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Classification and grading criteria for neuroendocrine neoplasms of the gastrointestinal tract and hepatobiliary organs, World Health Organization (WHO), 2019

Classification and grading criteria for neuroendocrine neoplasms of the gastrointestinal tract and hepatobiliary organs, World Health Organization (WHO), 2019
Terminology Differentiation Grade Mitotic rate* (mitoses/2 mm2) Ki-67 index* (percent)
NET, G1 Well differentiated Low <2 <3
NET, G2 Well differentiated Intermediate 2 to 20 3 to 20
NET, G3 Well differentiated High >20 >20
NEC, small cell type (SCNEC) Poorly differentiated HighΔ >20 >20
NEC, large cell type (LCNEC) Poorly differentiated HighΔ >20 >20
MiNEN Well or poorly differentiated Variable Variable Variable
NET: neuroendocrine tumor; NEC: neuroendocrine carcinoma; SCNEC: small cell neuroendocrine carcinoma; LCNEC: large cell neuroendocrine carcinoma; MiNEN: mixed neuroendocrine-nonneuroendocrine neoplasm.
* Mitotic rates are to be expressed as the number of mitoses/2 mm2 (equalling 10 high-power fields at 40× magnification and an ocular field diameter of 0.5 mm) as determined by counting in 50 fields of 0.2 mm2 (ie, in a total area of 10 mm2); the Ki-67 proliferation index value is determined by counting at least 500 cells in the regions of highest labelling (hot-spots), which are identified at scanning magnification; the final grade is based on whichever of the two proliferation indexes places the neoplasm in the higher grade category.
¶ In most MiNENs, both the neuroendocrine and nonneuroendocrine components are poorly differentiated, and the neuroendocrine component has proliferation indexes in the same range as other NECs, but this conceptual category allows for the possibility that one or both components may be well differentiated; when feasible, each component should therefore be graded separately.
Δ Poorly differentiated NECs are not formally graded but are considered high grade by definition.
Reprinted with permission from: WHO Classification of Tumours. Digestive System Tumours, 5th ed, Klimstra DS, Kloppel G, La Rosa S, Rindi G, the WHO Classification of Tumours Editorial Board (Ed), the WHO classification of neuroendocrine neoplasms of the digestive system, p.16, Copyright © 2019 International Agency for Research on Cancer.
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