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A Revised Classification System and Recommendations From the Baltimore Consensus Meeting for Neoplastic Precursor
Olca Basturk1, Seung-Mo Hong, Laura D Wood
1*Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY ‡Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD §Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, GA §§Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH †Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Ulsan, Korea ∥Department of Pathology, Medica Sur Clinic and Foundation, Mexico City, Mexico ¶Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow, UK #Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands **Department of Pathology, Jichi Medical University, Shimotsuke ††Department of Pathology, Cancer Institute, Japanese Foundation for Cancer Research ¶¶Department of Pathology, Hakujikai Memorial Hospital †††Division of Cancer Genomics, National Cancer Center Research Institute §§§Institute for Integrated Medical Sciences, Tokyo Women's Medical University, Tokyo ##Department of Surgery, Kyoto University, Kyoto, Japan ‡‡Department of Pathology, Technical University Munich, Munich ∥∥Department of General, Visceral, Thoracic and Vascular Surgery, University of Bonn, Bonn ‡‡‡Institute of Pathology, Heinrich-Heine University and University Hospital of Düsseldorf, Düsseldorf, Germany ***Service d'Anatomie Pathologique, Hôpital Cochin, Paris, France.
Abstract:
International experts met to discuss recent advances and to revise the 2004 recommendations for assessing and reporting precursor lesions to invasive carcinomas of the pancreas, including pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm, and other lesions. Consensus recommendations include the following: (1) To improve concordance and to align with practical consequences, a 2-tiered system (low vs. high grade) is proposed for all precursor lesions, with the provision that the current PanIN-2 and neoplasms with intermediate-grade dysplasia now be categorized as low grade. Thus, "high-grade dysplasia" is to be reserved for only the uppermost end of the spectrum ("carcinoma in situ"-type lesions). (2) Current data indicate that PanIN of any grade at a margin of a resected pancreas with invasive carcinoma does not have prognostic implications; the clinical significance of dysplasia at a margin in a resected pancreas with IPMN lacking invasive carcinoma remains to be determined. (3) Intraductal lesions 0.5 to 1 cm can be either large PanINs or small IPMNs. The term "incipient IPMN" should be reserved for lesions in this size with intestinal or oncocytic papillae or GNAS mutations. (4) Measurement of the distance between an IPMN and invasive carcinoma and sampling of intervening tissue are recommended to assess concomitant versus associated status. Conceptually, concomitant invasive carcinoma (in contrast with the "associated" group) ought to be genetically distinct from an IPMN elsewhere in the gland. (5) "Intraductal spread of invasive carcinoma" (aka, "colonization") is recommended to describe lesions of invasive carcinoma invading back into and extending along the ductal system, which may morphologically mimic high-grade PanIN or even IPMN. (6) "Simple mucinous cyst" is recommended to describe cysts >1 cm having gastric-type flat mucinous lining at most minimal atypia without ovarian-type stroma to distinguish them from IPMN. (7) Human lesions resembling the acinar to ductal metaplasia and atypical flat lesions of genetically engineered mouse models exist and may reflect an alternate pathway of carcinogenesis; however, their biological significance requires further study. These revised recommendations are expected to improve our management and understanding of precursor lesions in the pancreas.