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.
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.
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.
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.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Surgery
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Tumors of the pancreas.in: Silverberg S.G. Sobin L.H. Atlas of tumor pathology, AFIP fourth series, fascicle 6. American Registry of Pathology, Washington, DC2007: 75-110
- International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas.Pancreatology. 2012; 12: 183-197
- Clonality and field cancerization in intraductal papillary-mucinous tumors of the pancreas.Cancer. 2001; 92: 1807-1817
- Prevalence of activating K-ras mutations in the evolutionary stages of neoplasia in intraductal papillary mucinous tumors of the pancreas.Ann Surg. 1997; 226: 491-498
- Clinicopathological characteristics and molecular analyses of multifocal intraductal papillary mucinous neoplasms of the pancreas.Ann Surg. 2012; 255: 326-333
- Treatment strategy for main duct intraductal papillary mucinous neoplasms of the pancreas based on the assessment of recurrence in the remnant pancreas after resection: a retrospective review.Ann Surg. 2014; 259: 360-368
- Barrett’s oesophagus: from metaplasia to dysplasia and cancer.Gut. 2004; 54: i6-i12
- Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development.Sci Transl Med. 2011; 3: 92ra66
- Whole-exome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas.Sci Rep. 2011; 1: 161
- Intraductal papillary-mucinous neoplasms of the pancreas.in: Bosman F.T. Carneiro F. Hruban R.H. Theise N.D. World Health Organization classification of tumors, pathology and genetics of tumors of the digestive system. IARC Press, Lyon, France2010: 304-313
- Role of intraoperative cytology combined with histology in detecting continuous and skip type intraductal cancer existence for intraductal papillary mucinous carcinoma of the pancreas.Cancer. 2006; 107: 2567-2575
- Intraoperative irrigation cytology of the remnant pancreas to detect remnant distinct pancreatic ductal adenocarcinoma in patients with intraductal papillary mucinous neoplasm undergoing partial pancreatectomy.Surgery. 2014; 155: 67-73
- Distant metastasis occurs late during the genetic evolution of pancreatic cancer.Nature. 2010; 467: 1114-1117
- High-throughput mutation profiling in intraductal papillary mucinous neoplasm (IPMN).J Gastrointest Surg. 2011; 15: 503-511
- Intraductal papillary mucinous neoplasm.Hum Pathol. 2012; 43: 1-16
- GNAS-activating mutations define a rare subgroup of inflammatory liver tumors characterized by STAT3 activation.J Hepatol. 2012; 56: 184-191
- Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways.Proc Natl Acad Sci U S A. 2011; 108: 21188-21193
- Clinicopathological correlates of activating GNAS mutations in intraductal papillary mucinous neoplasm (IPMN) of the pancreas.Ann Surg Oncol. 2013; 20: 3802-3808
- Mutant GNAS detected in duodenal collections of secretin-stimulated pancreatic juice indicates the presence or emergence of pancreatic cysts.Gut. 2013; 62: 1024-1033
- Intraductal papillary mucinous neoplasms of the pancreas with distinct pancreatic ductal adenocarcinomas are frequently of gastric subtype.Ann Surg. 2013; 258: 141-151
- Preoperative histological subtype classification of intraductal papillary mucinous neoplasms (IPMN) by pancreatic juice cytology with MUC stain.Ann Surg. 2013; 257: 1103-1111
- Prognosis of invasive intraductal papillary mucinous neoplasm depends on histological and precursor epithelial subtypes.Gut. 2011; 60: 1712-1720
- Invasive carcinoma derived from the nonintestinal type intraductal papillary mucinous neoplasm of the pancreas has a poorer prognosis than that derived from the intestinal type.Surgery. 2010; 147: 812-817
- Pathohistological subtype predicts survival in patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas.Ann Surg. 2013; 258: 324-330
Published online: December 16, 2014
Accepted: September 10, 2014
Conflicts of interest and source of funding: The authors declare no conflicts of interest. This study was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Numbers 24390318, 24390319, 23390327, 25293285, 25670586, 25670585, 25670584, 25670582, and 24592030.
© 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.