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Surgical Pathology Criteria

Barrett Esophagus


  • Intestinal type mucosa with goblet cells present above the gastroesophageal junction

Alternate/Historical Names

  • Distinctive metaplasia
  • Specialized metaplasia

Diagnostic Criteria

  • The diagnosis of Barrett esophagus is clinicopathological and requires both of the following:
    • Endoscopic identification of columnar mucosa extending proximally into the tubular esophagus
    • Histopathologic identification of columnar epithelium with goblet cells
      • Distended, sharply defined, mucin-filled cytoplasm
        • Alcian blue positive at pH 2.5
      • Fundic or cardiac type mucosa may be present but are not specific
  • The presence of dysplasia in Barrett esophagus appears to be related to the development or presence of adenocarcinoma
  • Note:
    • The gastroesophageal junction is the anatomic junction of the saccular stomach with the tubular esophagus
    • The squamo-columnar junction is where the glandular mucosa meets the squamous mucosa
    • The lower esophageal sphincter is the distal 1 cm of the tubular esophagus, a region of increased pressure
  • A hiatal hernia is the presence of a portion of the saccular stomach above the diaphragmatic notch
  • Barrett esophagus may be defined by its length
    • Long segment at least 3 cm
    • Short segment <3 cm
    • Ultra-short segment <1 cm
      • Extremely difficult to distinguish from an irregular EG junction
  • Pancreatic metaplasia is seen frequently in biopsies from the EGJ
    • It is not clear if this represents metaplasia or heterotopia
    • No clinical significance

    Robert V Rouse MD
    Department of Pathology
    Stanford University School of Medicine
    Stanford CA 94305-5342

    Original posting/updates : 11/11/09, 2/3/10, 10/25/10


Differential Diagnosis

  • Esophageal submucosal glands are also Alcian blue positive
    • Rounded nests of glands below the muscularis mucosae
  • Distended foveolar cells
    • Weakly Alcian blue positive
    • Form a linear array
    • Form a spectrum with obvious non-distended foveolar cells
  • Cardiac intestinal metaplasia
    • Requires clinical correlation of site of biopsy
  • Cervical inlet patch with intestinal metaplasia
    • Requires clinical correlation of site of biopsy


  • 2008 Recommendations of the Practice Parameters Committee of the American College of Gastroenterology (Wang 2008)
    • No dysplasia
      • Repeat endoscopy with biopsies within one year then every 3 years
    • Indeterminate or low grade dysplasia
      • Anti-reflux therapy with repeat endoscopy and biopsies every 6 months
        • If still present, repeat above
        • If resolved for two consecutive sets of biopsies, repeat endoscopy with biopsy every 3 years
    • High grade dysplasia
      • Anti-reflux therapy with repeat endoscopy and biopsies after 3 months
        • If persistent or multiple sites involved, repeat endoscopy and biopsies every 3 months or consider endoscopic mucosal resection
    • Intramucosal carcinoma
      • Consider endoscopic mucosal resection or equivalent
    • Adenocarcinoma invasive into submucosa
      • Consider surgery
  • As many as 30-40% of patients with high grade dysplasia are found to have carcinoma on resection
    • Only 13% of these are invasive into submucosa or deeper (Konda 2008)
    • One meta-analysis finds an incidence of 6 cases of invasive carcinoma per 100 patient-years for the first few years (Rastogi 2008)
  • Some studies find a low rate of development of dysplasia and carcinoma in patients with no evidence of dysplasia at presentation

Dysplasia in Barrett Esophagus

  • Barrett esophagus and dysplasia appear to be precursors or markers of adenocarcinoma development
    • 10% of patients with gastroesophageal reflux will have Barrett esophagus
    • 10% of patients with Barrett esophagus will have dysplasia
    • 10% of patients with Barrett esophagus will have adenocarcinoma at the time of initial diagnosis
    • Longterm followup of patients with low grade dysplasia in Barrett esophagus (Sharma 2004)
      • 10% progress to high grade dysplasia
      • 3% progress to carcinoma
    • Followup of patients with high grade dysplasia in Barrett esophagus (Konda 2008)
      • 40% develop carcinoma
        • 87% of these are intramucosal
        • Only 13% are invasive into submucosa or beyond
  • Notes on the diagnosis of dysplasia in Barrett esophagus
    • Dysplasia is best evaluated in areas without significant acute inflammation (see indefinite for dysplasia below)
    • Dysplastic features should be present on the lumenal surface
      • Reactive atypia rarely extends to the lumenal surface
    • Dysplasia may be focal, requiring adequate sampling
    • A diagnosis of dysplasia should be confirmed by an experienced gastrointestinal pathologist
  • Criteria for dysplasia
    • Negative for dysplasia
      • Orderly glandular architecture
      • Regenerative basal glands may have cytologic atypia
        • Hyperchromasia
        • Pleomorphism
        • Nuclear stratification
        • Nucleus:cytoplasm ratio usually normal or only slightly increased
        • Atypia tends to be more uniform than in dysplasia
      • The cells mature at the surface where these features are lost
    • Most dysplasia is of intestinal type, resembling the changes seen in colonic adenomas
      • Low grade intestinal type dysplasia
        • Architecture preserved or minimally abnormal
        • Nuclei elongated and crowded at base but not at apex of cells
          • Pseudostratification may be extensive
        • Nuclear enlargement
        • Mild to moderate nuclear hyperchromasia and irregularity
        • Mitotic figures may be present at surface
        • Cytologic atypia extends to cells on the bowel lumenal surface
        • Surface villous transformation may be present
      • High grade intestinal type dysplasia demonstrates markedly atypical features
        • Marked cytologic atypia
        • Nuclear stratification to surface of cell with loss of polarity
          • Nuclei no longer radially oriented
        • Abnormal architecture
          • Lateral budding
          • Branching
          • Intraglandular bridging
          • Villus formation
          • Dilated glands containing necrotic debris
          • No single cell or small cluster infiltration (intramucosal carcinoma)
    • Gastric foveolar type dysplasia has been reported in up to 20% of cases
      • Single layer of basally oriented round to oval nuclei
        • Lacks pseudo- and real stratification of intestinal type
        • Frequently mixed with intestinal type
        • Has also been called "nonadenomatous dysplasia"
      • Grading criteria have only recently been proposed by Mahajan
        • Primarily based on nuclear size
          • Low grade foveolar type dysplasia
            • Nuclei enlarged to 2-3x size of lymphocytes
            • Variably prominent nucleoli
            • Pleomorphism absent to mild
            • Full thickness population of uncrowded glands
            • Cytoplasm is usually mucinous
          • High grade foveolar dysplasia
            • Nuclei enlarged to 3-4x size of lymphocytes
            • Prominent nucleoli
            • Pleomorphism mild to moderate
            • Glandular crowding
            • Cytoplasm frequently eosinophilic/oncocytic
            • Variable features
              • Villiform growth
              • Cribriform glands
              • Dilated glands with lumenal debris
    • Indefinite for dysplasia should be used if the lesion is suggestive of but not diagnostic of dysplasia
      • Significant atypia with lack of surface maturation in the context of inflammation
      • Significant atypia with surface maturation in the absence of inflammation
      • Significant atypia with partial surface maturation
      • If acute inflammation is present, dysplasia should be diagnosed with caution and then only if the dysplastic findings are clearly disproportionate to the degree of inflammation


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  • Wang KK, Sampliner RE; Practice Parameters Committee of the American College of Gastroenterology. Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett's esophagus. Am J Gastroenterol. 2008 Mar;103(3):788-97.
  • Rastogi A, Puli S, El-Serag HB, Bansal A, Wani S, Sharma P. Incidence of esophageal adenocarcinoma in patients with Barrett's esophagus and high-grade dysplasia: a meta-analysis. Gastrointest Endosc. 2008 Mar;67(3):394-8.
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  • Rucker-Schmidt RL, Sanchez CA, Blount PL, Ayub K, Li X, Rabinovitch PS, Reid BJ, Odze RD. Nonadenomatous dysplasia in barrett esophagus: a clinical, pathologic, and DNA content flow cytometric study. Am J Surg Pathol. 2009 Jun;33(6):886-93.
  • Mahajan D, Bennett AE, Liu X, Bena J, Bronner MP. Grading of gastric foveolar-type dysplasia in Barrett's esophagus. Mod Pathol. 2010 Jan;23(1):1-11.
  • Goldblum JR. Controversies in the diagnosis of Barrett esophagus and Barrett-related dysplasia: one pathologist's perspective. Arch Pathol Lab Med. 2010 Oct;134(10):1479-84.
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