Histology and genetics of cancer of the papilla, distal common bile duct, and duodenum

Abstract

The ampulla of Vater, as a transitional organ converging multiple different anatomic structures (each with different functional and histologic characteristics), gives rise to much more versatile cancers than common bile duct and pancreas. Unlike distal common bile duct carcinomas (DCBCs) and nonampullary duodenal carcinomas (NADCs), the ampullary carcinomas (ACs) are often found to arise in association with adenomatous lesions (adenomas of ampullary-duodenum, or intraampullary papillary tubular neoplasm). In contrast, the NADCs, especially those from the proximal duodenum, often arise de novo (without an overt adenoma component, forming a more plaque-like or ulcerative lesion instead), and some presumably arise from Brunner glands or gastric type cells on the duodenal mucosa, and thus show a different histologic repertoire from pancreatic and common bile duct carcinoma. ACs and NADCs not only often form mixed/hybrid histologic carcinomas that combine features of intestinal and pancreatobiliary types but also, not uncommonly, other adenocarcinoma types such as undescribed carcinoma types as well as signet ring (poorly cohesive cell), medullary, and mixed mucinous which are otherwise exceedingly uncommon in DCBCs or pancreas. Along with this histologic versatility, the molecular genetic alterations in AC and NADC are also fairly different from DCBC and pancreatic. For example, mismatch repair protein alteration (“microsatellite instability”) rate is very similar to the colon cancers in ACs, and is exceedingly uncommon in DCBC and pancreatic. Conversely, mutation in KRAS is less common in NADCs and ACs than it is in pancreatic and DCBC. Proper dissection of resection specimens in the pathology gross room (with close correlation with imaging and clinical findings) is crucial for accurate classification and staging of cancers of this region. For example, recent studies have elucidated that cancers arising from the four compartments of the ampulla itself also have different clinicopathologic characteristics and thus ACs are now regarded in four distinct groups: ampullary-duodenal, ampullary-ductal, intraampullary papillary-tubular neoplasm-associated, and NOS origin, all with different prognostic and histologic associations. Recently, studies have shown that anatomic variations of this region such as pancreatobiliary maljunction and low union of cystic duct into common duct may have a causal role in the development of pancreas and biliary tract cancers. Employment of proper pathologic dissection protocols has also led to better understanding the three-dimensional spread patterns of the cancers of these anatomically highly complex regions, which in turn is leading to major revisions in the reporting and TNM staging of these organs.