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Kidney
& Urinary Tract
Neoplasms Jaroslava Dušková Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague http://www1.lf1.cuni.cz/~jdusk/
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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
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Symptoms silent for a long time
- discovered by chance
hematuria, backache, abdominal
mass, metastatic spread
early hematogenic spread
possible
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WHO classification of tumours of the kidney (2004)
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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 (-)
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Epithelial Neoplasms of the Pelvis
Benign - papillomas
Malignant - carcinomas
papillocarcinomas
squamous cell
Urinary ways
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Kidney Tumours Benign
Malignant
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Kidney AdenomaDefinition:
Formerly - diam. 2-3 cm
Recently – only diam. less than 5mmwithout a clear cell component
– tubulopapillary architecture– lack of atypiae & mitoses
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Epithelial Kidney Tumours
benign
ADENOMAS
papillary tubulopapillary
(<5mm!)
oncocytic (oncocytoma)
metanephric
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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
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Kidney Tumours - mesenchymal
Angiolipoleiomyoma – mixed mesenchymal tumour
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Metanephric Adenoma
small dark cells acinar and glomeruloid formations calkospherites, calcifying
non agressive
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Benign Kidney Tumours Mimicking Carcinomas and
Sarcomas Metanephric adenoma - large & cellular
Oncocytoma - large with atypiae
Angioleiomyolipoma - large with atypiae
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Epithelial Kidney Tumours
malignant
CARCINOMAS
Clear Conventional Cell Papillary (chromophillic)
type 1 type 2
Chromophobe classical eosinophillic
Sarcomatoid Cystic Collecting Duct
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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
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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
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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
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Collecting Duct Carcinoma Starts in the medulla Micro
adenocarcinoma & urothelial like hobnail cells papillary fibroplasia, mucin production
Imuno cytokeratin 13, vimentin, lectin
Prognosis unfavourable
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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
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Role of the Pathologist in the Kidney Tumour Diagnostics
Typing
Biological Behaviour
Grading
Staging
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Grading
Nuclear – Fuhrman et al. 1982 Nuclear plus architecture Proliferation factors - PCNA, Ki 67, Bcl 2 Morphometry
DNA Analysis AgNOR Angiogenesis
Cytometry Flow cytometry
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Staging
Size Kidney capsule infiltration Angioinvasion Metastases in the lymph nodes Number of lymph nodes involved Metastases in the surrounding organs
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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
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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
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Kidney Cancer – complications 1.
metastatic spread & generalisation
manifestation via solitary bloodborne
metastasis possible (pathological
fracture, struma neoplastica…)
hematuria – anemia
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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
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Urothelial Tumours
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Urothelial Cancer approx. 3% of total human cancer
burden increasing incidence industrialized countries risk factors: TOBACCO SMOKING
aniline dye industry phenacetin schistosomiasis
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hematuria(obstruction)(metastases)
Symptoms
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Terminology
…the term
UROTHELIAL be used rather than
„transitional“...
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Normal urothelium
multilayered
variable number of layers
empty bladder 4 - 6
full bladder 2 - 3
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„Variations“ of Urothelium– slight reactive changes
von Brunn´s nests
mucinous metaplasia
squamous metaplasia
(nonkeratinising, vagina type)
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Metaplasia
Def: change of one differentiated
structure into another one
(e.g. urothelium – squamous epithelium)
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Metaplasia Significance:
dif. dg. problem
with atypia
precancerosis
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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
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The WHO/ISUP Consensus Classification
I. Hyperplasia
II. Flat lesions with atypia
III. Papillary neoplasms
IV. Invasive neoplasms
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The WHO/ISUP Consensus Classification
I. Hyperplasia
Flat
Papillary
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Hyperplasia
Def: regular increase in number of uroth.
layers (min. >7, mostly >10)
slight increase in cell nuclei size,
preserved architecture
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Hyperplasia
Significance: precancerosis
70% of patients with
urothelial ca identical
mutations
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The WHO/ISUP Consensus Classification
I. Hyperplasia
II. Flat lesions with atypia
III. Papillary neoplasms
IV. Invasive neoplasms
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II. Flat lesions with atypiaReactive (inflammatory) atypia
Atypia of unknown significance
Dysplasia (LG IUN)
CIS (HG IUN)
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Dysplasia
DEF:
disturbance of normal
urothelium architecture &
cytology
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Dysplasia LG IUN – low grade intraurothelial
neoplasia
HG IUN/ CIS – high grade intraurothelial
neoplasia
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The WHO/ISUP Consensus Classification
I. Hyperplasia
II. Flat lesions with atypia
III. Papillary neoplasms
IV. Invasive neoplasms
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III. Papillary neoplasms Papilloma Inverted papilloma Papillary Urothelial Neoplasm
of Low Malignant Potential PUNLMP
Papillary carcinoma, low grade
Papillary carcinoma, high grade
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Papilloma WHO 1973 G0
Def: circumscribed solitary
papillary lesion covered with
cytologically and architecturally
normal urothelium.
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Papillary neoplasm of low malignant
potential
Def.:
well stratified urothelium bering features of
slight dysplasia and increased number of
layers
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The WHO/ISUP Consensus Classification
I. Hyperplasia
II. Flat lesions with atypia
III. Papillary neoplasms
IV. Invasive neoplasms
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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)
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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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Non-Epithelial Bladder Tumours - Mesenchymal
leiomyomas and leiomyosarcomas rhabdomyosarcoma botryoides
rhabdoid fibrohistiocytic vascular (capilllary, cavernous and
angiovenous hemangiomas and hemangiosarcomas)
malignant lymphomas
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Non-Epithelial Bladder Tumours - Neuroectodermal
neurofibromas in Recklinghausen´s disease
melanoma paraganglioma composite pigmented paraganglioma-
ganglioneuroma
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Urinary Bladder Pseudotumors
inflammatory malakoplakia amyloid deposits pseudosarcoma
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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
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Urinary Blader Cancer - complications
local recidives progression metastases