Varying grades of epithelial atypia in the pancreatic ducts of humans: Classification based on morphometry and multivariate analysis and correlated with positive reactions of carcinoembryonic antigen

To establish an adequate statistical classification of epithelial atypia in the pancreatic duct, a total of 78 areas of duct epithelia with varying grades of atypia were subjected to nine-parameter morphometry and nine- dimensional multivariate cluster analysis. The material was derived from 53 pancreases resected for various epithelial tumors or acute or chronic pancreatitis. The result was correlated with immunohistochemical findings in which the pattern of intraepithelial distribution of carcinoembryonic antigen changed with the degree of ductal atypia. Finally, atypical cells classified by cluster analysis and immunohistochemistry were subjected to computer- aided three-dimensional mapping to visualize their distribution in the ductal free. Cluster analysis demonstrated that the various epithelial forms were classifiable into Clusters 1, 2, and 3, representing ordinary epithelia and mild and severe dysplasias, respectively. The last category was created so as to include not only in situ and invasive carcinoma but the so-called borderline atypical lesions. The reproducibility of this classification was proved by two sorts of discriminant analyses. Also, the grades of atypia shown by the clustering proved to correlate with the reaction patterns for carcinoembryonic antigen. In the computer-aided three-dimensional mapping, severely dysplastic areas were shown surrounded by zones of mild dysplasia, justifying the assumption of a stepwise carcinogenesis in the pancreatic ducts.