Esophagus
Premalignant lesions
Barrett esophagus (BE)

Author: Elliot Weisenberg, M.D. (see Authors page)

Revised: 22 January 2018, last major update April 2013

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed Search: Barrett esophagus[TI] free full text[sb]

Cite this page: Weisenberg, E. Barrett esophagus (BE). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/esophagusBarrettsgeneral.html. Accessed July 21st, 2018.
Definition / general
  • Distal squamous mucosa is replaced by metaplastic specialized (intestinalized columnar) epithelium, e.g. goblet cells, as a response to chronic injury; may regress after treatment
  • Also called columnar lined esophagus
Terminology
  • Long segment: Barrett mucosa extends 3 cm or more
  • Short segment: Barrett mucosa extends less than 3 cm
  • Ultra short segment: Barrett mucosa extends less than 1 cm
Pathophysiology
Etiology
  • Usually due to chronic gastroesophageal reflux (odds ratio 12.0, World J Gastroenterol 2007;13:1585; Barrett is present in 3 - 12% of GERD patients who are biopsied)
  • Columnar epithelium of Barrett may be more resistant to acid, pepsin and bile
  • Often associated with sliding hiatal hernia; also bile / pancreatic juice reflux, chemotherapy, decreased resting pressure of lower esophageal sphincter, esophageal stricture, lye ingestion, peptic ulceration
Diagrams / tables

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Topographic distribution

Patterns

Esophageal biopsy protocol

Clinical features
  • Overwhelming majority are acquired (World J Gastroenterol 2006;12:1521), rare cases may be congenital (Arch Pathol Lab Med 1981;105:546)
  • Incidence higher in whites, males, obese (especially with central adiposity); also with hiatal hernia and high degree of duodenal gastric reflux
  • Mean age at diagnosis is 63 years; usually white men, rarely children with cystic fibrosis (causes reflux) or after chemotherapy (Nat Rev 2003;3:676, CA Cancer J Clin 2005;55:334, N Engl J Med 2011;365:1375)
  • Symptoms: long history of heartburn and other reflux symptoms; more massive reflux with more numerous and longer episodes than most reflux patients
  • Major risk factor for esophageal adenocarcinoma; however, relative risk varies from 11 - 100x; the absolute annual risk is 0.12 to 0.5
  • Other types of carcinoma are uncommon
  • Barrett patients have similar mortality rate as general population and death from esophageal adenocarcinoma is rare (Gut 2003;52:1081); of note, 95% with adenocarcinoma did NOT have Barrett (Gastroenterology 2002;122:633, Gastroenterology 2002;122:26, Clin Gastroenterol Hepatol 2010;8:235)
  • Both long segment and short segment Barrett esophagus have similar staining patterns to each other and to intestinal metaplasia of GE junction but different from intestinal metaplasia associated with H. pylori gastritis (Am J Surg Pathol 2001;25:87)
  • Barrett should be differentiated from intestinal metaplasia at GE junction or in gastric cardia; H. pylori infection is major cause of intestinal metaplasia of gastric cardia but risk of progression of cardia intestinal metaplasia to dysplasia and adenocarcinoma is significantly lower than in Barrett
Diagnosis
  • Characteristic endoscopic appearance plus characteristic histologic findings; 8 random biopsies recommended (Am J Gastroenterol 2007;102:1154); routine use of Alcian blue staining to detect goblet cells (pH 2.5, detects acid mucins) is not recommended as pseudogoblet cells may be reactive (Odze: Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas, 2nd Edition, 2009); report should include type of epithelium present and presence / absence of dysplasia, grade of dysplasia and extent of dysplasia
  • In children, endoscopic Barrett esophagus may have only cardiac type epithelium without intestinal metaplasia
  • Recommended to take biopsies beginning in stomach, then every 1 - 2 cm until obvious squamous epithelium is reached
  • In some locations outside of North America (e.g. Great Britain), presence of goblet cells is not necessary (Gut 2006;55:442)
Laboratory
  • Specimen processing: obtain 4 levels of step sections to document goblet cell metaplasia; may want additional levels in patients with known Barrett to evaluate dysplasia (Am J Clin Pathol 2005;123:886)
Treatment
Clinical images

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Endoscopic
appearance of hiatus
hernia mimicking
Barrett esophagus

Normal and Barrett



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Endoscopy:
mucosal erythema
of lower esophagus

Gross description
  • Red velvety GI type mucosa between pale squamous mucosa of lower esophagus and lush pink gastric mucosa; may have tongues extending up from GE junction or a broad band displacing the GE junction proximally; may have preserved squamous islands
Gross images

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Adenocarcinoma in Barrett esophagus



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Tongues of tan orange mucosa

Microscopic (histologic) description
  • Esophageal squamous epithelium is replaced by columnar epithelium of intestinal type (stomach, small bowel, colon) with goblet cells (distended, mucin filled cytoplasm with a barrel shaped configuration); may be villiform or contain Paneth cells or pancreatic acini (probably metaplastic, Am J Surg Pathol 1995;19:1172); lamina propria is fibrotic with mild chronic inflammation; muscularis mucosae may be thickened or splayed (also called duplicated, Hum Pathol 1991;22:1158); esophageal glands usually are cystically dilated
  • May have Helicobacter pylori gastritis but usually negative in esophagus (Hum Pathol 1997;28:1007)
  • Erosions / ulceration may mimic carcinoma due to exuberant granulation tissue or sarcoma due to atypical macrophages; may also be fundic and cardiac type epithelium with mucosal distortion, glandular atrophy and mild inflammation, although these findings are not diagnostic of Barrett; rarely heterotopic bone formation (Arch Pathol Lab Med 1996;120:666)
  • Associated with multilayered epithelium of 4 - 8 layers of cells that are squamoid in basal aspect and columnar in luminal aspect, superficial columnar cells may show morphologic, immunohistochemical and genetic similarities to Barrett
  • Posttreatment histology: partial squamous reepithelialization of metaplastic columnar epithelium and residual glandular mucosa beneath the squamous epithelium (Am J Surg Pathol 1998;22:239); reepithelialization is often incomplete and intestinalized glands, representative of residual Barrett often remain Underneath areas of reepithelialized Squamous Islands (BUSI); BUSI shows less severe proliferative abnormalities than typical surface BE (Am J Surg Pathol 2005;29:372); occult adenocarcinoma can develop from BUSI (Gastrointest Endosc 2003;58:183) but is rare (Odze: Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas, 2nd Edition, 2009)
Microscopic (histologic) images

Images hosted on PathOut server:

Histology of Barrett esophagus

Tongue of Barrett mucosa

With mucosal erosion and bizarre stromal cells

Exuberant granulation tissue

Small island of squamous epithelium


Villous pattern seen in areas of erosion with regeneration

Intestinalized epithelium

Dysplastic foveolar epithelium

Mucin stains of Barrett mucosa


Adenocarcinoma associated with Barrett



Images contributed by Dr. Mark R. Wick:

Low grade dysplasia

Metaplasia, high grade dysplasia

Metaplastic

Metaplasia with dysplasia



Images hosted on other servers:

Barrett: various images

Gastroesophageal junction: H&E and Alcian blue

Classic staining pattern: CK7 & CK20

Nonclassic staining pattern

Positive stains
Electron microscopy description
  • Mucin granules in metaplastic cells; gastric foveolar-like columnar cells contain Alcian blue+ mucin
Differential diagnosis