Molecular Pathology of Ampullary, Intra-Pancreatic Bile Duct and Duodenal Cancers

Abstract

Periampullary cancers include carcinomas of the pancreatic head, ampullary cancers at the papilla of Vater, duodenal cancers and distal bile duct cancers. Due to their anatomical location close to the orifice of the biliary tract into the duodenum, they often present with similar symptoms. Likewise, curative treatment approaches such as Whipple procedure or its variants, are applied similarly for most periampullary cancers. However, striking differences in survival are consistently being observed between the different periampullary tumor types, and histological classification is sometimes difficult due to overlapping histopathological phenotypes. During recent years, increasing effort has been made to elucidate the molecular alterations underlying the observed histopathological and prognostic differences among periampullary tumors. This chapter concentrates on the molecular pathology of the three non-pancreatic carcinoma types located in the periampullary region: Ampullary, duodenal and distal bile duct cancer. Immunohistochemically, ampullary carcinomas are subclassified into an intestinal-type and a pancreaticobiliary-type. Intestinal-type ampullary cancers closely resemble duodenal cancers and both are molecularly related to other bowel cancers such as colorectal cancer. In contrast, distal bile duct carcinomas and ampullary carcinomas of the pancreatico-biliary type are more related to ductal pancreatic cancer. However, the prognosis varies considerably, with survival rates being greatest for ampullary and duodenal cancers and least for pancreatic cancer. Periampullary cancers may be associated with familial cancer syndromes such as familial adenomatous polyposis (FAP) or hereditary non-polypous colon cancer (HNPCC). In these cases, the underlying molecular alterations have been elucidated. In contrast, data on the molecular patterns characterizing sporadic periampullary non-pancreatic cancers are still fragmentary and further studies are required to better understand their genetic, transcriptional and epigenetic characteristics.