Urinary Bladder Flashcards
Acute Cystitis
Coliforms (75-90%): E Coli, Proteus, Klebsiella, Enterobacter
Staphylococcus saprophyticus (10-15%)
Clamydia, mycoplasma
immunocompromised: mycobacteria (TB), fungi (Candida), viruses (adenovirus), protozoa (Schistosoma)-
Radiation
• Nonspecific acute inflammation
• Hyperemia of mucosa, neutrophil infiltrate sometimes with exudate
Triad: frequency, suprapubic pain, dysuria
Women
Antecedent to pyelonephritis
Predisposing factors: bladder calculi, urinary obstruction/structural abnormalities, DM, instrumentation, immune deficiency
Hemorrhagic cystitis
Adenovirus infection
Cytotoxic anti-tumor drugs (cyclophosphamide)
• Focal/diffuse hemorrhagic areas
Triad: frequency, suprapubic pain, dysuria
Chronic cystitis
Persistence of acute infection
• Thickened bladder wall, bladder stones
• Mononuclear inflammatory infiltrates
Triad: frequency, suprapubic pain, dysuria
Interstitial cystitis (Hunner ulcer)
Idiopathic
Autoimmune
• Inflammation and fibrosis of bladder walls
• Fissues, punctate hemorrhages (glomerulations) in mucosa after luminal distention
• Chronic mucosal ulcers – increased mast cells
• Late: transmural fibrosis, contracted bladder
Intermittent severe suprapubic pain, urinary frequency, urgency, hematuria, dysuria without bacterial infection
Women 30-40
Malacoplakia
Defective phagosome function Chronic infection (E. coli, Proteus)
• 3-4 cm soft, yellow, raised mucosal plaques, may involve entire bladder
• Bladder wall thickening w/ inflammatory exudate
• Granulomas with foamy macrophages, multinuclear giant cells, interspersed lymphocytes
• Michaelis-Gutmann bodies – laminated mineralized concentrations in macrophages
F»M, middle aged, immunocompromised transplant its
Can involve other GU tract organs
Polypoid cystitis
Indwelling catheters
• Inflammation from irritation of mucosa
• Extensive submucosal edema →broad bulbous polypoid projections
Mis-dx as papillary carcinoma
Cystitis cystica (CC) and cystitis glandularis (CG)
Chronic irritation – infection, calculi, outlet obstruction, tumor
• urothelial metaplasia
• Nests of von Brunn – urothelial bud grow into lamina propria
• CC: buds differentiation to cystic deposits – flat urothelium
• CG: buds differentiation into intestinal columnar (cuboidal) mucin-secreting glands (goblet cells)
Frequency, dysuria, urgency, hematuria
Any age, children with UTI, Males
Squamous metaplasia
Injury
• Urothelium → nonkeratinized squamous epithelium (durable lining)
Nephrogenic adenoma
Injured urothelium
• Implantation of shed renal tubular cells at sites of injury → cuboidal epithlium replacement
• Papillary growth pattern
• Tubular proliferation can infiltrate lamina propria and superficial detrusor m.
Mimic malignant process
Follicular cystitis
Chronic infection
• Aggregation of lymphocytes in lymphoid follicles in mucosa and underlying wall
Eosinophilic cystitis
Systemic allergic reaction, autoimmune disorder, parasitic infestation, radiation or chemo
• Infiltration of submucosal eosinophis – nonspecific subacute inflammation
Urothelial tumors - pathogenesis
Rarely familial
Aneuploidy of Chr 3, 7, 17; 9p deletions
Noninvasive Low-grade superficial papillary: FGFR3, RAS, Chr 9 deletions
High grade flat or papillary: TP53, Chr 9 loss
- FGFR3 gain of function: activates FGFR3 receptor tyrosine kinase
- TP53 and RB loss of fxn: high grade muscle invasive
- HRAS activating mutation: low-grade noninvasive
- Chr 9: monosomy or 9p/9q deletions
- CDKN2A: 9p20 deletion – encodes CDK inhibitor p16/INK4a and ARF
- PTCH: 9q deletion- negative regulator of Hedgehog, TSC1 negative regulator of mTOR signaling
Precursor lesions to invasive: Noninvasive papillary tumors**, flat noninvasive urothelial carcinoma
Urothelial tumors pathology
- Noninvasive papillary tumors: arise from papillary urothelial hyperplasia; red, elevated excrescences
- Most arise from lateral or posterior walls at base
- Papillomas: single, small, delicate, superficial attachment to mucosa with stalk – exophytic papillomas; papillae center core- loose fibrovascular tissue covered by epithelium; inverted papillomas – benign, interanastomosing cords into lamina propria
- Papillary urothelial of low malignant potential: thicker urothelium, larger than papillomas, recurrent
- Low-grade papillary urothelial carcinomas: orderly architecture/cytology, cells evenly spaced, cohesive; mild nuclear atypia: scattered hyperchromatic nuclei, infreq. Mitotic figures toward base, slight size/shape variations; may invade; low threat to life
- High-grade papillary urothelial cancers: dyscohesive cells, large hyperchromatic nuclei, highly anaplastic, mitotic figures (atypical), architectural disarray, loss of polarity; high muscular layer invasion; significant met potential
- Flat urothelial carcinoma (CIS): cytologically malignant cells within flat urothelium (scattered (pagetoid spread) or full thickness); lack of cohesiveness – shed into urine denudes BM; mucosal reddening, granularity, thickening without intraluminal mass; may involve most of bladder surface, extend to ureters and urethra; 50-75% → invasive cancer
- Invasive urothelial cancer: invade muscularis mucoasae; high grade
- Mixed urothelial carcinoma with areas of squamous carcinoma: invasive, fungating tumors or infiltrative and ulcerative; well differentiated producing keratin to anaplastic tumors
- Adenocarcinomas: urachal reminants – extensive intestinal metaplasia – worse prognosis
- Small cell carcinoma – urothelial, squamous, adenocarcinoma association
Urothelial tumors clinical features
Painless hematuria
Frequency, urgency, dysuria
Papillomas – younger; hematuria
Flat: discomfort
Males, Whites, developed nations, urban; 50-80 yo
Invasion of lamina propria worsens prognosis
Much worse prognosis with invasion of muscularis propria (Detrusor m.) – 30% mortality rate for 5 yr
Ta, Tis, T1 – low stage; 90% survival
T2-T4: muscle invasion; 50% survival
Grade 0/I: normal, thick
Grade II: atypical hyperplasia – low grade
Grade III: CIS, invasive cancer – high grade
Urothelial tumors -other
Any site from renal pelvis to distal urethra
Risk factors: cigarette smoking**; aryl amine exposure (2-naphthylamine) – CA 15-40 y after first exposure; schistosoma haematobium (70% squamous cell carcinoma, worse prognosis); long-term use of analgesics; heavy, long term cyclophosphamide exposure; irradiation (years after)
BCG treatment – bacillus Calmette-Guerin
