On the histogenesis of experimental pancreatic endocrine tumors. An immunocytochemical and electron microscopical study.

In order to identify the early stage of the development of experimental pancreatic endocrine tumors, Wistar rats were treated with streptozotocin and nicotinamide. One to 11 months after the treatment, the pancreata were examined for neoplastic lesions, using immunocytochemistry and electronmicroscopy. The earliest changes consisted of focal adenomatous proliferation of small ducts, occasionally including endocrine cell clusters. They occurred in the same frequency throughout the whole period examined, regardless whether the pancreata contained tumors or not, and were also present, though in lower numbers, in controls. Immunocytochemistry revealed no true budding off of endocrine cells from ductular epithelium. Thus the histogenetic relationship of the ductal proliferations to the endocrine tumors remains unclear. The earliest tumors were recognized at the fourth month. At the eleventh month 31% of the animals beared tumors. Insulin-positive cells predominated in the tumors, followed by somatostatin-, glucagon- and PP-positive cells. The multihormonal appearance of the neoplasmas is well comparable with the findings in human insulinomas.