title: Management of neuroendocrine carcinomas of the pancreas (WHO G3): A tailored approach between proliferation and morphology.
abstract: Neuroendocrine carcinomas (NEC) of the pancreas are defined by a mitotic count > 20 mitoses/10 high power fields and/or Ki67 index > 20%, and included all the tumors previously classified as poorly differentiated endocrine carcinomas. These latter are aggressive malignancies with a high propensity for distant metastases and poor prognosis, and they can be further divided into small- and large-cell subtypes. However in the NEC category are included also neuroendocrine tumors with a well differentiated morphology but ki67 index > 20%. This category is associated with better prognosis and does not significantly respond to cisplatin-based chemotherapy, which represents the gold standard therapeutic approach for poorly differentiated NEC. In this review, the differences between well differentiated and poorly differentiated NEC are discussed considering both pathology, imaging features, treatment and prognostic implications. Diagnostic and therapeutic flowcharts are proposed. The need for a revision of current classification system is stressed being well differentiated NEC a more indolent disease compared to poorly differentiated tumors.
authors.affiliation: Stefano Crippa, Stefano Partelli, Marco Palucci, Francesca Muffatti, Olga Adamenko, Massimo Falconi, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, 20132 Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Crippa
authors.affiliation: Stefano Crippa, Stefano Partelli, Marco Palucci, Francesca Muffatti, Olga Adamenko, Massimo Falconi, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, 20132 Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Partelli
authors.affiliation: Stefano Crippa, Stefano Partelli, Marco Palucci, Francesca Muffatti, Olga Adamenko, Massimo Falconi, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, 20132 Milan, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Belfiori
authors.affiliation: Stefano Crippa, Stefano Partelli, Marco Palucci, Francesca Muffatti, Olga Adamenko, Massimo Falconi, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, 20132 Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Palucci
authors.affiliation: Stefano Crippa, Stefano Partelli, Marco Palucci, Francesca Muffatti, Olga Adamenko, Massimo Falconi, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, 20132 Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Muffatti
authors.affiliation: Stefano Crippa, Stefano Partelli, Marco Palucci, Francesca Muffatti, Olga Adamenko, Massimo Falconi, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, 20132 Milan, Italy.
authors.forename: Olga
authors.initials: O
authors.lastname: Adamenko
authors.affiliation: Stefano Crippa, Stefano Partelli, Marco Palucci, Francesca Muffatti, Olga Adamenko, Massimo Falconi, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, 20132 Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Cardinali
authors.affiliation: Stefano Crippa, Stefano Partelli, Marco Palucci, Francesca Muffatti, Olga Adamenko, Massimo Falconi, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, 20132 Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.affiliation: Stefano Crippa, Stefano Partelli, Marco Palucci, Francesca Muffatti, Olga Adamenko, Massimo Falconi, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, 20132 Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zamboni
authors.affiliation: Stefano Crippa, Stefano Partelli, Marco Palucci, Francesca Muffatti, Olga Adamenko, Massimo Falconi, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, 20132 Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Falconi
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D018278:Carcinoma, Neuroendocrine / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D049109:Cell Proliferation; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D019394:Ki-67 Antigen; D008940:Mitotic Index; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D011379:Prognosis
chemical_list: D019394:Ki-67 Antigen; D005047:Etoposide; D016190:Carboplatin; D002945:Cisplatin
keywords: Chemotherapy; Metastases; Morphology; Neuroendocrine carcinomas; Pancreatic neuroendocrine tumors; Prognosis; Proliferation; Surgery