Fatty Pancreas Disease: An Integrated Study on Frozen Tissues Shows Distinct Compartments of Interlobular/Intralobular, Intra-Acinar, and Intra-Islet Fat Deposition

Obesity-related diseases and perturbations of fat metabolism represent some of the most common health challenges. In this complex scenario, recent evidence has suggested the emergence of a condition related to fat accumulation in the pancreas, which is generally referred to as fatty pancreas disease. This study aimed to clarify the different compartments of intrapancreatic fat deposition. The study cohort is represented by 100 patients who underwent pancreatic surgical resection. The pancreatic neck margin was analyzed with hematoxylin and eosin for evaluating tissue composition and with Oil Red O, a fat-specific histochemical staining, highlighting lipid droplets as red signals, for evaluating the presence of intracellular fat. Two cases were also analyzed with electron microscopy as cross-sectional validation. Regarding tissue composition, the most prevalent component was normal pancreatic parenchyma (mean value, 71.8%), followed by fibrosis (17.3%) and interlobular/intralobular fat (10.9%). Regarding intracellular fat deposition, Oil Red O–positive intracytoplasmic lipid droplets were present in most patients. The tissue areas with the highest levels of fat deposition were Langerhans’ islets, with neuroendocrine/insular cells showing more commonly a diffuse pattern of fat accumulation (>75% of cells). Electron microscopy confirmed the presence of intracytoplasmic lipid vacuoles in neuroendocrine/insular cells. Our findings showed the presence of different compartments of intrapancreatic fat deposition, both in terms of tissue composition and intracellular compartmentalization. Understanding the mechanisms of fat deposition in the pancreas is crucial toward improving the general knowledge on fatty pancreas disease, also opening new perspectives for the study of lipid metabolism and the treatment of fat-related diseases.