Congenital Disease & Tumours of Kidney and Bladder

1. Congenital Disease & Tumours of Kidney and Bladder Dr. Barbara Dunne

2. Congenital Anomalies of Kidney • Agenesis • Hypoplasia • Ectopic • Horseshoe kidney

3. Cystic Diseases of Kidney • Hereditary /Developmental • Acquired • Miscellaneous

4. Cystic Diseases of Kidney- Hereditary Adult Polycystic Kidney Disease • Autosomal Dominant- APKD1 on chrom 16 • Usually progress to chronic renal failure • Can get cysts in liver (40%) and in circle of willis (up to 30%)

6. Cut section of adult polycystic kidney disease • Cysts of various sizes • Some containing fluid and blood clot

7. Polycystic liver

8. Cystic Diseases of Kidney- Hereditary Infantile Polycystic Kidney Disease • Autosomal recessive • Renal failure in infancy • Congenital Hepatic Fibrosis

10. Cystic Disease of Kidney- Developmental Cystic Renal Dysplasia • Sporadic • Associated with ureteropelvic abnormality • Can be unilateral or bilateral

12. Cystic Diseases of Kidney Medullary Cystic Disease • Medullary Sponge Kidney- adults • Familial nephronophthisis- medullary cystic disease (FN-MCD complex)- childhood

13. Cystic diseases of Kidney- Acquired • Dialysis asssociated is the commonest • Multiple cysts but kidneys normal size

14. Cystic diseases of Kidney-misc • Simple Cyst • Common finding at autopsy • Variable size • Lined by cuboidal epithelium

15. Renal neoplasms- Benign • Adenoma (papillary adenoma) • <5mm - bland papillary structures • common- seen in up to 1/3 autopsies

16. Renal neoplasms- Benign Oncocytoma • 3-5% of renal tumours • Tan/ mahogany brown with central scar

17. Renal neoplasms- Benign Oncocytoma • Nests of oncocytic (pink) cells • Important to differentiate from carcinoma- lack of atypia

18. Oncocytoma

19. Renal neoplasms- Benign Metanephric adenoma • Closely packed tubules/papillae • Can grow to a large size

20. Metanephric adenoma

21. Renal Cell Carcinoma:Epidemiology • Overall 12th commonest cancer in males and 17th commonest cancer in females • 2-3 times more common in men • Peak age in 6th and seventh decade • Commoner in developed countries

22. Renal Cell Carcinoma:Aetiology • Tobacco smoking • Arsenic compounds, asbestos , cadmium and pesticides • ↑ Risk with ↑ BMI • Long term haemodialysis

23. Renal Cell Carcinoma: Symptoms • Haematuria, flank pain, mass • Weight loss, anorexia, fever • Paraneoplastic endocrine syndromes: ↑ Epo, ↑ ca ++, ↑ renin, prolactin • Hepatic Dysfunction • Amyloidosis

24. Renal Cell Carcinoma • Clear cell (conventional ) :75% • Papillary:7-15% • Chromophobe:3-5% • Collecting Duct Carcinoma-<1% • RCC unclassified eg sarcomatoid • Others eg urothelial

25. Clear Cell Carcinoma:Genetics • 95% sporadic: most have somatic 3p deletions • 5% familial: Von- Hippel Lindau disease (VHL) RCC, haemangioblastomas, phaeochromocytoma Germline 3p25-26 deletions Loss of pVHL protein

26. Function of pVHL • Involved in cell cycle regulation and angiogenesis • HIF1α stimulates VEGF, PDGFb, TGFa • pVHL degrades HIF1α • When pVHL absent- HIF1 α accumulates-tumorigenesis is facilitated • VEGF is potential target for treatment in RCC

27. Classic renal cell carcinoma

28. Classic renal cell carcinoma

30. Renal Cell Carcinoma • Clear cell (classic) :75% • Papillary:7-15% • Chromophobe:3-5% • Collecting Duct Carcinoma-<1% • RCC unclassified eg sarcomatoid • Others eg urothelial

31. Papillary Renal Cell Carcinoma-Genetics • Sporadic vast majority Trisomy 7, 17, loss of chromosome Y • Hereditary (HPRC) Multiple bilateral tumours Mutations of MET oncogene 7q31

32. Papillary renal cell carcinoma

34. Renal Cell Carcinoma • Clear cell (conventional ) :75% • Papillary:7-15% • Chromophobe:3-5% • Collecting Duct Carcinoma-<1% • RCC unclassified eg sarcomatoid • Others eg urothelial

35. Chromophobe renal cell carcinoma

37. Collecting duct carcinoma

38. Renal Cell Carcinoma • Clear cell (conventional ) :75% • Papillary:7-15% • Chromophobe:3-5% • Collecting Duct Carcinoma-<1% • RCC unclassified eg sarcomatoid • Others eg urothelial

39. Sarcomatoid renal cell carcinoma

41. Renal Cell Carcinoma- Spread of Disease • Haematogenous spread via renal vein/IVC → Lungs → Bone → Liver • Direct spread through capsule into adjacent organs

42. Urothelial carcinoma of renal pelvis

44. Staging of Renal Carcinoma • pT1- < 7cm, limited to kidney • pT2->7cm, limited to kidney • pT3-adrenal/perinephric/major vein invasion • pT4- Beyond Gerotas fascia

45. Nephroblastoma (Wilms Tumour) • 2-5 year olds • 90% sporadic • 10% associated with syndromes WAGR-WT1 mutations, 11p13 Beckwith-Wiedemann-WT2 mut, 11p15

46. Wilms tumour

47. Non-epithelial renal neoplasm • Angiomyolipoma Benign • Sporadic (80%) or Associated with tuberous sclerosis(20%) autosomal dominant, caused by LOH at TSC1( 9q34) or TSC2 (16p13)

48. Congenital Anomalies of Bladder • Diverticulum (can also be acquired) • Exstrophy- failure of closure of anterior wall of bladder • Anormality of vesicoureteral junction • Vesical fistulas (to vagina, rectum, uterus) • Persistant urachas

49. Bladder Carcinoma- Epidemiology • 2nd commonest cancer in the UK • Male:female ratio 3:1 • Predominantly 5th, 6th and 7th decade

50. Aetiology of bladder carcinoma • Occupational- aniline dyes, chlorinated HC • Cigarette smoking • Drugs eg phenacetin, cyclophosphamide • Chronic irritation eg Shistosoma haematobium ~ squamous ca • Most are non- familial