Ampullary adenocarcinoma – differentiation matters

Junctions between two different types of epithelial lining do not only give rise to unique types of diseases, but are also interesting and relevant areas with regards to tumorigenesis. Typically, carcinomas arising in these areas may show a differentiation resembling either of the colliding epithelia (and sometimes a mixture or an intermediate of both). Especially in larger tumors, this adds to the difficulties in defining the exact anatomical origin of a given tumor.The ampulla of Vater is one of these epithelial junctions, but its tumors have gained considerably less attention, which is probably due to their relatively low number, their reduced diagnostic accessibility, and the fact that differentiating clinical concepts with regards to neoadjuvant or adjuvant treatment strategies are lacking so far. Surgical treatment of ampullary cancer reaches curative rates of above 50% whereas the treatment of pancreatic cancer still has a very low cure rate of around 10% [1,2]. In particular, lymphatic involvement has been described as limiting the curative possibilities [3] and recently different molecular changes in metastasis associated genes have been shown in ampullary and pancreatic cancers [4]. Thus, from a clinical point of view, surgeons have found that ampullary cancer prognosis also depends on other factors besides resectability, TNM staging, and lymphatic involvement.It was first described by Kimura and coworkers in 1994 [5] that adenocarcinomas of the ampulla, which comprise 90% of all its malignancies, are constituted of two main histological subtypes, the intestinal and the pancreatobiliary subtypes. This can be attributed to the fact that bile and pancreatic duct epithelia meet the duodenal mucosa. Over the years several other studies have confirmed the findings of the original publication. While the intestinal type is indistinguishable by histological means from its colonic counterpart, the same is true for the pancreatobiliary type when compared to its rela