Guido Rindi 1 , David S. Klimstra 2 , Behnoush Abedi-Ardekani 3 , Sylvia L. Asa 4 , Frederik T. Bosman 5 , Elisabeth Brambilla 6 , Klaus J. Busam 2 , Ronald R. de Krijger 7 , Manfred Dietel 8 , Adel K. El-Naggar 9 , Lynnette Fernandez-Cuesta 3 , Günter Klöppel 10 , W. Glenn McCluggage 11 , Holger Moch 12 , Hiroko Ohgaki 3 , Emad A. Rakha 13 , Nicholas S. Reed 14 , Brian A. Rous 15 , Hironobu Sasano 16 , Aldo Scarpa 17 , Jean-Yves Scoazec 18 , William D. Travis 2 , Giovanni Tallini 19 , Jacqueline Trouillas 20 , J. Han van Krieken 21 , Ian A. Cree , 3
23 August 2018
The classification of neuroendocrine neoplasms (NENs) differs between organ systems and currently causes considerable confusion. A uniform classification framework for NENs at any anatomical location may reduce inconsistencies and contradictions among the various systems currently in use. The classification suggested here is intended to allow pathologists and clinicians to manage their patients with NENs consistently, while acknowledging organ-specific differences in classification criteria, tumor biology, and prognostic factors. The classification suggested is based on a consensus conference held at the International Agency for Research on Cancer (IARC) in November 2017 and subsequent discussion with additional experts. The key feature of the new classification is a distinction between differentiated neuroendocrine tumors (NETs), also designated carcinoid tumors in some systems, and poorly differentiated NECs, as they both share common expression of neuroendocrine markers. This dichotomous morphological subdivision into NETs and NECs is supported by genetic evidence at specific anatomic sites as well as clinical, epidemiologic, histologic, and prognostic differences. In many organ systems, NETs are graded as G1, G2, or G3 based on mitotic count and/or Ki-67 labeling index, and/or the presence of necrosis; NECs are considered high grade by definition. We believe this conceptual approach can form the basis for the next generation of NEN classifications and will allow more consistent taxonomy to understand how neoplasms from different organ systems inter-relate clinically and genetically.