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.

Neuroendocrine neoplasms revisited—the challenges of reclassifying tumor

“…Despite increasing options for systemic therapy in advanced NEN, surgery is still the only curative approach for (localized) disease and we appreciate the article of Ulla Klaiber and Stefan Stättner [5] who provide a comprehensive overview on current standards in the surgical management of GEP-NETs. Furthermore, Iva Brcic and Hanna Henzinger present the pathologist's view in diagnosing GEP-NENs [7] and highlight the molecular background. Finally, Markus Raderer shares the medical oncologist's view of managing patients with NET G3 and "how to deal" with such a new entity [6].…”