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

TLDR

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, and is intended to allow pathologists and clinicians to manage patients consistently while acknowledging organ‑specific differences in criteria, biology, and prognostic factors. The framework, developed at an IARC consensus conference in November 2017 and refined by experts, distinguishes differentiated NETs from poorly differentiated NECs—both expressing neuroendocrine markers—and grades NETs as G1–G3 by mitotic count, Ki‑67 index, or necrosis, while NECs are defined as high grade. The dichotomous NET/NEC subdivision is supported by genetic, clinical, epidemiologic, histologic, and prognostic evidence, and the authors believe this approach can underpin future NEN classifications, enabling a more consistent taxonomy to elucidate inter‑organ clinical and genetic relationships.

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.