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Urothelial CA: Cancers of the Bladder, Ureter, and Renal Pelvis

Urothelial CA: Cancers of the Bladder, Ureter, and Renal Pelvis. Garzon , Gatchalian , Gaw , Geraldoy , Geronimo, Geronimo, Geronimo, Go August 18, 2009. Bladder Carcinoma. Bladder Carcinoma. Second most common CA of genitourinary tract 7% men; 2% women Ave. age at dx is 65 years old

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Urothelial CA: Cancers of the Bladder, Ureter, and Renal Pelvis

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  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 • 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 • Supraclavicularlymphadenopathy • 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 • 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 • 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.

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