| How is bladder histology? | • Layers of bladder wall (from inside out)
– Mucosa
– Muscularis propria (detrusor muscle) consists of 3 layers (inner longitudinal, middle circular and outer longitudinal)
– Serosa / adventitia: serosa is loose connective tissue covering bladder dome; the remaining area is covered by adventitia
Urothelium: specialized stratified lining epithelium, impermeable barrier
Lamina propria:
connective tissue containing vessels, lymphatics, nerve endings and a few elastic fibers |
| What are main histological types of bladder cancer? | • Urothelial carcinoma (UC)(˃90%)
• Squamous cell carcinoma
• Primary adenocarcinoma of the bladder or
Urachal Adenocarcinoma
• Smal cell / Large cell neuroendocrine
carcinoma |
| What is urothelial carcinoma? | Etiology
• Tobacco smoking: population attributable risk for ever
smoking is 50% for both men and women in U.S.
• Occupational exposures: aromatic amines, chlorinated
hydrocarbons and polycyclic aromatic hydrocarbons
including benzidine
• Genetic predisposition
Diagnosis
Cystoscopy and biopsy / transurethral resection of
bladder tumor (TURB T) |
| How is urine cytology in UC? | • Voided urine: Non invasive, easiest to obtain
Obtaining 3 second morning voided
midstream urine samples collected over 3
consecutive days appears to optimize the
detection of urothelial malignancies
• Instrumented urine: Catheterization of the
bladder or irrigation of bladder
Paris system for reporting of urinary cytology, Enlarged nuclei with high N/C ratio (> 0.7), hyperchromasia, clumped chromatin |
| How is use of urine cytology in bladder cancer? | • Non-invasive test but is not very sensitive (many false negatives).
• Urine cytology is of value only if positive. In the event of an abnormality (tumor, atypical or suspicious), a cystoscopy must be performed.
• Main indications for urinary cytology:
– initial diagnosis of bladder tumor (but always followed by cystoscopy)
– monitoring of patients at risk (occupational exposure to carcinogens)
– follow-up of patients with a history of bladder tumor not infiltrating the muscle.
• Most sensitive and highly specific for high grade tumors (diagnosis or follow-up) whether flat (carcinoma in situ), papillary or mixed
• Low sensitivity (difficult to diagnose) for papilloma and low malignant potential lesions |
| What are non-invasive urothelial neoplasms? | . |
| What is urothelial dysplasia? | • Flat lesion with appreciable cytologic and architectural abnormalities that are believed to be preneoplastic but that fall short of the diagnostic threshold urothelial CIS. |
| How is grading of urothelial tumors? | • 2016 WHO Classification continues to
recommend the 2004 WHO / ISUP Consensus
Classification.
• Low grade v/s High grade distinction : for non
infiltrating and pT1 tumors
• > 95% of (pT2-pT4) tumors are high grade.
Exception: Nested variant
• Grade the tumor according to the highest grade
–%, if <10% comment |
| How is assessment of papillary urothelial neoplasms? | . |
| What are urothelial proliferation of uncertain malignant potential? | • Replaces papillary and flat hyperplasia.
• Two thirds of patients have a history of prior,
concurrent, or subsequent urothelial neoplasia.
• Has been reported de novo, and in this setting,
clinical follow up is suggested.
• Early manifestation of a papillary neoplasm.
• Clonal, high incidence of ch. 9 deletions+ FGFR3
abnormalities.
• The 5-year risk of developing urothelial neoplasia
~40%.
• Marked thickening of the urothelium
• No or minimal cytological atypia
• No true papillary formation. |
| What are papillary neoplasms of low malignant potential? | • Noninvasive papillary urothelial neoplasm with exophytic or endophytic (inverted) configuration
• Epithelial lining of fibrovascular cores is thicker than normal urothelium:
• No variation in nuclear size, shape or chromatin pattern
• Preserved polarity of urothelial cells
• Mitoses are rare and basally located
• Solitary or multiple.
• Ordered urothelium with variable thickness
• Papillae with frequent branching/fusion and variation in nuclear polarity.
• Visible architectural and cytologic atypia at medium power.
• Frequent mitosis at any level. |
| How are papillary urothelial neoplasms high grade? | • Solitary or multiple.
• Urothelium obviously disordered with cytologic atypia at low power.
• Frequently fused papillae with architectural and cytologic atypia and loss of polarity recognized at scanning power.
• Variable thickness.
• Nuclear pleomorphism present with frequent mitosis. |
| How are urothelial carcinoma w/divergent differentiation? | • A % of ‘‘usual type’’ urothelial carcinoma is present along with other morphologies.
• Most commonly in association with highgrade and locally advanced disease.
• Incidence (cystectomy) : 33%.
• Association with adverse outcome on univariate analysis, the effect does not remain significant on multivariable analysis
• Squamous, Glandular, Trophoblastic, Mullerian
• Report the % of divergent histologies |
| How are micropapillary urothelial carcinoma? | • Well recognized variant (0.6-2.2%)
• Present at a high pathologic stage, and exhibit aggressive clinical behaviour
• Commonly associated with lymphovascular invasion
• c-erb-b2 expression : 70%
• Any amount even <10% is significant and should be reported. |
| How is squamous cell carcinoma of baldder? | • Infiltrating squamous cell carcinoma with surface in situ squamous carcinoma
Etiology:
– Schistosomiasis (Schistosoma haematobium)
• Major risk factor for bladder SCC in geographic regions with high prevalence of schistosomiasis (Egypt and other parts of Africa)
– Smoking: 5x increased risk compared with nonsmokers
– Chronic bladder irritation / inflammation associated with:
• Long term catheterization, Bladder calculi or foreign bodies, Neurogenic bladder, Bladder exstrophy
– Renal pelvis / ureter
• Nephrolithiasis, such as staghorn calculi, Anatomic anomalies of the kidney, Chronic recurrent infections |
| How is morphology of squamous cell carcinoma? | • Bladder mucosa with noncalcified Schistosoma haematobium eggs and surrounding inflammation.
• Keratin pearl formation. |
| What are molecular subtypes of urothelial carcinoma? | • Complex mutational landscape of urothelial tumors.
>300 mutations
>200 copy number alterations
>20 rearrangements per tumor.
• Only lung cancer has been shown to harbour a higher rate of mutations |
| Table of molecular subtypes of urothelial carcinoma? | . |
| What are molecular subtypes of basal carcinoma? | • Molecular signatures may help defining subsets of “responders”, while sparing other patients (p53-like tumors) from unnecessary therapy related toxicity, and delay of cystectomy.
• Find potential therapeutic targets
• No published recommendation concerning routine use of molecular profiling |
| How is staging of bladder carcinoma? | . |
| What is frozen section indication? | Indications
• Frozen sections usually performed for ureteral margin
evaluation for carcinoma in situ or invasive carcinoma (
More useful if CIS present in bladder)
• Frozen sectioning may be useful for evaluating lymph nodes
Procedure
• Recommended to obtain cross section of distal ureter, not
shaved margin
• Frozen section is highly sensitive for malignant ureteral
margins, but reresection often does not convert positive
margins to negative margins |
| What are prognostic factors of bladder cancer? | • Grade
• Stage, with histologic characterization and involvement of the muscularis propria is an important factor for determining prognosis.
• 5 year relative survival:
– 69% with local disease
– 37% with regional disease
– 6% with distant disease.
• Morphological variants associated with poor prognosis, possibly due to late stage diagnosis and aggressive behavior include:
– Poorly differentiated, sarcomatoid
– Micropapillary urothelial carcinoma
– Plasmacytoid urothelial carcinoma
– Nested urothelial carcinoma |
| What are epithleial tumors arising in bladder diverticulum? | • Epithelial neoplasms : up to 14% of bladder
diverticula.
• Majority of tumours arise in acquired diverticula
• Up to 50% of invasive tumors are of urothelial
type.
• Similar to vesical primaries, pathologic stage is
the most important prognostic factor.
• Bladder Cancer arising in a diverticulum cannot
be staged as pT2. Don't do it! |
