Epithelial lineage and transformation.

Discussion of the lineage and transformation of esophageal epithelium as they relate to gastroesophageal reflux disease (GERD) requires consideration of both the native squamous epithelium and the acquired columnar epithelium of Barrett's esophagus. The non-keratinizing squamous epithelium has a proliferative basal zone where cells undergo mitosis, then migrate toward the luminal surface, and differentiate in the prickle cell layer where they flatten out as they reach the luminal surface and accumulate glycogen [1]. In response to injury induced by GER, the squamous epithelium undergoes reactive changes characterized by widening of the basal zone with increased mitotic figures, increased numbers and length of vascular papillae from the lamina propria, and immaturity of the superficial cell layers, including reduced glycogen content [2]. Chronic injury from gastroesophageal reflux can also result in adaptive replacement of the native squamous epithelium by more resistant columnar epithelium, termed columnar metaplasia, for which the eponym of "Barrett's esophagus" is usually applied [3-5]. Barrett's mucosa has a wide variety of histopathologic appearances due to heterogeneity of villous and glandular architecture as well as epithelial differentiation. Distinctive-type (specialized) Barrett's mucosa has incompletely intestinalized columnar epithelium characterized by goblet cells and absorptive cells of intestinal type interspersed with columnar mucous cells of the gastric type. Paneth cells are sometimes present. A gradient of differentiation in individual glands is usually event with cardiac-type glands deep in the distinctive-type Barrett's mucosa and intestinalized epithelium in the upper glandular and villous epithelium as it migrates upward from the glands to reach the luminal surface. The cardiac-type and fundal-type Barrett's mucosae resemble the corresponding gastric mucosae. Pancreatic acinar cell meta-