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Endocrine Abstracts (2018) 60 NETS1 | DOI: 10.1530/endoabs.60.NETS1

Department of Cellular Pathology, Royal Free London NHS Foundation Trust, London, UK.


The classification and nomenclature of neuroendocrine neoplasms (NENs) is complex, can be confusing and has undergone major changes over the last three decades, as illustrated by the evolution in classification of GEP-NENs by the WHO. The 4th edition of the WHO’s classification of GEP-NENs was published in 2010. This edition is currently in use for gastrointestinal neuroendocrine neoplasm (GI-NEN) classification. The WHO 2010 classification introduced a strict separation between well-differentiated neoplasms (defined as NETs) and poorly differentiated neuroendocrine carcinomas (defined as NECs). NETs are, by definition, either grade G1 or G2 only and NECs are, by definition, always grade G3. There is no ‘well-differentiated neuroendocrine carcinoma’ in the WHO 2010 classification. Accumulating evidence strongly suggests that the G3 category of pancreatic neuroendocrine neoplasms (PanNENs), with Ki-67>20%, is a heterogeneous group and actually includes two different entities that profoundly differ in their biology, prognosis and molecular genetics: i) well-differentiated NET with an elevated proliferative rate; and ii) poorly differentiated NEC with small cell or large cell morphology. Based on this new evidence, in 2017, the WHO classification of the PanNENs applied the three tier grade system to the well-differentiated NENs, introducing the well-differentiated neuroendocrine neoplasm of high grade or NET G3 category. Further changes of the 2017 WHO Classification of PanNEN include the new definition of mixed tumour category as mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN), replacing the previous term mixed adenoneuroendocrine carcinoma (MANEC). The new 2017 WHO Classification of PanNENs should now be used for PanNEN classification. Though not formally published by WHO yet, this new pancreatic NET G3 category and new term for mixed tumours MiNEN can be adopted for all other GI sites. The 5th edition of WHO classification of GI-NENs is expected to be published in 2019.

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