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.

Keywords: diagnosis; functioning pancreatic neuroendocrine tumors; molecular alterations; pancreatic neuroendocrine tumors; treatment.

Figure 1

The last WHO’s classification of PanNENs (2019). PanNENs: pancreatic neuroendocrine neoplasms; PanNET: pancreatic neuroendocrine tumor; PanNEC: pancreatic neuroendocrine carcinoma; MiNEN: mixed neuroendocrine/non-neuroendocrine neoplasm.

Figure 2

Future perspectives in functioning PanNENs. The multidisciplinary approaches, based on high-throughput techniques and recent tools (i.e., NETest, liquid biopsy) might lead to the identification of targeted molecular alterations in functioning PanNENs. PanNENs: pancreatic neuroendocrine neoplasms; ctDNA: circulant tumor DNA.