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World J Gastroenterol. Dec 7, 2016; 22(45): 9944-9953
Published online Dec 7, 2016. doi: 10.3748/wjg.v22.i45.9944
Management of neuroendocrine carcinomas of the pancreas (WHO G3): A tailored approach between proliferation and morphology
Stefano Crippa, Stefano Partelli, Giulio Belfiori, Marco Palucci, Francesca Muffatti, Olga Adamenko, Luca Cardinali, Claudio Doglioni, Giuseppe Zamboni, Massimo Falconi
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
Giulio Belfiori, Luca Cardinali, Department of Surgery, Università Politecnica delle Marche, Ospedali Riuniti, 60121 Ancona, Italy
Claudio Doglioni, Department of Pathology, Pancreas Translational and Clinical Research Center San Raffaele Scientific Institute, Vita e Salute University, 20132 Milan, Italy
Giuseppe Zamboni, Department of Pathology, Ospedale Sacro Cuore-Don Calabria, 37024 Negrar, Italy
Author contributions: Crippa S designed the study, performed the literature review, drafted the manuscript and approved the final version; all other authors contributed to this paper in its critical revision and editing, and approved the final version.
Conflict-of-interest statement: No potential conflicts of interest, no financial support.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Stefano Crippa, MD, PhD, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy. crippa1.stefano@hsr.it
Telephone: +39-2-26437687 Fax: +39-2-26437807
Received: July 21, 2016
Peer-review started: July 25, 2016
First decision: September 28, 2016
Revised: October 27, 2016
Accepted: November 12, 2016
Article in press: November 13, 2016
Published online: December 7, 2016
Processing time: 138 Days and 11.5 Hours
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.

Keywords: Pancreatic neuroendocrine tumors; Surgery; Neuroendocrine carcinomas; Chemotherapy; Prognosis; Metastases; Morphology; Proliferation

Core tip: In this study, we reviewed the available literature for neuroendocrine carcinomas of the pancreas with a special focus on the differences between morphological poorly-differentiated and well-differentiated tumors. Although the quality of current evidence is suboptimal because of the retrospective design of the available studies, morphological well-differentiated tumors are associated with lower ki67 proliferative index, are less responsive to standard platinum-based chemotherapy and are associated with improved survival. The current category of neuroendocrine carcinomas should be revised taking into account these differences and new diagnostic criteria should be considered in order to clearly define poorly- and well-differentiated tumors.