Kidney

& Urinary Tract

NeoplasmsJaroslava Dušková

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

Symptoms silent for a long time

- discovered by chance

hematuria, backache, abdominal

mass, metastatic spread

early hematogenic spread

possible

WHO classification of tumours of the kidney (2004)

WHO Histogenetic groups

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

Epithelial Neoplasms of the Pelvis

Benign - papillomas

Malignant - carcinomas

papillocarcinomas

squamous cell

Urinary ways

Kidney Tumours Benign

Malignant

Kidney AdenomaDefinition:

Formerly - diam. 2-3 cm

Recently – only diam. less than 5mmwithout a clear cell component

– tubulopapillary architecture– lack of atypiae & mitoses

Epithelial Kidney Tumours

benign

ADENOMAS

papillary tubulopapillary

(<5mm!)

oncocytic (oncocytoma)

metanephric

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

Kidney Tumours - mesenchymal

Angiolipoleiomyoma – mixed mesenchymal tumour

Metanephric Adenoma

small dark cells acinar and glomeruloid formations calkospherites, calcifying

non agressive

Benign Kidney Tumours Mimicking Carcinomas and

Sarcomas Metanephric adenoma - large & cellular

Oncocytoma - large with atypiae

Angioleiomyolipoma - large with atypiae

Epithelial Kidney Tumours

malignant

CARCINOMAS

Clear Conventional Cell Papillary (chromophillic)

type 1 type 2

Chromophobe classical eosinophillic

Sarcomatoid Cystic Collecting Duct

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 Cytogenetics deletion of the short arm

chromosome 3 (3p)

Prognosis: G, pT dependentSarcomatoid variant is the most malignant

Papillary (Chromophillic) Ca (10%)

In dialysed more frequent X-ray hypovascular Histology – papillary/ tubulopapillary

type 1 – cubic cellstype 2 - cylindric cells (worse prognosis)

Genetics – trisomy or tetrasomy 7 and 17

in men often Y chromosome missing

mutation of c-met oncogen

Prognosis : G, pT dependentslightly better than in conventional ca

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

Collecting Duct Carcinoma Starts in the medulla Micro

adenocarcinoma & urothelial like hobnail cells papillary fibroplasia, mucin production

Imuno cytokeratin 13, vimentin, lectin

Prognosis unfavourable

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

Role of the Pathologist in the Kidney Tumour Diagnostics

Typing

Biological Behaviour

Grading

Staging

Grading

Nuclear – Fuhrman et al. 1982 Nuclear plus architecture Proliferation factors - PCNA, Ki 67, Bcl 2 Morphometry

DNA Analysis AgNOR Angiogenesis

Cytometry Flow cytometry

Staging

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

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

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

p53 Expression

Kidney Cancer – complications 1.

metastatic spread & generalisation

manifestation via solitary bloodborne

metastasis possible (pathological

fracture, struma neoplastica…)

hematuria – anemia

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

Urothelial Tumours

Urothelial Cancer approx. 3% of total human cancer

burdenincreasing incidence industrialized countriesrisk factors: TOBACCO SMOKING

aniline dye industry phenacetin schistosomiasis

hematuria(obstruction)(metastases)

Symptoms

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

Cause: iritation

Types:

– squamous

nonkeratinizing

keratinizing

– mucinous

– nephrogenic clear cell

Metaplasia Significance:

dif. dg. problem

with atypia

precancerosis

Submucose

– discontinual muscularis mucosae

– continual row of vessels

– important for staging of urothelial ca

(pT1a, pT1b, pTx)

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

The WHO/ISUP Consensus Classification

I. Hyperplasia

II. Flat lesions with atypia

III. Papillary neoplasms

IV. 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. Hyperplasia

II. Flat lesions with atypia

III. Papillary neoplasms

IV. 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. Hyperplasia

II. Flat lesions with atypia

III. Papillary neoplasms

IV. Invasive neoplasms

III. Papillary neoplasms Papilloma Inverted papilloma Papillary Urothelial Neoplasm

of Low Malignant Potential PUNLMP

Papillary carcinoma, low grade

Papillary carcinoma, high grade

Papilloma WHO 1973 G0

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. Hyperplasia

II. Flat lesions with atypia

III. Papillary neoplasms

IV. Invasive neoplasms

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)

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

Non-Epithelial Bladder Tumours - Mesenchymal

leiomyomas and leiomyosarcomas rhabdomyosarcoma botryoides

rhabdoid fibrohistiocytic vascular (capilllary, cavernous and

angiovenous hemangiomas and hemangiosarcomas)

malignant lymphomas

Non-Epithelial Bladder Tumours - Neuroectodermal

neurofibromas in Recklinghausen´s disease

melanoma paraganglioma composite pigmented paraganglioma-

ganglioneuroma

Urinary Bladder Pseudotumors

inflammatory malakoplakia amyloid deposits pseudosarcoma

Cystectomy – Biopsy Report MICRO: type, grade (G) and stage (pT) of the tumor further urothelial abnormities lymphatic and blood vessel invasion presence / absence of the tumor in the

resection margins and neighbouring organs further abnormities of the neighbouring

organs

Urinary Blader Cancer - complications

local recidives progression metastases