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Kidney & Urinary Tract Neoplasms

Kidney & Urinary Tract Neoplasms. Jaroslava Dušková Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague http://www1.lf1.cuni.cz/~jdusk/. Kidney Cancer. 2% of the total human cancer burden, M:F 2:1, middle age preference for developed (industrialized) countries

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Kidney & Urinary Tract Neoplasms

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  1. Kidney & Urinary Tract Neoplasms • Jaroslava Dušková • Inst. Pathol. ,1st Med. Faculty, • Charles Univ. Prague • http://www1.lf1.cuni.cz/~jdusk/

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

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

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

  35. 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

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

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

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

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

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

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

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

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

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

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

  46. Papilloma WHO 1973 G0 Def:circumscribed solitary papillary lesion covered with cytologically and architecturally normal urothelium.

  47. Papillary neoplasmof low malignant potential Def.: well stratified urothelium bering features of slight dysplasia and increased number of layers

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

  49. Invasive neoplasms • lamina propria invasion (pT1a,b) • muscularis propria (detrusor muscle) invasion (pT2a,b) • perivesical tissue macro/micro (pT3a,b) • surrounding organs/ abdominal wall (pT4a,b)

  50. Less Common Types of Urinary Bladder Cancer • microcystic carcinoma • with  pseudosarcomatose stroma • with bone or chondroid stromal metaplasia • spinocellular • adenocarcinoma • undifferenciated ca • with trophoblastic differentiation • neuroendocrine

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