Bladder - Intestinal metaplasia

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Bladder

Metaplasia

Intestinal metaplasia

Reviewer: Rugvedita Parakh, M.D. (see Reviewers page)
Revised: 9 February 2013, last major update July 2010
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
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● Replacement of urothelium by colonic mucosa or isolated / clusters of goblet cells in Brunn’s nests
● See also cystitis cystica / glandularis

Terminology
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● Also called glandular metaplasia, colonic metaplasia or goblet cell metaplasia

Epidemiology
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● Identified in 71-90% of bladders at autopsy
● Incidence increases with age

Sites
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● Trigone is most commonly affected area
● Also seen in ureter and renal pelvis
● Affects the bladder mucosa, typically the lamina propria (J Urol 1968;100:462, J Urol 2006;175:1119)
● Mostly focal but occasionally diffuse

Etiology
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● Variation of normal anatomy
● Also due to chronic inflammation, ureteral reimplantation, neurogenic bladder, bladder exstrophy (J Urol 1981;126:822, J Urol 1987;137:764), paraplegia, stones, long term catheterization

Clinical features
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● Incidental finding or associated with hematuria, mucosuria, dysuria, urgency or obstructive symptoms
● May be confused cystoscopically with carcinoma, particularly if mucin extravasation is present

Prognostic factors
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● Is it a precursor lesion for adenocarcinoma?

Yes:
● Five large series; associated with 10-42% of reported cases of adenocarcinoma
● If extensive, patient is at high risk for adenocarcinoma (Cancer 1987;59:2086)
● Molecular findings support the hypothesis that intestinal metaplasia is a precursor lesion to and could be a marker in the development of adenocarcinoma of the urinary bladder (Clin Cancer Res 2007;13:6232)
● Nuclear beta catenin positivity suggests the potential to progress to malignancy as the signaling mechanism is similar to Barrett’s esophagus (J Urol 2003;170:1892)

No:
● Does not appear to increase risk of adenocarcinoma (Urology 2008;71:915, Urology 1997;50:427)

Case reports
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● Case arising in residual native bladder in association with intestinal metaplasia and dysplasia of bladder mucosa 17 years following gastrocystoplasty (J Pediatr Urol 2010;6:525)
● Case arising in spina bifida patient (Ann Diagn Pathol 2007;11:453)

Treatment
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● May regress completely if pathogenic factor is removed

Gross description
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● Irregular rounded focal elevations of mucosa
● Rarely polypoidal with mucinous extravasations

Micro description
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● Replacement of urothelium by colonic mucosa (tall columnar cells)
● Also goblet cells (single or aggregates) within Brunn’s nests, variable presence of Paneth cells
● May coexist with cystitis cystica or cystitis glandularis
● Mucin may be occasionally extravasated into the stroma
● No atypia, no involvement of muscularis propria

Micro images
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Cystitis glandularis with intestinal metaplasia and mucin extravasation
Fig 1: marked edema of mucosa
Fig 2: proliferation of glands in lamina propria
Fig 3: glands are lined by columnar epithelium with goblet cells and Paneth cells, with no signet ring cells, atypia or mitotic figures
Fig 4: focal mucin extravasation

Cystitis glandularis intestinal type (intestinal metaplasia)

Colonic-type glands in the lamina propria

Resembles colonic mucosa	Uniform glands, no cytologic atypia or desmoplastic response	Abrupt transition from urothelium to intestinal-type epithelium
Mucin extravasation	Mucin extravasation	H&E and stains (fig a-e)
Intestinal metaplasia replacing urothelium	Surface goblet cells with glandular distention of Brunn nests	Bladder mucosa shows a focal intestinal and squamous metaplasia

Cytology description
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● Cuboidal, columnar and mucin secreting cells
● Intestinal-type goblet cells may be seen
● Bland cytologic features
● Rare mitoses (Diagn Cytopathol 2008;36:181)

Positive stains
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● Mucin stains have variable positivity
● CDX2 (83%), CK20 (Mod Pathol 2006;19:1395)
● Neuroendocrine markers in neuroendocrine cells (Histopathology 1990;16:365)
● Nuclear beta-catenin

Negative stains
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● CK7 (usually), HEP (100%)
● Note: in the urinary bladder, intestinal metaplasia and typical cystitis glandularis have sharply contrasting immunoprofiles despite similar morphology (Mod Pathol 2006;19:1395)

Electron microscopy description
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Cystitis cystica:
● Lining cells: short microvilli on luminal surface
● Taller cells: numerous membrane-bound electron-dense secretory granules (Br J Urol 1993;71:28)

Molecular / cytogenetics description
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● Associated with significant telomere shortening and cytogenetic abnormalities (Clin Cancer Res 2007;13:6232)

Differential diagnosis
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● Adenocarcinoma-primary, metastatic or from renal pelvis / ureter: infiltrative with extensive muscle invasion, anaplasia, mitotic figures and extensive mucinous pools (Hum Pathol 1997;28:1152)
● Neobladder derived from intestine (normal epithelium): clinical history, villous atrophy, reactive atypia, lymphoid aggregates
● Urothelial carcinoma: florid metaplastic changes can mimic urothelial carcinoma, particularly the nested variant (Am J Surg Pathol 2003;27:1243)

End of Bladder > Metaplasia > Intestinal metaplasia

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