in histology exams.

### Risk Factors for Clear Cell RCC
- Smoking (1.5–2× risk)
- Obesity
- Hypertension
- Chronic kidney disease
- Von Hippel–Lindau (VHL) syndrome → nearly 100% lifetime risk

**Mnemonic: VHL-CCC** — VHL mutations drive Clear Cell Carcinoma commonality.

Answer

A. Chromophobe renal cell carcinoma

Answer

C. Papillary renal cell carcinoma

Answer

D. Collecting duct carcinoma

Explanation

Most Common Histological Subtype of RCC

Histopathological Features of Clear Cell RCC

Molecular Basis

Comparative Frequency Table

Risk Factors for Clear Cell RCC

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Subtype	Frequency	Key Feature	Prognosis
Clear cell	70–80%	Clear cytoplasm, VHL mutation	Intermediate
Papillary	10–15%	Papillary architecture, MET mutation	Generally better
Chromophobe	5–10%	"Vegetable cells", binucleate, pale cytoplasm	Best
Collecting duct	<1%	Aggressive, tubulopapillary	Worst