1. Urothelial CA: Cancers of the Bladder, Ureter, and Renal Pelvis
Garzon, Gatchalian, Gaw, Geraldoy, Geronimo, Geronimo, Geronimo, Go
August 18, 2009

2. Bladder Carcinoma

3. Bladder Carcinoma Second most common CA of genitourinary tract
7% men; 2% women
Ave. age at dx is 65 years old
75% localized in the bladder
25% spread to regional lymph nodes and distant sites

4. Bladder CA: Risk Factors
Cigarette smoking
50% men, 31% women
α- and β-naphthylamine
Occupational exposure
15-35% men, 1-6% women
chemical, dye, rubber, petroleum,leather, and printing industries
benzidine, betanaphthylamine and 4 -aminobiphenyl,
Cyclophosphamide (Cytoxan)
Ingestion of artificial sweeteners
Physical trauma to the urothelium
induced by infection,instrumentation, and calculi

5. Bladder CA: Pathogenesis
Activation of oncogenes
Inactivation or loss of tumor suppressor genes
“Field Defect” - loss of genetic material on chromosome 9
Chromosome 11p
contains the c-Ha-ras proto-oncogene
deleted in approximately 40% of bladder cancers
Increased p 21
Expressed by the c-Ha-ras protein product
detected in dysplastic and high-grade tumors but not in low-grade bladder cancers
Deletions of chromosome 17p
detected in over 60% of all invasive bladder cancers, but have not been described in superficial tumors

6. Bladder CA: Staging Tis - In-situ disease Ta - Epithelium only
T1 - Lamina propria invasion
T2 - Superficial muscle invasion
T3a - Deep muscle invasion
T3b - Perivesical fat invasion
T4 - Prostate or contiguous muscle
T4a - Invasion of prostate, uterus, vaginal
T4b - Invasion of pelvic wall, abdominal wall

7. Bladder CA: Staging Nodal (N) stage Nx – cannot be assessed
N0 – no nodal metastases
N1 – single node <2cm involved
N2 – single node involved 2–5cm in size or multiple nodes none >5 cm
N3 – one or more nodes >5 cm in size involved
Metastases (M) stage
Mx – cannot be defined
M0 – no distant metastases
M1 – distant metastses present

8. Bladder CA: Histopathology
98% of all bladder cancers are epithelial malignancies, with most being transitional cell carcinomas (TCCs)

9. Normal Urothelium
3–7 layers of transitional cell epithelium resting on a basement membrane
Basal cells
are actively proliferating cells
rests on the basement membrane
Luminal cells
most important feature of normal bladder epithelium
larger umbrella-like cells that
bound together by tight junctions

10. Normal Urothelium Lamina propria Muscularis propria
occasional smooth-muscle fibers
Muscularis propria
deeper, more extensive muscle elements
Muscle wall of the bladder
inner and outer longitudinally oriented layers
middle circularly oriented layer

11. Papilloma
Papillary tumor with a fine fibrovascular stalk supporting an epithelial layer of transitional cells with normal thickness and cytology (WHO)
Rare
Benign
Affects younger patients

12. Transitional Cell CA 90% of all bladder cancers are TCCs
Most commonly appear as papillary, exophytic lesions (SUPERFICIAL)
Less commonly - sessile or ulcerated (INVASIVE)
Carcinoma in situ (CIS)
flat, anaplastic epithelium
Urothelium lacks the normal cellular polarity
Cells contain large, irregular hyperchromatic nuclei with prominent nucleoli

13. frond-like papillary projections

14. Nontransitional Cell CA: Adenocarcinoma
<2% of all bladder cancers
Primary adenocarcinomas of the bladder
preceded by cystitis and metaplasia
arise along the floor of the bladder
Mucus-secreting
Glandular, colloid, or signet-ring patterns
Localized
Muscle invasion
5 year – survival = 40%

15. Nontransitional Cell CA: Squamous cell carcinoma
60% of all bladder cancers in Egypt, parts of Africa, and the Middle East
5% and 10% of all bladder cancers in US
History of chronic infection, vesical calculi, or chronic catheter use
Bilharzial infection owing to Schistosoma haematobium

16. Nontransitional Cell CA: Squamous cell carcinoma
Nodular and invasive
Poorly differentiated neoplasms
Polygonal cells with characteristic intercellular bridges
(+) Keratinizing epithelium (small amounts)

17. Nontransitional Cell CA: Undifferentiated bladder carcinomas
Rare, <2%
No mature epithelial elements
Very undifferentiated tumors
Neuroendocrine features
Small cell carcinomas
aggressive
present with metastases

18. Nontransitional Cell CA: Mixed Carcinomas
4–6% of all bladder cancers
Composed of a combination of transitional, glandular, squamous, or undifferentiated patterns
Most common: transitional and squamous cell
Large and infiltrating at the time of diagnosis

19. Rare Epithelial Carcinomas
Villous adenomas
Carcinoid tumors
Carcinosarcomas
Melanomas

20. Rare Nonepithelial Cancers
Pheochromocytomas
Lymphomas
Choriocarcinomas
Various mesenchymal tumors
Hemangioma
Osteogenic sarcoma
Myosarcoma

21. Tumors Metastatic to the Bladder
Melanoma
Lymphoma
Stomach, breast, kidney, lung and liver

22. Clinical Findings: Symptoms
Hematuria (85–90%)
Accompanied by symptoms of vesical irritability
Frequency
Urgency
Dysuria
Irritative voiding symptoms seem to be more common in patients with diffuse CIS
Advanced disease:
bone pain from bone metastases
flank pain from retroperitoneal metastases or ureteral obstruction.

23. Clinical Findings: Signs
Bimanual examination under anesthesia
bladder wall thickening or a palpable mass
Bladder is not mobile = fixation of tumor to adjacent structures by direct invasion
Signs of metastatic disease
Hepatomegaly
Supraclavicular lymphadenopathy
Occasionally, lymphedema from occlusive pelvic lymphadenopathy
Rarely, unusual sites such as the skin presenting as painful nodules with ulceration

24. Laboratory Findings Routine Laboratory Results Hematuria
Pyuria (infection)
Azotemia
Anemia

25. Laboratory Findings Urinary Cytology Exfoliated cells
low sensitivity for low-grade superficial tumors
inter-observer variability
Exfoliated cells
Detecting cancer in symptomatic patients
Assess response to treatment
Detection rates are high for tumors of high grade and stage as well as CIS

26. Laboratory Findings BTA test (Bard Urological,Covington, GA)
BTA stat test (Bard Diagnostic Sciences,Inc, Redmond, WA)
BTA TRAK assay (Bard Diagnostic Sciences, Inc)
Determination of urinary nuclear matrix protein (NMP22; Matritech Inc, Newton,MA)
Immunocyt (Diagnocure, Montreal, Canada)
UroVysion (Abbott Labs, Chicago, IL)

27. Laboratory Findings
Detect cancer specific proteins in urine (BTA/NMP22)
Augment cytology by identifying cell surface or cytogenetic markers in the nucleus

28. Imaging Cystoscopy and biopsy Evaluation of the upper urinary tract
(+) infiltrating bladder tumors → assess the depth of muscle wall infiltration and the presence of regional or distant metastases

29. IV Urography vs. CT Urography
IV and CT urography - one of the most common imaging tests for the evaluation of hematuria
CT urography
more accurate
evaluation of the entire abdominal cavity, renal parenchyma, and ureters in patients with hematuria

30. IV urogram - represents a papillary bladder cancer.

31. Bladder Tumors
Pedunculated, radiolucent filling defects projecting into the lumen
Nonpapillary, infiltrating tumors → fixation or flattening of the bladder wall
Ureteral obstruction →Hydronephrosis
usually associated with deeply infiltrating lesions and poor outcome after treatment

32. Cystoscopy

33. Cystoscopy Superficial, low-grade tumors Higher grade lesions CIS
single or multiple papillary lesions
Higher grade lesions
larger and sessile
CIS
flat areas of erythema and mucosal irregularity

34. Fluorescent Cystoscopy
Enhance the ability to detect lesions by as much as 20%
Hematoporphyrin derivatives that accumulate preferentially in cancer cells are instilled into the bladder
Fluorescence incited using a blue light
Cancer cells with accumulated porphyrin such as 5-aminolevulenic acid or hexaminolevulinate (HAL) are detected as glowing red under the fluorescent light

35. Transurethral Resection (TUR)

36. Transurethral Resection (TUR)
Palpable mass and mobility of the bladder are noted and any degree of fixation to contiguous structures
Cystoscopy is repeated with one or more lenses (30° and 70°)
Resectoscope is then placed into the bladder
Visible tumors are removed by electrocautery.