An Insight on Functioning Pancreatic Neuroendocrine Neoplasms

Abstract

Pancreatic neuroendocrine neoplasms (PanNENs) are rare neoplasms arising from islets of the Langerhans in the pancreas. They can be divided into two groups, based on peptide hormone secretion, functioning and nonfunctioning PanNENs. The first group is characterized by different secreted peptides causing specific syndromes and is further classified into subgroups: insulinoma, gastrinoma, glucagonoma, somatostatinoma, VIPoma and tumors producing serotonin and adrenocorticotrophic hormone. Conversely, the second group does not release peptides and is usually associated with a worse prognosis. Today, although the efforts to improve the therapeutic approaches, surgery remains the only curative treatment for patients with PanNENs. The development of high-throughput techniques has increased the molecular knowledge of PanNENs, thereby allowing us to understand better the molecular biology and potential therapeutic vulnerabilities of PanNENs. Although enormous advancements in therapeutic and molecular aspects of PanNENs have been achieved, there is poor knowledge about each subgroup of functioning PanNENs.Therefore, we believe that combining high-throughput platforms with new diagnostic tools will allow for the efficient characterization of the main differences among the subgroups of functioning PanNENs. In this narrative review, we summarize the current landscape regarding diagnosis, molecular profiling and treatment, and we discuss the future perspectives of functioning PanNENs.

Transformation of pancreatic nonfunctioning neuroendocrine tumor into metastatic insulinoma: A rare case report

“…Sunitinib is a tyrosine kinase inhibitor that directly inhibits tumor growth, thereby reducing insulin production, but it can sometimes cause paradoxical hypoglycemia on its own 14,21 . Malignant insulinomas carry a good prognosis with a 5‐year survival rate of 62% and a medium survival time of 40 months in patients with low‐grade tumors doing much better 22 . These patients also benefit from new therapies and often reach remission.…”

“… 14 , 21 Malignant insulinomas carry a good prognosis with a 5‐year survival rate of 62% and a medium survival time of 40 months in patients with low‐grade tumors doing much better. 22 These patients also benefit from new therapies and often reach remission. However, patients with high‐grade tumors and/or distant metastatic disease do significantly worse with a median survival time less than 24 months.…”

An Overview of Circulating Biomarkers in Neuroendocrine Neoplasms: A Clinical Guide

“…Insulin is a peptide hormone secreted by the beta cells of pancreatic islets as a response to high blood glucose levels. High levels of insulin are associated with insulinoma causing the Whipple's triad (hypoglycemia, low plasma levels of glucose, and resolution of symptoms after correction of the hypoglycemia) [81]. Once a hypoglycemic event is confirmed (glucose levels ≤ 2.1 mmol/L), the levels of insulin and pro-insulin must be monitored during a supervised 48-72-h fast [82].…”

“…Somatostatin is a hormone secreted by pancreatic delta cells and gastric antrum D cells [12]. When secreted in excess it is associated with somatostatinoma, thereby causing the classic triad of somatostatinoma syndrome (diabetes/glucose intolerance, cholelithiasis, and diarrhea/steatorrhea) [81]. Given the rare incidence of these rare functioning pancreatic NENs, serum somatostatin levels should be measured only in the presence of somatostatinoma syndrome.…”

Emerging therapies for advanced insulinomas and glucagonomas

“…Glucagonomas are panNEN derived from α pancreatic cells (Cardoso Filho Fde et al 2015) predominantly involving the tail of the pancreas (Martin et al 2022, Bevere et al 2023. Glucagonomas may behave aggressively, with high reported rates of locally, and regionally advanced disease or distant metastases (Keutgen et al 2016).…”