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 12 th commonest cancer in males and 17 th commonest cancer in females  2-3 times more common in men  Peak age in 6 th 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

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  2 nd commonest cancer in the UK  Male:female ratio 3:1  Predominantly 5 th, 6 th and 7 th 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

51. Types of Bladder Carcinoma  Urothelial/transitional cell carcinoma-90%  Squamous Cell -5%  Adenocarcinoma- 2%  Other-3% small cell carcinoma spindle cell carcinoma lymphoepithelioma-like carcinoma nested variant of TCC micropapillary carcinoma

53. Types of Urothelial Carcinoma  Non-invasive-papillary (pTa) ca in-situ (pTis)  Invasive TCC pT1- invasion of submucosa pT2- invasion of muscle pT3- beyond muscle pT4- invades other organs

58. Natural History of Bladder Carcinoma  Superficial TCC 95% 5 year survival frequent recurrences 10-20% risk of disease progression  Carcinoma in-situ >50% risk of disease progression  Muscle invasive TCC 35% 5 year survival

59. Mesenchymal Lesions in Bladder  Leiomyoma  Leiomyosarcoma  Post-operative spindle cell nodule  Inflammatory pseudotumour

60. Thank You