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Classification, morphology and molecular pathology of premalignant lesions of the pancreas

Cooper, Caroline L.*,†; O’Toole, Sandra A.*,†,‡,§; Kench, James G.*,†

doi: 10.1097/PAT.0b013e32835f2205

Summary: Over the past few years there have been substantial advances in our knowledge of premalignant lesions of the pancreas. Given the dismal prognosis of untreated pancreatic cancer, and the small proportion of patients who are operative candidates, an understanding of these premalignant lesions is essential for the development of strategies for early diagnosis and prevention. The 2010 WHO classification has added new entities, including intraductal tubular papillary neoplasms (ITPNs), and clarified the nomenclature and grading of previously recognised precursor lesions of pancreatic adenocarcinoma, such as intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs) and pancreatic intraepithelial neoplasia (PanIN). In particular, there has been an upsurge of interest in the natural history of IPMN, driven partly by improvements in imaging modalities and the consequent apparent increase in their incidence, and partly by recognition that subtypes based on location or histological appearance define groups with significantly different behaviours. In mid 2012 revised international guidelines for the classification and management of IPMNs and MCNs were published, although in several respects these guidelines represent a consensus view rather than being evidence-based. In recent years major advances in molecular technologies, including whole-exome sequencing, have significantly enhanced our knowledge of pancreatic premalignancy and have identified potentially highly specific diagnostic biomarkers such as mutations in GNAS and RNF43 that could be used to pre-operatively assess pancreatic cysts.

Author Information

*Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown

Sydney Medical School, University of Sydney

Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst

§St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia

Address for correspondence: Professor J. Kench, Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia. E-mail:

Abbreviations: ACC, acinar cell carcinoma; IPMN, intraductal papillary mucinous neoplasm; ISH, in situ hybridisation; ITPN, intraductal tubulopapillary neoplasm; MCN, mucinous cystic neoplasm; PanIN, pancreatic intraepithelial neoplasia; SNP, single nucleotide polymorphism

Received 19 November, 2012

Accepted 20 December, 2012

© 2013 Royal College of Pathologists of Australasia

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