Oncocytic papillary neoplasms of the biliary tract: a clinicopathological, mucin core and Wnt pathway protein analysis of four cases

Aims: Oncocytic change in papillary neoplasms of the biliary tract is a very uncommon finding with little known about pathogenesis, immunophenotype and prognosis, especially in comparison to similar lesions in the pancreatic ductal system. We report four cases of oncocytic biliary intraductal papillary neoplasms (IPNs), highlighting the clinicopathological characteristics of these tumours, the immunohistochemical profile with regard to Writ pathway proteins and mucin core protein (MUC) status, and compare these findings with the oncocytic variant of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Methods: Four cases of oncocytic IPN of the extrapancreatic, biliary tree (two with accompanying invasive carcinomas) were examined for mucin profiles and Writ signalling proteins. The cases were stained for: beta-catenin, c-myc, glutathione synthase kinase (GSK), E-cadherin, cyclin D1, and adenomatous polyposis coli (APC), and MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B and MUC6, using standard immunohistochemistry. Results: The cases occurred in three males and one female, ranging in age from 59 to 81 years. The lesions caused obstructive symptoms related to the biliary tree as well as non-specific abdominal symptoms. Typically, cystic lesions were noted grossly. All four of the IPNs were composed of distinctive oncocytic cells. The invasive carcinomas accompanying two of the cases were also composed of oncocytes. None of the cases showed aberrant expression of the Writ signalling proteins, although cyclin D1 was markedly overexpressed in all four cases. Three of four cases showed the following mucin profile: MUC3, MUC4, MUC5AC, MUC5B and MUC6 positive. Conclusions: The Writ pathway proteins (especially beta-catenin and E-cadherin) are expressed normally in oncocytic variants of intraductal papillary neoplasms of the biliary tree, and the mucin profile is similar to their counterparts in the pancreas.