STEPTRACKERRENAL + ONCOLOGY | PATHOLOGY + GENETICS | HIGH-YIELD REVIEW

Renal & Urothelial Tumors

Adult kidney cancer and its hormones, the benign masses that mimic it, the childhood tumor with its syndromes, and bladder cancers.

FOCUS ON
Clear cell RCC: VHL (3p) loss → HIF → VEGF; smokers, obesity; hematuria, flank pain, mass; EPO, renin, PTHrP; renal vein invasion (left varicocele). Wilms: child 2–4, flank mass, WT1/WT2 syndromes. Urothelial carcinoma: smoking, aromatic amines, cyclophosphamide → painless hematuria, recurrent and multifocal. Schistosoma → bladder SCC.
TUMOR
MECHANISM · RISK
FEATURES
CLUE
Clear cell RCC
most common adult kidney cancer
Proximal tubule; VHL (chr 3p) loss → ↑ HIF → VEGF, PDGF; smoking, obesity, hypertension, dialysis cysts, VHL syndrome
Golden-yellow mass; clear cells (lipid + glycogen); hematuria, flank pain, palpable mass (late triad)
Often found incidentally on CT
RCC — spread & paraneoplastic
Grows into renal vein → IVC; hematogenous spread
Left varicocele (left gonadal vein drains to left renal vein); "cannonball" lung and bone mets · EPO (polycythemia), renin, PTHrP, ACTH
Nephrectomy; TKIs (sunitinib), immunotherapy · resistant to chemo/radiation
Papillary & chromophobe RCC
Papillary: MET, trisomy 7/17, dialysis · chromophobe: intercalated cells
Papillary: often multifocal · chromophobe: pale cells with perinuclear halos
Chromophobe has good prognosis
Oncocytoma
Benign; collecting duct intercalated cells
Large eosinophilic cells packed with mitochondria; mahogany-brown with central scar
Often removed because it mimics RCC
Angiomyolipoma
Benign PEComa: blood vessels + smooth muscle + fat; tuberous sclerosis (TSC1/2 → mTOR)
Fat-containing mass on CT; may bleed (retroperitoneal hemorrhage)
HMB-45 ⁺ · mTOR inhibitors (everolimus)
Wilms tumor
most common childhood kidney cancer
Embryonal (nephrogenic rests); WT1 (11p13), WT2 (11p15)
Age 2–4: large unilateral flank mass, often doesn't cross midline; hematuria, hypertension; triphasic (blastema, stroma, epithelium)
Good prognosis with treatment
Wilms syndromes
Gene deletions or imprinting defects
WAGR: Wilms, aniridia, GU anomalies, developmental delay · Denys-Drash: early nephrotic disease, gonadal dysgenesis (WT1) · Beckwith-Wiedemann: macroglossia, organomegaly, hemihyperplasia, omphalocele (11p15)
Aniridia in a child → screen kidneys
Urothelial carcinoma
most common bladder cancer
Smoking (top risk), aniline dyes/aromatic amines (2-naphthylamine, benzidine), cyclophosphamide, phenacetin
Painless gross hematuria; bladder, renal pelvis, ureter; multifocal and recurrent ("field effect")
Cystoscopy · BCG for superficial disease
Urothelial pathways
Papillary low-grade (FGFR3, HRAS) vs flat high-grade carcinoma in situ (TP53)
Papillary: recurs but rarely invades · flat CIS: invades early
Prognosis depends on depth (muscle invasion)
Squamous cell carcinoma of bladder
Chronic irritation → squamous metaplasia: Schistosoma haematobium (Egypt, Africa), long-term catheters, stones
Hematuria, dysuria
Parasite eggs with terminal spine
Bladder adenocarcinoma
Urachal remnant (dome), bladder exstrophy, cystitis glandularis
Mass at the dome; mucus in urine
Persistent urachus → urine from umbilicus

Mechanism — VHL loss drives clear cell RCC

VHL proteinTags HIF for degradation
→
VHL lost (3p)Two hits
→
HIF accumulatesEven with O₂
→
VEGF, PDGF, EPOVascular tumor, polycythemia

VHL syndrome (autosomal dominant): bilateral RCC, hemangioblastomas (cerebellum, retina), pheochromocytoma, pancreatic serous cysts.

Kidney masses at a glance

TUMOR
AGE
KEY CLUE
BEHAVIOR
Clear cell RCC
Adult smoker
Clear cells, VHL
Malignant
Oncocytoma
Adult
Mitochondria, central scar
Benign
Angiomyolipoma
Adult, TSC
Fat on CT
Benign, bleeds
Wilms
Child 2–4
Triphasic, WT1
Malignant
Neuroblastoma (adrenal)
Child < 2
Crosses midline, ↑ VMA/HVA
Malignant

How it's tested

COMMON CONFUSIONWilms and neuroblastoma are both pediatric flank masses. Wilms arises in the kidney and rarely crosses the midline; neuroblastoma is adrenal, crosses the midline, calcifies and raises urine catecholamine metabolites.
THE TRAPA new left-sided varicocele in an older man that doesn't empty when lying down suggests left renal vein obstruction by RCC.
YOUR APPROACHAge + syndrome + paraneoplastic clue + imaging (fat, scar, calcification) → tumor → gene → how it spreads.

If you see… think…

Smoker with hematuria, flank mass and polycythemia → renal cell carcinoma
Hypercalcemia + renal mass → RCC with PTHrP
New left varicocele in a 60-year-old → RCC invading the left renal vein
Bilateral RCC + cerebellar hemangioblastoma → von Hippel-Lindau
Renal mass with fat on CT in a patient with seizures and ash-leaf spots → angiomyolipoma (tuberous sclerosis)
Mahogany mass with central scar, mitochondria-rich cells → oncocytoma
3-year-old with a flank mass and aniridia → Wilms tumor (WAGR)
Aniline dye worker with painless hematuria → urothelial carcinoma
Hematuria after cyclophosphamide → hemorrhagic cystitis (acrolein) — mesna
Egyptian farmer with bladder mass and terminal-spined eggs → SCC from Schistosoma haematobium