Key Points

• The presence of columnar mucosa in the esophagus with intestinal metaplasia defines Barrett’s esophagus.
• The prevalence of Barrett’s esophagus of any length in reflux subjects is 10% to 12%. However, a “silent majority” with Barrett’s esophagus remain unrecognized in the general population.
• Chronic exposure to acid and duodenal-content secretions during reflux causes damage in the esophageal epithelium and the appearance of columnar epithelium in genetically predisposed individuals.
• Stem cells contained in the proliferative layer of the squamous epithelium or associated gland ducts may be the cell of origin of Barrett’s epithelium, changing their commitment choice to a glandular phenotype. However, upward migration from stem cells of the proximal gastric or cardiac epithelium cannot be discarded as a potential origin.
• Cardiac-type epithelium (a nonspecialized columnar type epithelium) represents an intermediate step in the acquisition of intestinal-type epithelium.
• Dysregulation of the SHH-BMP4/pSMAD embryological signaling pathways have been implicated in the development of nonspecialized columnar epithelium whereas CDX2 expression plays a relevant role in the acquisition of an intestinal phenotype.

Columnar-lined esophagus, or Barrett’s esophagus (BE), is an acquired condition secondary to gastroesophageal reflux disease (GERD) in which the normal stratified squamous epithelium lining the distal esophagus is replaced to a variable extent by metaplastic columnar epithelium containing goblet cells, also known as specialized intestinal metaplasia (SIM). The term long-segment BE (LSBE) refers to SIM extending more than 3 cm above the esophagogastric junction. Patients with less than 3 cm of endoscopically evident columnar-appearing mucosa, often as tongues, containing SIM are labeled as having short-segment BE (SSBE). This definition distinguishes SSBE from intestinal metaplasia found just below a normally located squamocolumnar junction, which is termed intestinal metaplasia of the cardia.[1],[2] Investigators recommend maintaining the distinction between endoscopically apparent long segments (>3 cm) and short segments (< 3 cm) of SIM because most of our current knowledge of the pathophysiology, incidence, prevalence, and risk of malignant transformation of BE has come from studies of patients with LSBE (Figure 1). Indeed, the definition of BE has changed over time, and earlier definitions had restricted BE to SIM that was 3 cm or more above the esophagogastric junction. BE and GERD are the major recognized risk factors for esophageal adenocarcinoma, a tumor whose frequency has increased profoundly in Western countries over the past several decades.[3]

Figure 1 

Endoscopic images of columnar epithelium (A) in the distal esophagus extending more than 3 cm above the esophagogastric junction (LSBE) or (B) in the form of a single tongue (SSBE) 1 cm in length. C, Microscopic section of Barrett’s epithelium. Note the villiform surface of Barrett’s epithelium and the characteristic presence of goblet cells (dark blue).