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Mod Pathol. 2018 Dec;31(12):1770-1786. doi: 10.1038/s41379-018-0110-y. Epub 2018 Aug 23.

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

Author information

1
Istituto di Anatomia Patologica, Università Cattolica-Fondazione Policlinico Universitario A. Gemelli, Rome, Italy.
2
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
3
International Agency for Research on Cancer (IARC), World Health Organization (WHO), Lyon, France.
4
University Health Network, University of Toronto, Toronto, ON, Canada.
5
University of Lausanne Medical Center, Lausanne, Switzerland.
6
CHUGA, UniversitéUGA, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France.
7
Department of Pathology, University Medical Center Utrecht and Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
8
Charité - University Hospital Berlin, Berlin, Germany.
9
University of Texas MD Anderson Cancer Center, Houston, TX, USA.
10
Department of Pathology, Technical University of München, München, Germany.
11
Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK.
12
University Hospital Zurich, Zurich, Switzerland.
13
University of Nottingham, Nottingham, UK.
14
Beatson West of Scotland Cancer Centre, Glasgow, UK.
15
National Cancer Registration and Analysis Service, Fulbourn, UK.
16
Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
17
Section of Pathology, ARC-Net Research Center and Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona, Italy.
18
Departement of Pathology, Gustave Roussy Cancer Campus, Villejuif, France.
19
University Medical Center, University of Bologna, Bologna, Italy.
20
Faculté de Médecine Lyon Est, Lyon, France.
21
Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
22
International Agency for Research on Cancer (IARC), World Health Organization (WHO), Lyon, France. creei@iarc.fr.

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.

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