Primary Motility  Disorders of the  Esophagus
 The Esophageal
 Esophagogastric  Junction

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Volume: Barrett's Esophagus
Chapter: Diagnosis

What is the significance of pancreatic metaplasia at the gastroesophageal junction?

R.H. Riddell (Toronto)

Pancreatic metaplasia in the gastric mucosa was first characterized by Doglioni et al. in 1993. Pancreatic acinar-like cells characterized was found in 101 cases (84 gastric biopsies and 17 gastrectomies) of 8,430 gastrectomies and gastric biopsies. These cells, arranged in nests or in variably sized lobules among the gastric glands. They were consistently immunoreactive for pancreatic lipase and trypsinogen and, in 75% of the cases, for pancreatic alpha-amylase. The appearance of these cells within the gastric mucosa was correlated significantly with chronic gastritis and with the simultaneous occurrence of intestinal and pyloric types of gastric metaplasia [1]. Since this paper, it has become clear that pancreatic metaplasia is very common in the gastric cardia. The reason that the cardia was poorly recognized as a site for pancreatic metaplasia is likely because until recently the cardia was not regularly biopsied; biopsies for gastroesophageal reflux disease (GERD) were taken from at least 2 cms above the Z-line because the lower squamous mucosa frequently had reactive changes, and the Z-line itself was not biopsied.

The occurrence of pancreatic metaplasia in Barrett's esophagus soon followed, and focal clusters of cells resembling pancreatic acinar cells were found in 11 of 350 biopsies of Barrett's mucosa from 120 patients with Barrett's, and 3 other patients [2]. Immunoreactivity for trypsin and chymotrypsin was present in all cases, while stains for alpha-amylase and lipase were each positive in 12 of 13. A few cells were also positive for chromogranins (12 of 13 cases), serotonin (seven of 13 cases), somatostatin (three of 12), gastrin (four of 11), and pancreatic polypeptide (two of 13). No staining was seen for insulin or glucagon. Ultrastructural studies performed in one case showed features of pancreatic exocrine and endocrine (PP-type) cells. It was postulated that pancreatic parenchyma in Barrett's mucosa is most likely of metaplastic origin, and could be derived from the transitional zone cells or from pluripotent stem cells in the esophageal mucosa, or from metaplasia of mucus cells. The development of pancreatic metaplasia in Barrett's esophagus appears to be unrelated to drug therapy.

One study looked specifically for pancreatic metaplasia in a blinded prospective manner. Pancreatic metaplasia was present in 24% of patients, but was not associated with any of the reported symptoms, endoscopic evidence of esophagitis, columnar epithelium in the distal esophagus, or any of the histologic features evaluated. This included active esophagitis, intestinal metaplasia at the gastroesophageal junction, active and chronic gastritis, intestinal metaplasia in the stomach, and Helicobacter pylori infection. It was concluded that pancreatic metaplasia is an incidental finding and possibly congenital, rather than an acquired [3]. A study of consecutive resections also found that the region of the Zline was the most frequent site but could not find an association with gastritis, atrophy or carcinoma [4], and a similar surgical study of patients with normal Z-line pancreatic metaplasia was found in 14% of patients, and appeared to be related to inflammation [5]. An identical figure of 14% was also found in a series of cardiac biopsies in patients undergoing endoscopy for GERD, none being associated with H. pylori [6].

Finally, in 65 patients with GERD and 71 controls pancreatic metaplasia was found in 15 of 65 and foveolar hyperplasia in 19 of 65 cases but neither was related to gastroesophageal disease [7].

In summary, there is a suggestion that pancreatic metaplasia in the stomach appears to be common, being found in about 15% of patients. There is a suggestion of an association with chronic inflammation, but this is weak, and overall it appears to be an incidental finding, with no well established relationship with GERD.


1. Doglioni C, Laurino L, Dei Tos AP, et al. Pancreatic (acinar) metaplasia of the gastric mucosa. Histology, ultrastructure, immunocytochemistry, and clinicopathologic correlations of 101 cases. Am J Surg Pathol 1993;17:1134-1143.

2. Krishnamurthy S, Dayal Y. Pancreatic metaplasia in Barrett's esophagus. An immunohistochemical study. Am J Surg Pathol 1995;19:1172-1180.

3. Wang HH, Zeroogian JM, Spechler SJ, Goyal RK, Antonioli DA. Prevalence and significance of pancreatic acinar metaplasia at the gastroesophageal junction. Am J Surg Pathol 1996;20:1507-1510.

4. Nokubi M. Pancreas like acinar glands in the esophagogastric junctional mucosa. Nippon Shokakibyo Gakkai Zasshi 1996;93:876-883.

5. Polkowski W, van Lanschot JJ, ten Kate FJ, et al. Intestinal and pancreatic metaplasia at the esophagogastric junction in patients without Barrett's esophagus. Am J Gastroenterol 2001;95:617-625.

6. Rotterdam H. Pathology of the gastric cardia. Verh Dtsch Ges Pathol 1999;83:37-42.

7. el-Zimaity HM, Verghese VJ, Ramchatesingh J, Graham DY. The gastric cardia in gastro-oesophageal disease. J Clin Pathol 2001;53:619-625.

Publication date: August 2003 OESO©2015