Intra-ampullary Papillary-Tubular Neoplasm (IAPN)

In the past decade, there have been major developments in classification of and terminology for preinvasive neoplasms of the pancreatic ductal system and biliary tract. It is now well established that mass-forming preinvasive neoplasms (which we regard as tumoral intraepithelial neoplasms) in these regions constitute a distinct group that is distinctly different from both conventional adenocarcinomas (for which they are often mistaken because of their tumoral nature), and from “flat” (ordinary) dysplasias, with which they share their “preinvasive” (precursor) nature.3-6,8-10,14,22,25-26,29,40,48,53,59 In the pancreas, intraductal papillary mucinous neoplasm (IPMN) has been widely accepted as a unifying category25,26,29,52 embracing a spectrum ranging from very innocuous-appearing lesions lined by gastric-type epithelium (previously referred to as “hyperplasia” in the Japanese literature) to those indistinguishable from colonic villous adenomas, and finally to those that are extensively invasive [previously classified by the World Health Organization (WHO) as “papillary-mucinous carcinoma”].33 More recently, nonmucinous examples of tumoral intraepithelial neoplasia occurring in this region have also been characterized, namely intraductal tubulopapillary neoplasms (ITPNs; originally referred to as intraductal tubular neoplasms),31,55,56,64 which will also be recognized in the new WHO classification as a separate category. Recognition of pancreatic IPMNs has led to the reappraisal of preinvasive lesions occurring in the biliary tract,2,3,29,69 and many authors have adopted the terminology established in the pancreas and begun to classify such lesions of the biliary tract as “biliary IPMN,” a category that encompasses tubular, papillary, and villous preinvasive neoplasms including papillomatosis.2,3,28,32,38,46,53,54,68-71 However, some authors object to the term IPMN for this unification, citing differences in the morphologic repertoire of biliary versus pancreatic IPMNs, in particular, the reduced mucin production of the former.32,39,69 Thus, biliary tract counterparts of these lesions (both extrahepatic and intrahepatic) are now being unified under intraductal papillary neoplasm (IPN) for both intrahepatic and extrahepatic lesions.1 Meanwhile, the intra-ampullary counterpart of these lesions remains poorly characterized. Although duodenal adenomas, which can also involve the papilla of Vater (ie, the duodenal surface of the ampulla) have been fairly well-documented, as have virtually all intestinal (INT)-type adenomas (sporadic or related to familial adenomatous polyposis),12,13,18,24,44,45,50 the data on those that arise specifically within the ampulla have been very limited. Such cases have thus far been analyzed either as a part of studies on duodenal (surface) adenomas, or those on conventional cancers of the ampulla.11,24,57,63 In the upcoming WHO blue book, those that resemble INT adenomas will continue to be classified as INT adenomas, along with the adenomas of duodenal surface, whereas those with pancreatobiliary (PB) phenotype will now be recognized under a separate name (separate category) as “noninvasive PB-type neoplasms.” Here, we document the morphologic spectrum, immunophenotypic features, and clinical characteristics of 82 preinvasive mass-forming intra-ampullary neoplasms and their associated invasive carcinomas. We provisionally propose the descriptive term intra-ampullary papillary-tubular neoplasm (IAPN) for this group until their nature and kinship to other preinvasive neoplasms occurring in this region are further elucidated.