Management Options for Advanced Low or Intermediate Grade Gastroenteropancreatic Neuroendocrine Tumors: Review of Recent Literature

Table 1

Nomenclature and classification of neuroendocrine tumors.

Differentiation and grade	Mitotic count (/10 HPF)	Ki-67 index (%)	Traditional classification	ENETS/WHO classification	Moran et al. [30]
Well differentiated
Low grade (grade 1)	<2	≤2	Carcinoid, islet cell, PNET	Neuroendocrine tumor, grade 1	Neuroendocrine carcinoma, grade 1
Intermediate grade (grade 2)	2–20	3–20	Carcinoid, atypical carcinoid, islet cell, PNET	Neuroendocrine tumor, grade 2	Neuroendocrine carcinoma, grade 2
Poorly differentiated
High grade (grade 3)	>20	>20	Small-cell carcinoma	Neuroendocrine carcinoma, grade 3, small cell	Neuroendocrine carcinoma, grade 3, small cell
			Large-cell neuroendocrine carcinoma	Neuroendocrine carcinoma, grade 3, large cell	Neuroendocrine carcinoma, grade 3, large cell

HPF, high-power field; ENETS, European Neuroendocrine Tumor Society; PNET, pancreatic neuroendocrine tumor; HPF = 2 mm²; at least 40 fields (at ×40 magnification) were evaluated in areas of highest mitotic density. Cutoff values were taken from American Joint Committee on Cancer staging system (seventh edition); Ki67/MIB1 antibody; percentage of 2,000 tumor cells in areas of highest nuclear labeling. Cutoff values were taken from American Joint Committee on Cancer staging system (seventh edition); The term atypical carcinoid only applies to intermediate grade neuroendocrine tumor of the lung.