Transcript Pigmenty

Kidney
& Urinary Tract
Neoplasms
Jaroslava 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 Adenoma
Definition:
Formerly diam. 2-3 cm
 Recently – only diam. less than 5mm

without 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
Clear Conventional Cell
 Papillary (chromophillic)

malignant

CARCINOMAS


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 dependent
Sarcomatoid variant is the most malignant
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 or tetrasomy 7 and 17
in men often Y chromosome missing
mutation of c-met oncogen
Prognosis : G, pT dependent
slightly better than in conventional ca
Chromophobe Carcinoma (5%)
 Macro
 Mikro
-
 Elmi
 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, pT dependent
Collecting Duct Carcinoma
 Starts

in the medulla
Micro




adenocarcinoma & urothelial like
hobnail cells
papillary
fibroplasia, mucin production
 Imuno
Prognosis
cytokeratin 13, vimentin, lectin
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
 Grade
II

Grade III

Grade IV
small, uniform, round (10  )
inaparent or missing nucleoli
larger irregular (15 )
nucleoli small
large, irregular margins (20 )
nucleoli large
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

Symptoms

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:
–
Cause: iritation
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 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.
II.
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.
II.
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.
II.
III.
IV.
Hyperplasia
Flat lesions with atypia
Papillary neoplasms
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.
II.
III.
IV.
Hyperplasia
Flat lesions with atypia
Papillary neoplasms
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 paragangliomaganglioneuroma
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
