Islet Aggregation around Early Duct Lesions in Human Donor Pancreas

Background: The link of pancreatic cancer to diabetes (type 3c) suggests that islets are influenced by the cancer lesion progression. However, at an early stage, i.e., when the pancreas appears to be normal, how the endocrine pancreas is affected by the initial duct lesion formation remains unclear. Aims. To apply panoramic 3-D histology to detect early duct lesions in human cadaveric donor pancreases and examine the peri-lesional islet environment. Methods: Tissue clearing was applied to the freshly perfused donor pancreases (target) and cancer surgical biopsies (malignant control) for 3-D microscopy. Results: Large-scale tissue scanning detects early duct lesions (PanIN 1A/B) in three donor pancreases (3/5; nondiabetic; age (yr)/BMI: 40/24, 53/28, and 51/20). High-definition 3-D fluorescence and 2-D transmitted-light and H&E images reveal: 1) peri-lesional islet aggregation, 2) epithelium-islet complex (e.g., intra-islet duct), 3) adipocyte association, 4) inflammation, 5) stromal activation, and 6) Ki-67+ ductal and stromal cells but not the β- or α-cells. Conclusions: We systematically developed a 3-D/2-D integrative imaging approach to detect and characterize the islet microenvironment around early duct lesions. Our data indicate a proliferative setting, but the islet aggregation appears not to arise from β- or α-cell division; instead, it may be due to lobular atrophy and/or evolve from duct-to-islet differentiation. Disclosure H. Chien: None. T. Chiang: None. S. Peng: None. M. Chung: None. C. Lee: None. Y. Tien: None. S. Tang: None.