Kidney & Urinary Tract Neoplasms

1. Kidney & Urinary Tract Neoplasms Jaroslava Dušková

2. Kidney Cancer • 2% of the total human cancer burden, M:F 2:1, middle age • preference for developed (industrialized) countries • risk factors: TOBACCO SMOKING, OBESITY

3. silent for a long time - discovered by chance hematuria, backache, abdominal mass, metastatic spread early hematogenic spread possible Symptoms

4. WHO classification of tumours of the kidney (2004)

5. Renal cell (12) Metanephric (3) Nephroblastic (3) Mesenchymal (18) Mixed mesenchymal and epithelial (3) Neuroendocrine (5) Hematopopietic and lymphoid (3) Germ cell (2) Metastatic (-) WHO Histogenetic groups (& number of nosology units identified)

6. Epithelial Neoplasms of the Pelvis • Benign - papillomas • Malignant - carcinomas • papillocarcinomas • squamous cell Urinary ways

7. Benign Malignant Kidney Tumours

8. Kidney Adenoma Definition: • Formerly - diam. 2-3 cm • Recently – only diam. less than 5mm without a clear cell component • tubulopapillary architecture • lack of atypiae & mitoses

9. benign ADENOMAS papillary tubulopapillary (<5mm!) oncocytic (oncocytoma) metanephric Epithelial Kidney Tumours

10. Oncocytoma • Kidney cortex • may be multicentric and bilateral • Macro – tan with a central stellate scar • Micro - eosinophillic granular cytoplasm bizarre nuclei • Elmi – mitochondria filling up the cytoplasm • Biological behaviour benign

11. Angiolipoleiomyoma – mixed mesenchymal tumour Kidney Tumours - mesenchymal

12. Metanephric Adenoma • small dark cells • acinar and glomeruloid formations • calkospherites, calcifying non agressive

13. Benign Kidney Tumours Mimicking Carcinomas and Sarcomas • Metanephric adenoma - large & cellular • Oncocytoma - large with atypiae • Angioleiomyolipoma - large with atypiae

14. malignant CARCINOMAS Clear Conventional Cell Papillary (chromophillic) type 1 type 2 Chromophobe classical eosinophillic Sarcomatoid Cystic Collecting Duct Epithelial Kidney Tumours

15. Clear Cell Ca (Grawitz tumour) (75%) • Solid / cystic • Unilocullar or multilocular • Micro - solid or tubulocystic clear cytoplasm (fat & glycogen) • Immunohistochemistry cytokeratins, vimentin, CD10, EMA, S-100 • Cytogeneticsdeletion of the short arm chromosome 3 (3p) Prognosis: G, pT dependent Sarcomatoid variant is the most malignant

16. Papillary (Chromophillic) Ca (10%) • In dialysed more frequent • X-ray hypovascular • Histology –papillary/ tubulopapillary type 1 – cubic cells type 2 - cylindric cells (worse prognosis) • Genetics –trisomy ortetrasomy 7 and 17 in men often Y chromosome missing mutation of c-met oncogen Prognosis : G, pT dependent slightly better than in conventional ca

17. Chromophobe Carcinoma (5%) • Macro - brown color • Mikro - solid, cytoplasms clear or eosinophillic, positive in Hale´s colloidal iron staining, raisin-like cell nuclei • Elmi microvesicles in cytoplasm • Genetics missing chromosomes - 1, 2, 10, 13, 6, 21, 17 Prognosis: G, pT dependent

18. Collecting Duct Carcinoma • Starts in the medulla • Micro • adenocarcinoma & urothelial like • hobnail cells • papillary • fibroplasia, mucin production • Imunocytokeratin 13, vimentin, lectin Prognosis unfavourable

19. Nephroblastoma (Wilms´tumour) • syn. - embryonal adenosarcoma • Children - preschool age • Macro: gray-white large retroperitoneal mass palpable through abdominal wall • Micro: undifferentiated renal blastema, tubular and glomeruloid formations may be present • Prognosis: curable (stage!) • Follow up: - nephroblastomatosis

20. Role of the Pathologist in the Kidney Tumour Diagnostics • Typing • Biological Behaviour • Grading • Staging

21. Grading • Nuclear – Fuhrman et al. 1982 • Nuclear plus architecture • Proliferation factors - PCNA, Ki 67, Bcl 2 • Morphometry • DNA Analysis • AgNOR • Angiogenesis • Cytometry Flow cytometry

22. Staging • Size • Kidney capsule infiltration • Angioinvasion • Metastases in the lymph nodes • Number of lymph nodes involved • Metastases in the surrounding organs

23. Nuclear Grading in Kidney Cancer (Fuhrman et al. 1982) • Grade I small, uniform, round (10  ) inaparent or missing nucleoli • Grade II larger irregular (15 ) nucleoli small • Grade III large, irregular margins (20 )nucleoli large • Grade IV large, bizarre, pleomorphic

24. Factors with an Adverse Prognosis Influence in Kidney Cancer Sizediam. more than 12 cm Invasion to venes recidives GradingG III and G IV Staging most important Proliferation Index p53Expression

25. Kidney Cancer – complications 1. • metastatic spread & generalisation • manifestation via solitary bloodborne metastasis possible (pathological fracture, struma neoplastica…) • hematuria – anemia

26. Kidney Cancer – complications 2. • hormon production – erythropoietin polyglobulia Wood L, Swanepoel C, du Toit A, Jacobs P.Clinically silent renal tumour producing erythropoietin.S Afr Med J. 2003 Feb;93(2):128-9. Shaheen M, Hilgarth KA, Hawes D, Badve S, Antony AC.A Mexican man with "too much blood". Lancet. 2003 Sep 6;362(9386):806. • insulin, glukagon, renin, HPL like substances

27. Urothelial Tumours

28. Urothelial Cancer • approx. 3% of total human cancer burden • increasing incidence • industrialized countries • risk factors: TOBACCO SMOKING aniline dye industry phenacetin schistosomiasis

29. Symptoms hematuria (obstruction) (metastases)

30. Terminology …the term UROTHELIAL be used rather than „transitional“...

31. Normal urothelium multilayered variable number of layers empty bladder 4 - 6 full bladder 2 - 3

32. Normal urothelium Cells: basal superficial („umbrella“) polyploid, binuclear neuroendocrine

33. „Variations“ of Urothelium – slight reactive changes von Brunn´s nests mucinous metaplasia squamous metaplasia (nonkeratinising, vagina type)

34. Metaplasia Def:change of one differentiated structure into another one (e.g. urothelium – squamous epithelium)

35. Cause: iritation Types: squamous nonkeratinizing keratinizing mucinous nephrogenic clear cell Urothelium Metaplasia

36. Metaplasia Significance: • dif. dg. problem • with atypia precancerosis

37. Submucose discontinual muscularis mucosae continual row of vessels important for staging of urothelial ca (pT1a, pT1b, pTx)

38. The WHO/ISUP Consensus Classification of Urothelial Neoplasmsof the Urinary Bladder Epstein JI, Amin MB,Reuter VR, Mostofi FK, & the Bladder Consensus Conference Committee Am.J. Surg. Pathol.,22,1998,1435-8 WHO 2004

39. The WHO/ISUP Consensus Classification • Hyperplasia • Flat lesions with atypia • Papillary neoplasms • Invasive neoplasms

40. The WHO/ISUP Consensus Classification I. Hyperplasia Flat Papillary

41. Hyperplasia Def:regular increase in number of uroth. layers (min. >7, mostly >10) slight increase in cell nuclei size, preserved architecture

42. Hyperplasia Significance: precancerosis 70% of patients with urothelial ca identical mutations

43. The WHO/ISUP Consensus Classification • Hyperplasia • Flat lesions with atypia • Papillary neoplasms • Invasive neoplasms

44. II. Flat lesions with atypia • Reactive (inflammatory) atypia • Atypia of unknown significance • Dysplasia (LG IUN) • CIS (HG IUN)

45. Atypia of uncertain significance Def.: urothelial changes similar to reactive (inflammatory) ones where anusually high intensity of atypiae compared to minimal inflammatory background is present

46. Dysplasia DEF: disturbance of normal urothelium architecture & cytology

47. Dysplasia • with an inflammatory background • without -“- in a flat urothelium in the papillary urothelium

48. Dysplasia LG IUN – low grade intraurothelial neoplasia HG IUN/ CIS – high grade intraurothelial neoplasia

49. The WHO/ISUP Consensus Classification • Hyperplasia • Flat lesions with atypia • Papillary neoplasms • Invasive neoplasms

50. III. Papillary neoplasms • Papilloma • Inverted papilloma • Papillary Urothelial Neoplasm of LowMalignant Potential PUNLMP • Papillary carcinoma, low grade • Papillary carcinoma, high grade