Histogenesis of pancreatic carcinogenesis in the hamster: ultrastructural evidence.

Abstract

Pancreatic carcinogenesis in the Syrian hamster, induced by 3-oxidized derivatives of N-nitroso-di-npropylamine, constitutes a valuable model of human cancer of the exocrine pancreas. In both species the majority of tumors are adenocarcinomas: superficially, on the basis of their histological appearance, these appear to be ductal in origin. However, sequential analysis, by electron microscopy, of the development of pancreatic neoplasia in the hamster model indicates that acinar cells may participate in the histogenesis of "ductal" adenomas and carcinomas. Acinar cells appear to undergo changes in differentiation, including pseudoductular transformation, giving rise to a new population of cells that resemble ductular or centroacinar types. This new population may then proliferate to form, first, cystic foci and subsequently cystadenomas and adenocarcinomas. Mucous metaplasia appears to develop at late stages of tumor development. Although the participation of ductular and centroacinar cells in pancreatic carcinogenesis cannot be excluded, very few tumors arise from the ductal epithelium.It is possible that some human pancreatic adenocarcinomas may also have their origin from dysplastic acinar cells, by analogy with the hamster model: focal acinar dysplasia being common in human pancreatic cancer patients.

Acinar‐Ductal‐Carcinoma Sequence in Transforming Growth Factor‐α Transgenic Mice

“…Ultrastructural studies suggest that the earliest lesions in a hamster cancer model involve the centroacinar cells or cells of acinar origin. 36,37 In this model there is evidence that centroacinar cells are the origin for tubular formations. Early neoplastic features are hypertrophy and hyperplasia of centroacinar cells, which form initially tiny and long processes that overlie and underlie the adjacent acinar cells.…”

“…Early neoplastic features are hypertrophy and hyperplasia of centroacinar cells, which form initially tiny and long processes that overlie and underlie the adjacent acinar cells. 37…”

Alpha fetoprotein-producing acinar cell carcinoma of the pancreas showing multiple lines of differentiation

“…In two recently published series, CEA and CA19-9, which are well known markers of pancreatic ductal adenocarcinomas [7,19], were found to be positive in 18% [14] and 41% [8] of ACCs, respectively. Ductal differentiation within ACCs, sometimes considered as mucous metaplasia of turnout cells [5], probably reflects the capacities of ACCs for differentiating into several directions, including ductally [8].…”

“…Wiedenman et al [33] demonstrated immunohistochemically and electron microscopically coexpression of zymogen granules and neuroendocrine vesicles in the cells of a rat acinar carcinoma [5], which seems to be amphicrine in origin. Scattered neuroendocrine cells are encountered in approximately 40% of human ACCs [8,14], but the unequivocal immunocytochemical demonstration of exocrine (pancreatic enzymes) and neuroendocrine markers in the same turnout cells is infrequent [8,15].…”

Interface between adaptive and neoplastic growth in the pancreas.

“…A recent report suggests that the formation, growth or progression of tubular ductal complexes to carcinomas can be stimulated by injections of CCK. 16 The development of hepatocyte like foci within the pancreas of carcinogen treated hamsters and rats has been characterised in the hamster by Rao et al,6 and seems to be a florid metaplastic change of acinar or ductal cells that reflects the close embryonic relation-ship of the pancreas and liver. Hepatocyte like foci seem to have low growth potential and no carcinoma of this cell type has been described in hamster pancreas.…”