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Normal histology

Reviewer: Alcides Chaux, M.D., Johns Hopkins University School of Medicine (see Reviewers page)
Revised: 12 June 2011, last major update April 2011
Copyright: (c) 2003-2011, PathologyOutlines.com, Inc.


● Bladder layers are mucosa (urothelium, lamina propria, discontinuous muscularis mucosa), muscularis propria, adventitia, serosa/peritoneum at dome
● No submucosa is present

Micro description

● 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 distal urethra
● Superficial urothelium (umbrella cell layer) 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; they are inconspicuous in distended bladder; contain 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 with well defined borders and amphophilic cytoplasm rich in glycogen; nuclei are regularly arranged, ovoid with long axis at right angles to surface; chromatin is finely granular; have 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:
● Located between the mucosal basement membrane and the muscularis propria, is thinner at the trigone and bladder neck
● Contains loose to dense connective tissue, variably sized blood vessels that may be close to epithelium, lymphatics, variable adipose tissue
● Discontinuous muscular mucosa (wisps of smooth muscle, Am J Surg Pathol 1987;11:668), usually associated with intermediate-sized arteries and veins; only 5% of bladders have well developed, continuous muscularis mucosa
● Occasionally muscularis mucosa is hyperplastic (more common in women), and may resemble muscularis propria (Am J Surg Pathol 2007;31:1420)
● Adipose tissue often is present within deep lamina propria, usually as small localized aggregates, and is always found within muscularis propria (superficial and deep); beware of inappropriate staging of tumors as pT3 due to tumor infiltration of adipose tissue, particularly in TURBT specimens (Am J Surg Pathol 2000;24:1286)
● It is advisable to separate lamina propria invasion into above or beneath muscularis mucosae since the former is more likely to behave as a Ta tumor

Muscularis propria:
● Consists of inner longitudinal, circular and outer longitudinal layers of thick muscle bundles, may also contain adipose tissue between muscle fascicles, paraganglia
● Muscle layers are distinct only near bladder neck and in the remaining areas the longitudinal and circular layers mix freely without definite orientation
● Hyperplastic muscular mucosa may resemble muscularis propria (Am J Surg Pathol 2007;31:1420)
● Muscularis propria may be greatly thickened if obstruction to urine flow develops
● Smoothelin antibody, a marker of terminally differentiated smooth muscle, is useful in distinguishing muscularis propria (positive) from muscularis mucosa (negative, Am J Surg Pathol 2010;34:792)

von Brunnís nests (proliferative cystitis):
● Reactive proliferative change present in 85-95% of bladders; frequency increases with age; more common at the trigone
● Nests of cytologically benign urothelium in lamina propria; nests have regular spacing, extend to same horizontal level at base of proliferation
● May or may not have continuity with surface epithelium; inflammation is usually minimal; stromal reaction is absent
● Florid cases may mimic nested variant of urothelial carcinoma, but there is no muscle invasion (Am J Surg Pathol 2003;27:1243)
● Can also be confused with inverted papilloma, carcinoid tumors, paraganglioma and normal paraganglionic cells

Micro images

Bladder Layers

Wisps of muscularis mucosa smooth muscle (arrow) in lamina propria differ from muscle bundles of muscularis propria

Normal urothelium with umbrella cells

Nucleoli are accentuated by fixation in Hollande solution (picric acid based)

Brunnís nests

Florid hyperplasia of Brunnís nests

normal urothelium

Cytology images

Umbrella cells

Umbrella cells (arrows) retain their shape; they are much larger and have larger nuclei than intermediate and basal cells

Intermediate cells and basal cells

Virtual slides

Normal bladder

Positive stains

● Blood group antigens A, B, H, uroplakins; cytokeratin 7, 8/18, 19



EM images

Transmission EM shows basal lamina (arrowheads), indented and condensed basal cell nuclei (N) and clusters of mitochondria; most nuclei have 1-2 nuclear bodies and prominent nucleoli

End of Bladder > Normal histology

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