ENETS Consensus Guidelines for High-Grade Gastroenteropancreatic Neuroendocrine Tumors and Neuroendocrine Carcinomas

are not a homogenous entity and can be further subclassified into biologically relevant subgroups.A separation based on the proliferative index (Ki-67 >55%) was shown to have clinical implications regarding response to chemotherapy and prognosis: NEC with Ki-67 >55% responded better to platinum-based chemotherapy and, nevertheless, had a 4 months' shorter median survival than G3 NEN in the lower proliferative range (20-55%) [1] .More recent publications show that morphological differentiation and Ki-67 are able to separate prognostic groups among G3 cases, and therefore a separation of well-differentiated G3 NET from poorly differentiated G3 NEC is emerging [2][3][4] .The exact criteria need to be defined both on the morphological and on the molecular level.The spectrum of mutations of well-differentiated