Bladder

Trigone develops from dilation, fusion and incorporation of caudal mesonephric ducts into urogenital sinus, forming a triangular area that is site of future ureters; mesonephric ducts are gradually absorbed and replaced by endodermal epithelium of urogenital sinus; thus, there are no mixed mesodermal tumors of the bladder

Posterior walls, dome and part of lateral walls arise from mesenchyme surrounding urogenital sinus

Anterior wall and part of lateral walls develop with closure of infraumbilical portion of abdominal wall

Note: neither urachus or allantois are involved in formation of bladder

Allantois: rudimentary structure lined by endoderm that is connected to urachus

Urachus: formed during descent of abdominal wall, connects umbilicus to apex (dome) of bladder, torn apart as embryo elongates but remnants persist in anterior abdominal wall and may persist in bladder wall

Drawings: development of bladder #1; #2

Normal anatomy

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Epithelial lined muscular viscus that can distend and hold up to 400-500 ml of urine without a change in intraluminal pressure

Can also initiate and sustain a contraction until empty

Has superior surface (apex, dome), posterior surface (base) and inferolateral surfaces

Trigone is area between ureteral and urethral orifices, continuous with bladder neck

Bladder located in part within the abdomen in children, enters pelvis major at age 6, found entirely within pelvis minor after puberty

Adult bladder rests on rectum and seminal vesicles (males) or cervix and vagina (females); thus cystectomy for tumor may be combined with removal of prostate and seminal vesicles (males) or hysterectomy and partial vaginectomy (females)

Bladder neck occasionally contains prostate ducts (males)

Lymphatic drainage: internal and external iliac nodes; bladder neck drains to sacral or common iliac nodes

Blood supply: superior and inferior vesical arteries, derived from internal iliac artery; drained by vesical venous plexus, which empties into internal iliac veins

Nerve supply: sympathetic from T11-L2 nerves, play no role in micturition; parasympathetic from S2-4, travel to bladder via pelvic nerve and inferior hypogastric plexus, cause contraction of muscularis propria fibers, which puts traction on bladder neck, which opens internal sphincter

Gross: hollow viscus resembling inverted pyramid when empty, sphere when distended

Gross drawings: position of bladder in male pelvis #1; #2; bladder and seminal vesicles; position of bladder in female pelvis; interior of bladder

Normal histology

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Bladder layers are mucosa (urothelium, lamina propria, discontinuous muscularis mucosa), muscularis propria, adventitia, serosa/peritoneum at dome

No submucosa is present

Urothelium: formerly called transitional epithelium since intermediate between nonkeratinizing squamous and pseudostratified columnar epithelium; 5-7 cell layers thick in contracted bladder, 2-3 cells thick in distended bladder; lines renal pelvis, ureters, bladder, most of urethra but not terminal urethra

Superficial urothelium is single layer of umbrella cells, which are large and elliptical with abundant eosinophilic cytoplasm and often binucleation or prominent nucleoli; one umbrella cell covers several underlying cells; inconspicuous in distended bladder; contains trilaminar (asymmetric) unit membrane composed of two dense layers of unequal thickness and a central lucent layer, and apical plaques containing uroplakins

Intermediate urothelial cells are cuboidal to low columnar cells with well defined borders, amphophilic cytoplasm rich in glycogen; nuclei are regularly arranged, ovoid with long axis at right angles to surface; chromatin is finely granular; small nucleoli; usually no mitotic figures

Basal urothelial cells are more cylindrical, can be flat when bladder wall is stretched; some have longitudinal nuclear grooves; lie on continuous basal lamina

Lamina propria: contains loose to dense connective tissue, thin-walled blood vessels that may be close to epithelium, lymphatics, variable adipose tissue; also discontinuous muscular mucosa (wisps of smooth muscle, AJSP 1987;11:668), which should not be confused with muscularis propria when assessing depth of invasion

Only 5% of bladders have well developed muscularis mucosa

Muscularis propria: consists of inner longitudinal, circular and outer longitudinal layers of thick muscle bundles (layers are distinct only near bladder neck), may also contain adipose tissue between muscle fascicles, paraganglia; muscularis propria may be greatly thickened if obstruction to urine flow develops

von Brunn’s nests (Brunn’s nests): nests of urothelium in lamina propria; present in 85%+ of bladders at autopsy; nests have regular spacing, extend to same horizontal level at base of proliferation; florid cases may mimic nested variant of urothelial carcinoma, but there is no muscle invasion (AJSP 2003;27:1243)

Micro drawings: layers of bladder (note: no submucosa is present, despite the drawing)

Micro images: bladder layers #1; #2; normal urothelium with umbrella cells #1; #2; #3; various images; Brunn’s nests #1; #2; florid hyperplasia of Brunn’s nests #1; #2

Cytology images: umbrella cells, umbrella cells, intermediate cells and basal cells #1; #2

Virtual slides: normal bladder

Positive stains: blood group antigens A, B, H; cytokeratin 7, 8/18, 19

Bladder - congenital anomalies

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Usually are not isolated, but one of many manifestations of developmental failure of GU mesenchyme

Arteriovenous malformation

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By definition, direct communication is present between arterioles and venules

Very rare in bladder; more common in CNS, intestine, lung, extremities

May cause massive hematuria

Micro: abrupt changes in the thickness of the medial and elastic layers of the vessels; also abnormal vascular dilation, often advanced small vessel disease, hemorrhage, ulceration

Cloacogenic bladder

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Also called persistent cloaca

Defined as confluence of rectum, vagina and urethra into a single common chamber

A surgical challenge to achieve bowel and bladder control and normal sexual function

Occurs in 1/20,000 births, only in girls

Gross images: cloaca serves as convergence of rectum and both ureters #1; #2

Duplication of bladder

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Bladder is separated into compartments

Either double bladder, septal bladder or hourglass bladder

Incomplete emptying causes urinary tract infections

Ectopic prostate

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Gross: polypoid mass at bladder base

DD: post-surgical ingrowth of prostatic tissue

Exstrophy

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Developmental failure in lower abdominal wall or anterior wall of bladder due to failure of cloacal membrane to property differentiate; bladder communicates with body surface or lies as an opened sac

Associated with glandular metaplasia and adenocarcinoma (<10% of exstrophied bladders) or squamous metaplasia and squamous cell carcinoma (~7% of patients)

Also associated with infections and ulceration

Drawings: diagrams of exstrophy

Gross images: exstrophy in male

Hypoplasia

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Normal but small bladder, seen in Potter syndrome

Hyperplasia

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Boys only

Structurally and functionally abnormal bladder, shaped like cone, heart or cloverleaf

Does not empty completely

Associated with obstruction at urethral outlet but normal histology

Urachus

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5 cm vestigial structure connecting dome of bladder and umbilicus; in fetus, connects bladder dome with allantois (embryonic diverticulum of hindgut, vessels are precursors to those in umbilical cord)

After birth, becomes median umbilical ligament

Arises from superior urogenital sinus

In midline or posterior bladder wall; fragmentation occurs post-partum when bladder descends into pelvis

Remnants seen at autopsy in 50% of fetuses, 33% of adults

Associated with urachal cysts, sinus, fistula, diverticulum, infections, adenocarcinoma of bladder; also urothelial carcinoma, villous adenoma, squamous cell carcinoma

Gross: remnants located in bladder dome

Micro: usually persists as fragmented tubules separated by fibrous cords, but without a desmoplastic tissue response; composed of stratified epithelium, columnar epithelium or urothelium; no goblet cells, no atypia

Micro images: dilated urachal remnant

Patent urachus

Also called persistent urachus

Rare; leads to urination through umbilicus

May be associated with infections

Gross drawings: patent urachus; excision of urachus

Acquired non-neoplastic anomalies

Amyloidosis

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Either a generalized process or amyloid tumor; often with marked giant cell or histiocytic reaction

Usually AL type (immunoglobulin light chain)

Patients present with gross hematuria

Treatment: excision of amyloid tumor usually curative (and controls bleeding), since not associated with myeloma

Gross: nodular mucosal lesions resembling carcinoma; rarely is diffuse involvement of bladder wall

Micro: large masses of eosinophilic proteinaceous material with hemorrhage in lamina propria; variable foreign body giant cell reaction to amyloid; rarely perivascular amyloid deposits; rare/no inflammatory cells

Micro images: eosinophilic proteinaceous material in lamina propria #1; #2

Positive stains: Congo red (apple green birefringence when exposed to polarized light)

EM: non-branching fibrils and associated ground substance

Collagen polyp

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Injected collagen is used to control urinary stress incontinence or improve function of urinary pouches

Polypoid lesions show submucosal accumulation of eosinophilic, homogeneous, poorly cellular material

Positive stains: trichrome (strong), PAS (weak)

References: Mod Path 1999;12:1090

Cystocele

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Pouch created due to pelvic relaxation, which causes uterine prolapse and protrusion of bladder into vagina; associated with urinary tract infections since does not empty completely

Diverticula

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Pouchlike evaginations of bladder wall

If congenital, due to obstruction or failure of muscle development

Acquired are more common and usually due to prostatic enlargement causing muscular hypertrophy and focal mucosal herniation without muscularis propria in areas of weakness, often near ureteral orifices, bladder dome or urethral orifice

Often multiple in posterior wall or trigone

Associated with infections and stones (due to urine stasis), perforation; also urothelial or other carcinomas; tumors often large because location is hidden

Gross: narrow necks, round/ovoid pouch from 1-10 cm

Gross images: drawing, image with case history

Micro: wall consists of fibrous tissue with no/scant muscularis propria; squamous or glandular metaplasia present if inflamed

Endocervicosis

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Women, mean age 39 years, range 34-65 years

Rare; benign

Associated with endometriosis, cesarean section

Gross: mass between bladder and uterus in posterior bladder wall, dome or trigone

Micro: prominent endocervical type glands in muscularis propria; glands may be cystically dilated and contain mucinous secretions with neutrophils; glands usually lined by tall mucinous columnar cells, less commonly flat or cuboidal, rare ciliated cells; cells rarely have nuclear atypia; no desmoplasia, no mitotic figures

Micro images: prominent endocervical glands in muscularis propria #1; #2; #3; #4 with mucin extravasation

DD: adenocarcinoma, adenoma malignum from uterine cervix

References: Hum Path 1996;27:816, AJSP 1992;16:533

Endometriosis

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Usually associated with history of local surgery or female GU symptoms

Bladder is most common site in urinary tract, but only occurs in <2% of all patients with endometriosis

Also occurs in men after estrogen therapy for prostate carcinoma

May develop into endocervicosis (mucinous metaplasia), endometrioid adenocarcinoma, clear cell carcinoma, adenosarcoma

Treatment: hormones, resection

Gross: usually serosal; palpable mass in 50%; may be blue mucosa at cystoscopy

Micro: endometrial glands, endometrial stroma, hemosiderin

DD: neoplasm

Endosalpingiosis

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Called mullerianosis if two of three (endocervicosis, endometriosis or endosalpingiosis) are present

Associated with endocervicosis (glands lined by columnar mucinous cells) and endometriosis

Gross: mass of posterior wall

Micro: involvement of lamina propria and muscularis propria by tubules and cysts of mullerian-type epithelium; may replace urothelium and form polypoid projections into bladder lumen; tubules and cysts are round/oval, may have prominent branching; glands lined by tubal type epithelium (ciliated cells, intercalated cells, peg cells)

DD: adenocarcinoma

References: Mod Path 1996;9:731

Lithiasis (stones)

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More common in males, usually elderly, associated with prostatic nodular hyperplasia

Common in quadriplegia/paraplegia

Usually solitary phosphate stones; may be urate or oxalate

Treatment: mechanical removal, cystolithotripsy, extracorporeal shock wave therapy

Recur in 10% of patients after removal

References: more information

Obstruction

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Commonly due to prostatic hypertrophy (men) or cystocele (women); also urethral narrowing/strictures, mechanical obstructions, neurogenic bladder

Gross: trabeculation of bladder wall, diverticula

Gross image: prostatic hypertrophy

Tamm-Horsfall protein

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High molecular weight glycoprotein normally synthesized by ascending loop of Henle and distal tubule

May accumulate in renal parenchyma, perirenal soft tissue, renal hilar lymph nodes or bladder with pathologic conditions

Found in 60% of cystectomy specimens, 4% of bladder biopsies

In bladder, 85% found in men, mean 61 years, range 45-78 years

Associated with urothelial carcinoma, nephrogenic adenoma, cystitis; deposited in areas of necrosis, inflammation, fibrinous exudates, ulcer, crystalline material

No clinical significance

Micro: large, waxy, pale or weakly eosinophilic mass; may also appear as strands of eosinophilic material obscured by fibrinous exudates or necrotic tissue

Positive stains: PAS, trichrome (pale blue), anti Tamm-Horsfall protein antibody

EM: nonbranching 4 nm wide parallel fibrils

References: AJSP 1994;18:615

Treatment effect

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