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8/9/2019 Kidney & Urothelial Tumours
http://slidepdf.com/reader/full/kidney-urothelial-tumours 1/74
KIDNEY TUMOURS & UROTHELIAL TUMOURS
Speaker : Dr. Joram Khopey
Moderator : Dr. Sushma Kh.
Asstt. Professor
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WHO histological classification of tumours of the kidney
I. Renal cell tumours
a. Clear cell renal cell carcinoma
b. Multilocular clear cell renal cell carcinoma
c. Papillary renal cell carcinoma
d. Chromophobe renal cell carcinoma
e. Carcinoma of the collecting ducts of Bellini
f. Renal medullary carcinoma
g. Xp11 translocation carcinomas
h. Carcinoma associated with neuroblastoma
i. Mucinous tubular and spindle cell carcinoma
j. Renal cell carcinoma, unclassified
k. Papillary adenoma
l. Oncocytoma
II. Metanephric tumours
a. Metanephric adenoma
b. Metanephric adenofibroma
c. Metanephric stromal tumour
III. Nephroblastic tumours
a. Nephroblastomab. Nephrogenic rests
c. Cystic partially differentiated
nephroblastoma
IV. Mesenchymal tumours
1. Occurring Mainly in Children
a. Clear cell sarcoma
b. Rhabdoid tumour
c. Congenital mesoblastic nephroma
d. Ossifying renal tumour of infants
2. Occurring Mainly in Adults
a. Leiomyosarcoma (including renal vein)b. Angiosarcoma
c. Rhabdomyosarcoma
d. Malignant fibrous histiocytoma
e. Haemangiopericytoma
f. Osteosarcoma
g. Angiomyolipoma
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Occuring mainly in adults (contd)
i. Leiomyoma j. Haemangioma
k.Lymphangioma
l. Juxtaglomerular cell tumour
m. Renomedullary interstitial cell tumour
n. Schwannoma
o. Solitary fibrous tumour
V.Mixed mesenchymal and epithelial tumours
Cystic nephroma
Mixed epithelial and stromal tumour
Synovial sarcoma
VI.Neuroendocrine tumours
CarcinoidNeuroendocrine carcinoma
Primitive neuroectodermal tumour
Neuroblastoma
Phaeochromocytoma
VII.Germ cell tumours
TeratomaChoriocarcinoma
VIII.Metastatic tumours
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,p53 overexpression
Renal cell neoplasms : putative cell of origin, classification, and genetic correlates
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Renal Cell Carcinoma
Def: Renal cell carcinoma is a group of malignancies arising from
the epithelium of the renal tubules.
- Usually occurs in adults ( most common at 5th & 6th decades of
life)
- Male: female 2:1
- Bilateral in 1% cases
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Classification of RCC
Benign Malignant1. Oncocytoma 1. Clear cell RCC
2. Papillary adenoma 2. Papillary RCC
3. Chromophobe RCC
4. Collecting duct Ca* Renal medullary Ca
5. Xp11 translocation Ca
6. Ca asso. with neuroblastoma
7. mucinous tubular & spindle cell Ca8. Renal cell Ca , unclassified
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Aetiology
Cigarette smoking causes 39% in males
Exposure to carcinogenic arsenic compounds
Exposure to asbestos, cadmium, pesticides, fungal toxins over
prolonged periods Oestrogen implicated in over wt. persons
Genetics:
- terminal deletion of short arm of chr. 3, beginning at 3p13
seen in non-papillary carcinoma of all types except in
oncocytic & papillary types
- overexpression of p53, loss Rb gene function
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Gross
- Well delineated & centred on the cortex- May arise in any portion of kidney but occurs commonly in the
poles esp upper pole
C/S
- Solid golden-yellow separated from surrounding tissue bypseudocapsule
- Occurrence of haemorrhage,necrosis, calcification & cystic
changes give the tumour a variegated appearance
characteristic of this neoplasm
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.
Renal cell carcinoma developing in the adult
form of polycystic renal disease
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Gross appearance of renal cell carcinoma
Tumor is relatively well circumscribed and variegated, with a combination of
cystic, solid, and hemorrhagic areas.
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Renal cell carcinoma well circumscribed and relatively
homogeneous
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Involves almost the entire kidney and extends into the renal vein
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Microscopic
- tumour cells are large, cytoplasmic appearance ranging fromoptically clear with sharp boundaries to deeply granular with
many transitional forms according to the type
Types
1. Clear cell carcinoma2. Papillary carcinoma
3. Chromophobe renal carcinoma
4. Collecting duct carcinoma
5. Renal medullary carcinoma6. Sarcomatoid renal cell carcinoma/spindle cell carcinoma
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Renal cell carcinoma, clear cell type.
Diffuse pattern of growth.
Clear cell typeThe most common type > 70-80%
Most are sporadic , in familial type it occurswith VHL disease
loss of sequences in the short arm of chr. 3
by deletion or translocation
Histologic patterns:
a. solid (most common)
b. glandular
c. papillary
d. spindled
- have a network of small, delicate, blood
vessels of uniform calibre that invest
alveolar clusters of ca cells ( this vascularpattern unique to CCRCC )
- prone to the formation of small & large
cysts
Cell morphology:
a. clear cells are polygonal, cuboidal or
columnar with distinct cell borders
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High-power view showing optically clear cytoplasm and sharply outlined cell membrane
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Papillary type
accounts for 10-15% of renal cancers
occurs in familial & sporadic forms
characterised by papillary growth
pattern cytogenetic abnormalities:
a. trisomies of 3q,7,8,12,16,17 & loss of Y in
males pts. in sporadic form
b. trisomy 7 in familial form
has better prognosis than conventional RCC
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Papillae are compressed, imparting the tumora trabecular growth pattern.
Papillary renal cell carcinoma
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The cells have a well-defined cell membrane,
faintly granular cytoplasm, and perinuclear
clear halo. The pattern of growth is solid.
Chromophobe type
- accounts for 5% of all cases
- nesting arrangement of tumour cells
- tumour cells have sharp borders &
abundant cytoplasm
- cytoplasm has pale, acidophilic quality
with a clear perinuclear region due to
+nce of cytoplasmic vesicles that stain for
Hales colloidal iron ( acidic mucin +nt)
- has better prognosis than conventional
RCC, can metastasize to lungs,liver
- can undergo a sarcomatoid change that is
prognostically unfavourable
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Positive Hales colloidal iron stain in chromophobe carcinoma.
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Collecting duct carcinoma
Tumour centered in the medullary portion of
the kidney and extends into the renal pelvis.
- contributes 1-2% of all cases, common in males
- thought to arise from intercalated cells
-lesions centred in the medullary region &
surrounded by desmoplastic reaction (tic clue)
-aggressive behaviour with distant mets at time of presentation
- mucin stain is +ve in contrast to conventional RCC
-Vinculin is immunohistochemical marker of choice
- genetics:Monosomies of chr. 1,6,14,15,22 have
been documented
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Collecting duct carcinoma
Cellular stroma
Tubules
A cellular stroma separates the well-differentiated tubules
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Collecting duct carcinoma showing branching
tubules lined by cuboidal cells.
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Medullary Renal cell carcinoma
- is rare & occurs in young blacks with sickle cell disease
- very aggressive behaviour with very poor outcome
Oncocytoma
- adds ~7% of all primary non-urothelial epithelial renalneoplasms
Gross
- are solid & mahogany brown
- has a central stellate scar- may acquire huge size & invade renal capsule & vein
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Central stellate( fibrous) scar
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Microscopic- composed of cells with abundant
eosinophilic granular cytoplasm
growing in nesting or tubular fashion
- nuclei are round with small clumps of
chromatin & nucleoli
- mitotic figures absent or rarely present
- cytoplasm filled with mitochondria
(EM view)
D/D
* Chromophobe RCC (Eosinophilic variant)+ Oncocytoma tumour cells ve for CK7 or
express CK7 in scattered single cells or small
clusters of cells while Chromophobe RCC
express CK7 in almost all cells
++ CK20 is always negative
+++ No reactivity for vimentin (contrast to Conv.
RCC)
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-also c/a sarcomatoid renal cell carcinoma,
anaplastic carcinoma or carcinosarcoma
- makes up ~1% of all renal tumours in adults
-composed of spindle or pleomorphic tumour
giant cells-Is an extremely aggressive neoplasm &
extrarenal mets present during operation
Spindle cell RCC
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Spindle cells
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Pleomorphic giant cell appearance
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Prognostic criteria in RCC
1. Staging
2. Nuclear grading
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ROBSON SYSTEM TNM SYSTEM
Stage 1
Confined within renal capsule
T1 - confined by renal capsule & 70 µm
T1a - 40 µmT1b - 40 µm but 70 µm
T2 confined by renal capsule & 70 µm
Stage 2
Confined by Gerotas fascia
T3a - Invasion of adrenal or fat within Gerotas
fascia
T3b - Gross extension into veins or vena
cava below diaphragm
Stage 3
A- Grossly visible extension into renal vein or
vena cava
B- Lymphatic metastasis
C- both vascular extension & metastasis to nodes
T3c - Intravascular extension above
diaphragm or invades wall of vena cava
N1 - Single regional node
N2 - More than 1 regional node
Stage 4
Invasion of adjacent organ(xcept T4 Adrenal)
Haematogenous metastasis
Extension beyond Gerotas fascia
M1 -Distant metastasis
Staging of Renal cell carcinoma
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5 Year survival rates following nephrectomy for RCC
Stage I ----- 60-80%
Stage II ----- 40-70%
Stage III ----- 10-40%
Stage IV ----- 5%
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FUHRMAN NUCLEAR GRADING OF RCC
Grade Nuclear contour Size of nucleus Nucleoli
I Round, uniform ~10 µm Minute or absent
II Slightly irregular ~15 µm Visible at 400X
III Moderate to markedly ~20 µm Large, visible at 100X
irregular
IV Same as in III
multilobular,multiple or bizrre with heavy clumping of chromatin
Correlates the nuclear features with survival
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Mesenchymal tumors
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Clear cell sarcoma of kidney
- originally c/a Bone-metastasizing renal tumour of childhood
- highly malignant neoplasm resistant to conventional therapy
for Wilms tumour, responsive to doxorubicin-containingregimens
- occurs in same age range as Wilms tumour - at 12-36 months
- comprises 6% of paediatric renal tumours with male
preponderance (66%)- high potential for skeletal metastasis esp. to skull
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Gross :
- c/s variable with homogenous,
grayish & lobular or variegated
appearances
- may produce mucin giving a
slimy glistening appearance
- well circumscribed
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Microscopic :
- monotonous diffuse array of
small cells with round normo-
chromatic nuclei
- nuclei contain finely dispersed
chromatin & small nucleoli- cytoplasm is light-staining or
vacoulated with indistinct
borders
- branching array of small blood
vessels are present
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THE MASQUERADES
Despite the name, the cytoplasm of MOST of the cells in clear
cell sarcoma of kidney is much less clear than that of CCRCC
(20% are clear)
These lesions are in no way related to clear cell sarcoma of soft
tissue
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Distinguishing features of Clear cell sarcoma from Wilms tumour
1. No blastema foci seen
2. No non-renal elements
3. Are unilateral
4. Typical vascular pattern on microscopy
5. No specific genetic abnormalities detected
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Angiomyolipoma
Def: is a benign mesenchymal tumour composed of a variable
proportion of adipose tissue, smooth muscle & abnormal
thick-walled blood vessels.
- has a female:male ratio of 4:1
- mostly are adults of age 45-55 yrs at sis
- Angiomyolipoma pts. suffer from Tuberous sclerosis also
Localization
- may arise in the cortex or medulla of kidney
- lesions may be multifocal & if so indicates a presumptive sis of
TS
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Gross
- tumours are golden yellow but colour variesaccording to the proportion of smooth muscle,
fats & blood vessels
- though well demarcated, are not encapsulated
- may resemble a lipoma
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Microscopic
- shows mature adipose tissue, tortousthick-walled blood vessels with
eccenterically placed or very small lumen,
lack elastic lamina
- bundles of smooth muscles seem to
emanate from the vessel wall
- +ve for smooth muscle actin/or desmin,HMB45/or MelanA
D/D
. Lipoma
. Sarcomatoid RCC
. Malignant fibrous histiocytoma
Tx
Surgical excision is usually curative
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Renal cell carcinoma, unclassified
- is a diagnostic category
- assigned to renal ca that do not fit into any category
Qualifying criteria or features of tumour for RCC , unclassified
+nce of :1. apparent composites of recognized types
2. sarcomatoid ca without recognizable epithelial elements
3. production of mucin
4. mixtures of epi. & stromal elements5. unrecognizable cell types
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Nephroblastic tumours
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Nephroblastoma
Synonymns: Wilms Tumour, embryoma, carcinosarcoma, adenosarcoma,adenomyosarcoma
Def: is a malignant embryonal neoplasm derived from nephrogenic blastemal
cells that both replicates the histology of developing kidneys and often
showing divergent patterns of differentiation.
- Accounts for 20% of all malignant tumours in children but can occur inadults also
- Mean age at sis is 37 & 43 months for & respectively
- No particular inclination for either sex
- Race : Blacks > Orientals > Whites
- Both kidneys equally affected - synchronous or metachronous bilat.involvement being 5-10%
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Clinically
Abdominal mass
Abdominal pain or acute abd. crisis
Haematuria
Hypertension
Anaemia Polycythemia
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A. For pretreated cases
I. Low risk tumours
¥ Cystic partially differentiated
nephroblastoma
¥ Completely necrotic nephroblastoma
II. Intermediate risk tumours
¥ Nephroblastoma epithelial type
¥ Nephroblastoma stromal type
¥ Nephroblastoma mixed type
¥ Nephroblastoma regressive type
¥ Nephroblastoma focal anaplasia
III. High risk tumours
¥ Nephroblastoma blastemal type
¥ Nephroblastoma diffuse anaplasia
B. For Primary nephrectomy cases
I. Low risk tumours
¥ Cystic partially differentiated
nephroblastoma
II. Intermediate risk tumours
¥ Non-anaplastic nephroblastoma
and its variants
¥ Nephroblastoma-focal anaplasia
III. High risk tumours
¥ Nephroblastoma diffuse anaplasia
Revised SIOP Working Classification of Nephroblastoma
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Syndromes asso. c increased risk of nephroblastoma
1. WAGR syndrome
2. Beckwith-Wiedmann syndrome
3. Hemihypertrophy
4. Denys-Drash synd.
5. Familial nephroblastoma
6. Bloom synd.
7. Klippel-Trenaunay syndrome
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Wilms tumour(variegated appearance)
Gross
- are solitary, well circumscribed, soft consistency
- variable size
- c/s may show areas of cystic changes, necrosis
& haemorrhage
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Microscopic
3 major components
1. Undifferentiated blastema
2. Mesenchymal tissue
3. Epithelial tissue
in varying proportions
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1. Blastematous area
- extremely cellular- composed of small round to oval primitive cells with scanty
cytoplasm
- growth pattern nodular, diffuse or cord-like
2. Mesenchymal area
- have a spindle cell fibroblast-like configuration or may showdifferentiation towards smooth muscle & skeletal muscle
3. Epithelial component
- characterised by +nce of tubules of various maturity or
glomeruloid structures- arranged haphazardly or in lobules separated by scant
mesenchymal component
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Wilms tumor
Low-power view showing blastema, stroma, and immature tubular formations
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Wilms tumor
High-power microscopic view showing a combination
of blastema, stroma, epithelial tubular formation, and
immature glomeruli.
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Histochemical & Immunohistochemical properties
1. Blastematous elements focal +tivity for vimentin
2. Epithelial elements react for keratin, EMA, lectins
3. Mesenchymal elements myogenin & desmin
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Genetics
- genetic loci predisposing to Wilms tumour are WT1 & WT2
- WT1 located at 11p13
- WT2 located at 11p15.5
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Metastasis
- Locally to perirenal soft tissue adrenals, bowel,liver, vertebrae
- Distant mets to liver, lungs, peritoneum & CNS
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Staging of Wilms tumour
Stage I - Tumour confined to kidney & completely resected
Stage II - Tumour extends locally outside the kidney but is
completely resected
Stage III - Residual tumour confined to the abd. without
haematogenous spread
Stage IV -Blood-borne metastasis or spread beyond abdomen
Stage V - Tumours present in both kidneys
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1. Favourable histology - absence of anaplasia - Better response to chemotherapy2. Unfavourable histology - +nce of anaplasia - Poor response to chemotherapy
Anaplasia
- def as combination of cells with very large hyperchromaticnuclei & multipolar mitotic figures
- enlarged nuclei to be atleast 3 times as large as typical
blastemal nuclei in both axes with obvious hyperchromasia
- hyperdiploid mitotic figures must be present
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Aniridia in a child associated with Nephroblastoma
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UROTHELIAL TUMOURS
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- renal pelvis, ureter & urinary bladder are lined by transitional
(urothelial) epithelium
- transitional epithelium is a stratified epithelium composed of
many layers of cells
- are better suited to cope with stretching , act as osmotic barrier
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Transitional cell carcinoma of bladder
- 90% of primary tumour of bladder is of transistional cellcarcinoma
-Aetiological factors
* Cigarette smoking
* Exposure to aniline dyes (benzidine & -naphthylamine)* Long term use of phenacetin containing analgesics
* Cyclophosphomide
* Shistosoma haematobium infection
Age: Occurs in persons >50 yrsSex: Males> Females
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Cytogenetic abnormalities
- monosomy of chr. 9
- deletion of 9p,9q,17p,13q,11p,14q
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Sites of occurences in bladder
1. Lateral walls - 37%
2. Posterior wall - 18%
3. Trigone - 12%
4. Neck - 11%
5. Ureteric orifice - 10%
6. Dome - 8%
7. Anterior wall - 4%
May present as:
a. exophytic - adopts a papillary or solid appearanceb. endophytic - clusters of tumour in lamina propria
c. both
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Grading of Urothelial tumours
WHO/ISUP Grades
I. Urothelial papilloma
II. Urothelial neoplasm of low malignant potential
III. Papillary urothelial carcinoma, low grade
IV. Papillary urothelial carcinoma, high grade
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Pathologic staging of primary urothelial tumours
AJCC/UICC Depth of invasion
Non-invasive, papillary Ta
Carcinoma in-situ (Noninvasive,flat) Tis
Lamina propria invasion T1
Muscularis propria T2
Microscopic extravesicle invasion T3a
Grossly apparent extra vesicle invasion T3b
Invades adjacent structures T4
-extent of invasion is of prognostic value
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Normal urothelial lining
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Low grade urothelial neoplasm with
increased cell lining & scattered
hyperchromatic nuclei , cell order &cohesiveness maintained
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Low grade carcinoma-in-situ with slight loss of cell cohesiveness & enlarged pleomorhic
nucei
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High grade urothelial ca
* Loss of polarity
* Loss of cohesiveness
* Nuclear atypia
* Mitotic figures
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Exophytic and papillary pattern of growth of a
transitional cell carcinoma arising in a bladder
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Transtional cell ca of renal pelvis
Papillary tumors fill and distort the renal
pelvis
8/9/2019 Kidney & Urothelial Tumours
http://slidepdf.com/reader/full/kidney-urothelial-tumours 74/74
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