Ch 92. Tumours of the Bladder – Flashcards
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List the benign tumours of the bladder. (7)
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Cystitis cystica Cystitis glanduralis Leiomyoma Leukoplakia Epithelial metaplasia Nephrogenic adenoma Inverted papilloma
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What kinds of transformed urothelium are seen epithelial metaplasia? Appearance? Association?
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Squamous and Glandular Squamous = knobby, white, flaky material on trigone Glandular = clumps of raised red areas *Females*, infection, trauma or surgery
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Leukoplakia appearance? Malignant potential?
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Squamous metaplasia with keratin deposition = white flaky substance Benign in bladder.
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What is characteristic of inverted papilloma ? Association and location? Treatment?
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Normal urothelial cells invaginating into lamina propria but not into muscularis propria Chronic inflammation, BOO Located usually on trigone TURBT. <1% incidence of recurrence
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What do you pathologically see in nephrogenic adenomas and etiology? Usual presenting sign? Treatment?
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Tubules similar to renal tubules Metaplasia caused by chronic irritation Gross hematuria. Vascular tumours. TURBT. Eliminate source of irritation.
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What is cystitis cystica/glandularis pathologically? Association? Presenting features ? Treatment ?
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Cystic nests lined by cuboidal and columnar cells, proliferation of von Brunn nests Inflammation, BOO Irritative voiding symptoms / hematuria TURBT, elimination of obstruction/inflammation
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What can cystitis glandularis potentially transform into?
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Adenocarcinoma. Case reports.
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What's the most common type of non epithelial benign tumour of the bladder? Appearance? How can diagnosis be confirmed?
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Leiomyoma Smooth indentations of bladder with normal urothelium overlying tumour MRI
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Who is at highest risk of bladder cancer? Reduced risk?
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Old, white males African-american female ; african american male/white female
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What is the median age of bladder cancer diagnosis?
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70 years
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Lifetime risk of developing urothelial cancer for white male?
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3.7%
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What histological types of urothelial cancer is most common in North America and Europe Africa and Egypt?
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Urothelial carcinoma SCC
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What genes may be associated with bladder cancer and why?
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Null GSTM1 and slow NAT-2 Detoxify nitrosamines. Lead to high levels of 3-aminobiphenyl
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What are risk factors for urothelial carcinoma?
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*Smoking* Caffeine Occupational exposure (aromatic amines) Family history (no clear mendelian inheritance pattern) Phenacetin Chronic inflammation/infection Radiation Cyclophosphamide
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How is the risk of BCa related to the degree of smoking? Second hand smoke? Smoking cessation?
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Linear relationship between intensity and duration Low, not statistically different from that for nonsmokers Decreases the risk in a linear fashion
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What nutritional behaviour is associated with a reduced risk BCa?
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Fruits and vegetables, mediterranean diet
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What is the primary mutagenic metabolite from cyclophosphamide?
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Phosphoramide mustard
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What are the different histologic proportions?
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90% urothelial 5% SCC 2-5% Adenocarcinoma / other variants
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What are precursor lesions to BCa?
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Hyperplasia Atypia Dysplasia
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What is the significance of dysplasia?
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Urothelial instability Can be a marker of recurrence and progression in those with know Ca
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What does PUNLMP stand for? Natural history?
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Papillary urothelial neoplasia of low malignant potential Recur but rarely progress/invade
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What is CIS characterized as ? Genetic abnormalities associated with CIS/high-grade disease? Cystoscopic appearance?
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Non papillary, flat, high-grade tumours Alteration of RB, TP53 and PTEN genes Reddish with heaped-up mucosa
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What if CIS is associated with invasive tumour?
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Worse prognosis. Reduced OS.
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How do you clinically distinguish between T3a and T3b disease?
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T3a = palpable mass at time of TURBT that can no longed be appreciated after resection T3b = palpable mass before and after TURBT
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What's the significance of prostatic stromal invasion?
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Worse prognosis Extension to prostatic urethra without stromal invasion does not carry adverse prognosis
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What falls under the classification of NMIBC?
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Tis Ta low grade Ta high grade PUNLMP T1
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What percentage of low grade tumours recur and invade? High grade?
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60% recur, 10% progress to invasion 80% recur, ~50% progress to invasion
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What's the earliest mutation seen in low risk NMIBC?
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Deletion of Xm 9, FGFR-3 gene mutation HRAS and PI3K
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What are the theories for the recurrent nature of BCa?
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Field change effect Tumour implantation
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What is pagetoid spread? Association?
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Cancer cells growing underneath a layer of normal-appearing surface urothelium CIS and following multiple doses of intravesical therapies Supports need for random bladder/prostatic biopsies in pts with +cytology and negative cystos
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What are predictors for poor prognosis?
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*Grade* *Stage* +LVI Genetic instability - molecular markers
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What are the traditional pathways of urothelial cancer formation?
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Normal urothelium --> papilloma, PUNLMP, hyperplasia, low grade Ca Normal urothelium --> dysplasia --> CIS Normal urothelium --> hyperplasia/dysplasia --> high grade NMIBC
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What is the genetic hallmark of invasive disease?
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Low to absent FGFR-3 High TP53 mutation Genetic instability
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What gene mutations are associated with high grade cancer?
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TP53 mutation RB PTEN Loss of Xm17
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What's the sensitivity and specificity of urine cytology?
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Sens: 40-60% Spec: 94-100%
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What percentage of pts presenting with a painless gross hematuria will have a urological malignancy? What % of patients with a newly diagnosed bladder tumour will have gross hematuria as their presenting symptom?
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20% 85%
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What role do urinary markers play in the detection of BCa?
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Little role. The current sensitivity is not good enough to replace cystoscopy *Remains the gold standard*
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What current evidence exists for the prevention of BCa?
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Quitting or never smoking is best BCG with high dose vitamins may prevent recurrence
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List some of the histologic variants of urothelial cancer (5) Which responds to chemotherapy?
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Micro papillary Nested variant Clear cell variant *Glandular or adenocarcinoma* Plasmacytoid
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What is recommended treatment for micro papillary?
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Urgent surgical resection *Neoadjuvant chemotherapy is ineffective and will delay time to treatment*
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What is significant about the clear cell variant?
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70% of urothelial carcinomas will have foci of clear cells *No worse prognosis*
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How should glandular or adenocarcinoma differentiated variants be treated?
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Neoadjuvant chemotherapy with radical cystectomy
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What is the growth pattern of plasmacytoid and why is this a problem? Treatment?
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Non papillary, sessile Delay of gross hematuria presentation Usually present at advanced stage Surgery. Poor response to chemotherapy
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What can nested variant be confused with and why is this a problem?
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Benign von Brunn nests, cystitis cystica and inverted papilloma Very aggressive variant
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What are some nonurothelial malignancies? (4)
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Sarcomas Small cell Signet Ring Cell SCC
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What patients are at risk of developing SCC?
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Patients infected with S. haematobium SCI pts - those with chronic catheters/inflammation
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How should small cell carcinoma be treated?
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Considered and treated as though metastatic disease is present even if not Chemosensitive Chemoradiation +/- surgery
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How does signet cell cancer typically present?
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Typically understaged Usually locally advanced and metastatic at presentation
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What is primary prostatic urethral cancer strongly associated with? Incidence of secondary prostatic urethral cancer? Risk factors for secondary prostatic urethral cancer?
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Urothelial cancer (CIS) 3%, increases with time *CIS and history of intravesical chemotherapy*
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How should noninvasive prostatic urethral disease be treated?
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TURP + BCG
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How is noninvasive prostatic urethral cancer at final pathology staged?
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No longer T4a Only T4a when there's stromal invasion (direct or indirect)
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What % of women and men will have squamous metaplasia of the bladder?
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40% women 5% men
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Where is the incidence of bladder cancer highest?
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In developed countries
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Where is the mortality rate from bladder cancer highest in?
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Egypt
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What is the increased risk of developing bladder cancer if you have a first degree relative with bladder cancer?
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2-fold increased
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What was one of the first and most common chemical agents implicated in the formation of bladder cancer?
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beta-naphthylamine
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What food compound is associated with a reduced risk of bladder Ca?
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Citrus
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What is the increased risk with developing bladder cancer with radiation exposure (and what threshold of radiation)?
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2-fold increased if ;50 mSv Risk is not age dependent, latency period of 10-15 years
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What is the risk of malignancy in a patient with recurrent gross hematuria who has had a previous negative workup?
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0 at 6 years
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What % of bladder cancer is related to smoking in males?
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30-50%
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What % of patients will have prostatic urethral disease when they undergo radical cystectomy?
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40%
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What is this image called and associated with?
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Pseudodiverticulosis Associated with bladder cancer
