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Committed to improving knowledge and care in NETs

Pancreatic Neuroendocrine Tumors An educational guide for healthcare professionals

Overview Pancreatic neuroendocrine tumors (pancreatic NETs) comprise a group of neoplasms that are believed to arise from pancreatic endocrine cells,1 which are scattered among the exocrine tissue of the pancreas.2 Pancreatic NETs are also called islet cell tumors,3 because the endocrine cells of the pancreas are commonly located in clusters, anatomically called islets of Langerhans.4 Pancreatic NETs can also arise from cells other than islet cells2 as well as occur outside of the pancreas, for example, in the duodenum.5,6 Long-term data from the US Surveillance, Epidemiology, and End Results (SEER) Program registries (1973-2004) demonstrate that 64% of patients diagnosed with well-differentiated pancreatic NETs have distant metastases and a poor prognosis—the 5-year survival rate in these patients is 27%.7 A word about neuroendocrine nomenclature The NET Alliance™ uses the nomenclature established in the 2010 WHO Classification of Tumours of the Digestive System8 to classify 2 broad types of neuroendocrine neoplasms: • Neuroendocrine neoplasms: the entire spectrum of neoplastic cell types with endocrine properties and phenotypes that express neural markers •N  euroendocrine tumors (NETs): well-differentiated neuroendocrine neoplasms that can be divided into grade 1 (G1) and grade 2 (G2) depending on proliferation and histology • Neuroendocrine carcinomas: poorly differentiated grade 3 (G3) neuroendocrine neoplasms NETs may be referred to using a variety of terms, such as “carcinoids,” “carcinoid tumors,” or “endocrine tumors.” These terms can be used interchangeably with “NETs” as defined above. 2

Characteristics of Pancreatic NETs Most pancreatic NETs are well-differentiated (grade 1 and grade 2) tumors9,10 with very diverse presentations (Table 1).3,5,6 These presentations are often related to the ability of some pancreatic NETs to secrete hormones or peptides, such as insulin, gastrin, glucagon, vasoactive intestinal polypeptide (VIP), and somatostatin, causing characteristic hormonal syndromes.3-5 However, not all pancreatic NETs are associated with secretion of hormone products related to clinical symptoms; such tumors are considered nonfunctional.5,11,12 Table 1. Characteristics of Pancreatic NETs* Type of pancreatic NET6

Incidence (cases per million)13

Prevalence in patients Prevalence of with pancreatic NETs metastases (in surgical series)

Related syndrome3,5,6

Major signs/ symptoms3,5,6,14

1-2†

None

May be first diagnosed due to mass effect, weight loss, hepatomegaly, abdominal mass, or incidentally Occasionally symptomatic

58%-71%14,15‡

>50%6

Insulinoma

1.0-2.0

Insulin

Hypoglycemia

23%-33%14,15