Gallbladder neuroendocrine carcinoma diagnosis, treatment and prognosis based on the SEER database: A literature review

Table 2 2019 World Health Organization and 2017 international Agency for Research on Cancer classification and grading criteria for neuroendocrine neoplasms of the gastrointestinal tract and hapatopancreatobiliary organs

Terminology	Differentiation	Grade	Mitotic1 rate (mitoses/2 mm2)	Ki-67 index	Molecular differences
NET Gl	Well-differentiated NET (carcinoid)	Low	< 2	< 3%	Mutations in MEN1, DAXX .ATRX
NET G2		Intermediate	2-20	3% - 20%	Mutations in MEN1, DAXX .ATRX
NET G3		High	> 20	> 20%	Mutations in MEN1, DAXX .ATRX
NEC2	Poorly differentiated NEC	High	> 20	> 20%	Mutations in TP53 or RB1
Mixed NENs2	Well or poorly differentiated	Variable3	Variable	Variable

¹Mitotic rates arc expressed as number of mitoses/2 mm² as determined by counting in 50 fields of 0.2 mm² (in a total area of 10 mm²); The Ki-67 proliferation index is determined by counting at least 500 cells in regions of highest labeling (hot-spots) which arc identified at scanning magnification; The Grade is based on whichever of the two proliferation indexes place the neoplasm in the higher grade category[6].

²NEC including {NEC, small-cell lype [SCNEC; NEC; large cell typc (LCNEC)]}; Mixed NENs including [mixed neuroendorine-non-neuroendorine neoplasms (MiNENs)]; Mixed adenoneuroendocrine carcinomas (MANECs).

³Vriablc means: Changeable.

NET: Neuroendocrine tumors; NEC: Neuroendocrine carcinoma.