Barrett’s Esophagus

Abstract

This review provides a summary of our current understanding of, and the controversies regarding, the diagnosis, pathogenesis, histopathology, and molecular biology of Barrett's esophagus (BE) and associated neoplasia. Barrett's esophagus is defined as columnar metaplasia of the esophagus. There is worldwide controversy regarding the diagnostic criteria of BE, mainly with regard to the requirement to histologically identify goblet cells in biopsies. Patients with BE are at increased risk for adenocarcinoma which develops via a metaplasia-dysplasia-carcinoma sequence. Surveillance of patients with BE relies heavily on the presence and grade of dysplasia. However, there are significant pathologic limitations and diagnostic variability in evaluating dysplasia, particularly with regard to the more recently recognized unconventional variants. Identification of non-morphology based biomarkers may help risk stratification of BE patients and this is a subject of ongoing research. Due to recent achievements in endoscopic therapy, there has been a major shift in the treatment of BE patients with dysplasia or intramucosal cancer, away from esophagectomy and towards endoscopic mucosal resection and ablation. The pathologic issues related to treatment and its complications are also discussed in this review article.

Beyond Dysplasia Grade

“…Assuming adequate biopsies are taken, technical or processing artifact of the tissue can hinder accurate determine of dysplasia. 10 Histological interpretation of biopsies is more challenging when active inflammation and ulceration are present, which is not uncommon in patients with Barrett’s esophagus. Inflammation induces regenerative changes in the Barrett’s epithelium and these regenerative changes can mimic dysplasia.…”

“…This can lead to diagnostic uncertainty and may result in a biopsy specimen labeled “indefinite for dysplasia”, leading to the need for repeat endoscopy with biopsies. 10 This issue of inflammation mimicking dysplasia is the rationale underlying the recommendation in the American College of Gastroenterology (ACG) guidelines which advises against taking biopsies in areas of erosive esophagitis until after intensive anti-secretory therapy has healed any mucosal injury. 3 …”

“…There are no scientifically validated morphologic features to distinguish low-grade dysplasia (LGD) from high-grade dysplasia (HGD), leading to variations in interpretation between pathologists. 10–12 In addition to the difficulties in distinguishing low-grade from high-grade dysplasia, there is also a substantial disagreement among pathologists when distinguishing HGD from intramucosal cancer. 10, 13 To compound the problem, there is a high degree of inter-observer and intra-observer variability in the diagnosis and grading of dysplasia in Barrett’s esophagus, which has been seen in multiple studies.…”

“…10–12 In addition to the difficulties in distinguishing low-grade from high-grade dysplasia, there is also a substantial disagreement among pathologists when distinguishing HGD from intramucosal cancer. 10, 13 To compound the problem, there is a high degree of inter-observer and intra-observer variability in the diagnosis and grading of dysplasia in Barrett’s esophagus, which has been seen in multiple studies. 13, 14 In studies in which expert gastrointestinal pathologists reviewed histopathology slides from cases of non-dysplastic and dysplastic (both LGD and HGD) Barrett’s esophagus, the inter-observer agreement for non-dysplastic BE was fair to moderate, with a kappa statistic (K) of 0.2.-0.58, higher for HGD/carcinoma (K=0.43–0.65), and lower for LGD (K=0.11-0.4) 12–14 These findings among expert gastrointestinal pathologists with a research interest in Barrett’s esophagus emphasizes the limitations of using dysplasia to stratify the risk of cancer in patients with Barrett’s esophagus.…”

Progression of Barrett’s esophagus toward esophageal adenocarcinoma: an overview

“…There are many theories concerning the origin of a BE and no consensus has been reached, as was stated by the authors of a recent review [3]. They concluded that Barrett glands are more complex and possibly unique within the human gastrointestinal epithelium.…”