BLADDER TUMORS

BY KHALED AL-KOHLANY- MD ASSISTANT PROF. MEDICAL COLLEGE SANAA UNIVERSITY

HEADLINES
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Introduction Classification Bladder cancer -Epidemiology Bladder cancer -Etiology Bladder cancer -Pathogenesis Bladder cancer -pathology Bladder cancer -Staging and grading Bladder cancer -Diagnosis Bladder cancer -Treatment Nonurothelial & nonepithelial bladder tumors

INTRODUCTION
Urinary bladder (UB)hollow muscular organreservoir for urine Capacity- 350-500 ml Empty UB- pelvic organ Full UB- pelviabdominal Parts: apex-bladder neckfour surfaces (superior-2 inferolateral basal)

INTRODUCTION
Interior of UB: trigone-ureteric orificesinterureteric ridgebladder walls(posterior,late ral, anterior)

INTRODUCTION
BLADDER HISTOLOGY Normal mucosa - urothelium-transitional cells-3-7 layers on basement membrane - Lamina propria- fibro-elastic connective tissue - Muscularis mucosa-scattered smooth muscle fibers Detrusor muscle meshwork of smooth muscle fibers Adventia and perivesical fat

CLASSIFICATION -WHO
Epithelial tumors
-transitional cell papilloma -transitional cell carcinoma -adenocarcinoma -squamous cell papilloma -squamous cell carcinoma -undifferentiated carcinoma

Nonepithelial tumors
-benign- fibroma, lipoma, angioma -malignant- rhabdomyosarcoma - angiomyosarcoma -pheochromocytoma -malignant melanoma -metastatic tumors -leiomyosarcoma, - liposarcoma -lymphomas -Carcinosarcoma

Epithelial abnormalities
-papillary (polypoid )cystitis -cystitis cystica -squamous metaplasia -Brunns nests -glandular metaplasia -nephrogenic adenoma -malakoplakia -endometriosis -Cysts

Tumorlike lesions
-follicular cystitis -amyloidosis -hamartomas

BLADDER CANCER EPIDEMIOLOGY

Incidence-2005/ 63210 new case in USA In USA, the 4th cancer in males (prostatelung-colon-bladder) The second most prevalent malignancy after prostate cancer Age: any age but mainly middle age and elderly Sex: male : female 3:1(unexplained) Race: white : black 2:1 Geography: Egypt > USA > Japan

BLADDER CANCER ETIOLOGY

1. 2. 3. 4. 5. 6. 7. Unknown definitely Risk factors Smoking- 4times higher risk Occupational risk-aromatic amines (painters, leather workers, rubber workers, chemical workers,gas &tar workers, printing) Drugs- cyclophosphamide, analgesics Infection- bilharziasis, viruses, chr. Cystitis Chronic trauma- indwelling catheters, stones Pelvic irradiation- 2-4 times higher risk Hereditary- unproved

BLADDER CANCER PATHOGENESIS

Normal cell cycle: unidirectional process that allows an ordered replication of each cell's genome (DNA) followed by division into two daughter cells. Apoptosis (programmed cell death) : occurred when a normally functioning cell is unable to induce cell cycle arrest or to repair damaged DNA Oncogens: are the mutated form of normal genes often associated with cell proliferation. They allow the cell to escape from the normal growth (P21ras; Cmyc oncogens) Tumor suppressor genes: regulate cell growth, DNA repair and apoptosis. Deletion or inactivation of these genes may cause uncontrolled cell growth (P53, retinoblastoma suppressor genes) Carcinogen: substance (chemical, physical, viral etc) that can affect normal gene function resulting in deviated cellular growth

1. 2. 3.

4.
5.

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Atypical hyperplasia-No. of cell layers with nuclear abnormalities Cystitis glandularis: submucosal nests of columnar cells(TC undergone glandular metaplasia) suurrounding liquefied center. adenocarcinoma Dysplasia:nuclear and arrangement changes with no increase in No. of cell layers (low-moderate-high grade) Inverted papilloma: papillary fronds projecting down words into the wall Nephrogenic adenoma: metplastic changes into primitive renal tubules as response to chronic trauma, infection or radiation Vesical Leukoplakia: Keratinized squamous metplasia due to chronic infection, stone disease , BilharziasisSCC Pseudosarcoma:benign lesion of spindle cells in response to surgical trauma or infection

BLADDER CANCER PRENEOPLASTIC LESIONS

 1. 2. 3. 4. 5. 1. 2. 3. 1. 2. 3.

According to the hystologic type Transitional cell carcinoma-TCC Squamous cell carcinoma- SCC Adenocarcinoma Mixed carcinoma Undifferentiated carcinoma According to the degree of invasion Carcinoma in situ- CIS Superficial bladder tumors Invasive bladder tumors According to growth pattern Papillary (villous tumor) Solid (nodular, fungating, ulcerative) Fibrillary (verrocus carcinoma-SCC)

BLADDER CANCER TYPES

BLADDER CANCER STAGING

Wallace clinical staging T1-mass movable with and within the bladder (bladder mouse) T2- mass movable with but not within the bladder with smooth surface T3- mass movable with the bladder with rough surface T4- mass fixed to the pelvic wall

BLADDER CANCER STAGING

TNM-staging system-2009 Ta- non invasive papillary carcinoma Tis- carcinoma in situ- flat tumor T1-invades lamina propria T2- invades muscle layer - T2a- supperficial muscle layer(inner half) - T2b- deep muscle layer (outer half) T3-invades preivesical fat - T3a- microscopically - T3b- macroscopically T4-invads surrounding organs and structures - T4a- prostate, uterus, vagina - T4b- pelvic wall , abdominal wall N1-single regional L.node (in the true pelvis) N2-multiple regional L.nodes (in the true pelvis) N3-metastasis in a common iliac L.node M1- distant metastasis

BLADDER CANCER GRADING

WHO-system-1973-basd on degree of cellular anaplasia - Grade I: well differentiated - Grade II: moderately differentiated - Grade III: poorly differentiated
New WHO grading system- 2004 - papillary urothelial neoplasm of low malignant potential - low grade papillary urothelial carcinoma - high grade papillary urothelial carcinoma

BLADDER CANCER DIAGNOSIS

Presentation - haematuria- irritative LUTS- necroturia-painconstitutional symptoms Examination - DRE- PVE-abdominal mass-L.L lymphedema Laboratory Investigations - urine- blood tests- urine cytology- DNA flowcytometry- tumor markers Radiologic investigations - US-IVU-CT-MRI-CXR-Chest CT- Bone scan-PETlymphangiography Cystoscopy and biopsy - EUA- cystourethroscopy- cold biopsy- hot biopsy

BLADDER CANCER PRESENTATION

1. Hematuria- 85% -microscopic or gross, painless,intermittent,clot retention 2. Irritative LUTS: 35% -urgency, frequency, dysuria- more with CIS and invasive disease 3. Necroturia: more with SCC may cause retention 4. Pain: S.pubic, perineal, penile, loin, back pain, sciatica 5. Constitutional symptoms: malaise, fatigue, loss of weight, loss of apetite, pallor

BLADDER CANCER EXAMINATION

DRE, PVE- mass or induration S.pubic mass- anterior tumor, full bladder Abdominal mass- hydronephrotic kidneys, liver or abdominal metastasis Supraclavicular L. Node Lower limb edema: venous or lymphatic in advanced cases

BLADDER CANCER LABORATORY INVESTIGATIONS

Urine analysis

CBC, creatinin, alk. Phosphatase, calcium

Urine cytology: voided urine or bladder wash outfixation and staining of the exfoliated cells. More for CIS, tumor in diverticulum and follow up.sensitivity-70% Tumor markers: substances that may be detected in urine, blood or tumor tissue whose presence or absence is related to preogression or recurrence of the tumors - P53 protein; retinoblastoma protein; growth factors, oncogens; antigens etc

BLADDER CANCER RADIOLOGICAL INVESTIGATIONS

Ultrasound: screening, diagnosis, follow up IVU: in superficial tumors for upper tract evaluation, ureteral obstruction, filling defects CT abdomen and pelvis: radiological staging (TNM) MRI: same role as CT. if high creatinin, more detailes, better in L.node detection CXR and chest CT: for exclusion of chest metastasis Bone scan: for detection of bony metastasis in patients with bony symptoms or with high Alk. Phosphatase Positrone emession tomography PET: valuable in detection of metastases or local recurrence after cystectomy but not primary tumor Lymphangiography: for detection of L.node metastasis better than CT and MRI. High morbidity. Not in use

BLADDER CANCER CYSTOSCOPY AND BIOPSY

Examination under anesthesia(EUA): asses the operability of the tumor (Wallace staging system) Cystourethroscopy: - anterior urethra, posterior urethra, bladder - tumor: site-size-shape-number-relation to BN - remaining mucosa Biopsy: - cold biopsy (punch): tissue diagnosis - hot biopsy (TUR): tissue diagnosis & staging - random biopsies: asses the entire bladder mucosa

BLADDER CANCER TREATMENT

Carcinoma in situ: flat intraepithelial neoplasia = high
1. 2. 3. 1. 2.

grade dysplasia Types: primary-secondary-concomitant Histology: TCC- SCC- adenocarcinoma Treatment: - primary focal CIS: fulguration, TUR+ intravesial immunochemotherapy Phototherapy Laser - primary diffuse CIS TUR+ intravesical imunochemotherapy Cystourethrectomy and high diversion of the ureters - concomitant CIS: treatment of the main tumor

BLADDER CANCER TREATMENT

Superficial bladder tumors- Ta, T1 and CIS
Depends on size, stage , grade,1ry or recurrent Primary ttt is TURBT followed by intravesical immunotherapy, chemotherapy or both Multicentric, large, recurrent, high grade tumors: radical cystectomy and diversion Intravesical chemotherapy: mitomycin, doxirubicin, Epirubicin Intravesical immunotherapy: BCG Follow up: cystoscopy and cytology - every 3months for 2 years - every 6months for 2 years - anually

BLADDER CANCER TREATMENT- INVASIVE TUMORS

Organ confined bladder cancer (T2a; T2b; T3) Radical cystectomy Partial cystectomy Aggressive TURBT Radiotherapy (TCC) Systemic chemotherapy (TCC) Combined treatment Locally advanced bladder cancer (T4a) Palliative cystectomy+ chemo-radiotherapy Chemo-radiotherapy

BLADDER CANCER TREATMENT-INVASIVE TUMORS

Locally advanced & Metastatic bladder cancer (controversial) No intervention-supportive treatment Palliative radiotherapy Palliative chemotherapy Embolization or ligation of internal iliac arteries (if hematuria) High diversion if renal impairment

NONEPITHELIAL BLADDER TUMORS

Represent 1-5% of all bladder tumors Neurofibroma: benign tumor of the nerve sheath resulting from overgrowth of Schwann's cells Pheochromocytoma: arise from paraganglionic cells within the bladder wall, usually in the region of the trigone, hormonally active and malignant in 10 % Primary Lymphoma: arises in the submucosal lymphoid follicles. Treated as other lymphomas Angiosarcoma: extremely rare tumors that arise within the bladder wall. May develop from angioma. Hemangioma:quite small rare lesions usually diagnosed because they cause macroscopic hematuria. can be managed by complete endoscopic resection. Leiomyosarcoma: the most common malignant mesenchymal tumor that arises in the bladder of adults

NONUROTHELIAL BLADDER TUMORS

Small Cell Carcinoma: derived from neuroendocrine stem cells or dendritic cells. may be mixed with elements of TCC. Aggressive T Carcinosarcomas: highly malignant tumors containing malignant sarcoma (chondro or osteo) and epithelial elements (TCC,SCC, adeno) Metastatic carcinoma: The most common primaries are prostate, ovaries, uterus, colon, lung, breast, kidney and stomach

RHABDOMYOSARCOMA (RMS)
Malignant tumor arising from the embryonal mesenchyme giving rise to striated skeletal muscles The most common soft tissue sarcoma of childhood Genitourinary RMS-15-20% of all RMS Common genitourinary sites: bladder; prostate; paratestes Uncommon sites: vagina and uterus Types: embryonal; alveolar and undifferentiated Two peaks: 2-6 Y 15-19 Y Presentation: irritative and obstructive LUTS; hematuria, urine retention, bilateral renal obstruction with uremia Treatment: chemotherapy +/- radiotherapy according to the response If failure : surgical intervention