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
Noffsinger A, Fenoglio-Preiser CM, Maru D, Gilinisky N. Gastrointestinal Diseases, AFIP Atlas of Nontumor Pathology, First Series, Fascicle 5, 2007.
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.
