Intraductal proliferation in the pancreas and its relationship to human and experimental carcinogenesis

Abstract

In 21 patients who had undergone total pancreatectomy for pancreatic head carcinoma, the uninvolved pancreas was examined with regard to the type, incidence and regional distribution of duct epithelial proliferation. The results were compared with those in 37 operative specimens from patients with chronic pancreatitis, in 46 normal pancreases from autopsies and with findings in experimental pancreatic carcinogenesis. While the incidence of squamous metaplasia and non-papillary epithelial hypertrophy varied little in the different groups, papillary epithelial hyperplasia was found three times more often in cases of carcinoma, with associated mild duct obstruction. Atypical epithelial proliferation was only detected in the vicinity of carcinomas. Unequivocal transition from papillary hyperplasia to atypical proliferation was not observed. In hamsters treated with dihydroxy-di-n-propylnitrosamine (DHPN) for induction of pancreatic duct carcinomas, the early duct lesions closely resembled atypical epithelial proliferation of human pancreas. It is concluded that (1) papillary epithelial hyperplasia is probably only indicative of early duct obstruction and/or a general neoplastic stimulus, (2) intraductal epithelial proliferation with atypia is a true precursor of duct carcinoma, and (3) chronic pancreatitis lacks atypical duct lesions.

Dysplasia and carcinoma in situ of the exocrine pancreas.

“…Our moderate to severe dysplasia may correspond to their papillary hyperplasia with atypic. In the present series, squamous metaplasia, simple hyperplasia, dysplasia, and carcinoma in situ were noted more frequently than in previous reports (Cubilla and Fitzgerald 1976;Kozuka et al 1979;Seifert and Kloppel 1979;Kloppel et al 1980). This may in part be attributable to the systematized observation employed in our study.…”

Neoplasms of the Ampulla of Vater with Concurrent Pancreatic Intraductal Neoplasia: A Histological and Molecular Study

“…Since then, many studies have shown an association between pancreatic adenocarcinoma and intraductal neoplasia (6,7,9). PanIN has been estimated to occur commonly in patients without a history of pancreatic cancer in autopsy samples and in pancreatic tissue removed for nonneoplastic disease, with different studies having a prevalence of around 20 to 30%, though it is considerably more frequent in patients with carcinoma (6,7,8,21). High-grade PanIN occurs only rarely in patients without a history of pancreatic neoplasia (6,7).…”

The K-ras mutation pattern in pancreatic ductal adenocarcinoma usually is identical to that in associated normal, hyperplastic, and metaplastic ductal epithelium

“…This proportional distribution generally confirms the results of other investigations. 10,17,23,24 To study the spatial association between pancreatic ductal lesions and invasive ductal adenocarcinoma, we compared the frequency of ductal lesions adjacent to the tumors with their frequency at the tumor free resection margin that was at a distance of at least 1 cm from the tumor. This examination revealed that, irrespective of type, the lesions were distributed evenly in adjacent and remote tissues.…”

“…The ductal lesions included mucinous cell hypertrophy, ductal papillary hyperplasia, adenomatoid hyperplasia, and squamous metaplasia. Severe ductal dysplasia, or as it has been synonymously called, atypical hyperplasia, 17 was not included in our investigations because these lesions may represent intraductal extensions of carcinoma invading elsewhere and have been shown to have the same K-ras mutation pattern as the invasive primary tumor. 18 The stained slides were analyzed microscopically for changes in the ductal epithelium in the vicinity of the carcinomas and in the resection margins at an average distance of 1 cm from the primary tumor.…”