Pathologic classification of “pancreatic cancers”: current concepts and challenges

Abstract

As the most common and most important cancer of the pancreas, with rapid mortality and now also as the third leading cause of cancer-related deaths in the United States, pancreatic ductal adenocarcinoma (PDAC) has become synonymous with "pancreas cancer". PDAC is also the prototype of the "pancreatobiliary-type" adenocarcinomas, along the biliary tract, ampullary and gallbladder cancers with the similar morphology and behavior. Recent molecular profiling studies have identified distinct subsets of PDAC, potentially with different behaviors and targetability. Moreover, while PDAC is by far the most common cancer of the pancreas, there are various other types that occur in this organ and are erroneously classified together with PDAC. Many of these have different molecular and biologic characteristics that warrant their management separately although they are also technically "pancreatic cancers". While some are closely related to PDAC and have as aggressive behavior (such as adenosquamous carcinomas which are recently recognized under "basal" like category in profiling studies, which are actually even worse prognostically than PDACs), in the meantime, others such as colloid carcinoma has a much better behavior than PDAC, and as a carcinoma with intestinal lineage (MUC2/CDX2) colloid carcinoma may require an entirely different treatment approach as well. Similarly, medullary carcinomas also appear to have different biology. Additionally, non-ductal cancers such as acinar, neuroendocrine, solid-pseudopapillary neoplasms and pancreatoblastoma have their respective clinicopathologic and molecular associations and warrant careful elimination in the management and study protocols. Another very problematic aspect in the classification of "pancreas cancer" is its delineation from the cancers of neighboring organs, in particular, ampullary/duodenal and common bile duct (CBD) cancers, for which recently more refined criteria have been provided. Additionally, the possibility of metastasis from another site and lymphomas also need to be considered. In summary, there is a whole host of cancers that occur in the pancreas that ought to be considered carefully before a case is classified as an ordinary "pancreas cancer" (PDAC).

Nomograms for predicting overall survival and cancer-specific survival in young patients with pancreatic cancer in the US based on the SEER database

“…Additionally, it was worth noting that the impact of pathological types on prognosis was even greater than that of surgery. Mostafa et al (2017) pointed out that although ductal adenocarcinoma was the most common pathological type of PC, there were many other pathological types of PC in the real world, such as solid pseudopapillary tumors, neuroendocrine tumors, and so on. They had different clinicopathological characteristics and biological behavior.…”

High mobility group AT‑hook 2 and c‑MYC as potential prognostic factors in pancreatic ductal adenocarcinoma

“…Pancreatic ductal adenocarcinoma (PDAC) is the most common type of malignant pancreatic tumor and is the fourth leading cause of cancer-associated mortality worldwide in 2014 (1)(2)(3). Surgical resection remains the only optimal treatment regimen for patients with PDAC (4).…”

Cancer Associated Fibroblast (CAF) regulation of PDAC parenchymal (CPC) and CSC phenotypes is modulated by ECM composition.

“…Here we nd that the CAFs further activate these two malignant phenotypes to exerbate these parenchymal CPC and CSCs cell interactions that contribute to the vascular [40] and invasive phenotype of the early stage tumor.…”

“…Indeed, it has been reported [5] that growth on Matrigel-rich ECM activates the CSC program driving their transdifferentiation into an endothelial-like VM network via a VEGF/VEGFR-2 mediated cascade while the more differentiated CPCs have a high invadopodia-driven invasive capacity that is stimulated by EGF [39], which is highly secreted by the CSCs. In this way, parenchymal CPC cells and CSCs interact to contribute to the vascular [40] and invasive phenotype of the early stage tumor.…”