From morphology to molecular targets—the pathologist’s view in diagnosing gastroenteropancreatic neuroendocrine neoplasms

Abstract

SummaryIn the last decade, a number of genetic alterations in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have been identified. In addition, differences in tumor morphology as well as proliferation index (Ki-67) or number of mitoses have led to changes in the classification of these neoplasms. According to the new World Health Organization (WHO) classification, GEP-NENs are now divided into two genetically and prognostically different categories: (i) well-differentiated neuroendocrine tumors (NET) subdivided into low (G1), intermediate (2) and high (G3) grade tumors, and (ii) poorly differentiated neuroendocrine carcinomas (NEC). In addition, a group of mixed neuroendocrine–non-neuroendocrine neoplasms (MiNEN) has been defined. This review focuses on the clinical, morphological, immunohistochemical and molecular findings of the GEP-NENs and their key diagnostic features that can help the pathologist to differentiate between tumors in this heterogeneous group. In challenging cases, additional immunohistochemical and/or molecular analysis can be helpful to determine the correct diagnosis and proper treatment for the patient.