title: Clinicopathological characteristics and molecular analyses of multifocal intraductal papillary mucinous neoplasms of the pancreas.
abstract: OBJECTIVE
  To examine the clinicopathologic features and clonal relationship of multifocal intraductal papillary mucinous neoplasms (IPMNs) of the pancreas.
  
  
  BACKGROUND
  Intraductal papillary mucinous neoplasms are increasingly diagnosed cystic precursor lesions of pancreatic cancer. Intraductal papillary mucinous neoplasms can be multifocal and a potential cause of recurrence after partial pancreatectomy.
  
  
  METHODS
  Thirty four patients with histologically documented multifocal IPMNs were collected and their clinicopathologic features catalogued. In addition, thirty multifocal IPMNs arising in 13 patients from 3 hospitals were subjected to laser microdissection followed by KRAS pyrosequencing and loss of heterozygosity (LOH) analysis on chromosomes 6q and 17p. Finally, we sought to assess the clonal relationships among multifocal IPMNs.
  
  
  RESULTS
  We identified 34 patients with histologically documented multifocal IPMNs. Synchronous IPMNs were present in 29 patients (85%), whereas 5 (15%) developed clinically significant metachronous IPMNs. Six patients (18%) had a history of familial pancreatic cancer. A majority of multifocal IPMNs (86% synchronous, 100% metachronous) were composed of branch duct lesions, and typically demonstrated a gastric-foveolar subtype epithelium with low or intermediate grades of dysplasia. Three synchronous IPMNs (10%) had an associated invasive cancer. Molecular analysis of multiple IPMNs from 13 patients demonstrated nonoverlapping KRAS gene mutations in 8 patients (62%) and discordant LOH profiles in 7 patients (54%); independent genetic alterations were established in 9 of the 13 patients (69%).
  
  
  CONCLUSIONS
  The majority of multifocal IPMNs arise independently and exhibit a gastric-foveolar subtype, with low to intermediate dysplasia. These findings underscore the importance of life-long follow-up after resection for an IPMN.
authors.affiliation: Department of General, Visceral, Thoracic and Vascular Surgery, University of Bonn, Germany.
authors.forename: Hanno
authors.initials: H
authors.lastname: Matthaei
authors.forename: Alexis L
authors.initials: AL
authors.lastname: Norris
authors.forename: Athanasios C
authors.initials: AC
authors.lastname: Tsiatis
authors.forename: Kelly
authors.initials: K
authors.lastname: Olino
authors.forename: Seung-Mo
authors.initials: SM
authors.lastname: Hong
authors.forename: Marco
authors.initials: M
authors.lastname: dal Molin
authors.forename: Michael G
authors.initials: MG
authors.lastname: Goggins
authors.forename: Marcia
authors.initials: M
authors.lastname: Canto
authors.forename: Karen M
authors.initials: KM
authors.lastname: Horton
authors.forename: Keith D
authors.initials: KD
authors.lastname: Jackson
authors.forename: Paola
authors.initials: P
authors.lastname: Capelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zamboni
authors.forename: Laura
authors.initials: L
authors.lastname: Bortesi
authors.forename: Toru
authors.initials: T
authors.lastname: Furukawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Egawa
authors.forename: Masaharu
authors.initials: M
authors.lastname: Ishida
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ottomo
authors.forename: Michiaki
authors.initials: M
authors.lastname: Unno
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Motoi
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Wolfgang
authors.forename: Barish H
authors.initials: BH
authors.lastname: Edil
authors.forename: John L
authors.initials: JL
authors.lastname: Cameron
authors.forename: James R
authors.initials: JR
authors.lastname: Eshleman
authors.forename: Richard D
authors.initials: RD
authors.lastname: Schulick
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology; D002999:Clone Cells; D005260:Female; D006801:Humans; D061346:Laser Capture Microdissection; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000235:genetics / Q000473:pathology; D016609:Neoplasms, Second Primary / Q000235:genetics / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins