Renal Tumours — Renal Cell Carcinoma Subtypes, Paraneoplastic Syndromes and Wilms Tumour

Renal cell carcinoma (RCC) accounts for more than 9 in 10 kidney cancers in adults and more than 3% of all adult malignancies. It is a tumour of the 50–70 age group with a male-to-female ratio of about 2:1. Other kidney malignancies include transitional cell carcinoma of the renal pelvis (which behaves like bladder cancer) and rare renal sarcomas. In children, the commonest renal cancer is Wilms tumour (nephroblastoma), followed by clear cell sarcoma of the kidney.

RCC arises from the epithelium of the nephron: clear cell RCC (CCRCC) from the proximal tubule, papillary RCC (PRCC) from the distal tubule and chromophobe RCC from the intercalated cells of the collecting duct. The 2016 WHO classification lists more than 14 types; the four to know are clear cell, papillary, chromophobe and collecting duct (Bellini) carcinoma.

Smoking is the strongest risk factor (cigarettes, pipes and cigars), followed by obesity, hypertension, chronic renal failure, occupational exposure (for example trichloroethylene) and a family history. About 4% of RCC is hereditary. Sporadic and familial clear cell RCC both implicate the VHL gene.

Over 50% of RCCs are now found incidentally on imaging, and many tumours are asymptomatic until late. The classic triad of flank pain, haematuria and flank mass is found in only 10–15% and indicates advanced disease. Haematuria is the commonest sign, with gross haematuria being the single most important sign of renal malignancy. Other features: fatigue, weight loss, fever, night sweats, anaemia and hypertension. A varicocele (notably acute-onset or right-sided) can develop when tumour grows into the renal vein or IVC and blocks the testicular vein.

Metastases at presentation occur in about one-third of patients: lung (75%), bone (20%), liver (18%), CNS (8%). Bone metastases are typically osteolytic and cause pathological fractures and hypercalcaemia.

Renal ultrasound is usually the first test, then a contrast CT of the abdomen and pelvis (staging CT) and chest imaging. Clear cell RCC is hypervascular, most papillary RCCs are hypovascular, and chromophobe RCC is homogeneous with a central stellate scar and spoke-wheel enhancement. MRI is used for venous invasion. Urinalysis, blood count, ESR, renal function, calcium and liver tests look for paraneoplastic features.

Stage I = T1 N0 M0; stage II = T2 N0 M0; stage III = T1–2 N1 or T3; stage IV = T4 or M1. Renal vein thrombus is staged T3a, because such tumours have a relatively favourable prognosis. Treatment is stage-dependent: stage 1a — nephron-sparing partial nephrectomy; stage 1b — partial or radical nephrectomy; stages 2–3 — radical nephrectomy; stage 4 — VEGF-targeted tyrosine kinase inhibitors (sunitinib, sorafenib, pazopanib, axitinib) or mTOR inhibitors (temsirolimus, everolimus), which have replaced interferon-based immunotherapy. Small renal masses (< 4 cm) in the elderly or unfit may be managed by active surveillance.

Wilms tumour (nephroblastoma) is the most common renal cancer of childhood, the most common abdominal cancer of childhood and the fourth most common paediatric cancer overall, named after Max Wilms (1899). Median age at diagnosis is 3.5 years, 90% are diagnosed before 6 years, and girls are slightly more affected. It develops from persistent metanephric tissue (nephrogenic rests) — present in up to 100% of bilateral Wilms tumours and about 35% of unilateral ones. Bilateral disease is about 5%. Associated genes are WT1, CTNNB1 and WTX; TP53 and loss of heterozygosity at 1p, 1q, 11p15 and 16q signal a poorer prognosis.

Most Wilms tumours present as an asymptomatic abdominal mass, often found by a caregiver while bathing the child. Abdominal pain is the commonest initial symptom (30–40%), followed by hypertension (about 25%, which normalises after nephrectomy) and haematuria (12–25%). Other features: fever, anaemia, urinary infection, and a varicocele. Grossly the tumour is well circumscribed with a pseudocapsule.

Benign renal neoplasms include adenomas, angiomyolipomas (hamartomas), fibromas, haemangiomas, lipomas and oncocytomas. Most renal masses are benign in the general population, but a significant number need evaluation; small renal masses below 4 cm tend to grow slowly (up to about 3 mm a year) and carry a very low risk of metastasis. For the embryology of the kidney and nephrogenic tissue see development of the genitourinary system, and for hamartoma terminology see neoplasia nomenclature.