Does the WHO 2010 classification of pancreatic neuroendocrine neoplasms accurately characterize pancreatic neuroendocrine carcinomas?

BACKGROUND: The WHO classified pancreatic neuroendocrine neoplasms in 2010 as G1, G2, and neuroendocrine carcinoma (NEC), according to the 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 NEC (WDNEC) and poorly differentiated NEC (PDNEC). The latter was further subdivided into large-cell and small-cell subtypes. RESULTS: The median Ki67 LI was 69.1 % (range 40–95 %). Eleven WHO-NECs were subclassified into 4 WDNECs and 7 PDNECs. The latter was further separated into 3 large-cell and 4 small-cell subtypes. Comparisons of WDNEC vs. PDNEC revealed the following traits: 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); Rb immunopositivity, 100 % (4/4) vs. 14 % (1/7) (P = 0.015); KRAS mutations, 0 % (0/4) vs. 86 % (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 profiles of Ki67 LI, Rb immunopositivity and KRAS mutation, and distinct response to chemotherapy. Further studies for the reevaluation of the current WHO 2010 classification are warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00535-014-0987-2) contains supplementary material, which is available to authorized users.