Figure 2

a) Numerous Helle Zelle (light cells) in hyperplastic ductal epithelium corresponding to PanIN2 (arrows). The cells are small with light cytoplasm and hyperchromatic round or oval nuclei. Some cells seem to have two nuclei (the second and third arrows from left). H&E × 120. b) A lesions comparable to PanIN1 to PanIN3 showing clear cells with a small round nuclei surrounded by a halo (arrow). One of the clear cells (arrowhead) presents two nuclei (post mitotic division?). H&E × 120. c) Electron microscopic findings of a similar lesion. Note several clear cells with one or two nuclei. The cells are poor on cell organelles and lay between the basal membran and tumor cells. × 7,200. d) Hyperplastic ductules in an elderly man. Several clear cells are seen within the epithelium. A small group of these cells have interrupted the continuity of the epithelium (bottom arrow) or extended into the stroma (top arrow). H&E × 120. f) Many of the clear cells that can form a circular layer all along the duct, are immunoreactive with antibodies against islet hormones, especially to anti-glucagon and -chromogranin A and against drug-metabolizing CYP450 enzymes. ABC method, Anti-glucagon, × 120. f) A large number of endocrine cells reactive with anti-chromogranin A antibody in a malignant gland. ABC method, × 120. g) A large malignant gland exhibiting papillary infolding of the epithelium. A remarkably large number of overlapping endocrine cells are present in the basal layer of the malignant epithelium. ABC, combination of anti-insulin and anti-glucagon, 120.