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Surgical Pathology Criteria
http://surgpathcriteria.stanford.edu/

Barrett Esophagus

Definition

  • 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

Clinical

  • 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

Bibliography

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  • Haggitt RC. Barrett's esophagus, dysplasia, and adenocarcinoma. Hum Pathol. 1994 Oct;25(10):982-93.
  • Dulai GS, Shekelle PG, Jensen DM, Spiegel BM, Chen J, Oh D, Kahn KL. Dysplasia and risk of further neoplastic progression in a regional Veterans Administration Barrett's cohort. Am J Gastroenterol. 2005 Apr;100(4):775-83.
  • Goldblum JR. Barrett's esophagus and Barrett's-related dysplasia. Mod Pathol. 2003 Apr;16(4):316-24.
  • Katz D, Rothstein R, Schned A, Dunn J, Seaver K, Antonioli D. The development of dysplasia and adenocarcinoma during endoscopic surveillance of Barrett's esophagus. Am J Gastroenterol. 1998 Apr;93(4):536-41.
  • 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.
  • Sharma P. Low-grade dysplasia in Barrett's esophagus. Gastroenterology. 2004 Oct;127(4):1233-8.
  • Konda VJ, Ross AS, Ferguson MK, Hart JA, Lin S, Naylor K, Noffsinger A, Posner MC, Dye C, Cislo B, Stearns L, Waxman I. Is the risk of concomitant invasive esophageal cancer in high-grade dysplasia in Barrett's esophagus overestimated? Clin Gastroenterol Hepatol. 2008 Feb;6(2):159-64.
  • Reid BJ, Haggitt RC, Rubin CE, Roth G, Surawicz CM, Van Belle G, Lewin K, Weinstein WM, Antonioli DA, Goldman H, et al. Observer variation in the diagnosis of dysplasia in Barrett's esophagus. Hum Pathol. 1988 Feb;19(2):166-78.
  • 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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