Pancreatic cystic changes in adults are increasingly identified through advanced cross-sectional imaging. However, the impact of initial/intralobular epithelial remodeling on the local β-cell population remains unclear. In this study, we examined 10 human cadaveric donor pancreases (tail and body regions) via integration of stereomicroscopy, clinical hematoxylin and eosin histology, and three-dimensional (3D) immunohistochemistry, identifying 36 microcysts (size: 1.22 ± 0.56 mm) alongside 54 low-grade pancreatic intraepithelial neoplasias (positive control of epithelial remodeling; size: 2.42 ± 1.05 mm). Both conditions exhibited significant increases in cytokeratin 7 (CK7) and insulin immunoreactive signals compared with normal lobules. Importantly, despite luminal contents of microcysts causing false positives (autofluorescence) in fluorescence imaging, the defined cystic epithelium showed distinct duct–β-cell associations—including β-cells in the epithelium and duct–β-cell clusters—visualized via antifade 3D/Airyscan superresolution imaging in the high-refractive-index polymer. The periluminal β-cells displayed insulin-positive vesicles residing near the basal domain, while the CK7+ cytokeratins in duct cells accumulated in the apical domain, underlining polarized tissue and cellular organizations. Overall, in microcyst formation, we demonstrate local and associated pancreatic exocrine and endocrine tissue remodeling. Because artifacts are a concern in β-cell investigations in a novel environment, our work using 3D-labeled human pancreas with cytokeratin and vesicle resolving powers provides a robust approach for characterizing the duct–β-cell association in a clinically relevant setting.
Article Highlights
- The prevalence of pancreatic cysts is rising due to an aging population and advancements in cross-sectional imaging. However, at the microscopic level, how benign epithelial/exocrine remodeling influences local β-cell population remains unclear.
- Using a multimodal imaging approach—including stereomicroscopy, hematoxylin-eosin histology, and fluorescent three-dimensional/Airyscan superresolution imaging—we identified microcysts in cadaveric donor pancreases and uncovered duct–β-cell clusters within remodeled lobules while avoiding false positives (autofluorescence) from cystic luminal contents.
- By analyzing duct–β-cell clusters, we demonstrate localized pancreatic exocrine and endocrine remodeling, with periluminal β-cells containing insulin-positive vesicles near the basal domain, juxtaposed with duct cells where cytokeratin 7-positive cytokeratins accumulate in the apical domain.
- Given the challenges posed by artifacts in studying duct-β-cell associations, we present a reliable approach for pancreatic three-dimensional/superresolution imaging to investigate duct-β-cell clusters in clinically relevant contexts.
