Mechanism of pseudoductular (tubular) formation during pancreatic carcinogenesis in the hamster model. An electron-microscopic and immunohistochemical study.

Electron-microscopic and immunohistochemical studies performed during pancreatic carcinogenesis in hamsters demonstrated that hypertrophy and hyperplasia of centroacinar cells were the earliest changes occurring in the pancreas. These altered centroacinar cells differentiated into either endocrine-type cells or elongated agranular cells with remarkably long cytoplasmic processes (CyPs). These CyPs seemed gradually to overlie and underlie the adjacent acinar cells and resulted in progressive degeneration and loss of acinar cells, which subsequently were replaced by altered centroacinar cells. The initially rather tiny and slender CyPs were characterized by the expression of blood group substances, which were also found in the surface of altered ductal cells. Because these antigens could not be demonstrated in normal pancreatic cells, they seemed to represent specific markers for altered ductal/ductular (centroacinar) cells. In no instance was there evidence of dedifferentiation of acinar cells into ductlike cells. The present data, along with our previous findings, demonstrate that centroacinar cells are the foundation for pseudoductular structures and are the progenitor cells of tumors arising from them.