Glucagonoma of the pancreas: diagnostic approach and therapeutic algorithm for a rare nosological entity

Glucagonoma remains a very rare neuroendocrine tumor of the pancreas, accounting for 2% of all islet-cell carcinomas. The aim of this review is to highlight important aspects of pancreatic glucagonoma, including epidemiology, clinical presentation and diagnostic evaluation, and to elucidate the current therapeutic management of this nosologic entity. A combined automated and manual systematic search of the literature was performed using electronic search engines (Medline/PubMed, Scopus, Ovid and Cochrane Library), until April 2025. Glucagonoma originates from the a-cells of the pancreatic Langerhans islets. Its reported incidence is 1 in 20,000,000 per year. Typical clinical manifestations include necrolytic migratory erythema, diabetes mellitus (DM), weight loss and anemia, along with elevated serum glucagon levels. Other symptoms, such as venous thrombosis, neuropsychiatric findings known as 4D (dermatitis, DM, deep-vein thrombosis, depression), or diarrhea can also be present. Unfortunately, metastases are encountered in the majority of patients. Prompt diagnosis is usually accomplished by computed tomography and magnetic resonance imaging. The only treatment option is the surgical resection of the tumor. Conservative management, based on the administration of chemotherapy, somatostatin analogs, molecular targeted therapy and peptide receptor radionuclide therapy is also an alternative.