Pancreatic intraepithelial neoplasia - A new nomenclature and classification system for pancreatic duct lesions

Proliferative epithelial lesions in the smaller caliber pancreatic ducts an d ductules have been the subject of numerous morphologic, clinical, and gen etic studies; however, a standard nomenclature and diagnostic criteria for classifying these lesion have not been established. To evaluate the uniform ity of existing systems for grading duct lesions in the pancreas, 35 micros copic slides with 35 representative duct lesions were sent to eight expert pathologists from the United States, Canada. and Europe. Kappa values for i nterobserver agreement could not be calculated initially because more than 70 different diagnostic terms were used by the eight pathologists. In sever al cases, the diagnoses rendered for a single duct lesion ranged from "hype rplasia," to "metaplasia," to "dysplasia," to "carcinoma in situ." This rev iew therefore demonstrated the need for a standard nomenclature and classif ication system. Subsequently, during a working group meeting, the pathologi sts agreed to adopt a single standard system. The terminology pancreatic in traepithelial neoplasia (or PanIN) was selected, and diagnostic criteria fo r each grade of PanIN were established (http://pathology.jhu.edu/pancreas_p anin This new system was then evaluated by having the eight pathologists re review the original 35 cases. Only seven different diagnoses were rendered. and kappa values of 0.43, 0.14, and 0.42 were obtained for PanINs 1, 2. an d 3 respectively. Cases assigned other diagnoses (e.g., squamous metaplasia ) collectively had a kappa value of 0.41. These results show both the poten tial of the classification system, and also the difficulty of classifying t hese lesions even with a consistent nomenclature. However, even when there is lack of consensus, having a restricted set of descriptions and terms all ows a better understanding of the reasons for disagreement. It is suggested that we adopt and apply this system uniformly, with continued study of its reliability and use, and possibly further refinement. The acceptance of a standard classification system will facilitate the study of pancreatic duct lesions, and will lead ultimately to a better understanding of their biolo gic importance.