Background: The WHO classified pancreatic neuroendocrine neoplasms (pNEN) in 2010 as G1, G2, and neuroendocrine carcinoma (NEC), according to Ki67 labeling index (LI). However, the clinical behavior of NEC is still not fully studied. We aimed to clarify the clinicopathological and molecular characteristics of NECs. Methods: We retrospectively evaluated the clinicopathological characteristics, KRAS mutation status, treatment response, and the overall survival of eleven pNEC patients diagnosed between 2001 and 2014 according to the WHO 2010. We subclassified WHO-NECs into well-differentiated (WDNEC) and poorlydifferentiated NEC (PDNEC), the latter further subdivided into large and small cell type. Results: The median Ki67 LI was 69.1% (range, 40% - 95%) and the median tumor size was 35 mm. 11 WHO-NECs were subclassified 4 WDNEC and 7 PDNEC, and further separated PDNEC into 3 large cell and 4 small cell subtypes. Comparisons of WDNEC vs. PDNEC revealed hypervascularity on CT, 50% (2/4) vs. 0% (0/7) (P = 0.109); median Ki67 LI, 46.3% (40% - 53%) vs. 85% (54% - 95%) (P = 0.001); KRAS mutations, 0% (0/4) vs. 85.7% (6/7) (P = 0.015); response rates to platinum-based chemotherapy, 0% (0/2) vs.100% (4/4) (P = 0.067) and median survival, 227 vs. 186 days (P = 0.227). Conclusions: The WHO-NEC category may be composed of heterogeneous disease entities, namely WDNEC and PDNEC. These subgroups tended to exhibit differing Ki67 and KRAS mutation profiles, and distinct response to chemotherapy. Further studies for the re-evaluation of the current WHO 2010 classification is warranted.

Background: The WHO classified pancreatic neuroendocrine neoplasms (pNEN)in 2010 as G1, G2, and neuroendocrine carcinoma (NEC), according to Ki67labeling index (LI). However, the clinical behavior of NEC is still not fully studied.We aimed to clarify the clinicopathological and molecular characteristics ofNECs.Methods: We retrospectively evaluated the clinicopathological characteristics,KRAS mutation status, treatment response, and the overall survival of elevenpNEC patients diagnosed between 2001 and 2014 according to the WHO 2010.We subclassified WHO-NECs into well-differentiated (WDNEC) and poorlydifferentiatedNEC (PDNEC), the latter further subdivided into large and smallcell type.Results: The median Ki67 LI was 69.1% (range, 40% - 95%) and the mediantumor size was 35 mm. 11 WHO-NECs were subclassified 4 WDNEC and 7PDNEC, and further separated PDNEC into 3 large cell and 4 small cell subtypes.Comparisons of WDNEC vs. PDNEC revealed hypervascularity on CT, 50% (2/4)vs. 0% (0/7) (P = 0.109); median Ki67 LI, 46.3% (40% - 53%) vs. 85% (54% -95%) (P = 0.001); KRAS mutations, 0% (0/4) vs. 85.7% (6/7) (P = 0.015); responserates to platinum-based chemotherapy, 0% (0/2) vs.100% (4/4) (P = 0.067) andmedian survival, 227 vs. 186 days (P = 0.227).Conclusions: The WHO-NEC category may be composed of heterogeneousdisease entities, namely WDNEC and PDNEC. These subgroups tended to exhibitdiffering Ki67 and KRAS mutation profiles, and distinct response to chemotherapy.Further studies for the re-evaluation of the current WHO 2010 classification iswarranted.