Management of Pancreatic Neuroendocrine Tumors Daniel M. Halperin, MD a , Matthew H. Kulke, MD b,c, * KEYWORDS • Neuroendocrine tumor • Pancreatic neuroendocrine tumor • Islet cell tumor • Diagnosis • Prognosis • Management Pancreatic neuroendocrine tumors (PNETs) account for less than 5% of all pancreatic cancers and have an estimated overall incidence of 5 cases per 1 million population annually. 1,2 In recent years the diagnosed incidence of neuroendocrine tumors has been increasing, probably due at least in part to improved detection and diagnosis. 3 PNETs are best known for their association with characteristic syndromes of hormone hypersecretion. Such symptoms can often be effectively controlled with medical therapy, and when tumors are localized they can be successfully resected. However, the majority of PNETs are clinically silent, presenting at a more advanced clinical stage. Treatment options for patients with advanced PNET have previously been limited. Recently, new biologically targeted therapies have been approved for these tumors and offer improved treatment opportunities for patients with this disease. CAUSES AND GENETICS PNETs, also termed islet cell tumors, were originally thought to arise from the hormone-producing islet cells of the pancreas. Recent studies have suggested that PNETs may, in fact, arise from ductal progenitor cells, which are putative embryonic and adult pancreatic stem cells. 4 A minority of PNETs are associated with inherited genetic syndromes, including multiple endocrine neoplasia type I (MEN1), von Hippel-Lindau disease, von Recklinghausen disease/neurofibromatosis, and the tuberous sclerosis complex. PNETs are present in the majority of MEN1 patients but are less commonly associated with the other inherited genetic syndromes. 5 Financial disclosures: DMH has no financial disclosures to report. MHK has served as a consultant to Novartis, Pfizer, Ipsen, and Molecular Insight. a Department of Medicine, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA b Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA c Harvard Medical School, Boston, MA, USA * Corresponding author. Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115. E-mail address: Matthew_Kulke@dfci.harvard.edu Gastroenterol Clin N Am 41 (2012) 119 –131 doi:10.1016/j.gtc.2011.12.003 gastro.theclinics.com 0889-8553/12/$ – see front matter © 2012 Published by Elsevier Inc.