Pancreatic Acinar Tissue in Liver Explants

Abstract

Pancreatic acini-like tissue is occasionally seen in the liver. It is uncertain whether its presence represents heterotopia or metaplasia. To gain further insight into this issue, we performed a pathologic and immunohistochemical study in liver explants to identify pancreatic acinar tissue. A total of 382 liver explants transplanted from 1995 to 2000 were examined. Formalin-fixed, paraffin-embedded tissues were stained with hematoxylin-eosin, and immunohistochemical analyses using antibodies against CK7, CK8, and CK19 (biliary type cytokeratins), CD56 (positive in reactive bile ductules), chromogranin A (positive in reactive bile ductules and human oval-like/hepatic progenitor cells), pancreatic amylase, and PDX-1 were performed. The immunohistochemical comparison group consisted of 3 gastric biopsies diagnosed as autoimmune gastritis with pancreatic metaplasia and 3 normal pancreatic tissues from pancreatectomy specimens. Sixteen (4.2%) of 382 liver explants contained pancreatic acini-like tissue. Fifteen of these were cirrhotic livers due to cryptogenic cirrhosis (n=1), primary biliary cirrhosis (n=3), primary sclerosing cholangitis (n=1), chronic hepatitis C-related cirrhosis (n=5), and cirrhosis with hepatitis C and hepatocellular carcinoma (n=5). There was 1 noncirrhotic explant, the result of isoniazid hepatotoxicity. The pancreatic acini-like tissue appeared as small clusters of compactly packed cells that either blended imperceptibly with or were in close proximity to adjacent bile ducts or ductules. The pancreatic acinar tissue was diffusely reactive for amylase, was occasionally positive for keratin 8 and chromogranin A, and was negative for CD56, keratin 7, and keratin 19. Biliary type epithelium (bile ducts and ductules) and the ductules within the acini was always diffusely positive for keratin 7, 8, and 19, occasionally reactive for CD56 and chromogranin A, and typically negative for amylase. Our results collectively indicate that pancreatic acini-like tissue in liver represent aggregates of pancreatic acinar cells admixed with small intra-acinar terminal ductules. Given the close spatial relationship with reactive bile ductules and the apparent transition in immunophenotype from bile ductules to pancreatic acinar tissue, the latter is likely of metaplastic origin derived from a hepatic progenitor lineage.