The pathological diagnosis of neuroendocrine tumors: common questions and tentative answers

Neuroendocrine neoplasms (NEN) develop in many organs, and although they share some pathological and clinical features, significant differences do exist among different tumor types and locations. The correct classification of NENs is based on the recently published WHO classification according to the various locations, and is relevant for the appropriate treatment in each group. The apparently easy diagnostic categorization in well-differentiated NENs, called neuroendocrine tumors, and poorly differentiated NENs, called neuroendocrine carcinomas, is complicated by the existence, among others, of different terminologies, morphological criteria of malignancy, combined exocrine-endocrine tumors, as well as of heterogeneous diagnostic, prognostic, and predictive markers. The present paper is an overview of the most frequently asked questions and an attempt to provide practical answers related to NEN diagnosis in the daily pathology work.