Pathologic stage (AJCC 8th ed.)................................................. pT__N__M__
Response Options to "Histologic Type and Grade"
___ G1: Well-differentiated neuroendocrine tumor
___ G2: Well-differentiated neuroendocrine tumor
___ G3: Well-differentiated neuroendocrine tumor
___ Other (specify): _________________________
___ GX: Well-differentiated neuroendocrine tumor, grade cannot be assessed
___ Not applicable
Grade Mitotic Rate (per 10 HPF) # Ki-67 Index (%)##
G1 <2 <3
G2 2 to 20 3 to 20
G3 >20 >20
# Mitotic rate should be reported as number of mitoses per 2 mm2 , by evaluating at least 10 mm2 in the most mitotically active part of the tumor (eg, if using a microscope with a field diameter of 0.55 mm, count 42 high-power fields [10 mm2 ] and divide the resulting number of mitoses by 5 to determine the number of mitoses per 2 mm2 needed to assign tumor grade). See CAP checklist for further information. ## Ki-67 index is reported as percent positive tumor cells in area of highest nuclear labeling (“hot spot”), although the precise method of assessment has not been standardized. A number of methods have been used to assess Ki-67 index, including automatic counting and “eyeballing”. Eye-balling can be used for most tumors; however, for tumors with Ki-67 index close to grade cut-offs, it is recommended to perform the manual count on the print of camera-captured image of the hot spot. It has been recommended that a minimum of 500 tumor cells be counted to determine the Ki-67 index, and a notation is made if less cells are available. Grade assigned based on Ki-67 index is typically higher than that based on mitotic count, and the case is assigned to the higher of the 2 if both methods are performed.
It is important to note that there are a small group of well-differentiated neuroendocrine tumors with a Ki-67 index >20% and a mitotic rate usually <20 per 10hpf. In WHO-2010, these tumors were considered as G3 poorly differentiated neuroendocrine carcinomas. However, they have typical morphology of well-differentiated tumors. In the WHO-2017 blue book of endocrine tumors and AJCC 8th edition, those with typical morphology of well differentiated tumors are classified as “well-differentiated neuroendocrine tumor” but as grade 3.
Note: For poorly differentiated (high-grade) neuroendocrine carcinomas, the College of American Pathologists (CAP) protocol for carcinoma of the appendix should be used.