Kidney Urinary Tract Neoplasms Jaroslava Dukov Kidney Cancer

Kidney & Urinary Tract Neoplasms Jaroslava Dušková

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

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

WHO classification of tumours of the kidney (2004)

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

Epithelial Neoplasms of the Pelvis v Benign - papillomas v Malignant - carcinomas v papillocarcinomas v squamous cell Urinary ways

Kidney Tumours v Benign v Malignant

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

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

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

Kidney Tumours - mesenchymal Angiolipoleiomyoma – mixed mesenchymal tumour

Metanephric Adenoma v small dark cells v acinar and glomeruloid formations v calkospherites, calcifying non agressive

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

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

Clear Cell Ca (Grawitz tumour) (75%) v Solid / cystic v Unilocullar or multilocular v Micro - solid or tubulocystic clear cytoplasm (fat & glycogen) v Immunohistochemistry cytokeratins, vimentin, CD 10, EMA, S-100 v Cytogenetics deletion of the short arm chromosome 3 (3 p) Prognosis: G, p. T dependent Sarcomatoid variant is the most malignant

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

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

Collecting Duct Carcinoma v Starts in the medulla v Micro v adenocarcinoma & urothelial like v hobnail cells v papillary v fibroplasia, mucin production v Imuno cytokeratin 13, vimentin, lectin Prognosis unfavourable

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

Role of the Pathologist in the Kidney Tumour Diagnostics v Typing v Biological Behaviour v Grading v Staging

Grading v Nuclear – Fuhrman et al. 1982 v Nuclear plus architecture v Proliferation factors - PCNA, Ki 67, Bcl 2 v Morphometry v DNA Analysis v Ag. NOR v Angiogenesis v Cytometry Flow cytometry

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

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

Factors with an Adverse Prognosis Influence in Kidney Cancer Size diam. more than 12 cm Invasion to venes recidives Grading G III and G IV Staging most important Proliferation Index p 53 Expression

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

Kidney Cancer – complications 2. v 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. v insulin, glukagon, renin, HPL like substances

Urothelial Tumours

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

Symptoms v hematuria (obstruction) (metastases)

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

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

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

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

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

Urothelium Metaplasia Types: – squamous v nonkeratinizing Cause: iritation v keratinizing – mucinous – nephrogenic clear cell

Metaplasia Significance: v dif. dg. problem v with atypia precancerosis

Submucose – discontinual muscularis mucosae – continual row of vessels – important for staging of urothelial ca (p. T 1 a, p. T 1 b, p. Tx)

The WHO/ISUP Consensus Classification of Urothelial Neoplasms of 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

The WHO/ISUP Consensus Classification I. III. IV. Hyperplasia Flat lesions with atypia Papillary neoplasms Invasive neoplasms

The WHO/ISUP Consensus Classification I. Hyperplasia Flat Papillary

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

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

The WHO/ISUP Consensus Classification I. III. IV. Hyperplasia Flat lesions with atypia Papillary neoplasms Invasive neoplasms

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

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

Dysplasia DEF: disturbance of normal urothelium architecture & cytology

Dysplasia – with an inflammatory background – without -“ in a flat urothelium in the papillary urothelium

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

The WHO/ISUP Consensus Classification I. III. IV. Hyperplasia Flat lesions with atypia Papillary neoplasms Invasive neoplasms

III. Papillary neoplasms v Papilloma v Inverted papilloma v Papillary Urothelial Neoplasm of Low Malignant Potential PUNLMP v Papillary carcinoma, low grade v Papillary carcinoma, high grade

Papilloma WHO 1973 G 0 Def: circumscribed solitary papillary lesion covered with cytologically and architecturally normal urothelium.

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

The WHO/ISUP Consensus Classification I. III. IV. Hyperplasia Flat lesions with atypia Papillary neoplasms Invasive neoplasms

Invasive neoplasms v lamina propria invasion (p. T 1 a, b) v muscularis propria (detrusor muscle) invasion (p. T 2 a, b) v perivesical tissue macro/micro (p. T 3 a, b) v surrounding organs/ abdominal wall (p. T 4 a, b)

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

Non-Epithelial Bladder Tumours - Mesenchymal v v v leiomyomas and leiomyosarcomas rhabdomyosarcoma botryoides rhabdoid fibrohistiocytic vascular (capilllary, cavernous and angiovenous hemangiomas and hemangiosarcomas) malignant lymphomas

Non-Epithelial Bladder Tumours - Neuroectodermal v neurofibromas in Recklinghausen´s disease v melanoma v paraganglioma v composite pigmented paragangliomaganglioneuroma

Urinary Bladder Pseudotumors v v inflammatory malakoplakia amyloid deposits pseudosarcoma

Cystectomy – Biopsy Report MICRO: v type, grade (G) and stage (p. T) of the tumor v further urothelial abnormities v lymphatic and blood vessel invasion v presence / absence of the tumor in the resection margins and neighbouring organs v further abnormities of the neighbouring organs

Urinary Blader Cancer - complications v local recidives v progression v metastases