Renal cell carcinoma

Comprise 1-2% of all malignant tumours Most common renal tumours in adults Male to female ratio is 2:1 Average age of presentation: 55 years

Genetics & Molecular biology Structural alterations of the short arm of chromosome 3 are associated with both sporadic and hereditary forms of renal cancer. o Genes tumour suppressors (VHL) or oncogenes (e.g. MET) An example of a hereditary syndrome is von Hippel-Lindau disease. o von Hippel-Lindau disease is an autosomal dominant disease that confers predisposition to a number of neoplasms including clear cell renal carcinoma and phaeochromocytoma. Mutations in the VHL gene is seen in a high percentage of tumours and results in the accumulation of hypoxia inducible factors (HIFs) that stimulate angiogenesis through VEGR and VEGFR, making them important new therapeutic targets. Pathology Macroscopic: highly vascular tumours Microscopic: Most common is the clear cell carcinoma, which arises from the proximal tubules. Clinical features Often asymptomatic but can present with the classical triad (10%) of haematuria, loin pain and flank mass, which is indicative of advanced disease. Most common features o Haematuria (40%) o Flanks pain (40%) o Palpable mass in flank or abdomen (25%) Other signs and symptoms o Weight loss (30%) o Malaise o Anorexia o Hypertension (30%) increased rennin secretion by tumour o Anaemia (30%) depression of EPO o Pyrexia (20%) o Hypercalcaemia (5%) o Polycythaemia (5%) o Left-sided varicocele (2%) - invasion of the renal vein causing obstruction to drainage of the left testicular vein Approxiamately 25% of patients with renal carcinoma will present with metastatic disease. Predisposing factors

Cigarette smoking the risk appears to increase with the amount of smoking in a dose-dependent manner Obesity - particularly in women Hypertension Acquired cystic disease of the kidney as a result of long-term dialysis Tuberous scelerosis Renal transplantation

Diagnosis Imaging o Ultrasonography demonstrate lesion and patency of the renal veins and inferior vena cava o CT further identifiy renal lesion and vessel involvement o MRI better than CT for tumour staging Laboratory results o Raised ESR o Abnormal liver function tests (AST and ALT), which should return to normal following surgery. Treatment Surgical o Nephrectomy o Partial nephrectomy when there are bilateral tumours or there is poor function of collateral kidney. Medical o Chemotherapy either single agent or combination and response rates are low, typically lower than 15%. Foxuridine, vinblastine, carboplatin. o Biologics Interleukin-2 and interferon produce remission in 20% of cases. o Newer therapies: temsirolimus (mTOR inhibitor) improves survial amongst patients. Also tyrosine kinase inhibitors including sorafenib and sunitinib. Bevacizumab (neutralising antibody to VEGF) a study has shown to increase the 5-year disease progression-free survival. o Medroxyprogesterone acetate may be of some use in controlling metastatic disease Prognosis Depends upon the type, grade and stage of the tumour. 5 year survival rate: o 60-70% if confined to the parenchyma o 15-35% with lymph node involvement o 5% with distant metatstases

Urothelial tumours
Renal urothelial carcinoma is a malignant tumour that arises from the urothelial epithelial cells of the renal calyces, renal pelvis (most common) and ureter. Renal pelvic tumours are most common and 90% are transitional cell carcinomas. Other types include squamous cell carcinoma (SCC)

Epidemiology Uncommon below the age of 40 Male to female ratio is 4:1 Clinical features Painless haematuria is the most common presentation o Gross haematuria (75-95%), microscopic haematuria (3-11%) Pain (dull or renal colic) may occur as a result of clot retention or nerve involvement. Rarely asymptomatic (1-2%) Classical triad (haematuria, pain and mass) is rare (15%) and indicative of advanced disease. Predisposing factors Cigarette smoking Industrial carcinogens e.g. -naphthylamine, aniline dyes, benzidine and plastics industries. Drugs e.g. phenacetin (analgesic used less commonly now) and cyclophosphamide (alkylating chemotherapeutic agent) Chronic inflammation e.g. schistosomiasis usually associated with SCC. Investigations Imaging o ultrasonography, CT (including CT urography), MRI Laboratory o Urine analysis and urine culture to assess presence haematuria and exclude urinary tract infection. o Cytology studies of urine Treatment Surgical Neuphroureterectomy Medical Immunotherapy, chemotherapy, radiotherapy Prognosis 5 year survival rate is 80-90%