title: American Gastroenterological Association guidelines are inaccurate in detecting pancreatic cysts with advanced neoplasia: a clinicopathologic study of 225 patients with supporting molecular data.
abstract: OBJECTIVE
  The American Gastroenterological Association (AGA) recently reported evidence-based guidelines for the management of asymptomatic neoplastic pancreatic cysts. These guidelines advocate a higher threshold for surgical resection than prior guidelines and imaging surveillance for a considerable number of patients with pancreatic cysts. The aims of this study were to assess the accuracy of the AGA guidelines in detecting advanced neoplasia and present an alternative approach to pancreatic cysts.
  
  
  METHODS
  The study population consisted of 225 patients who underwent EUS-guided FNA for pancreatic cysts between January 2014 and May 2015. For each patient, clinical findings, EUS features, cytopathology results, carcinoembryonic antigen analysis, and molecular testing of pancreatic cyst fluid were reviewed. Molecular testing included the assessment of hotspot mutations and deletions for KRAS, GNAS, VHL, TP53, PIK3CA, and PTEN.
  
  
  RESULTS
  Diagnostic pathology results were available for 41 patients (18%), with 13 (6%) harboring advanced neoplasia. Among these cases, the AGA guidelines identified advanced neoplasia with 62% sensitivity, 79% specificity, 57% positive predictive value, and 82% negative predictive value. Moreover, the AGA guidelines missed 45% of intraductal papillary mucinous neoplasms with adenocarcinoma or high-grade dysplasia. For cases without confirmatory pathology, 27 of 184 patients (15%) with serous cystadenomas (SCAs) based on EUS findings and/or VHL alterations would continue magnetic resonance imaging (MRI) surveillance. In comparison, a novel algorithmic pathway using molecular testing of pancreatic cyst fluid detected advanced neoplasias with 100% sensitivity, 90% specificity, 79% positive predictive value, and 100% negative predictive value.
  
  
  CONCLUSIONS
  The AGA guidelines were inaccurate in detecting pancreatic cysts with advanced neoplasia. Furthermore, because the AGA guidelines manage all neoplastic cysts similarly, patients with SCAs will continue to undergo unnecessary MRI surveillance. The results of an alternative approach with integrative molecular testing are encouraging but require further validation.
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Aatur D
authors.initials: AD
authors.lastname: Singhi
authors.affiliation: Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Zeh
authors.affiliation: Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Randall E
authors.initials: RE
authors.lastname: Brand
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Marina N
authors.initials: MN
authors.lastname: Nikiforova
authors.affiliation: Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Chennat
authors.affiliation: Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Fasanella
authors.affiliation: Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Asif
authors.initials: A
authors.lastname: Khalid
authors.affiliation: Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Georgios I
authors.initials: GI
authors.lastname: Papachristou
authors.affiliation: Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Slivka
authors.affiliation: Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Hogg
authors.affiliation: Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Lee
authors.affiliation: Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: Tsung
authors.affiliation: Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA; Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Amer H
authors.initials: AH
authors.lastname: Zureikat
authors.affiliation: Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: McGrath
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002272:Carcinoembryonic Antigen / Q000097:blood; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002864:Chromogranins / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases; D020420:Cyst Fluid; D018293:Cystadenoma, Serous / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D061765:Endoscopic Ultrasound-Guided Fine Needle Aspiration; D019160:Endosonography; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics; D010181:Pancreatic Cyst / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D017410:Practice Guidelines as Topic; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics; D055815:Young Adult
chemical_list: D002272:Carcinoembryonic Antigen; D002864:Chromogranins; C117307:KRAS protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs; D016283:Proto-Oncogene Proteins p21(ras); C497446:VHL protein, human