Table 2.
Classification and grading criteria for neuroendocrine neoplasms (NENs) of the GI tract and hepatopancreatobiliary organs
| Terminology | Differentiation | Grade | Mitotic rate* (mitoses/2 mm2) | Ki‐67 index* |
|---|---|---|---|---|
| NET, G1 | Well differentiated | Low | <2 | <3% |
| NET, G2 | Intermediate | 2–20 | 3–20% | |
| NET, G3 | High | >20 | >20% | |
| NEC, small‐cell type (SCNEC) | Poorly differentiated | High† | >20 | >20% |
| NEC, large‐cell type (LCNEC) | >20 | >20% | ||
| MiNEN | Well or poorly differentiated‡ | Variable‡ | Variable‡ | Variable‡ |
LCNEC, Large‐cell neuroendocrine carcinoma; MiNEN, Mixed neuroendocrine–non‐neuroendocrine neoplasm; NEC, Neuroendocrine carcinoma; NET, Neuroendocrine tumour; SCNEC, Small‐cell neuroendocrine carcinoma.
Mitotic rates are to be expressed as the number of mitoses/2 mm2 as determined by counting in 50 fields of 0.2 mm2 (i.e. 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.
Poorly differentiated NECs are not formally graded, but are considered high‐grade by definition.
In most MiNENs, both the neuroendocrine and non‐neuroendocrine components are poorly differentiated, and the neuroendocrine component has proliferation indices 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.