Pathology of pancreatic ductal adenocarcinoma: Facts, challenges and future developments

Abstract

Despite major improvements concerning its diagnosis and treatment, pancreatic ductal adenocarcinoma (PDAC) remains an aggressive disease with an extremely poor prognosis. Pathology, as interface discipline between basic and clinical medicine, has substantially contributed to the recent developments and has laid the basis for further progress. The definition and classification of precursor lesions of PDAC and their molecular characterization is a fundamental step for the potential identification of biomarkers and the development of imaging methods for early detection. In addition, by integrating findings in humans with the knowledge acquired through the investigation of transgenic mouse models for PDAC, a new model for pancreatic carcinogenesis has been proposed and partially validated in individuals with genetic predisposition for PDAC. The introduction and validation of a standardized system for pathology reporting based on the axial slicing technique has shown that most pancreatic cancer resections are R1 resections and that this is due to inherent anatomical and biological properties of PDAC. This standardized assessment of prognostic relevant parameters represents the basis for the successful conduction of multicentric studies and for the interpretation of their results. Finally, recent studies have shown that distinct molecular subtypes of PDAC exist and are associated with different prognosis and therapy response. The prospective validation of these results and the integration of molecular analyses in a comprehensive pathology report in the context of individualised cancer therapy represent a major challenge for the future.

Keywords: Pancreatic ductal adenocarcinoma, Precursor lesions, Atypical flat lesion, Molecular subtypes, R1, Pancreatic cancer

Core tip: Despite recent progresses, pancreatic ductal adenocarcinoma (PDAC) remains a disease with poor prognosis. Pathology has given fundamental contributions to these developments. In particular, precursor lesions have been identified and a model for PDAC development has been proposed and validated by molecular studies, which represent the basis for the identification of biomarkers for early diagnosis. A standardized protocol for the post-operative assessment of prognostic relevant parameters, such as the resection margin status, has been developed and has shown a high degree of interlaboratory reproducibility. Finally, the genome-wide analysis of PDAC has led to the identification of distinct molecular subtypes with different therapy response and clinical courses.