Kidney & Urinary Tract Neoplasms
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Transcript of 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
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
burden increasing incidence industrialized countries risk 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
„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)
Metaplasia Significance:
dif. dg. problem
with atypia
precancerosis
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 atypiaReactive (inflammatory) atypia
Atypia of unknown significance
Dysplasia (LG IUN)
CIS (HG IUN)
Dysplasia
DEF:
disturbance of normal
urothelium architecture &
cytology
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