Prevalence and Pathogenesis of Pancreatic Acinar Tissue at the Gastroesophageal Junction in Children and Young Adults.

Pancreatic acinar tissue (PAT), defined as the presence of islands of exocrine pancreas, has been reported at the gastroesophageal junction (GEJ). In adults, the origin of PAT is controversial. Some have suggested that PAT represents a metaplastic process,[1,2] whereas others think it constitutes a congenital abnormality.[3,4]

To clarify the origin of PAT at this site, we reviewed material obtained from the GEJ in a predominantly pediatric population.

MATERIALS AND METHODS

We reviewed upper Endoscopic mucosal specimens from 556 children and young adults obtained from 1989 to 1997. All specimens were fixed in 10% neutral-buffered formalin, processed for light microscopy, and stained with hematoxylin-eosin. From 556 upper endoscopic biopsy specimens, 69 patients were identified as having tissue from the GEJ. Each of these 69 patients had one biopsy specimen available from the GEJ. These were examined in 3 levels and evaluated blindly and independently by both pathologists (D.P. and E.K.) for the presence of PAT, Barrett esophagus (BE), esophagitis, and gastritis. Selected specimens that contained PAT were also studied for expression of trypsin (Biodesign International, Kennebunk, Me), lipase (Beckman Instruments Inc, Carlsbad, Calif), and amylase (Biodesign) using a biodin avidinlabeled method by an automatic immunostainer (Nexes). Esophagitis was defined as eosinophils in the squamous esophageal mucosa; gastritis as lymphocytes, plasma cells, or neutrophils in the cardiac mucosa; and BE as the presence of intestinal metaplasia-containing goblet cells above the GEJ.

RESULTS

In 11 of 69 patients (7 females, 4 males), PAT was identified in the biopsy specimens obtained from the GEJ (Figure 1). Selected specimens containing PAT stained positive for lipase, trypsin, and amylase. The intensity and extent of the positive-stained cells varied from case to case (Figure 2). The prevalence of PAT of the entire cohort was 16% and differed in each age group (Table). The median age was 15 years (range, 1-21 years). None of the patients with PAT had BE. In 7 patients (63%) mild esophagitis and/or gastritis was noted, whereas in 4 patients (37%) no other microscopic changes were seen. A similar frequency of esophagitis and/or gastritis (58%) was observed in the 58 patients (22 females, 36 males) without PAT (Yate's corrected [[Chi].sup.2] = 0.03, P = .86). The median age for the patients without PAT was 12 years (range, 1-22 years).

The Prevalence of PAT in Different Age Groups

Age, y   Number of Cases(%)
0.5      3 (27.3)
6-10     1 (9.1)
11-15    2 (18.2)

16-20    4 (36.4)
 21      1 (9)

[Figures 1-2 ILLUSTRATION OMITTED]

COMMENT

Pancreatic heterotopia or aberrant pancreas is defined as the occurrence of pancreatic tissue in an abnormal location and without direct connection to the pancreas,[5] Heterotopic pancreatic tissue is most frequently seen in the gastric antrum, duodenum, and jejunum as a well-circumscribed nodule in the submucosa or muscularis propria.[4] This aberrant pancreas is composed of pancreatic acini, ducts lined by columnar cells, and islets of Langerhans, and it is thought to represent a developmental anomaly.

First recognized by Doglioni et al,[1] PAT limited to the lamina propria of the gastric mucosa is characterized by nests of variably sized lobules composed of cells with apical, coarse granules and basely placed nucleus. In adults, there is a prevalence rate of PAT of 1% in gastric biopsy specimens and 12% in gastrectomy specimens. The prevalence rate was highest in the cardiac region (9.13%), followed by the fundus (0.16%) and the antrum (0.8%). In addition, PAT was strongly associated with chronic gastritis and intestinal metaplasia but not with Helicobacter pylori infection. A metaplastic origin for this entity has been proposed, thus the designation of "pancreatic acinar metaplasia."[1]

Two additional studies seem to reinforce the metaplastic origin of ectopic pancreatic tissue. Krishnamurthy and Dayal[2] reported PAT at the GEJ in 3% of adults with BE and Jhala et al[6] reported PAT at the GEJ in oxyntic mucosa of 41% of adults with autoimmune gastritis.

In contrast, Wang et al[7] reported PAT at the GEJ in 24% of subjects without histologic abnormalities in the esophagus or stomach. The only significant difference between patients with and without PAT was that those with PAT were a mean of 11 years younger than those without PAT. The higher incidence of PAT noted by these authors compared with that noted by Doglioni et al[1] can be explained by the fact that 3 levels of each biopsy specimen were examined and that the GEJ was selectively biopsied in the former study. These authors suggested a congenital origin for PAT.[7]

By examining biopsy specimens of the GEJ from a predominantly pediatric population, we demonstrated PAT in 16% of the patients, an incidence similar to that in adults.[1] The pancreatic nature of the nests was confirmed by immunohistochemical markers that targeted the exocrine pancreatic component with lipase, trypsin, and amylase. In our study population, PAT was not associated with BE and occurred in similar frequency with and without concomitant esophagitis and/or gastritis (63% vs 58%). It seems, therefore, that PAT at the GEJ has a congenital rather than a metaplastic origin.

These observations are reinforced by those of Integlia et al,[3] who described PAT in biopsy specimens of the antral mucosa of children without gastritis and/or intestinal metaplasia.

In summary, the data from our study suggest that PAT at the GEJ develops independently of inflammation and is, therefore, likely to be congenital. Our findings do not exclude a metaplastic origin for other sites.

References

[1.] Doglioni C, Laurino L, Dei Tos AP, et al. Pancreatic (acinar) metaplasia of the gastric mucosa. Am J Surg Pathol. 1993;17:1134-1143.

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

[3.] Integlia MJ, Krishnamurthy S, Berhane R, et al. Pancreatic metaplasia of the gastric mucosa in pediatric patients. Am J Gastroenterol. 1997;92:1553-1156.

[4.] Levin JK, Riddel RH, Weinstein WM. In Gastrointestinal Pathology and Its Clinical Implications. New York, NY: Igaku-Shoin; 1992:616.

[5.] Taylor AL. The epithelial heterotopias, of the alimentary tract. J Pathol Bacteriol. 1927;30:415-449.

[6.] Jhala N, Montemor J, Jhala D, et al. Pancreatic acinar cells in gastric oxyntic mucosa. Mod Pathol. 1990;12:76A.

[7.] Wang HH, Zeroogian JM, Spechler SJ, et al. Prevalence and significance of pancreatic acinar metaplasia at the gastroesophageal junction. Am J Surg Pathol. 1996;20:1507-1510.

Accepted for publication February 3, 2000.

From the Departments of Laboratories (Drs Popiolek and Kahn) and Pediatrics (Drs Markowitz and Daum), North Shore University Hospital, New York University School of Medicine, Manhasset. Dr Popiolek Is currently with the Department of Pathology, New York University Medical Center, Manhasset.

Presented in part at the Annual Meeting of the US and Canadian Academy of Pathology, Boston, Mass, March 1998.

Reprints: Ellen Khan, MD, Department of Pathology, North Shore University Hospital, 300 Community Dr. Manhasset, NY 11030 (e-mail: [e-mail]).