Renal Cell Carcinoma (RCC)
~Introduction
Renal Cell Carcinoma (RCC) is the most common primary malignancy of the kidney, originating from the renal tubular epithelium. It accounts for approximately 85–90% of all renal cancers and represents about 2–3% of adult malignancies worldwide. RCC is notorious for its silent clinical course, tendency for late presentation, and ability to metastasize early, even when the primary tumor appears small.
Advances in imaging have led to increased detection of incidental renal masses, improving early diagnosis. Despite this, RCC remains a challenging malignancy due to its biological heterogeneity and resistance to conventional chemotherapy and radiotherapy.
~Epidemiology
Most commonly diagnosed between 50–70 years of age
Male predominance (male : female ≈ 2 : 1)
Higher incidence in developed countries
Increasing global incidence due to widespread use of imaging modalities
~Etiology and Risk Factors
The exact cause of RCC is multifactorial, involving genetic susceptibility and environmental factors.
Major Risk Factors
Smoking
Strongest modifiable risk factor
Dose-dependent increase in risk
Obesity
Especially significant in women
Alters hormonal and metabolic pathways
Hypertension
Independent risk factor
Chronic Kidney Disease & Dialysis
Associated with acquired cystic kidney disease
Occupational Exposure
Cadmium, asbestos, petroleum products
Genetic Factors
Von Hippel–Lindau (VHL) syndrome
Hereditary papillary RCC
Birt–Hogg–Dubé syndrome
~Pathogenesis
Renal Cell Carcinoma arises from renal tubular epithelial cells, most commonly from the proximal convoluted tubules. The molecular pathogenesis varies among RCC subtypes.
VHL Gene Mutation
Seen in clear cell RCC
Leads to accumulation of hypoxia-inducible factors (HIF)
Results in increased angiogenesis via VEGF and PDGF
This explains the high vascularity and responsiveness of RCC to anti-angiogenic therapies.
~Classification of Renal Cell Carcinoma
1. Clear Cell Renal Cell Carcinoma
Most common type (70–80%)
Cells with clear cytoplasm due to lipid and glycogen
Highly vascular
Associated with VHL gene mutation
2. Papillary Renal Cell Carcinoma
10–15%
Papillary or tubular architecture
Two types:
Type 1: better prognosis
Type 2: aggressive
3. Chromophobe Renal Cell Carcinoma
5%
Derived from intercalated cells
Better prognosis
Pale eosinophilic cells with perinuclear halo
4. Collecting Duct Carcinoma
Rare and aggressive
Originates from collecting ducts
Poor prognosis
5. Unclassified RCC
Tumors not fitting into known categories
~Gross Pathology
Large, solitary, well-circumscribed mass
Yellow-orange appearance (lipid-rich)
Areas of hemorrhage, necrosis, and cystic degeneration
May invade:
Renal vein
Inferior vena cava
Perinephric fat
~Microscopic Pathology
Clear Cell RCC
Sheets of polygonal cells
Clear cytoplasm
Delicate branching vasculature (“chicken-wire” pattern)
Papillary RCC
Papillary structures
Foamy macrophages
Psammoma bodies
Chromophobe RCC
Large pale cells
Prominent cell membranes
Perinuclear clearing
~Clinical Features
Classic Triad (Rare)
Hematuria
Flank pain
Palpable abdominal mass
Common Presentations
Painless hematuria
Flank discomfort
Weight loss
Fever
Fatigue
Paraneoplastic Syndromes
RCC is notorious for producing ectopic hormones.
Polycythemia (↑ erythropoietin)
Hypercalcemia (PTHrP)
Hypertension (renin)
Cushing syndrome (ACTH)
Stauffer syndrome (hepatic dysfunction)
~Metastasis
RCC spreads via:
Hematogenous route (lungs, bones, liver, brain)
Lymphatic route (para-aortic lymph nodes)
Lung metastasis is the most common.
~Diagnosis
Investigations
Ultrasound
Initial screening tool
Contrast-Enhanced CT Scan
Gold standard
Defines size, extent, vascular invasion
MRI
Useful for IVC involvement
Laboratory Tests
Hematuria
Elevated calcium
Anemia or polycythemia
Biopsy
Reserved for selected cases
Not routinely required
~Staging (TNM System)
Stage I
Tumor ≤7 cm, confined to kidney
Stage II
Tumor >7 cm, confined to kidney
Stage III
Renal vein or lymph node involvement
Stage IV
Distant metastasis
~Treatment
1. Surgical Management
Radical Nephrectomy
Gold standard for localized RCC
Removal of kidney, adrenal gland, perinephric fat
Partial Nephrectomy
Small tumors (<4 cm)
Nephron-sparing approach
2. Targeted Therapy
Used in advanced or metastatic RCC:
VEGF inhibitors (Sunitinib, Sorafenib)
mTOR inhibitors (Everolimus)
3. Immunotherapy
Immune checkpoint inhibitors
Nivolumab, Pembrolizumab
IL-2 (rarely used now)
4. Radiotherapy
Limited role
Used for palliation of bone or brain metastases
~Prognosis
Prognosis depends on:
Stage
Histological subtype
Tumor grade
Patient’s performance status
5-Year Survival Rates
Stage I: 90–95%
Stage II: 70–80%
Stage III: 40–60%
Stage IV: <15%
Chromophobe RCC has the best prognosis, while collecting duct carcinoma has the worst.
~Complications
Metastatic disease
Renal vein thrombosis
Chronic kidney disease post-nephrectomy
Treatment-related toxicity
~Prevention and Early Detection
Smoking cessation
Weight control
Blood pressure management
Regular imaging in high-risk individuals
Early evaluation of hematuria
~Conclusion
Renal Cell Carcinoma is a biologically diverse and potentially aggressive malignancy of the kidney with unique clinical and molecular features. Early detection through imaging has improved outcomes, but advanced disease remains challenging. Surgical excision remains the cornerstone of treatment for localized disease, while targeted and immunotherapies have revolutionized management of metastatic RCC. Multidisciplinary care, individualized treatment strategies, and long-term follow-up are essential for improving survival and quality of life.
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