How to Identify Barrett's Esophagus on Pathology
Barrett's esophagus is diagnosed pathologically when metaplastic columnar epithelium is identified in biopsy specimens obtained from endoscopically visible columnar-lined esophagus (≥1 cm above the gastroesophageal junction), with the diagnosis requiring synthesis of both endoscopic and histologic findings. 1
Essential Histopathologic Features
Definitive Diagnostic Criteria
The most definitive pathologic diagnosis occurs when columnar mucosa (with or without intestinal metaplasia) is seen juxtaposed with native oesophageal structures such as submucosal glands, gland ducts, multi-layered epithelium, or squamous islands. 1 However, these native structures appear in only 10-15% of biopsy samples, meaning definitive oesophageal origin can be confirmed in less than one in six cases. 1
Types of Metaplastic Epithelium
The pathologist must identify and distinguish between two main types:
Barrett's with intestinal metaplasia: Contains specialized columnar epithelium with acid mucin-containing goblet cells (most commonly incomplete type II or III subtype with mucous cells and goblet cells, though complete type I with absorptive cells may occur). 1, 2 This carries the highest cancer risk with annual incidence of high-grade dysplasia/cancer of 0.38% versus 0.07% without intestinal metaplasia. 1
Barrett's with gastric metaplasia only: Contains cardiac/fundic-type epithelium without goblet cells. 1, 2 The British Society of Gastroenterology recognizes this as Barrett's esophagus, though it carries lower malignant potential. 1, 2
Critical Distinction: Esophageal vs. Gastric Cardia
Differentiating true Barrett's from intestinal metaplasia of the gastric cardia on morphological grounds alone is difficult in most circumstances, apart from when oesophageal native structures are present. 1 Cytokeratin 7 and 20 immunostaining patterns have not proven sufficiently reproducible for routine clinical use. 1 Therefore, this distinction must be made endoscopically through careful labeling of biopsy site location relative to endoscopic landmarks. 1
Minimum Pathology Dataset Required
The pathologist must document the following elements in every report: 1
- Number of biopsy levels analyzed and total number of biopsies at each level
- Presence of squamous mucosa (yes/no)
- Presence of native oesophageal structures (submucosal glands, gland ducts, multi-layered epithelium, squamous islands) (yes/no)
- Presence of glandular/columnar mucosa (yes/no)
- Type of metaplasia present: gastric (cardiac/fundic) versus intestinal metaplasia (yes/no)
- Presence and grade of dysplasia: indefinite, low-grade, high-grade, or intramucosal carcinoma (yes/no for each category)
Pathologic Reporting Categories
Based on the histologic findings, the pathologist should report one of three diagnostic categories: 1
- "Barrett's oesophagus with gastric metaplasia only" (glandular epithelium with cardiac/fundic metaplasia)
- "Barrett's oesophagus with intestinal metaplasia" (glandular epithelium with intestinal metaplasia, stating degree of dysplasia if present)
- "No evidence of Barrett's oesophagus" (squamous mucosa without glandular tissue)
Clinicopathologic Correlation Requirements
The histopathological diagnosis must be integrated with endoscopic findings to reach an accurate clinical diagnosis. 1 The endoscopist must carefully label the site from which biopsies were taken in reference to endoscopic landmarks (gastroesophageal junction identified by proximal gastric folds, distance from incisors, Prague C&M classification). 1
Common Pitfalls and Caveats
Sampling Error and Goblet Cell Detection
The presence and detectability of goblet cells varies depending on multiple factors and is subject to sampling error. 3 Systematic biopsy sampling with sufficient numbers (four-quadrant biopsies every 1-2 cm throughout the Barrett's segment) is essential to limit false-negative results for goblet cell detection. 4, 3
Inflammation-Related Diagnostic Challenges
Persistent esophageal inflammation may induce epithelial changes that mimic or mask dysplasia. 5 Biopsies should not be obtained when active erosive esophagitis (Los Angeles grade C/D) is present; instead, intensify acid suppression with twice-daily PPI for 8-12 weeks and repeat endoscopy after healing. 4
Dysplasia Grading Variability
Dysplasia diagnosis has significant interobserver variability, particularly when distinguishing indefinite from low-grade dysplasia. 2, 5 All dysplasia diagnoses must be confirmed by an expert gastrointestinal pathologist before treatment decisions are made. 4, 2, 3
Controversy Regarding Intestinal Metaplasia Requirement
There is ongoing international controversy about whether intestinal metaplasia (goblet cells) should be required for Barrett's diagnosis. 1, 3 The American Gastroenterological Association defines Barrett's as requiring intestinal metaplasia, while the British Society of Gastroenterology recognizes Barrett's with gastric metaplasia only. 1 However, the 2024 NICE guidelines acknowledge that individuals with intestinal metaplasia have higher cancer risk than those with gastric-type epithelium only. 1