Classification and Grading Criteria for Neuroendocrine Neoplasms of Gastrointestinal Tract and Hepatopancreatobiliary Organs (21)

TerminologyDifferentiationGradeMitotic rateKi-67 index
NET, grade 1Well differentiatedLow<2<3%
NET, grade 2Well differentiatedIntermediate2–203%–20%
NET, grade 3Well differentiatedHigh>20>20%
NEC, small-cell typePoorly differentiatedHigh*>20>20%
NEC, large-cell typePoorly differentiatedHigh*>20>20%
MiNENWell or poorly differentiatedVariableVariableVariable
  • * Poorly differentiated neuroendocrine carcinomas are not formally graded but are considered high-grade.

  • In most mixed neuroendocrine–nonneuroendocrine neoplasms, both neuroendocrine and nonneuroendocrine components are poorly differentiated, and neuroendocrine component has proliferation indices in same range as other neuroendocrine carcinomas, but this conceptual category allows for possibility that one or both components may be well differentiated; when feasible, each component should therefore be graded separately.

  • MiNEN = mixed neuroendocrine–nonneuroendocrine neoplasm; NEC = neuroendocrine carcinoma.

  • Mitotic rates are number of mitoses/2 mm2 as determined by counting 50 fields of 0.2 mm2 (i.e., in total area of 10 mm2); Ki-67 proliferation index value is determined by counting at least 500 cells in regions of highest labeling (hot spots), which are identified at scanning magnification; final grade is based on whichever of 2 proliferation indices places neoplasm in higher-grade category.