A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal

Guido Rindi,Günter Klöppel,William D Travis,Aldo Scarpa,J Han Van Krieken ,Manfred Dietel,Élisabeth Brambilla ,F Bosman ,David S Klimstra,Ronald R De Krijger,W Glenn Mccluggage ,Emad A Rakha,L Sylvia ,Nicholas Reed ,Holger Moch,Giovanni Tallini,Jean Yves Scoazec ,Behnoush Abedi‐Ardekani ,Brian Rous ,Hideaki Ohgaki ,Adel K El‐Naggar ,Lynnette Fernández-Cuesta ,Jacqueline Trouillas,Hironobu Sasano,Klaus J Busam,Ian A Cree

doi:10.1038/s41379-018-0110-y

Abstract

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.

Highlights

The current pathologic classifications of neuroendocrine neoplasms (NENs) across different organ systems use a range of site-specific terminologies and criteria, creating significant confusion among pathologists and treating clinicians
Neuroendocrine tumor (NET), in contrast, is intended to designate a family of welldifferentiated neoplasms whose potential to metastasize or invade the adjacent tissues depends on tumor site and type, and grade [1, 2]
In some sites, such as the pituitary and parathyroid, the vast majority exhibit very low risk of metastatic behavior; in others such as the pancreas and small intestine, most NETs behave in a malignant fashion

Summary

Introduction

The current pathologic classifications of neuroendocrine neoplasms (NENs) across different organ systems use a range of site-specific terminologies and criteria, creating significant confusion among pathologists and treating clinicians. A uniform classification framework for NENs at any anatomical location would reduce inconsistencies and contradictions among the various systems currently in use, allowing unification of classification concepts, despite organ-specific differences in classification criteria, tumor biology, and prognostic factors. The classification suggested here is intended to allow pathologists and clinicians to manage their patients with NENs consistently, and to facilitate comparisons between the different entities falling into this category of neoplasms. These authors contributed : Guido Rindi, David S.

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