: In 2010, the World Health Organization (WHO) classification of neuroendocrine
neoplasms was reviewed and validated the crucial role of the proliferative rate. According to the WHO classification 2010, gastroenteropancreatic neuroendocrine
neoplasms are classified as well-differentiated
neuroendocrine tumors (NETs) of grade 1 or 2 in up to 84%, or poorly differentiated
neuroendocrine carcinomas in 6%-8%.
Neuroendocrine carcinomas are of grade G. Recently, a proportion of
neuroendocrine tumors presenting a number of mitoses or a Ki-67 index higher than 20% and a well-differentiated morphology have been identified, calling for a new category, well-differentiated grade 3 NET (NET G-3). Studies that have reported the characteristics of neuroendocrine
neoplasms have identified more well-differentiated NET G-3 than
neuroendocrine carcinomas. The main localizations of NET G-3 are the pancreas, stomach, and colon. Treatment for NET G-3 is not standardized and is balanced between G-1/2
neuroendocrine tumor and
neuroendocrine carcinoma treatments. In nonmetastatic
neuroendocrine tumors, the European and American guidelines recommended a surgical resection for localized neuroendocrine
neoplasm, irrespective of the
tumor grading. In NET G-3,
chemotherapy is the benchmark if the main treatment goal is reduction of the
tumor mass, particularly if it would allow a secondary surgery. In the present work, we review the epidemiology and make recommendations for the management of NET G-3.
IMPLICATIONS FOR PRACTICE:
Neuroendocrine tumors presenting a number of mitoses or a Ki-67 index higher than 20% and a well-differentiated morphology have been identified and named well-differentiated grade 3
neuroendocrine tumors (NET G-3). The main localizations of NET G-3 are the pancreas, stomach, and colon. The prognosis is worse than that for NET G-2. In nonmetastatic NET G-3, surgery appeared to be the first option. The
chemotherapy regimen in pancreatic NET G-3 should be in line with that implemented in NET G-1/2 when the Ki-67 index is below 55% and should be in line with that implemented for
neuroendocrine carcinoma when Ki-67 is above 55%.