Pancreatic Neuroendocrine Tumors: Functional Vs Non-Functional

Pancreatic neuroendocrine tumors (PanNETs) originate from the islets of Langerhans — clusters of endocrine cells within the pancreas that include beta cells (insulin), alpha cells (glucagon), delta cells (somatostatin), PP cells (pancreatic polypeptide), and enterochromaffin-like cells. PanNETs are classified as functional (producing hormonal syndromes) or non-functional (hormonally silent, comprising 60-90% of cases). Functional tumors are named by the hormone they hypersecrete: insulinomas (most common functional PanNET) autonomously secrete insulin independent of blood glucose, causing recurrent fasting hypoglycemia with Whipple triad (symptoms + documented low glucose + resolution with glucose administration); gastrinomas cause Zollinger-Ellison syndrome through massive gastric acid hypersecretion leading to refractory peptic ulcers; glucagonomas produce a distinctive syndrome of necrolytic migratory erythema, new-onset diabetes, weight loss, and DVT; VIPomas cause profuse secretory diarrhea with hypokalemia and achlorhydria (WDHA/Verner-Morrison syndrome). WHO grading is based on proliferative index: G1 (Ki-67 <3%) are well-differentiated with indolent behavior, G2 (Ki-67 3-20%) are intermediate grade, and G3 (Ki-67 >20%) are high-grade neuroendocrine carcinomas with aggressive behavior. All PanNET cells express somatostatin receptors (especially SSTR2), which is exploited diagnostically with 68Ga-DOTATATE PET/CT imaging and therapeutically...