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Review
. 2020 Jun 1;9(6):1677.
doi: 10.3390/jcm9061677.

Well Differentiated Grade 3 Neuroendocrine Tumors of the Digestive Tract: A Narrative Review

Anna Pellat  1   2   3 , Romain Coriat  1   2
Affiliations
Review

Well Differentiated Grade 3 Neuroendocrine Tumors of the Digestive Tract: A Narrative Review

Anna Pellat et al. J Clin Med. .

Abstract

The 2017 World Health Organization (WHO) classification of neuroendocrine neoplasms (NEN) of the digestive tract introduced a new category of tumors named well-differentiated grade 3 neuroendocrine tumors (NET G-3). These lesions show a number of mitosis, or a Ki-67 index higher than 20% with a well-differentiated morphology, therefore separating them from neuroendocrine carcinomas (NEC) which are poorly differentiated. It has become clear that NET G-3 show differences not only in morphology but also in genotype, clinical presentation, and treatment response. The incidence of digestive NET G-3 represents about one third of NEN G-3 with main tumor sites being the pancreas, the stomach and the colon. Treatment for NET G-3 is not yet standardized because of lack of data. In a non-metastatic setting, international guidelines recommend surgical resection, regardless of tumor grading. For metastatic lesion, chemotherapy is the main treatment with similar regimen as NET G-2. Sunitinib has also shown some positive results in a small sample of patients but this needs confirmation. Peptide receptor radionuclide therapy (PRRT) and immunotherapy could be future available treatments after ongoing studies. The goal of this review was to sum up the latest data on the epidemiology and management of digestive NET G-3.

Keywords: grade 3; neuroendocrine tumor; well-differentiated.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Functional imaging for a patient with metastatic pancreatic grade 3 neuroendocrine tumor (NET G−3). (A) Images of DOTATOC-PET on the left and (B) FDG-PET on the right showing both positive uptakes in the liver, lungs and nodes.
Figure 2
Figure 2
Proposed algorithm for therapeutic management of NET G−3 of the digestive tract. G−1: grade 1, G−2: grade 2, G−3: grade 3, GEMOX: gemcitabine + oxaliplatine, FOLFIRI: 5-fluorouracile + irinotecan, FOLFOX: 5-fluorouracile + oxaliplatine, XELOX: capecitabine + oxaliplatine, PRRT: Peptide receptor radionuclide therapy.
See this image and copyright information in PMC

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