Etiopathogenesis Urinary bladder malignancy

CA BLADDER :
Dept of Urology
Govt Royapettah Hospital and Kilpauk Medical College
Chennai 1

Moderators:
Professors:
• Prof. Dr. G. Sivasankar, M.S., M.Ch.,
• Prof. Dr. A. Senthilvel, M.S., M.Ch.,
Asst Professors:
• Dr. J. Sivabalan, M.S., M.Ch.,
• Dr. R. Bhargavi, M.S., M.Ch.,
• Dr. S. Raju, M.S., M.Ch.,
• Dr. K. Muthurathinam, M.S., M.Ch.,
• Dr. D. Tamilselvan, M.S., M.Ch.,
• Dr. K. Senthilkumar, M.S., M.Ch.
Dept of Urology, GRH and KMC, Chennai. 2

• EPIDEMIOLOGY
• ETIOPATHOGENESIS
• CLASSIFICATION,
• CLINICAL FEATURES,
• HISTOPATHOLOGY OF BENIGN & MALIGNANT TUMOR
3
Dept of Urology, GRH and KMC, Chennai.

EPIDEMIOLOGY
4

5

M>F - More prevalence of smoking and exposure to environmental
toxins
• Adolescents and young adults - develop well-differentiated non
invasive, rather than invasive bladder cancer
6

ETIOLOGY
• Genetic abnormalities
• External risk factors
• Smoking
• Nutritional factors
• Fluid intake
• Inflammation
•Chemotherapy, Radiation.
7

Genetic
• Several polymorphisms - related & susceptibility to
environmental carcinogen
• N-acetyl transferase (NAT) & slow NAT-2 polymorphism is
related to bladder cancer
• Glutathione-S transferase (GSTM1) conjugates arylamines and
nitrosamines.
• The null GSTM1 and slow NAT-2 lead to high levels of 3-
aminobiphenyl - higher risk of bladder cancer.
8

N-acetyl transferase (NAT) detoxifies nitrosamines, a
known bladder carcinogen.
NAT-2 regulates the rate of acetylation of compounds such as
caffeine, which are related to bladder cancer formation.
Glutathione-S transferase (GSTM1) conjugates several reactive
chemicals, including arylamines and nitrosamines.
9

Genetic Abnormalities
Protooncogenes expression - Ras, p21
Tumour suppressor gene mutation -
p53, p21, p27
 LOH of chromosome 9
 Abnormalities of specific cell cycle regulatory proteins
CABLES, k167,cyclinD
10

External Risk Factors
• Exposure of chemical
Dye and Rubber industries
• Primary culprits -- Aromatic amines that bind
to DNA .
Benzidine and β-naphthylamine ,
• Polycyclic aromatic hydrocarbons (PAH), diesel exhaust, and
paint substances
• Environmental carcinogens –by inhalation or through skin
absorption
11

12

13

Smoking
•The intensity and duration of smoking is linearly
related to the increased risk, with no clear plateau
level
•Black tobacco appears to be worse than blonde
tobacco because of a greater amount of aromatic
amines in the former
•30 % Bladder Cancer associated with smoking
•Risk correlates with number, duration, degree of
inhalation
14

Nutritional Factors
• Moderately higher in coffee and tea drinkers
• Mediterranean diet -- Lowest urothelial cancer risk
• Fruits and vegetables—
Polyphenols,& antioxidants, are important in detoxification.
Can prevent DNA adduct formation and oxidative damage
• Micronutrients & antioxidants
Vitamins A, C and E; selenium and zinc
15

Inflammation
• Chronic infection with Schistosoma hematobium leads to
formation of Squamous cell carcinoma
• Chronic indwelling catheter , stones, and infections
• Chronic urinary tract infections
Escherichia coli and Pseudomonas
16

Chemotherapy
• Related to the duration and intensity of cyclophosphamide
Mutagenic metabolic – Phosphoramide mustard .
• Up to ninefold increased risk
• High grade, muscle infiltrating, younger, equal in both sexes
• Latency period = 6 to 13 years
• Uro protectant - MESNA (2-Mercaptoethanesulfonic acid)
17

18

19

• Radiation
Increased risk in patients with prostate or cervical cancer
treated with RT
• Heredity
First-degree relatives -- twofold increased risk
20

• Fluid Intake
Increased fluid intake  Decrease the concentration of
potential carcinogens  Decrease the risk of bladder
cancer
Consumers of artificial sweeteners, alcohol intake,
phenacetin - No evidence of Risk
• BMI-Causes hyperinsulimia –increases-growth factors
• Pioglitazone –increses cancer risk
21

22

PATHOPHYSIOLOGY
 Urothelium 3-7 layers thick
 BM
 Lamina propria -
muscularis mucosa, blood
vessels, lymphatic,
nerves
 Muscularis propria- inner
longitudinal, middle circular,
and outer longitudinal
 Serosa
23

24

Term usingfor....
 Hyperplasia :-increase in no of cell layers without nuclear or
cellular abnormalities.
 Atypical hyperplasia: -Increase in no of cells with nuclear or cellular
changes
 Metaplasia: - change in epithelium with squamous or adenomatous
development. Mild to moderate nuclear & cellular atypia
 Dysplasia: abnormal histology or anatomical structure
-Epithelial changes that are intermediate between normal
urothelium and CIS (severe dysplasia)
- Isolated dysplasia – 19% CIS & 15% TCC
- Dysplasia with previoush/o UC – 60% CIS
25

Pathogenesis of urothelial cancer formation
26

27

Pathogenesis of urothelial cancer formation
• Somatic mutations - more common than germline mutations
• Accumulation of the genetic event - phenotypic changes results
unregulated cell growth and invasion
28

• Lowgrade papillary tumors - genomic stability
allows tumor recurrence
• Genetic alterations - fibroblast growth factor
receptor–3 , deletions of 9p and 9q.
• High-grade papillary cancer and CIS - unstable genomes
Genetic alteration - HRAS, FGFR, 5q-, 6q-, 7q+
29

CLASSIFICATION
• WHO 1973 – G1/G2/G3, based on degree of cellular &
architectural atypia
• WHO/ISUP 1998 – introduction of term PUNLMP
define Papilloma, PUNLMP, CaLG, CaHG
30

• WHO 2004 – introduction of low grade & high grade PUC
PUNLMP term adopted by WHO
clear Histological features of UC &
dec. the diagnostic subjectivity of the WHO
1973 scheme
• WHO 2004/2016 – Division of pT1 tumors into LG & HG
- further differentiate Non-invasive LG &
HG papillary car. from Invasive urothelial carcinoma
31

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classifications & percentage
34

35

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37

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Histology
 Non–muscle-invasive bladder cancer (NMIBC) includes –
 Papillary urothelial neoplasia of low
malignant potential (PUNLMP),
 Low- and high-grade urothelial cancer
 CIS ( carcinoma in situ)
previously been called “superficial bladder cancer
39

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EPIDEMIOLOGY
• 9th most common cancer world wide
• Cancer of environment and advancing age
• Peak Incidence - 8th decade of life
• Strong association with environmental
toxins
41

Papillary urothelial neoplasia of low-
malignant potential (PUNLMP)
• Papillary growth with minimal
cytological atypia more than
seven cells thick
• Solitary and located on the trigone
42

PUNLMP
• Composed of thin papillary stalks
• Polarity of the cells is maintained
• Nuclei are minimally enlarged.
• Low proliferation, non invasive, non metastatic
43

PUNLMP
44

HGPUC
• Fused papillary stalks with high-grade
cancer in the urothelial layer.
• Disordered growth pattern,
numerous mitotic figures
pleomorphic cells
with exaggerated nuclei.
• Over 80% of high-grade cancers will
invade the underlying stroma
45

HGPUC
46

47

Tumor suppressor genes
Low grade papillry CIS and muscle
invasive
High grade papillary
and Muscle invasive
TP53 mutations (17p13) Uncommon Hallmark- 60% Hallmark-
>50%
PTEN (10q23) Rare Hallmark Hallmark- 30-35%
RB gene (13q14) Rare Hallmark Hallmark-37%
Deletions of Ch regions
9P16, 9p21
Hallmark Absent in pure CIS 70-80%
Loss of heterozygosity (LOH) of Ch 9 >50% Rare Rare
48

proto oncogenes
Low grade
papillry
CIS and muscle
invasive
High grade papillary
and Muscle invasive
Alterations in the
fibroblast growth factor receptor–3
(FGFR-3) - 4p16
Hallmark-75% Infrequent-20% Common
Deletions -9p14, 9q11-13, 9q33-34 Hallmark Absent in pure CIS 70-80%
H RAS mutations- (11p15) 15% 10-15% 10-15%
Point mutations in PIK3CA (3q26) 16% Rare Rare
Over expression of C-Erb B2 (7q) Uncommon 10-14% 10-14%
49

BENIGN LESIONS/ TUMORS OF
THE BLADDER
• EPITHELIAL METAPLASIA
• LEUKOPLAKIA
• INVERTED PAPILLOMA
• PAPILLOMA
• NEPHROGENIC ADENOMA
• CYSTITIS CYSTICA AND GLANDULARIS
• LEIOMYOMA
50

EpithelialMetaplasia
• Focal area of transformed urothelium surrounded by normal
urothelium
• Normal cellular & nuclear architecture
• Location- trigone
Composed of squamous (Squ.metaplasia) or glandular (glan
Metap. )
51

ON CYSTOSCOPY- knobby app.covered by white flaky, easily
disrupted
& lying on the trigone
Glandular Metaplasia appears as clumpy, raised, reddish
area that look like inflammatory, often confused for cancer
Approx 40% female
5% male have Squ. Metaplasia of the bladder
Biopsy & t/t not required.
52

Leukoplakia
• Similar to Squ. Metaplasia
with the addition of
• Keratin deposition that
appears as a white flaky
substance floating in the
bladder
• Benign lesion,
53

54

• Symptoms- vesical irritation & passage of flakes
• Premalignant
• Careful cystoscopic assessment & biopsy
• May require resection.
55

A. Epithelial metaplasia B. Leukoplakia
56

Benign proliferative lesions
Inverted Papilloma
• Associated with
-Chronic inflammation
-Bladder outlet obstruction.
• Located throughout the bladder
-Most common – Trigone
-Less than 1% of all bladder tumors
57

• Present with non-specific hematuria or irritative voiding
symptoms
• May be asso. with urothelial cancer or malignant changes
• Recurrence – 1%
58

InvertedPapilloma......
• Gross:
- usually smooth, solitary, polypoid, sessile or pedunculated
- Usually < 3 cm
- multiple lesions – 1.5 to 4.5%
• Microscopic ( Histologic )
- smooth surface & base with minimal to absent exophytic
components
- no/minimal cytologic atypia
59

• DDx:
- Urothelial cancer with inverted growth pattern
- Papillary urothelial neoplasm of LMP
• FISH – differentiate b/w benign & malignant
• Treatment - Transurethral resection
60

Inverted Papilloma.....
• Two main subtypes:
1. Trabecular subtype ( classic type)
- irregular, downward growth
- consisting of cords & trabeculae as a sheets arising from
the urothelial layer growing into the lamina propria
2. Glandular subtype
- morphologically overlap with Cystitis cystica
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1. Inverted growth pattern of papillary 2. Inverted growth pattern of lining cells
fronds of typical inverted Papilloma with central streaming & peripheral
composedof intact surface of bladder palisading without any atypia and
urothelium. ( H&E ; X10 ) mitosis. ( H&E ; x40 )
63

Papilloma
• Discrete Papillary growth with
a central fibrovascular core
lined by normal urothelium
• Small, single, exophytic lesion
• Younger pts ( mean age- 46yrs)
64

Posterior or lateral wall (close to UO)
R/F similar to urothelial cancer
C/F- asymptomatic, Hematuria
Benign behaviour, may recur but not progress or invade the
bladder
T/t – TUR of lesions
65

Papilloma.....
• Gross:
- Soft, pink, small isolated growth with discrete papillary
structure
- Usually pedunculated, mean 3 mm
• Microscopic(Histologic):
- Discrete Papillary fronds, minimal branching & fusion,
benign cells
- Papillae appear to float above urothelial surface
- Papillae usually small with scant stroma & slender
fibrovascular cores
- Lined by normal urothelium with prominent umbrella cells
66

• Molecular/cytogenetic discription:
- Negative stain – p53 & RB
. Positive stain – CK-20
- Diploid , 75% cases are FGFR3 mutations
67

DDX:PUNLMP: it has a thicker cell layer, large nuclei with occasional
mitotic figures, recurrence- 20-30%
68

Nephrogenic Adenoma
• Chronic irrigation of the
urothelium
- Trauma
- Previous surgery
- Renal transplantation
- Intravesical
chemotherapy
- Stones, catheters &
infection
- Immunosuppression
• Associated with
inflammation
69

Nephrogenic Adenoma......
• Usually adults,
• more common at bladder neck, 15% prostatic urethra
• In renal transplant recipients, derived from exfoliated &
implanted renal tubular cells in the bladder
• In other pts, appear to be metaplastic and not a neoplasm
• Involve mucosa & submucosa
70

Clinical features:
• Gross hematuria, irritative voiding symptoms
• Valvety app on cystoscopy, often mistaken for papillary
urothelial car.
• Benign, no malignant transformation
71

Neohrogenic adenoma.....
• Gross:
- Polypoid, sessile or Papillary, 20% multiple
• Microscopic (Histologic):
- small hollow tubules, on EM – similar to PCT
- usually lined by single layer of Cuboidal or Hobnail cells
- clear or eosinophilic cytoplasm, small nuclei, no prominent
nucleoli
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IHC:
Positive stains – PAX-2, PAX-8 Negativestains – p16
CK-7 & CK-20 S100
PAS+, A1+ CD10
74

• DDx
1. Papillary urothelial car.
multilayered, atypia, p16+
2. Prostatic carcinoma : prostatic urethra may resemble &
similar express AMACR+, but NA is PSA & PSAP –ve
more atypia in PC
3. Urothelial car. Nested variant
- cystic degeneration of nests,
- multilayered, marked atypia
-
75

Cystitis Cystica & Glandularis
UreteritisCystica
• Common incidental finding
in bladder specimens
• Reactive urothelial changes
76

• chronic Cystitis,
• Bladder extrophy,
• ureteral implantation,
• neurogenic bladder or
• any cause of mucosal irritation
77

Term using....
1. Brunn nests : invagination from the overlying urothelium into
lamina propria.
2. Cystitis Cystica: when Brunn nests become cystically dilated
( with or without eosinophilic secretions in the lumen)
.
3. Cystitis Glandularis: when the urothelial cell nests show central
cyst or lumen lined by columnar/ Cuboidal epithelium.
78

Cystitis Cystica& Glandularis
HP image:all threepattern
79

HPspecimen: (a)CystitisCystica. (b)cystitis Glandularis
80

Cystitis Cystica& Glandularis....
• C/F – incidental finding in biopsies ,
- on cystoscopy – may present as papillary or polypoid
mass
- usually asymptomatic, recurrent UTI
81

Histological two types ;
1. Usual type – more common, express membranous
beta-catenin
2. intestinal type – also called intestinal metaplasia
- presence of goblet & mucin cells
- express nuclear beta-catenin
- risk of adenocarcinoma more
Both type involved only lamina propria
82

• usual type – CK7+ , CDX2 & CK-20 –ve
Intestinal type – CDX2 & CK-20 + ve
• D/D-ADENOCARCINOMA
• ENDOCERVICOSIS
83

• Treatment: removal of source of infection/injury
long term antibiotics therapy
Surgical options reserved when conservative Mx not
respond.
84

HP specimens: CystitisGlandularis( usualtype)
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LEIOMYOMA
• Rare benign Mesenchymal tumor
• Till now, only 250 cases are reported
• Similar incidence in male and female
87

Leiomyoma
• Etiology is still unknown, but may be related to
- chromosomal alteration
- hormonal disturbance
- Repeated bladder wall & detrusor infection
- perivascular inflammation
88

• Based on location – 3 type 1. Endovesical - (65-85% )
2. Intramural - ( 3-7% )
3. Extravesical - ( 10-30% )
89

Histopathologicalspecimens:
(A) Proliferation of spindle
shaped cells,
Eosinophilic cytoplasm on H &
E stain,
No evidence of mitotic changes
or atypia
(B) Stain negatively for Ki-67
(C) Positive SMs staining for
Actin
90

Clinical presentation (30%)
• Obst. voiding symptoms (49%)-
• Irrit. Voiding symptoms (38%)
• Flank pain (13%)
• Hematuria (11% )
91

• Best imaging for diagnosis – MRI & cystoscopic biopsy
• Treatment : Endovesical – TURBT
Intramural & Extravesical – wide excision/partial cystectomy
open/laparoscopic
92

On USG: Smoothwall, Homogeneous, hypoechoic, solid mass
with echogenic surface
On CT(P):Hypodense mass, CT(c): Moderately enhancingmass
93

Carcinomain situ(CIS)
 Flat, high grade , non- invasive urothelial cancer
 surface epithelium contains cancer cells
• Spread – Distal ureters and prostatic urethra on the surface
or in a pagetoid manner
94

• Urine cytology - 80- 90 % positive
• 40 - 83% progress to muscle-invasive cancer
• Endoscopically, - reddish with heaped-up mucosa can be
mistaken for inflammatory changes or
radiation cystitis.
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Classificationof CIS intoclinicaltypes:
• Primary : isolated CIS with no previous or concurrent
Papillary tumors or previous CIS
• Secondary : CIS detected during follow-up of pts with a
previous tumor that was not a CIS
• Concurrent : CIS in the presence of any other urothelial
tumors in the bladder
97

• Muscle invasive
• Histology:
• Invading urothelium shows irregular nests, single cell
infiltration or tentacular finger-like projections
• Stromal response
-desmoplasia,
-retraction or
-inflammation.
98

99

• Assess level of invasion for staging
.
• Presence and status of involvement of muscularis propria
should be reported in TURBT specimen for adequate staging.
100

HISTOLOGICVARIANTS OF UROTHELIAL CARCINOMA
• Nested pattern
• Small tubular pattern
• Microcytic pattern
• Inverted pattern
• With squamous differentiation
• With glandular differentiation
• Micro papillary
• Sarcomatoid
• Clear cell
• With syncitiotrophoblasts
• With unusual stromal reaction
101

NESTEDVARIANTOFUROTHELIALCARCINOMA
• Rarebut aggressive cancer
• male-to-female ratio of 6 : 1
• confused with benign lesions
- von Brunn nests that are in the lamina propria,
- cystitis cystica,
-inverted papillomas.
littlenuclear atypia in the nested variant of urothelial carcinoma
102

Nested variant
• Tumor cells will often contain areas with
large nuclei and mitotic figures
103

CLEAR CELLVARIANTOFUROTHELIAL CARCINOMA
• 70% -will have foci of clear cells within the tumor.
• glycogen-rich vacuoles and may be confused with metastatic
clear cell carcinoma of the kidney.
Clear cell variant does not a significantly worse prognosis for
urothelial cancers
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GLANDULAROR ADENOCARCINOMA DIFFERENTIATION
• Mixed tumor differentiation is m/c with squamous cell
cancer,
• only 6% of urothelial cancer cases.
Diffi- two glandular spaces within the tumor
• Mucin production can occur, and tumor cells seem to be
floating in the mucin.
106

PLASMACYTOIDTUMOR
Recognized by the WHO classification system since 2004
• Urothelial tumor cells look like plasma cells due to abundant
eosinophilic cytoplasmhe ecentric nuclei & indistinct nucleoli.
• Invade the bladder wall and perivesical adipose tissue &
abdominal cavity at the time of diagnosis.
107

• diagnosed at an advanced stage, 64% T3 & 23% T4, 60%
metastasis.
• Positive stains: CK, CD138
• Negative stains: plasma cells & lymphocytes marker
• Delation of 9p21, p53 mutation in 30%
• Onset of hematuria is delayed –
• sessile and non-papillary tumor growth pattern.
108

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MICROPAPILLARY
• Incidence- 0.7-2.2%
• M:F - 10:1
• occurs at older age – 65 yrs
• Present at advanced stage,
• Edematous stroma with chronic inflammatory infiltrate
• Associated with conventional urothelial ca in 80%
110

• Histology- Small nests & papillae with surrounding retraction
spaces, similar to papillary serous ca of ovary ( no psammoma
bodies)
• Angiolymphatic invasion is common
• High progression from Non-muscle invasive -Muscle invasive
- Metastatic
111

HP image:Micropapillary(U)& UsualUC(L)
• Positive stains:
CK7, CK20, variable HER2 & CA-125
DDx: papillary car. Of ovary
papillary nephrogenic adenoma
invasive UC with stromal retraction
112

NONUROTHELIAL MALIGNANCY
•Sarcoma
•Signet ring cell ca
•Small cell ca
•Sq cell ca
•Prostatic urethral ca
•adenocarcinoma
113

Squamouscell carcinoma
• Risk factor for bladder SCC
- Smoking
- Stones/FBs
- Schistosomiasis haematobium
- Chronic UTIs
- Chronic indwelling catheter
114

- BCG
- Diverticula (bladder)
- Trauma
- prolonged cyclophosphamide-
115

116

SquamousCell Carcinoma
• Histological types: Usual
type,
• Verrucous,
• Variant,
• Basaloid with sarcomatoid
features
117

Mechanism may be due to
1.Increased proliferation rate
2.Chronic inflammation and exposure to environmental
agent – Generate: N-butyle N-Nitrosomaine
 Chronic infection converts nitrates – nitrites - nitrosamines
118

119

• Large ulcerated, necrotic
• 80% involved muscular wall
at diagnosis
• Squ. Metaplasia up to 60%
120

• LN metastasis- 10-27%
• Metastasis to bone & lung
• Positive stains: CK5/6( 77%)
CK5/14 (96%)
• Negative stains: CK-20 & Uroplakin III
• Grading is not reproducible
121

Adenocarcinoma
• Risk factors for adenocarcinoma of the bladder
- Urachal cyst/remnant,
- Cystitis glandularis,
- CIS,
- Chronic inflammation,
- Ureterosigmoidostomy,
- Bladder augmentation
- Exstrophy of bladder.
122

ADENOCARCINOMA
• <2% of primary bladder cancers
• Majority represent Mets from GI
tract, breast, lung , colon primary
• Usually arise in trigoneor in dome
(urachal)
123

• M/C – Exstrophy
&
associated with pelvic lipomatosis
Develop in response -
• chronic inflammation
• irritation
124

125

• Classifications of adenocarcinomas of the GU tract
• 1) primary vesical
• 2) urachal
• 3) metastatic
126

• Most are poorly differentiated and invasive
• More often associated with cystitis glandularis than CIS
• Glandular components predominant, resemble colonic CA
• Poor prognosis due to advanced stage at presentation.
• Positive stains: CK7, CK20, CEA, EMA, Villin, membranous
beta-catenin
• Negative stains: vimetin, Uroplakin III, nuclear beta-catenin
127

URACHAL ADENOCARCINOMA
• Located at the dome of the
bladder
• 90% of masses occur close
to the bladder
128

• Midline,
• infraumbilical,
• soft-tissuemass with calcification ( Stippled )
consideredto be urachal adenocarcinoma until
proved otherwise.
129

• Usually adenocarcinomas but can also be TCC, SCC, or even
sarcomas
• C/F- bloody or mucoid discharge from umbilicus
• palpable mass after forming mucocele.
130

Urachaladenocarcinoma...
• Staging is different than other
UC
• Sheldon staging system
• Positive stains: CK7, CK20,
CDX2
beta-catenin –ve
• Mets to LN, lungs, Peritoneal
cavity, liver & bone
131

• DDx: 1. local extension of colonic or other adenocarcinoma
2. Metastatic AC
3. Villous adenoma
4. Non urachal AC of bladder with
mucinous or colloidal histology
132

133

134

Urachal adenocarcinoma....
135

• Cystoscopy: Exophytic,
• sessile mass
• Grape like,
• Papillary lesions
• fulgrated area
136

T/t: clinically localised/feasibl case:
• Partial cystectomy with en block resection of MUL & Umbilicus
• RT, CT( 5-FU, Cisplatin)
• Targeted therapies: sunitinib, Gafitinib Bevacizumab & cetuximab
Advance cases: radical cystectomy
• Poor prognosis, 5 yrs SR – 25-50%
137

138

SIGNET CELL CARCINOMA:
• 1/3 urachal origin and 2/3 directly extend into the bladder
• Rare variant of adenocarcinoma
• High-grade, high-stage tumors at presentation
• Poor prognosis
139

• Carcinoembryonic antigen (CEA)- Elevated
• The prognostic significance – unclear
• Treatment is radical cystectomy
• Survival < 20 months
140

141

SMALLCELLCARCINOMA
• < 1% all primary bladder tumors
• Derived from neuroendocrinestem cells
or dendritic cells
• Stain +ve for Enolase
• May be mixed with elements of TCC
• Very aggressive with earlyvascular and
muscle invasion
142

• Small cell carcinoma of lung or prostate- Metastasized to the
bladder
Small cell carcinoma of the bladder should be considered
and treated as metastatic disease, even if there is no
radiologic evidence of disease outside the bladder.
Chemo-radiation
143

144

SARCOMA
• Leiomyosarcoma >
rhabdomyosarcoma
• M:F = 2:1, 6th decades of life ,
non- smoker
• Rhabdomyosarcoma- MC in
young children.
• Produce polyploidy lesions at
the base of the bladder,
described as botryoides
tumors
145

• Pelvic RT & CT (Cyclophosphamide)
• Most of sarcomas are high grade
• > 75% are confined to bladder muscle
• Gross painless hematuria
• local irritative symptoms
146

147

CECT abdo:(a) heterogeneousenhancingtumorin thebladder
(b) Delayed imaging showing siteof attachmentof tumorto the
domeof bladder 148

Cystoscopicimages:(a) Tumor(T) seeninside the bladder (UB)
(b) Narrowareaof attachmentof tumor
to bladder
149

• Mean size- 7cm,
• Invasive with ulcerative
surface
• necrosis in high grade
• Myxoid subtype: like
inflammatory
myofibroblastic tumor
150

• IHC: positive stains-
• Actin,
• h-caldesmin,
• desmin,
• vemetin
Negative stains –
EMA,
S100,
CK5/6
151

• DDx:
• 1. Sarcomatoid car.
2. Inflammatory myofibroblastic
tumor
• T/t: Radical cystectomy with wide margin
• CT for Mets or CT+RT before SX
• Poor prognosis
152

153

Prostatic Urethral Carcinoma
• Associatedwith urothelial Ca in 90%
of cases
• Isolatedcases only 3%
• Risk factors : CIS of the bladder neck,
h/o intravesicalCT
• Pts undergoing radical cystectomy for
UC – 40%
•
154

• Route of spread- Direct or pagetoid
• Diagnosis : Transurethral resection of prostatic urethra is
primary method
• Treatment : Non invasive-
• Transurethral resection of prostatic urethra + BCG
• Prostatic ductal ca- complete
transurethral prostatectomy + BCG
155

156

Pagetoid spread
• Cancer cells grow undermining the normal
surface urothelium
• Primary seen in urothelial CIS
• Can occur into the prostatic urethra & distal
ureters
157

• M/C after repeated doses of intravesical therapies
• Detection is very difficult, only 15% CIS
& 11% NMIBC shows this type of growth
• Biopsy should be considered
158

DIRECT EXTENSION
• Direct extension of tumors into deeper structure &
angiolymphatic system
• caused by genetic & epigenetic changes
• produce substance in ECM that invade these tissue
-collagenases,
motility &
growth factors,
cell adhesion molecules
• Proepithelin – critical role as autocrine growth factor
159

Directextension
• Others growth factors associated with UC invasion
• EGFs ,
TGFa ,
HBGF,
ILGF,
• Cell adhesion molecules: maintain cell-cell junction &
inhibition of cell growth
- E-cadherin integrins , CD-44, NCD-44
160

161

Prognosticfactors
• Tumor size
• Multiplicity
• Papillary vs Sessile configuration
• Absence/presence of Lymphovascular invasion
162

• Status of remaining urothelium
• Cytogenetic profile
• Stage & grade of tumor
Tumor Grade: growth potential of primary tumor/progression
Tumor stage: extent of the cancer & ability to invade/survival
163

•
THANK YOU
164

Etiopathogenesis Urinary bladder malignancy

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