Mixed Neuroendocrine-Nonneuroendocrine Neoplasms of the Pancreas: Unraveling the Concept and Applying It to Clinical Practice.

Abstract

Although most pancreatic epithelial neoplasms show differentiation predominantly along ductal, neuroendocrine, or acinar lines, minor elements with divergent differentiation are common, and some neoplasms have substantial components reflecting more than one line of differentiation. These rare mixed neoplasms can show any combination of phenotypes, but neuroendocrine differentiation mixed with either ductal or acinar components is the most frequent. The classification of mixed neoplasms with a neuroendocrine component has been standardized by the World Health Organization (WHO) under the label of "mixed neuroendocrine-nonneuroendocrine neoplasm (MiNEN)." However, the definition of MiNEN is complex and several distinct neoplastic entities fall within this conceptual category, leading to confusion about how to use the term MiNEN and what are its clinical utility and significance. To demystify the MiNEN concept and provide some guidance about how the specific neoplasms encompassed in the category should be diagnosed, prognosticated, and managed. Mixed neoplasms with amphicrine features are also discussed, although they are not classified as MiNENs according to the definition of that category. Publications describing pancreatic neoplasms with mixed differentiation have been reviewed, along with the range of WHO classifications related to gastrointestinal and endocrine neoplasms, for the past 45 years. The MiNEN concept, along with the evolving concept of mixed neoplasms with amphicrine features, can be helpful to describe groups of pancreatic neoplasms that exhibit evidence of differentiation along both neuroendocrine and nonneuroendocrine lineages. For individual neoplasms, however, the diagnosis should indicate the specific components represented to ensure appropriate clinical management.