Upload
graham-coleman
View
37
Download
2
Tags:
Embed Size (px)
DESCRIPTION
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 - PowerPoint PPT Presentation
Citation preview
Urothelial CA: Cancers of the Bladder, Ureter, and Renal
PelvisGarzon, 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 – 75% localized in the bladder– 25% spread to regional lymph nodes and distant
sites
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
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
Bladder CA: Staging
Tis - In-situ disease Ta - Epithelium onlyT1 - Lamina propria invasion T2 - Superficial muscle invasion T3a - Deep muscle invasion T3b - Perivesical fat invasion T4 - Prostate or contiguous muscleT4a - Invasion of prostate, uterus, vaginalT4b - Invasion of pelvic wall, abdominal wall
Bladder CA: StagingNodal (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 involvedMetastases (M) stage• Mx – cannot be defined• M0 – no distant metastases• M1 – distant metastses present
Bladder CA: Histopathology
• 98% of all bladder cancers are epithelial malignancies, with most being transitional cell carcinomas (TCCs)
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
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
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
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
frond-like papillary projections
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%
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
Nontransitional Cell CA:Squamous cell carcinoma
• Nodular and invasive• Poorly differentiated neoplasms • Polygonal cells with characteristic intercellular
bridges• (+) Keratinizing epithelium (small amounts)
Nontransitional Cell CA:Undifferentiated bladder carcinomas• Rare, <2%• No mature epithelial elements• Very undifferentiated tumors• Neuroendocrine features• Small cell carcinomas – aggressive – present with metastases
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
Rare Epithelial Carcinomas
• Villous adenomas• Carcinoid tumors• Carcinosarcomas• Melanomas
Rare Nonepithelial Cancers
• Pheochromocytomas• Lymphomas• Choriocarcinomas• Various mesenchymal tumors– Hemangioma– Osteogenic sarcoma– Myosarcoma
Tumors Metastatic to the Bladder
• Melanoma• Lymphoma• Stomach, breast, kidney, lung and liver
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.
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
Laboratory Findings
Routine Laboratory Results• Hematuria• Pyuria (infection)• Azotemia• Anemia
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
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)
Laboratory Findings
• Detect cancer specific proteins in urine (BTA/NMP22)
• Augment cytology by identifying cell surface or cytogenetic markers in the nucleus
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
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
• IV urogram - represents a papillary bladder cancer.
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
Cystoscopy
• Superficial, low-grade tumors– single or multiple papillary lesions
• Higher grade lesions – larger and sessile
• CIS – flat areas of erythema and mucosal irregularity
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
Transurethral Resection (TUR)
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.