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Volume: Barrett's Esophagus
Chapter: Etiology and origins of Barrett's epithelium

Is cardiac mucosa normal or is it metaplastic?

H.D. Appelman (Ann Arbor)

In standard medical school curricula and in almost all the recent textbooks, it is taught in anatomy and histology classes that the stomach has three types of mucosa [1-4]. The most proximal mucosa is traditionally designated as cardiac mucosa. It covers a short stretch of the stomach, usually not specified as to length, immediately below the point where the esophagus opens into the stomach. It is also taught that the fundus and body of the stomach are lined by acid and enzyme producing mucosa and that the distal stomach, the antrum and pylorus is lined by a mucus producing mucosa that also contains the G cells that produce gastrin. There has been no reason to doubt this teaching, and in fact, it persists to the present.

Subsequently it was discovered that in some normal individuals, cardiac mucosa actually lines the distal 2 cm or so of the tubular esophagus, so that the normal squamocolumnar junction between esophageal squamous and cardiac mucosae lies proximal to the anatomic gastroesophageal junction (GEJ). This fact has been incorporated into some of the most recent texts [1, 5].

Barrett's mucosa resembles cardiac mucosa in having pit-like structures, surface epithelium other than goblet cells that is similar to the surface epithelium in the stomach and deep mucus producing glands. Furthermore, as proven in numerous studies, perhaps as many as 1/5 of all adults who have upper endoscopic exams have goblet cells within their cardiac mucosae. Thus, a goblet cell-containing cardiac mucosa is likely to look much like Barrett's mucosa, although there is little published information on whether they are architecturally identical. What causes cardiac goblet cells to develop is not known for certain. Reflux and H. pylori have been implicated in different studies, and there is too much disagreement in these studies for any clear conclusion about cause. The discovery of cardiac goblet cells has resulted in two obvious questions. First, is a cardia with goblet cells the same as short segment Barrett's mucosa? Second, whether it is the same as Barrett's mucosa or not, does it have the same cancer risk? It would be helpful to know the answers to these questions. If goblet cell containing cardiac mucosa and Barrett's mucosa are the same, then pathologists will not have to be concerned about trying to tell them apart, and clinicians will be able to approach all patients with goblet cells slightly below to anywhere above the GEJ in the same way.

In a recent study from the United States, Chandrasoma et al. proposed that the cardiac mucosa, something we have considered to be part of the normal anatomy, is actually not normal but it is metaplastic [6,7]. Furthermore, they suggested that the cause of this metaplasia is gastroesophageal reflux, and that it occurs not in the proximal stomach but in the distal squamous esophagus. They based their conclusions on the following data. First, in adults, they found that the longer the length of the cardiac or mixed oxyntic-cardiac mucosa in the GEJ area, the greater the acid exposure. Second, in an autopsy study of 72 cases in which for each case single sections across the GEJ were examined microscopically, 74% had no cardiac mucosa. In fact, 29% didn't even have cardiac type mucous glands in this area, but had pure oxyntic mucosa abutting the esophageal squamous mucosa. This did not appear to be age related, but the authors evaluated very few children. In another autopsy study of 18 cases in which the entire junction was examined microscopically, pure cardiac mucosa was absent in 10% or 56%. However in all cases, there was mucosa with both cardiac mucous and oxyntic glands. There was a tendency for the presence and length of the pure cardiac mucosa to increase with age.

This study was challenged by others that concentrated on the junctions in young children. In one study of 30 autopsies of patients under 18 years, cardiac mucosa was present in all specimens, but the lengths of the cardiac segments were tiny, averaging less than 2 mm [8]. In another study that also included fetuses, oxyntic mucosa was found to develop in the fetal stomach first, and it was separated from the esophageal squamous mucosa by a short zone that changed with age [9]. Before 21 weeks gestation this zone had no deep glands in most of the cases. After 21 weeks, mixed mucous-oxyntic glands developed, and after the first postnatal week about half had cardiac mucosa in this zone. Thus it appeared to the authors of this study that cardiac mucosa is a gastric mucosal derivative and not a metaplasia in the lower squamous esophagus. In still a third study of biopsies of the squamocolumnar junction in 59 pediatric patients, 0.1 to 18 years, 59% had cardiac mucosa and the other 41% had a mixed mucosa with both cardiac and oxyntic glands, and this was not age related, suggesting that at least a small amount of cardiac mucosa is normal [10]. In the last 2 studies, pure cardiac mucosa was much more inflamed than the mixed mucosa, but the reasons for this remain enigmatic.

Some support for both points of view came from an Australian study of 170 patients [11]. Cardiac mucosa was present at the GEJ in 63% of the patients and was not age related, but its presence was associated with duration of reflux symptoms and the presence of erosive esophagitis in the squamous mucosa. This suggested some relation to reflux, although the authors did not specify how. They also felt that, since the presence of cardiac mucosa was not age related, it may be present from early life, but the study group had a mean age of 52, indicating that almost all were adults. Thus this study was unlikely to help determine whether cardiac mucosa is normal in children.

Finally, we know from biopsy studies and studies of resected esophagi that there are short stretches of Barrett's mucosa without goblet cells that look exactly like cardiac mucosa. Since these foci are within the Barrett's metaplastic zone, then presumably they are metaplastic as well, suggesting that there is a mucosa exactly like cardiac that occurs as a metaplasia in the squamous esophagus. The question that has yet to be answered is whether this metaplasia is the same as the more traditional cardiac mucosa that lies immediately below the GEJ.

The question to be answered from this review is the following: is cardiac mucosa normal, or is it metaplastic? The results of these studies are clearly frustrating. They present such disparate data and result in such disparate conclusions that we can say with great confidence that the answer to this question is, we do not know!


1. Antonioli DA, Madara JL. Functional anatomy of the gastrointestinal tract. In: Ming SC, Goldman H, eds. Pathology of the gastrointestinal tract. Baltimore: Williams & Wilkins, 1998:16-18.

2. Owen DA. Stomach. In: Sternberg SS, ed. Histology for pathologists. New York: Lippincott-Raven Publishers, 1997:481-483.

3. Lewin KJ, Appelman HD. Tumors of the esophagus and stomach, Fascicle 18, Third Series, Washington: Armed Forces Institute of Pathology, 1996:317.

4. Toner PG, Cameron CHS. The gastric mucosa. In: Whitehead R, ed. Gastrointestinal and oesophageal pathology. New York: Churchill Livingstone, 1995:16.

5. Denardi FG, Riddell RH. Esophagus. In: Sternberg SS, ed, Histology for pathologists. Philadelphia: Lippincott-Raven Publishers, 1997:461-480.

6. Chandrasoma PT, Der R, Ma Y, et al. Histology of the gastroesophageal junction. An autopsy study. Am J Surg Pathol 2000;24:402-409.

7. Chandrasoma PT, Lokuhetty DM, DeMeester TR, et al. Definition of histopathologic changes in gastroesophageal reflux disease. Am J Surg Pathol 2000;24:344-351.

8. Kilgore SP, Ormsby AH, Gramlich TL, et al. The gastric cardia: fact or fiction? Am J Gastroenterol 2000;95:921-924.

9. Zhou H, Greco MA, Kahn E. Origin of cardiac mucosa. Ontogenic considerations. Mod Pathol 1999;12:87A.

10. Glickman JN, Fox VL, Wang HH, et al. Histogenesis of gastric cardia epithelium in children. Gastroenterology 2000;118:A483.

11. Nandurkar S, Talley NJ, Martin CJ, et al. Prevalence and associations of cardia epithelium. Gastroenterology 2000;118:A226.

Publication date: August 2003 OESO©2015