Pancreatic Neuroendocrine Tumors of the Pancreas Excluding Gastrinoma

First described in 1869 and previously referred to as islet cell tumors, pancreatic neuroendocrine tumors (PNETs) are a heterogeneous group of tumors that arise from precursor cells in the pancreas. PNETs comprise approximately 7% of all neuroendocrine tumors, but only 1% to 3% of pancreatic neoplasms. Their incidence has been on the rise and is estimated at 0.5 per 100,000 persons per year. This is likely multifactorial, but primarily caused by the increased utilization and improved sensitivity of cross-sectional imaging for a variety of diagnoses leading to incidental findings of asymptomatic, nonfunctional PNETs. Eighty percent to ninety percent of PNETs are sporadic, while 10% to 20% are associated with familial disorders such as multiple endocrine neoplasia type 1 (MEN-1), von Hippel-Lindau (VHL) syndrome, tuberous sclerosis complex, and neurofibromatosis type 1. PNETs are broadly classified into functional PNETs (F-PNETs) and nonfunctional PNETs (NF-PNETs) based on whether they produce unregulated hormones that cause well-described syndromic symptoms. The majority of PNETs (60%-90%) are nonfunctional and are discovered incidentally during cross-sectional imaging done for other purposes. PNETs exhibit a wide range of malignant potential, ranging from slow-growing, discrete tumors to locally invasive, rapidly metastasizing ones. The classification of PNETs has evolved over the decades, but given the wide range of biologic behavior, standardization of the diagnosis, management, and follow-up surveillance is difficult. In this chapter, we will discuss both F-PNETs and NF-PNETs, except for gastrinomas, which are covered elsewhere in this book.