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  • Title: Assessment of clonality of multisegmental main duct intraductal papillary mucinous neoplasms of the pancreas based on GNAS mutation analysis.
    Author: Tamura K, Ohtsuka T, Matsunaga T, Kimura H, Watanabe Y, Ideno N, Aso T, Miyazaki T, Ohuchida K, Takahata S, Ito T, Ushijima Y, Oda Y, Mizumoto K, Tanaka M.
    Journal: Surgery; 2015 Feb; 157(2):277-84. PubMed ID: 25530484.
    Abstract:
    BACKGROUND: Main duct intraductal papillary mucinous neoplasms (MD-IPMNs) may occur in 1 or multiple segments of the pancreatic duct. Unlike multifocal branch duct (BD)-IPMNs, the clonality of multisegmental MD-IPMNs remains unclear. GNAS mutations are common and specific for IPMNs, and mutational assessment might be useful to determine the clonality of IPMNs as well as to detect high-risk IPMN with distinct ductal adenocarcinoma (pancreatic ductal adenocarcinoma [PDAC]). Our aim was to clarify clonality using GNAS status in multisegmental MD-IPMNs. METHODS: We retrospectively reviewed the medical records of 70 patients with MD-IPMN. Histologic subtypes and KRAS/GNAS mutations were investigated, and the clonal relationships among multisegmental MD-IPMNs were assessed. Mutational analysis was performed using high-resolution melting analysis and subsequent Sanger/pyrosequencing. RESULTS: Thirteen patients had multiple synchronous and/or metachronous lesions. Seven of these 13 patients had multiple MD-IPMNs; 3 had multiple MD-IPMNs and distinct BD-IPMNs; 1 had multiple MD-IPMNs and a distinct PDAC; 1 had a solitary MD-IPMN, BD-IPMN, and PDAC; and 1 had a solitary MD-IPMN and PDAC. KRAS/GNAS mutations were consistent in 10 of 11 multisegmental MD-IPMNs, whereas MD-IPMNs, BD-IPMNs, and PDACs tended to show different mutational patterns. The frequency of malignant IPMNs was significantly higher in the multisegment cohort; malignant IPMNs constituted 90% (9/10) of the multiple cohort and 56% (32/57) of the solitary cohort (P = .04). Mutant GNAS was more frequently observed in the intestinal subtype (94%) than the others. CONCLUSION: MD-IPMNs can be characterized by monoclonal skip progression. Close attention should be paid to the possible presence of skip areas during or after partial pancreatectomy.
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