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Ca Bladder :
Diagnosis
DR. DEEPESH KALRA
INSTITUTE OF UROLOGY
MMC, CHENNAI
 Hematuria
 Irritative LUTS - 30% , especially those with CIS
 Upper urinary tract obstruction - rare on initial presentation, a sign of
advanced disease
 Pain in suprapubic region, buttock, perineum may suggest invasion of
paravesical tissue
 Weight loss
 Bony pain
Hematuria
 Gross or microscopic?
 Timing ?
 Associated with pain?
 Clots?
 Hematuria, particularly in the adult, should be regarded as a symptom of
malignancy until proved otherwise and demands immediate urologic
examination
 Gross, painless hematuria - 85%
 Microscopic hematuria occurs in virtually all patients
 Intermittent and can be related to Valsalva
 Any episode of gross hematuria should be evaluated even if subsequent
urinalysis is negative.
 Gross - 12% will have a bladder tumor
 Microscopic - 4.1% risk of bladder cancer
Common Risk Factors for Urinary Tract Malignancy in
Patients with Microscopic Hematuria
 Male gender
 > 35 years
 Smoker
 Exposure to chemicals or dyes (benzenes or aromatic amines)
 Analgesic abuse
 History of gross hematuria
 History of irritative voiding symptoms
 History of pelvic irradiation
 History of chronic urinary tract infection
 Chemotherapy such as alkylating agents
 History of chronic indwelling foreign body
 A full hematuria evaluation for bladder cancer includes
Cystoscopy
Urine cytology
Upper-tract imaging
Symptomatic MH
 Cystoscopy is recommended in such patients, regardless of age
 Cytologic examination is considered an option in the setting of irritative
voiding symptoms
 Cystoscopy should not be omitted even if the cytologic findings are
negative
 The main diagnostic tests for bladder cancer are cystoscopy and biopsy
 White light cystoscopy (WLC) is the gold standard
 excellent sensitivity and specificity for papillary tumors but is relatively
poor for CIS
 Cystoscopy with porphyrin dye (commonly referred to as blue light
cystoscopy) may be more sensitive in the detection of CIS
 Porphyrin-induced fluorescence cystoscopy uses photoactive
porphyrins, such as 5-aminolevulinic acid (ALA) or hexyl-
aminolevulinate (HAL) , that accumulate preferentially in
neoplastic tissue and emit red fluorescence under blue-
wavelength light
 Blue light cystoscopy detected 58% of CIS compared with 15%
for WLC.
 The sensitivity of blue light was 87% and was 83% for white
light.
 Blue light cystoscopy has a false-positive rate of 39%
 The true impact of blue light cystoscopy on the detection of
bladder cancer is unclear
 Narrow-band imaging (NBI) is an endoscopic optical image
enhancement technique
 enhances the contrast between mucosal surfaces and
microvascular structures without the use of dyes.
 NBI illuminates the mucosal surface with light of a narrow
bandwidth in the blue (415 nm) and green (540 nm) light
spectrum, which are strongly absorbed by hemoglobin.
 Consequently, the vascular structures appear dark brown or
green against a pink or white mucosal background.
 For WLC and NBI cystoscopy, overall sensitivities were 87%
and 100% and the overall specificities were 85% and 82%,
respectively.
 A recent study suggests that NBI more accurately detects
tumor recurrence after BCG therapy than do urine cytology or
WLC
 and NBI can obviate the need for random bladder biopsies in
post-BCG bladders
Random biopsies
 High-risk individuals, such as those given post-intravesical
therapy
 Positive cytology and an endoscopically negative bladder.
Cytology
 Detection of cancer in high-risk patient
 Follow-up of patients with history of urinary tract neoplasia
 Patients with low-grade noninvasive tumors can be followed up cytologically
 Patients with negative cytologic findings have a very low risk of recurrence
 High-grade cytologic abnormalities predict an aggressive tumor course
 A positive cytology should always be confirmed histologically before
definitive therapy.
 False positive - stones, chemotherapy, radiation, viruses, BPH, prostatitis,
and pseudopapillary clusters.
 False-negative diagnosis may be of more clinical consequence.
 Cytologic diagnosis of papillomas and well-differentiated papillary
transitional cell carcinoma (TCC) can be difficult or impossible because the
cells are nearly normal appearing.
 Morning
 First void
 50 ml
 Refrigerated in 1 hour
 Cytologic diagnosis of papillomas and well-differentiated
papillary transitional cell carcinoma (TCC) can be difficult or
impossible because the cells are nearly normal appearing.
 PUNLMP and low grade urothelial neoplasia
Cytologic Criteria:
Cytoplasmic homogeneity
High nuclear to cytoplasmic ratio
Irregular borders.
Architectural criteria:
Papillary fragments with fibrovascular cores
Irregular cell clusters
 High grade urothelial carcinoma:
High nuclear to cytoplasmic ratio,
Marked nuclear hyperchromasia
Coarsely granular chromatin
irregular nuclear outline
large nucleoli (some cases).
 Squamous cell carcinoma
Cytoplasmic keratinization
Pearls,
Bridges
Angulated hyperchromatic nuclei.
 Adenocarcinoma
Glandular differentiation is common in otherwise typical urothelial carcinoma,
therefore the definitive diagnosis of pure adenocarcinoma is left to biopsy.
 Clear cell carcinoma:
abundant clear cytoplasm
large irregular nuclei,
vesicular chromatin
large nucleoli.
 Lymphoma
Rare but can potentially be diagnosed with urine cytology.
• Diagnostic categories for The Paris System for Reporting Urinary
Cytology
1 Nondiagnostic/unsatisfactory
2 Negative for high-grade urothelial carcinoma (NHGUC)
3 Atypical urothelial cells (AUC)
4 Suspicious for high-grade urothelial carcinoma (SHGUC)
5 High-grade urothelial carcinoma (HGUC)
6 Low-grade urothelial neoplasm (LGUN)
7 Other: primary and secondary malignancies and
miscellaneous lesions
Category Risk of malignancy % Management
Nondiagnostic/unsatisfactory < 5-10 Repeat
Negative for High grade 0-10 Clinical follow up
Atypical 8-35 Clinical follow up
Suspicious for high grade 50-90 Aggessive followup,Cystoscopy +
biopsy
Low grade 10 Cystoscopy + biopsy, staging
High grade >90 Cystoscopy + biopsy, staging
Other malignancy >90 Cystoscopy + biopsy, staging
Markers
Marker Median Sensitivity Median Specifcicity
BTA stat 70 75
BTA trak 69 65
NMP 22 73 80
FDP 61 79
ImmunoCyt 83 80
LEWIS X 83 85
FISH 84 95
Microsatellite 91 94
Cyfra 21 94 86
Cytoketin 20 91 84
 NMP-22 is a nuclear matrix protein that is used to form the cell nuclei.
 20-times higher concentration in the urine of bladder cancer patients
in noncancer controls
 With use of a cutoff level of 10 units/mL, the overall sensitivity and
specificity for detecting urothelial cancer were 49% and 87%, respectively.
 The Lewis blood group antigen X -
The sensitivity and specificity for the detection of bladder cancer are 75% and 85%,
respectively.
There is no commercially available test to date.
 FISH -
identifies fluorescently labeled DNA probes that bind to intranuclear chromosomes.
Commercially available probes evaluate aneuploidy for chromosomes 3, 7, and 17 and
homozygos loss of 9p 21 .
The median sensitivity and specificity of FISH analysis are 79% and 70%, respectively
 Multiple markers are available to identify short DNA repeats present
throughout the chromosomes that are lost in some tumor cells.
 Microsatellite analysis amplifies these repeats
 If the microsatellite analysis was persistently positive, there was an 83% 2-
year recurrence rate, but
 if the analysis was persistently negative, only 22% of patients had recurrent
tumors
 Together, because current evidence indicates that none of the available
urinary biomarkers, including cytology, appear to be sufficiently
sensitive or sufficiently validated to replace cystoscopy or imaging,
 these studies are not recommended in the initial evaluation of patients
with asymptomatic MH
 However, cytologic examination may be considered in patients with a
negative initial workup in whom urothelial carcinoma is still suspected,
as well as in patients with symptomatic MH.
 Patients with a negative complete evaluation can be released
from care if subsequent urinalyses confirm resolution of MH.
 Re-evaluation should be considered in patients with
persistent/recurrent MH and those with an incomplete initial
evaluation.
Imaging
 USG
Useful screening tool
To r/o other causes of hematuria
Helps to identify the growth(size/sessile or
polyp,number )
Helps to detect upper tract changes
CT
 Staging of the tumor
 Extent of primary tumor
 Rule out invasive bladder cancer
 Assess pelvic LN status ( > 1 cm )
 Visceral metastasis
 Evaluation of upper urinary tract
 Asymmetric mural thickening should be viewed with suspicion.
 The masses are of soft tissue attenuation and may be encrusted with small
calcifications.
 Although unable to distinguish between T1, T2 and T3a (microscopic extravesical
spread),
 CT is able to distinguish T3b tumors (stranding/nodules in perivesical fat) and T4
tumors (direct extension into adjacent structures/loss of normal fat plane)
MRI
 MRI is superior to other modalities in locally staging the tumor
 In some instances able to distinguish T1 from T2 tumors on T2 weighted images.
 T1: isointense compared to muscle
 T2
 slightly hyperintense compared to muscle
 useful in determining the low signal muscle layer and its discontinuity when muscle
wall invasion
T1
 Urine low signal
 Tumor and detrusor –
indeterminate
 Fat – high signal intensity
 luminal extension and perivesical
fat infiltration
T2
 Urine – high intense
 Tumor –indeterminate to high
intensity
 Detrusor – low signal
 Differentiate between non
muscle invasive and
invasive tumor
DWI
 Tumor is more cellular,
less ADC (apparent
diffusion coefficiant)
 Used to differentiate
between scar tissue
and recurrence .
 Chemotherapy
response
PET
 Unfortunately, FDG is excreted into the urine and thus accumulates in the
bladder, making it unsuitable for diagnosis of urinary tract tumors.
 It does have a role to play in the assessment of nodal or distant
metastases
THANK YOU

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Ca bladder diagnosis

  • 1. Ca Bladder : Diagnosis DR. DEEPESH KALRA INSTITUTE OF UROLOGY MMC, CHENNAI
  • 2.  Hematuria  Irritative LUTS - 30% , especially those with CIS  Upper urinary tract obstruction - rare on initial presentation, a sign of advanced disease  Pain in suprapubic region, buttock, perineum may suggest invasion of paravesical tissue  Weight loss  Bony pain
  • 3. Hematuria  Gross or microscopic?  Timing ?  Associated with pain?  Clots?  Hematuria, particularly in the adult, should be regarded as a symptom of malignancy until proved otherwise and demands immediate urologic examination
  • 4.  Gross, painless hematuria - 85%  Microscopic hematuria occurs in virtually all patients  Intermittent and can be related to Valsalva  Any episode of gross hematuria should be evaluated even if subsequent urinalysis is negative.  Gross - 12% will have a bladder tumor  Microscopic - 4.1% risk of bladder cancer
  • 5. Common Risk Factors for Urinary Tract Malignancy in Patients with Microscopic Hematuria  Male gender  > 35 years  Smoker  Exposure to chemicals or dyes (benzenes or aromatic amines)  Analgesic abuse  History of gross hematuria  History of irritative voiding symptoms  History of pelvic irradiation  History of chronic urinary tract infection  Chemotherapy such as alkylating agents  History of chronic indwelling foreign body
  • 6.  A full hematuria evaluation for bladder cancer includes Cystoscopy Urine cytology Upper-tract imaging
  • 7.
  • 8. Symptomatic MH  Cystoscopy is recommended in such patients, regardless of age  Cytologic examination is considered an option in the setting of irritative voiding symptoms  Cystoscopy should not be omitted even if the cytologic findings are negative
  • 9.  The main diagnostic tests for bladder cancer are cystoscopy and biopsy  White light cystoscopy (WLC) is the gold standard  excellent sensitivity and specificity for papillary tumors but is relatively poor for CIS  Cystoscopy with porphyrin dye (commonly referred to as blue light cystoscopy) may be more sensitive in the detection of CIS
  • 10.  Porphyrin-induced fluorescence cystoscopy uses photoactive porphyrins, such as 5-aminolevulinic acid (ALA) or hexyl- aminolevulinate (HAL) , that accumulate preferentially in neoplastic tissue and emit red fluorescence under blue- wavelength light
  • 11.  Blue light cystoscopy detected 58% of CIS compared with 15% for WLC.  The sensitivity of blue light was 87% and was 83% for white light.  Blue light cystoscopy has a false-positive rate of 39%  The true impact of blue light cystoscopy on the detection of bladder cancer is unclear
  • 12.  Narrow-band imaging (NBI) is an endoscopic optical image enhancement technique  enhances the contrast between mucosal surfaces and microvascular structures without the use of dyes.  NBI illuminates the mucosal surface with light of a narrow bandwidth in the blue (415 nm) and green (540 nm) light spectrum, which are strongly absorbed by hemoglobin.  Consequently, the vascular structures appear dark brown or green against a pink or white mucosal background.
  • 13.  For WLC and NBI cystoscopy, overall sensitivities were 87% and 100% and the overall specificities were 85% and 82%, respectively.  A recent study suggests that NBI more accurately detects tumor recurrence after BCG therapy than do urine cytology or WLC  and NBI can obviate the need for random bladder biopsies in post-BCG bladders
  • 14. Random biopsies  High-risk individuals, such as those given post-intravesical therapy  Positive cytology and an endoscopically negative bladder.
  • 15. Cytology  Detection of cancer in high-risk patient  Follow-up of patients with history of urinary tract neoplasia  Patients with low-grade noninvasive tumors can be followed up cytologically  Patients with negative cytologic findings have a very low risk of recurrence  High-grade cytologic abnormalities predict an aggressive tumor course
  • 16.  A positive cytology should always be confirmed histologically before definitive therapy.  False positive - stones, chemotherapy, radiation, viruses, BPH, prostatitis, and pseudopapillary clusters.  False-negative diagnosis may be of more clinical consequence.  Cytologic diagnosis of papillomas and well-differentiated papillary transitional cell carcinoma (TCC) can be difficult or impossible because the cells are nearly normal appearing.
  • 17.  Morning  First void  50 ml  Refrigerated in 1 hour
  • 18.
  • 19.  Cytologic diagnosis of papillomas and well-differentiated papillary transitional cell carcinoma (TCC) can be difficult or impossible because the cells are nearly normal appearing.
  • 20.  PUNLMP and low grade urothelial neoplasia Cytologic Criteria: Cytoplasmic homogeneity High nuclear to cytoplasmic ratio Irregular borders. Architectural criteria: Papillary fragments with fibrovascular cores Irregular cell clusters
  • 21.  High grade urothelial carcinoma: High nuclear to cytoplasmic ratio, Marked nuclear hyperchromasia Coarsely granular chromatin irregular nuclear outline large nucleoli (some cases).
  • 22.  Squamous cell carcinoma Cytoplasmic keratinization Pearls, Bridges Angulated hyperchromatic nuclei.  Adenocarcinoma Glandular differentiation is common in otherwise typical urothelial carcinoma, therefore the definitive diagnosis of pure adenocarcinoma is left to biopsy.
  • 23.  Clear cell carcinoma: abundant clear cytoplasm large irregular nuclei, vesicular chromatin large nucleoli.  Lymphoma Rare but can potentially be diagnosed with urine cytology.
  • 24. • Diagnostic categories for The Paris System for Reporting Urinary Cytology 1 Nondiagnostic/unsatisfactory 2 Negative for high-grade urothelial carcinoma (NHGUC) 3 Atypical urothelial cells (AUC) 4 Suspicious for high-grade urothelial carcinoma (SHGUC) 5 High-grade urothelial carcinoma (HGUC) 6 Low-grade urothelial neoplasm (LGUN) 7 Other: primary and secondary malignancies and miscellaneous lesions
  • 25. Category Risk of malignancy % Management Nondiagnostic/unsatisfactory < 5-10 Repeat Negative for High grade 0-10 Clinical follow up Atypical 8-35 Clinical follow up Suspicious for high grade 50-90 Aggessive followup,Cystoscopy + biopsy Low grade 10 Cystoscopy + biopsy, staging High grade >90 Cystoscopy + biopsy, staging Other malignancy >90 Cystoscopy + biopsy, staging
  • 27.
  • 28. Marker Median Sensitivity Median Specifcicity BTA stat 70 75 BTA trak 69 65 NMP 22 73 80 FDP 61 79 ImmunoCyt 83 80 LEWIS X 83 85 FISH 84 95 Microsatellite 91 94 Cyfra 21 94 86 Cytoketin 20 91 84
  • 29.  NMP-22 is a nuclear matrix protein that is used to form the cell nuclei.  20-times higher concentration in the urine of bladder cancer patients in noncancer controls  With use of a cutoff level of 10 units/mL, the overall sensitivity and specificity for detecting urothelial cancer were 49% and 87%, respectively.
  • 30.  The Lewis blood group antigen X - The sensitivity and specificity for the detection of bladder cancer are 75% and 85%, respectively. There is no commercially available test to date.  FISH - identifies fluorescently labeled DNA probes that bind to intranuclear chromosomes. Commercially available probes evaluate aneuploidy for chromosomes 3, 7, and 17 and homozygos loss of 9p 21 . The median sensitivity and specificity of FISH analysis are 79% and 70%, respectively
  • 31.  Multiple markers are available to identify short DNA repeats present throughout the chromosomes that are lost in some tumor cells.  Microsatellite analysis amplifies these repeats  If the microsatellite analysis was persistently positive, there was an 83% 2- year recurrence rate, but  if the analysis was persistently negative, only 22% of patients had recurrent tumors
  • 32.  Together, because current evidence indicates that none of the available urinary biomarkers, including cytology, appear to be sufficiently sensitive or sufficiently validated to replace cystoscopy or imaging,  these studies are not recommended in the initial evaluation of patients with asymptomatic MH  However, cytologic examination may be considered in patients with a negative initial workup in whom urothelial carcinoma is still suspected, as well as in patients with symptomatic MH.
  • 33.  Patients with a negative complete evaluation can be released from care if subsequent urinalyses confirm resolution of MH.  Re-evaluation should be considered in patients with persistent/recurrent MH and those with an incomplete initial evaluation.
  • 34. Imaging  USG Useful screening tool To r/o other causes of hematuria Helps to identify the growth(size/sessile or polyp,number ) Helps to detect upper tract changes
  • 35.
  • 36.
  • 37. CT  Staging of the tumor  Extent of primary tumor  Rule out invasive bladder cancer  Assess pelvic LN status ( > 1 cm )  Visceral metastasis  Evaluation of upper urinary tract
  • 38.  Asymmetric mural thickening should be viewed with suspicion.  The masses are of soft tissue attenuation and may be encrusted with small calcifications.  Although unable to distinguish between T1, T2 and T3a (microscopic extravesical spread),  CT is able to distinguish T3b tumors (stranding/nodules in perivesical fat) and T4 tumors (direct extension into adjacent structures/loss of normal fat plane)
  • 39. MRI  MRI is superior to other modalities in locally staging the tumor  In some instances able to distinguish T1 from T2 tumors on T2 weighted images.  T1: isointense compared to muscle  T2  slightly hyperintense compared to muscle  useful in determining the low signal muscle layer and its discontinuity when muscle wall invasion
  • 40. T1  Urine low signal  Tumor and detrusor – indeterminate  Fat – high signal intensity  luminal extension and perivesical fat infiltration
  • 41. T2  Urine – high intense  Tumor –indeterminate to high intensity  Detrusor – low signal  Differentiate between non muscle invasive and invasive tumor
  • 42. DWI  Tumor is more cellular, less ADC (apparent diffusion coefficiant)  Used to differentiate between scar tissue and recurrence .  Chemotherapy response
  • 43. PET  Unfortunately, FDG is excreted into the urine and thus accumulates in the bladder, making it unsuitable for diagnosis of urinary tract tumors.  It does have a role to play in the assessment of nodal or distant metastases