Neuroendocrine neoplasms of the pancreas

Abstract

Pancreatic neuroendocrine tumors (PanNETs) are relatively uncommon, accounting for approximately 2 % of all pancreatic neoplasms. They occur in a younger age group than pancreatic ductal adenocarcinomas. Traditionally, PanNETs have been classified according to their hormone secretory status as either functional or nonfunctional based on whether they produce a clinically recognizable syndrome due to hormone secretion. The majority of PanNETs today are discovered incidentally and are nonfunctional. The imaging and pathological features are not dependent on hormone status. The Octreoscan is the most commonly used method to image PanNET for both diagnosis and staging, but newer methods using somatostatin analogs labeled with gallium have been developed. While the histopathological features are fairly uniform, a number of morphological variants have been recognized, which can also be identified on cytopathology. Recent consensus guidelines developed by the European Neuroendocrine Tumor Society (ENETS), the North American Neuroendocrine Tumor Society (NANETs), and the WHO 2010 define criteria for grading of PanNET based on mitotic count and Ki-67 labeling index. Phosphohistone 3 (PHH3) is a newer proliferation marker which is being tested as a substitute for Ki-67. The molecular biology of PanNET has recently been further elucidated. Mutations in ATXX and DTRX play a role in low-grade PanNET. Palladin and RUNX1T1 contribute to metastasis of PanNET. Syndromic PanNETs are associated with mutations in the mTOR pathway. Nesidioblastosis (also called congenital hyperinsulinism) is a controversial entity, distinct from insulinoma, traditionally defined as proliferations of ß cells which do not form discrete masses. Adult-onset nesidioblastosis has unique molecular pathways. This chapter will review the clinicopathological features of PanNET and nesidioblastosis and their significant molecular alterations.