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Tumor Size (cm)
Histologic Type and Grade
A word about grading
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 10 HPF. In WHO-2010, these tumors were considered as G3 poorly differentiated neuroendocrine carcinomas. However, they have typical morphology of well-differentiated tumors.
Previous studies (most on pancreatic neuroendocrine tumors) have demonstrated that these tumors have a worse prognosis than grade 2 (Ki-67=3-20 % and mitosis <20/10 HPF) neuroendocrine tumors, but they are not as aggressive as poorly differentiated neuroendocrine carcinomas.12 In addition, these tumors do not have the genetic abnormalities seen in poorly differentiated neuroendocrine carcinomas.13 Furthermore, unlike poorly differentiated neuroendocrine carcinomas, they are less responsive to platinum-based chemotherapy.14 In the WHO-2017 blue book of endocrine tumors and AJCC 8th edition,15 those with typical morphology of well-differentiated tumors are classified as “well differentiated neuroendocrine tumor” but as grade 3. Here, the updated classification for “endocrine” tumors is adapted, and following grading scheme is recommended to
grade well-differentiated gastroenteropancreatic neuroendocrine tumors (Table 4).
A word about the mitotic rate
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. Only clearly identifiable mitotic figures should be
counted; hyperchromatic, karyorrhectic, or apoptotic nuclei are excluded. Because of variations in
field size, the number of high-power fields (HPF) (at 40X magnification) for 10 mm2 (thereby 2 mm2)
must be determined for each microscope (Table 3). For example, if using a microscope with a field
diameter of 0.55 mm, count 42 HPF and divide the resulting number of mitoses by 5 to determine the
number of mitoses per 2 mm2 needed to assign tumor grade.
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)