title: Gastroenteropancreatic Well-Differentiated Grade 3 Neuroendocrine Tumors: Review and Position Statement.
abstract: : 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.
  
  
  
  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%.
authors.affiliation: Department of Gastroenterology, Cochin Teaching Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France romain.coriat@cch.aphp.fr.
authors.forename: Romain
authors.initials: R
authors.lastname: Coriat
authors.affiliation: Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'Oncologie Digestive, Lyon Cedex 03, France Université Claude Bernard Lyon 1, Université de Lyon, , Lyon, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Walter
authors.affiliation: Department of Pathology, Cochin Teaching Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Terris
authors.affiliation: Department of Pathology, Bichat Hospital, Assistance Publique-Hôpitaux de Paris, Départements Hospitalo Universitaires, Paris, France Department of Gastroenterology and Pancreatology, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Départements Hospitalo Universitaires, Clichy, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Couvelard
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Paris, France Department of Gastroenterology and Pancreatology, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Départements Hospitalo Universitaires, Clichy, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ruszniewski
mesh_terms: D016461:Chemoembolization, Therapeutic; D003937:Diagnosis, Differential; D006801:Humans; D007414:Intestinal Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000628:therapy*; D019394:Ki-67 Antigen / Q000032:analysis; D058990:Molecular Targeted Therapy; D060787:Neoplasm Grading; D018358:Neuroendocrine Tumors / Q000453:epidemiology / Q000473:pathology / Q000628:therapy*; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000628:therapy*; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000628:therapy*
chemical_list: D019394:Ki-67 Antigen
keywords: Chemotherapy; Grade 3; Neuroendocrine tumor; Targeted therapy; WHO classification; Well-differentiated