title: Long-term outcomes and prognostic factors in neuroendocrine carcinomas of the pancreas: Morphology matters.
abstract: BACKGROUND
  Limited data are available for pancreatic neuroendocrine carcinomas (NEC) defined by 2010 World Health Organization (WHO) criteria (mitotic count >20 mitoses/10 high-power fields and/or a Ki67 index of >20%), because most studies encompass heterogeneous cohorts of extrapulmonary/gastrointestinal NEC. Our aim was to evaluate the clinicopathologic characteristics, treatment, and prognosis of patients with pancreatic NEC defined by the 2010 WHO criteria.
  
  
  METHODS
  We conducted a retrospective analysis of 59 patients with a histologic diagnosis of NEC between 1990 and 2012. All cases were re-reviewed and classified according to the WHO 2010 classification and the WHO 2000 criteria.
  
  
  RESULTS
  All patients had stage III pancreatic NEC (n = 34; 58%) or IV pancreatic NEC (n = 25; 43%). Overall, 49 (83%) had poorly differentiated (PD) and 10 (17%) had a well-differentiated (WD) morphology. Fifteen patients (26%) were operated with curative intent (R0/R1), and 8 (14%) were R2 resections. Median disease-specific survival (DSS) for the entire cohort was 14 months. Median DSS did not differ between patient not undergoing resection and those undergoing R2 resection (10 vs 12 months; P > .46), but DSS was greater for patients who underwent R0/R1 resection compared with those with no resection/R2 resection (35 vs 11 months; P < .005). WD morphologic NEC had a greater survival than PD ones (43 vs 12 months; P = .004). Performance status, R2 resection/no resection, PD morphologic NEC, and no medical treatment were independent predictors of poor survival.
  
  
  CONCLUSIONS
  Pancreatic NEC constitute a heterogeneous group of tumors. Although NEC is an aggressive disease, curative resection in localized disease is associated with improved survival. Morphologic WD pancreatic NEC represents a subgroup with what seems to be a markedly improved survival. Within the NEC category, tumor treatment should be individualized considering tumor morphology as well as the other 2010 WHO criteria.
authors.affiliation: Division of Pancreatic Surgery, Università Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Crippa
authors.affiliation: Division of Pancreatic Surgery, Università Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Partelli
authors.affiliation: Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Bassi
authors.affiliation: Department of Medical Oncology, Università Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Berardi
authors.affiliation: Department of Pathology, ARC-Net Research Centre, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Capelli
authors.affiliation: Department of Pathology, ARC-Net Research Centre, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
authors.affiliation: Department of Pathology, Ospedale Sacro Cuore-Don Calabria, Negrar, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zamboni
authors.affiliation: Division of Pancreatic Surgery, Università Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy. Electronic address: falconi.massimo@hsr.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Falconi
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D018278:Carcinoma, Neuroendocrine / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D016208:Databases, Factual; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy / Q000379:methods*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D010180:Pancreatectomy / Q000379:methods / Q000401:mortality; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D016019:Survival Analysis