Classify renal tumours. Describe renal cell carcinoma and Wilms tumour.

Classification

Renal Cell Carcinoma

• Arises from the renal tubular epithelium, chiefly the proximal tubule; peak age 60 to 70; male to female ratio 2:1
• Risk factors — smoking (the strongest), obesity, hypertension, chronic dialysis with acquired cystic disease, cadmium, von HIPPEL–LINDAU disease, tuberous sclerosis
• VHL gene on chromosome 3p is lost in the great majority of clear cell tumours, both sporadic and familial — loss of VHL stabilises HIF-1α, driving VEGF and making these tumours exceptionally vascular

Clinical features

• The classical triad — haematuria, flank pain and a palpable mass — occurs in only about 10%, and usually indicates advanced disease
• Painless haematuria is the commonest single presentation
• The "internist tumour" — it presents in many disguises through paraneoplastic syndromes: polycythaemia (erythropoietin), hypercalcaemia (PTHrP), hypertension (renin), stauffer syndrome (non-metastatic hepatic dysfunction that resolves on nephrectomy), Cushing syndrome, amyloidosis, and fever of unknown origin
• Invades the renal vein and may extend as a tumour thrombus into the inferior vena cava and right atrium; a left-sided varicocele that does not empty on lying down suggests left renal vein obstruction
• Metastasises early and widely — lung ("cannonball"), bone (lytic), liver, brain; late solitary metastases many years after nephrectomy are characteristic

Wilms Tumour (nephroblastoma)

• The commonest primary renal tumour of childhood, peaking at 2 to 5 years
• Arises from persistent nephrogenic rests — embryonal remnants that should have disappeared
• Genetics — WT1 on chromosome 11p13
• Associated syndromes — WAGR (Wilms, Aniridia, Genitourinary anomalies, mental Retardation); DENYS–DRASH (Wilms, gonadal dysgenesis, nephropathy); beckwith–wiedemann (organomegaly, macroglossia, hemihypertrophy)
• Morphology — a large, soft, pale grey, well-circumscribed tumour with a classical triphasic pattern: blastemal (sheets of small blue cells), epithelial (abortive tubules and glomeruli) and stromal (spindle cells, sometimes with muscle or cartilage)
• Anaplasia — large hyperchromatic nuclei with abnormal mitoses; associated with p53 mutation and a much worse prognosis
• Presents as a painless abdominal mass that does not cross the midline; haematuria and hypertension may occur

Comparison of the Two Principal Malignancies

Staging and Prognosis of Renal Cell Carcinoma

• Nuclear (Fuhrman/WHO-ISUP) grade and the presence of sarcomatoid change are the other important prognostic factors
• Tumour thrombus in the renal vein or vena cava does not preclude surgery, and long survival is possible after its removal — a distinctive feature of this tumour

Applied Aspects

• Any adult with painless haematuria needs full urological evaluation — imaging of the upper tracts and cystoscopy; attributing it to a urinary infection without investigation is a common and costly error
• Contrast-enhanced CT is the investigation of choice for a renal mass and also stages it; biopsy is often avoided in a typical solid enhancing mass, because the imaging is characteristic and there is a risk of seeding
• Radical or partial nephrectomy is the only curative treatment; renal cell carcinoma responds poorly to conventional chemotherapy and radiotherapy
• Metastatic disease is treated with anti-angiogenic tyrosine kinase inhibitors (sunitinib, pazopanib) and immune checkpoint inhibitors — the VHL–HIF–VEGF pathway made these tumours a natural target
• Wilms tumour is a triumph of paediatric oncology, with survival raised from under 10% to over 90% by combined surgery, chemotherapy and radiotherapy
• An abdominal mass in a child should not be repeatedly palpated, because rupture of a Wilms tumour disseminates it and upstages the disease
• The differential of a childhood abdominal mass includes neuroblastoma, which characteristically crosses the midline, calcifies, and raises urinary catecholamines — whereas Wilms tumour does not cross the midline
• Angiomyolipoma is the benign lesion that matters — fat within it on CT is diagnostic and avoids unnecessary nephrectomy; large ones may bleed catastrophically (Wunderlich syndrome) and are embolised
• Bilateral or familial renal tumours should prompt genetic assessment for von Hippel–Lindau disease, hereditary papillary carcinoma or Birt–Hogg–Dube syndrome