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 The Esophageal
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Volume: The Esophageal Mucosa
Chapter: Epidemiology

What is the cell line giving rise to the columnar mucosa?

PJ. Kahrilas (Chicago)

The most severe histologic consequence of chronic gastroesophageal reflux is Barrett's esophagus. Barrett's mucosa is metaplastic columnar epithelium that has replaced the native squamous epithelium thereby providing greater resistance to the effects of gastroesophageal reflux. Cell types encountered in Barrett's mucosa include constituents of gastric, small intestinal and colonic epithelium (e.g., columnar mucus containing cells that stain with PAS; goblet cells that stain with PAS, Alcian blue and mucicarmine; columnar cells with brush borders and a paucity of mucus vacuoles similar to small intestinal absorptive epithelial cells; Paneth cells; parietal cells; chief cells and endocrine cells) [1]. Barrett's mucosa may exhibit a variety of topographic appearances on endoscopic and pathologic examination. It may appear as a circumferential sheet, islands of columnar mucosa interspersed with squamous mucosa, or finger-like projections coming from the squamocolumnar junction. Furthermore, the architecture of the mucosa can include glands with deep and shallow pits as in gastric mucosa and villous structures resembling small intestinal mucosa. A given patient may exhibit one or more histopathologic appearance in either a mosaic [2] or zonal [3] pattern.

The histopathologic pattern of Barrett's epithelium seen in the vast majority of affected adult patients is a distinctive, specialized columnar epithelium with mucus cells, goblet cells and a villous structure. The columnar cells lack intestinal absorptive capabilities or ultrastructural characteristics of true intestinal cells making them an example of incomplete intestinal metaplasia [4]. Less common histopathologic patterns of Barrett's epithelium include: junctional or cardiac-type Barrett's mucosa with a predominantly foveolar surface pattern containing mucus glands and resembling the epithelium of normal gastric cardia, except that it is atrophic, fundic-type which is the only variety of Barrett's epithelium that contains both parietal and chief cells with sparse and atrophic glands, and an indeterminate category which

shows a wide spectrum of histopathologic and mucosal features [1]. These cells may secrete hydrochloric acid and pepsin. The glandular structures of the fundic epithelium, however, are sparse and foreshortened, causing it to appear atrophic compared to the normal gastric mucosa.

The origin and pathogenesis of the columnar epithelium lining the distal esophagus have been disputed since the time of their initial description by Barrett [5,6]. Initially, there was dispute as to whether the columnar mucosa was a congenital remnant as a result of incomplete replacement of the columnar epithelium by squamous epithelium during development, or acquired as a result of chronic gastroesophageal reflux. Although the persistence theory may well apply to inlet patches in the proximal esophagus, the overwhelming bulk of evidence supports the notion that columnar epithelium in the distal esophagus represents an acquired condition. Proposed mechanisms for acquisition of Barrett's epithelium are the upward growth of cardiac or gastric epithelium after destruction of the squamous epithelium [7], proliferation of the superficial cardiac glands of the esophagus [8], and replacement of the squamous epithelium by metaplastic epithelium [9-11].

Supportive evidence for the upward growth of cardiac epithelium in the pathogenesis of Barretts' comes from both dogs, in which the distal esophageal mucosa was denuded and allowed to regenerate in the presence of gastroesophageal reflux [7], and observation of humans after esophagogastrostomy [12]. In both instances, the distal esophageal mucosa sometimes regenerates with a columnar mucosa consistent with an upward growth of the junctional epithelium. However, the migration theory of pathogenesis has been effectively rejected by elegant studies of Gillen et al. [13]. In Gillen's experiments, the distal esophagus was again denuded of mucosa, but in this case a ring of squamous epithelium was left intact between the denuded area and the stomach, thereby making migration impossible. Dogs were then divided into five groups: acid reflux, acid and bile reflux, reflux plus cimetidine, no reflux and control. Only dogs in the acid reflux group and the acid plus bile reflux group developed a columnar epithelium in the upper denuded ring suggesting that acid (but not bile) reflux was a necessary condition for the development of a columnar mucosa and proving that the columnar did not arise by migration from the gastric cardia.

Another line of evidence strongly supporting the contention that Barrett's epithelium arises from a progenitor cell that can differentiate into either squamous or columnar epithelium comes from recent attempt to ablate Barrett's using laser photoablation [14,15]. In this study, ablation of the columnar epithelium was attempted in 10 men by first burning it with an argon laser, and then allowing the epithelium to regenerate during concomitant high dose acid suppressive therapy (omeprazole 40 mg q.i.d.). In 38 of 40 treated areas of columnar epithelium, squamous mucosa was partially or completely restored. The best success was achieved in areas that had a squamous border or, best of all, in columnar islands. Thus, there must be progenitor cells within the metaplastic tissue that can differentiate into squamous epithelium, provided that differentiation occurs in a neutral as opposed to an acid environment. As in other body tissues, Barrett's appears to be a reversible metaplastic change.


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12. Hamilton SR, Yardley JH. Regeneration of cardiac type mucosa and acquisition of Barrett mucosa after esophagogastros-tomy. Gastroenterology 1977:72:669-675.

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14. Berenson MM, Johnson TD, Markowitz NR, Buchi KM, Samowitz WS. Restoration of squamous mucosa after ablation of Barrett's esophageal epithelium. Gastroenterology 1993;104:1686-1691.

15. Spechler SJ. Laser photoablation of Barrett's epithelium: burning issues about burning tissues. Gastroenterology 1993:104:1855-1858.

Publication date: May 1994 OESO©2015