Unraveling the Mystery of the Gastroesophageal Junction: A Pathologist's Perspective

Abstract

The gastroesophageal junction (GEJ), which is defined as the point where the distal esophagus joins the proximal stomach (cardia), is a short anatomic area that is commonly exposed to the injurious effects of GERD and/or Helicobacter pylori infection. These disorders often lead to inflammation and intestinal metaplasia (IM) of this anatomic region. The true gastric cardia is an extremely short segment (<0.4 mm) of mucosa that is typically composed of pure mucous glands, or mixed mucous/oxyntic glands that are histologically indistinguishable from metaplastic mucinous columnar epithelium of the distal esophagus. In patients with GERD, whether physiologic or pathologic, the length of cardia-type epithelium increases and extends proximally above the level of the anatomic GEJ into the distal esophagus. Columnar metaplasia of the distal esophagus represents a squamous to columnar metaplastic reaction that develops from an esophageal stem cell and may pass through an intermediate phase characterized by the presence of a type of epithelium that possesses a mixture of squamous and columnar features, termed multilayered epithelium. In contrast, IM of the gastric cardia represents a columnar to columnar cell metaplastic reaction that develops from a gastric stem cell located in the deep foveolar compartment of the gastric mucosa. Intestinal metaplasia, particularly the incomplete type, is widely believed to represent the precursor lesion upon which dysplasia and cancer arises. The frequency of IM is probably greater in metaplastic columnar epithelium in the esophagus secondary to GERD, than in cases of true gastric carditis secondary to H. pylori, and may be a reason why there is a higher risk of carcinoma in the former compared to the latter. A variety of clinical, endoscopic, histologic, and histochemical methods can be used to distinguish GERD-induced columnar metaplasia of the distal esophagus from H. pylori-induced inflammation of true gastric cardia, and these are outlined in this review, but further controlled studies are needed to critically evaluate these techniques. Further prospective trials are needed to adequately evaluate the different etiologic and pathogenetic mechanisms and, most importantly, the risk of malignancy in these two conditions.

Expression of CDX2 and Villin in Gastric Cardiac Intestinal Metaplasia and the Relation with Gastric Cardiac Carcinogenesis

“…The other resembles adenocarcinoma of distal esophagus and is likely to be due to the damage of short-segment gastroesophageal reflux. These two chronic damages contributes to the high incidence of IM and inflammation at the cardiac mucosa (Odze, 2005;McColl, 2006). Our previous research showed that the incidence of IM in tissue adjacent to gastric cardiac adenocarcinoma is much higher than gastric cardiac biopsy tissue from normal population (Gao et al, 2005).…”

Unique Cellular Lineage Composition of the First Gland of the Mouse Gastric Corpus

“…9 Furthermore, the first gland may be connected to the observation of various extents of so-called cardia mucosa, which is characterized by an absence of parietal cells and chief cells adjacent to the gastroesophageal junction. 8,50 Recent studies have implicated the first gland as the source of reparative metaplasia in the setting of Barrett's epithelium.…”

“…8,9 Previous investigations have noted the presence of glands lacking parietal cells at the squamocolumnar junction in the mouse stomach. 10 Although other studies have noted the presence of large concentrations of tuft cells in the first gland of the rodent stomach distal to the limiting ridge, 2 few investigations have defined the characteristics of the other lineages that reside at this important transition point.…”

Esophageal Epithelial Resistance

“…2). The stratum granulosum is the most luminal layer and provides a permeability barrier [17,18,19,20]. This permeability barrier is composed of cell membranes in combination with junctional complexes that prevent direct diffusion of luminal contents into the cells or the intercellular spaces.…”