alpha-chymotrypsin and Metaplasia

Although pancreatic acinar metaplasia in the gastric mucosa is well recognized in chronic gastritis, gastric carcinoma with acinar differentiation is very rare. We encountered a case of gastric adenocarcinoma with prominent histologic and immunohistochemical features of pancreatic acinar differentiation in the absence of identifiable heterotopic pancreatic tissue. Distinct glandular and diffuse patterns of adenocarcinoma were also present, and there was focal mucin production. The tumor strongly expressed pancreatic exocrine enzymes trypsin and chymotrypsin, and focal neuroendocrine staining was also present. To investigate the prevalence of acinar differentiation in histologically typical gastric cancers, we performed immunohistochemical staining for trypsin and chymotrypsin on a tissue microarray containing 111 conventional gastric adenocarcinomas (60 intestinal, 28 mixed, 22 diffuse type, and 1 undifferentiated). No obvious morphologic evidence of acinar differentiation was identified in any of the 111 cases. Although some cases showed equivocal staining for at least 1 pancreatic exocrine enzyme on the initial tissue microarray sections, repeat immunohistochemical staining on representative whole-tissue sections failed to reproduce positive staining. Thus, acinar differentiation is rare in gastric adenocarcinomas, other than in histologically unusual cases such as the one we report, and in others from the literature, which are reviewed.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy; Carcinoma, Acinar Cell; Cell Differentiation; Chymotrypsin; Female; Gastrectomy; Humans; Immunohistochemistry; Male; Metaplasia; Middle Aged; Stomach Neoplasms; Tissue Array Analysis; Trypsin

While pancreatic metaplasia has been observed in gastric mucosa of patients with chronic gastritis, it has not been described in ectopic gastric mucosa. We have identified focal clusters of cells resembling pancreatic acinar cells (CPACs) in 11 of 350 biopsies of Barrett's mucosa from 120 patients with Barrett's esophagus enrolled in a clinical efficacy trial of omeprazole versus ranitidine for treatment of gastroesophageal reflux disease. Three additional cases from our surgical files were also studied. Immunoreactivity for trypsin and chymotrypsin was present in the CPACs of all 14 cases, while stains for alpha-amylase and lipase were each positive in 12 of 13. A few cells in the CPACs were also positive for chomogranins (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 in cells within CPACs. These results collectively indicate that the CPACs are aggregates of true pancreatic acinar cells admixed with a few endocrine cells. This 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. While the development of pancreatic metaplasia in Barrett's esophagus appears to be unrelated to drug therapy, the clinical relevance of this distinctive histological finding needs further investigation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; alpha-Amylases; Barrett Esophagus; Chromogranins; Chymotrypsin; Female; Gastric Mucosa; Humans; Immunohistochemistry; Lipase; Male; Metaplasia; Middle Aged; Pancreas; Pancreatic Polypeptide; Trypsin