Pathologic Classification and Biological Behavior of Pancreatic Neoplasia

Abstract

Pancreatic neoplasms are classified according to the normal cells they recapitulate. These neoplasms’ clinicopathologic and biologic characteristics are determined mostly by their cellular lineage. Most are of ductal lineage, characterized by tubular units, cysts, and papilla or mucin formation and expression of mucin-related glycoproteins and oncoproteins. There are also genetic and molecular alterations that are fairly tumor specific.

Invasive ductal adenocarcinoma (DA) constitutes the vast majority (>85%) of carcinomas of ductal lineage. DA is characterized by insidious infiltration and rapid dissemination, despite its relatively well-differentiated histologic appearance. Presumed precursors include microscopic intraductal proliferative changes now termed pancreatic intraepithelial neoplasia (PanIN). PanINs represent neoplastic transformation ranging from early mucinous change (low-grade PanIN) to frank carcinoma in situ (high-grade PanIN). A similar neoplastic spectrum characterizes intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), cystic ductal-mucinous tumors with papillae formation, which may be associated with DA. As such, these are regarded as mass-forming preinvasive neoplasia. Some IPMNs are associated with colloid-type invasive carcinoma, a clinicopathologically distinct indolent tumor.

Although most ductal pancreatic neoplasia show some degree of mucin formation, serous tumors, of which serous cystadenoma is the sole example, lack mucin formation, presumably because they recapitulate centroacinar ducts.

Among non-ductal pancreatic tumors, neuroendocrine neoplasms are the most common. The vast majority are well-differentiated, low-/intermediate-grade malignancies characterized by protracted clinical course. In contrast, poorly differentiated neuroendocrine carcinomas (small or large cell type) are exceedingly uncommon and highly aggressive. Pancreatic acinar lineage tumors, namely, acinar cell carcinomas and pancreatoblastomas – the latter mostly a childhood malignancy – are uncommon and are associated with aggressive clinical course, though not as dismal as DA. Solid pseudopapillary neoplasm is a female-predominant pancreatic tumor of undetermined lineage that follows a predominantly indolent course.