This document discusses bladder cancer and provides information on epidemiology, etiology, pathophysiology, classification, clinical features, and histopathology of benign and malignant bladder tumors. It is from the Department of Urology at Govt Royapettah Hospital and Kilpauk Medical College in Chennai, India. The document lists the moderators and their academic titles. It then covers topics such as the higher prevalence of bladder cancer in men compared to women, risk factors including smoking and occupational exposures, genetic factors, pathogenesis, WHO and other classification systems, clinical features of non-muscle invasive and muscle invasive bladder cancers, histopathology of benign lesions and different grades of bladder tumors.
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Etiopathogenesis Urinary bladder malignancy
1. CA BLADDER :
Dept of Urology
Govt Royapettah Hospital and Kilpauk Medical College
Chennai 1
2. 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
3. • EPIDEMIOLOGY
• ETIOPATHOGENESIS
• CLASSIFICATION,
• CLINICAL FEATURES,
• HISTOPATHOLOGY OF BENIGN & MALIGNANT TUMOR
3
Dept of Urology, GRH and KMC, Chennai.
6. 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
Dept of Urology, GRH and KMC, Chennai.
8. 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
Dept of Urology, GRH and KMC, Chennai.
9. 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
Dept of Urology, GRH and KMC, Chennai.
10. 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
Dept of Urology, GRH and KMC, Chennai.
11. 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
Dept of Urology, GRH and KMC, Chennai.
14. 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
Dept of Urology, GRH and KMC, Chennai.
15. 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
Dept of Urology, GRH and KMC, Chennai.
16. 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
Dept of Urology, GRH and KMC, Chennai.
17. 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
Dept of Urology, GRH and KMC, Chennai.
20. • Radiation
Increased risk in patients with prostate or cervical cancer
treated with RT
• Heredity
First-degree relatives -- twofold increased risk
20
Dept of Urology, GRH and KMC, Chennai.
21. • 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
Dept of Urology, GRH and KMC, Chennai.
25. 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
Dept of Urology, GRH and KMC, Chennai.
28. 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
Dept of Urology, GRH and KMC, Chennai.
29. • 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
Dept of Urology, GRH and KMC, Chennai.
30. 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
Dept of Urology, GRH and KMC, Chennai.
31. • 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
Dept of Urology, GRH and KMC, Chennai.
39. 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
Dept of Urology, GRH and KMC, Chennai.
41. 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
Dept of Urology, GRH and KMC, Chennai.
42. 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
Dept of Urology, GRH and KMC, Chennai.
43. PUNLMP
• Composed of thin papillary stalks
• Polarity of the cells is maintained
• Nuclei are minimally enlarged.
• Low proliferation, non invasive, non metastatic
43
Dept of Urology, GRH and KMC, Chennai.
45. 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
Dept of Urology, GRH and KMC, Chennai.
48. 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
Dept of Urology, GRH and KMC, Chennai.
49. 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
Dept of Urology, GRH and KMC, Chennai.
50. BENIGN LESIONS/ TUMORS OF
THE BLADDER
• EPITHELIAL METAPLASIA
• LEUKOPLAKIA
• INVERTED PAPILLOMA
• PAPILLOMA
• NEPHROGENIC ADENOMA
• CYSTITIS CYSTICA AND GLANDULARIS
• LEIOMYOMA
50
Dept of Urology, GRH and KMC, Chennai.
51. 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
Dept of Urology, GRH and KMC, Chennai.
52. 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
Dept of Urology, GRH and KMC, Chennai.
53. 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
Dept of Urology, GRH and KMC, Chennai.
57. 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
Dept of Urology, GRH and KMC, Chennai.
58. • Present with non-specific hematuria or irritative voiding
symptoms
• May be asso. with urothelial cancer or malignant changes
• Recurrence – 1%
58
Dept of Urology, GRH and KMC, Chennai.
59. 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
Dept of Urology, GRH and KMC, Chennai.
60. • DDx:
- Urothelial cancer with inverted growth pattern
- Papillary urothelial neoplasm of LMP
• FISH – differentiate b/w benign & malignant
• Treatment - Transurethral resection
60
Dept of Urology, GRH and KMC, Chennai.
61. 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
61
Dept of Urology, GRH and KMC, Chennai.
63. 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
Dept of Urology, GRH and KMC, Chennai.
64. Papilloma
• Discrete Papillary growth with
a central fibrovascular core
lined by normal urothelium
• Small, single, exophytic lesion
• Younger pts ( mean age- 46yrs)
64
Dept of Urology, GRH and KMC, Chennai.
65. 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
Dept of Urology, GRH and KMC, Chennai.
66. 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
Dept of Urology, GRH and KMC, Chennai.
68. DDX:PUNLMP: it has a thicker cell layer, large nuclei with occasional
mitotic figures, recurrence- 20-30%
68
Dept of Urology, GRH and KMC, Chennai.
69. Nephrogenic Adenoma
• Chronic irrigation of the
urothelium
- Trauma
- Previous surgery
- Renal transplantation
- Intravesical
chemotherapy
- Stones, catheters &
infection
- Immunosuppression
• Associated with
inflammation
69
Dept of Urology, GRH and KMC, Chennai.
70. 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
Dept of Urology, GRH and KMC, Chennai.
71. Clinical features:
• Gross hematuria, irritative voiding symptoms
• Valvety app on cystoscopy, often mistaken for papillary
urothelial car.
• Benign, no malignant transformation
71
Dept of Urology, GRH and KMC, Chennai.
72. 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
72
Dept of Urology, GRH and KMC, Chennai.
75. • 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
Dept of Urology, GRH and KMC, Chennai.
76. Cystitis Cystica & Glandularis
UreteritisCystica
• Common incidental finding
in bladder specimens
• Reactive urothelial changes
76
Dept of Urology, GRH and KMC, Chennai.
77. • chronic Cystitis,
• Bladder extrophy,
• ureteral implantation,
• neurogenic bladder or
• any cause of mucosal irritation
77
Dept of Urology, GRH and KMC, Chennai.
78. 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
Dept of Urology, GRH and KMC, Chennai.
81. Cystitis Cystica& Glandularis....
• C/F – incidental finding in biopsies ,
- on cystoscopy – may present as papillary or polypoid
mass
- usually asymptomatic, recurrent UTI
81
Dept of Urology, GRH and KMC, Chennai.
82. 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
Dept of Urology, GRH and KMC, Chennai.
83. • usual type – CK7+ , CDX2 & CK-20 –ve
Intestinal type – CDX2 & CK-20 + ve
• D/D-ADENOCARCINOMA
• ENDOCERVICOSIS
83
Dept of Urology, GRH and KMC, Chennai.
84. • Treatment: removal of source of infection/injury
long term antibiotics therapy
Surgical options reserved when conservative Mx not
respond.
84
Dept of Urology, GRH and KMC, Chennai.
87. LEIOMYOMA
• Rare benign Mesenchymal tumor
• Till now, only 250 cases are reported
• Similar incidence in male and female
87
Dept of Urology, GRH and KMC, Chennai.
88. Leiomyoma
• Etiology is still unknown, but may be related to
- chromosomal alteration
- hormonal disturbance
- Repeated bladder wall & detrusor infection
- perivascular inflammation
88
Dept of Urology, GRH and KMC, Chennai.
89. • Based on location – 3 type 1. Endovesical - (65-85% )
2. Intramural - ( 3-7% )
3. Extravesical - ( 10-30% )
89
Dept of Urology, GRH and KMC, Chennai.
90. 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
Dept of Urology, GRH and KMC, Chennai.
92. • Best imaging for diagnosis – MRI & cystoscopic biopsy
• Treatment : Endovesical – TURBT
Intramural & Extravesical – wide excision/partial cystectomy
open/laparoscopic
92
Dept of Urology, GRH and KMC, Chennai.
93. On USG: Smoothwall, Homogeneous, hypoechoic, solid mass
with echogenic surface
On CT(P):Hypodense mass, CT(c): Moderately enhancingmass
93
Dept of Urology, GRH and KMC, Chennai.
94. 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
Dept of Urology, GRH and KMC, Chennai.
95. • 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.
95
Dept of Urology, GRH and KMC, Chennai.
97. 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
Dept of Urology, GRH and KMC, Chennai.
98. • Muscle invasive
• Histology:
• Invading urothelium shows irregular nests, single cell
infiltration or tentacular finger-like projections
• Stromal response
-desmoplasia,
-retraction or
-inflammation.
98
Dept of Urology, GRH and KMC, Chennai.
100. • Assess level of invasion for staging
.
• Presence and status of involvement of muscularis propria
should be reported in TURBT specimen for adequate staging.
100
Dept of Urology, GRH and KMC, Chennai.
101. 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
Dept of Urology, GRH and KMC, Chennai.
102. 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
Dept of Urology, GRH and KMC, Chennai.
103. Nested variant
• Tumor cells will often contain areas with
large nuclei and mitotic figures
103
Dept of Urology, GRH and KMC, Chennai.
104. 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
104
Dept of Urology, GRH and KMC, Chennai.
106. 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
Dept of Urology, GRH and KMC, Chennai.
107. 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
Dept of Urology, GRH and KMC, Chennai.
108. • 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
Dept of Urology, GRH and KMC, Chennai.
110. 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
Dept of Urology, GRH and KMC, Chennai.
111. • 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
Dept of Urology, GRH and KMC, Chennai.
112. 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
Dept of Urology, GRH and KMC, Chennai.
117. SquamousCell Carcinoma
• Histological types: Usual
type,
• Verrucous,
• Variant,
• Basaloid with sarcomatoid
features
117
Dept of Urology, GRH and KMC, Chennai.
118. 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
Dept of Urology, GRH and KMC, Chennai.
120. • Large ulcerated, necrotic
• 80% involved muscular wall
at diagnosis
• Squ. Metaplasia up to 60%
120
Dept of Urology, GRH and KMC, Chennai.
121. • 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
Dept of Urology, GRH and KMC, Chennai.
122. Adenocarcinoma
• Risk factors for adenocarcinoma of the bladder
- Urachal cyst/remnant,
- Cystitis glandularis,
- CIS,
- Chronic inflammation,
- Ureterosigmoidostomy,
- Bladder augmentation
- Exstrophy of bladder.
122
Dept of Urology, GRH and KMC, Chennai.
123. ADENOCARCINOMA
• <2% of primary bladder cancers
• Majority represent Mets from GI
tract, breast, lung , colon primary
• Usually arise in trigoneor in dome
(urachal)
123
Dept of Urology, GRH and KMC, Chennai.
124. • M/C – Exstrophy
&
associated with pelvic lipomatosis
Develop in response -
• chronic inflammation
• irritation
124
Dept of Urology, GRH and KMC, Chennai.
126. • Classifications of adenocarcinomas of the GU tract
• 1) primary vesical
• 2) urachal
• 3) metastatic
126
Dept of Urology, GRH and KMC, Chennai.
127. • 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
Dept of Urology, GRH and KMC, Chennai.
128. URACHAL ADENOCARCINOMA
• Located at the dome of the
bladder
• 90% of masses occur close
to the bladder
128
Dept of Urology, GRH and KMC, Chennai.
129. • Midline,
• infraumbilical,
• soft-tissuemass with calcification ( Stippled )
consideredto be urachal adenocarcinoma until
proved otherwise.
129
Dept of Urology, GRH and KMC, Chennai.
130. • 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
Dept of Urology, GRH and KMC, Chennai.
131. 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
Dept of Urology, GRH and KMC, Chennai.
132. • 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
Dept of Urology, GRH and KMC, Chennai.
142. 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
Dept of Urology, GRH and KMC, Chennai.
143. • 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
Dept of Urology, GRH and KMC, Chennai.
145. 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
Dept of Urology, GRH and KMC, Chennai.
146. • Pelvic RT & CT (Cyclophosphamide)
• Most of sarcomas are high grade
• > 75% are confined to bladder muscle
• Gross painless hematuria
• local irritative symptoms
146
Dept of Urology, GRH and KMC, Chennai.
150. • Mean size- 7cm,
• Invasive with ulcerative
surface
• necrosis in high grade
• Myxoid subtype: like
inflammatory
myofibroblastic tumor
150
Dept of Urology, GRH and KMC, Chennai.
151. • IHC: positive stains-
• Actin,
• h-caldesmin,
• desmin,
• vemetin
Negative stains –
EMA,
S100,
CK5/6
151
Dept of Urology, GRH and KMC, Chennai.
152. • 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
Dept of Urology, GRH and KMC, Chennai.
154. 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
Dept of Urology, GRH and KMC, Chennai.
155. • 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
Dept of Urology, GRH and KMC, Chennai.
157. Pagetoid spread
• Cancer cells grow undermining the normal
surface urothelium
• Primary seen in urothelial CIS
• Can occur into the prostatic urethra & distal
ureters
157
Dept of Urology, GRH and KMC, Chennai.
158. • 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
Dept of Urology, GRH and KMC, Chennai.
159. 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
Dept of Urology, GRH and KMC, Chennai.
162. Prognosticfactors
• Tumor size
• Multiplicity
• Papillary vs Sessile configuration
• Absence/presence of Lymphovascular invasion
162
Dept of Urology, GRH and KMC, Chennai.
163. • 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
Dept of Urology, GRH and KMC, Chennai.