Analysis of KRAS Mutations in 518 Aspirated Pancreatic Cyst Fluid Samples: KRAS Is Highly Specific for Intraductal Papillary Mucinous Neoplasms but Fails To Detect Mucinous Cystic Neoplasms
Aatur D Singhi, Asif Khalid, Kenneth E Fasanella, Kevin M McGrath, Herbert J Zeh, N Paul Ohori, Karen E Schoedel, Sarah Navina, Marina N Nikiforova, Reetesh K Pai. UPMC Presbyterian Hospital, Pittsburgh, PA
Background: With improvements in abdominal imaging, incidental pancreatic cysts are becoming increasingly common. Analysis of pancreatic cyst fluid from fine needle aspiration (FNA) is particularly important in identifying intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN), which have significant implications in clinical intervention and follow-up. Previous controlled studies have shown that KRAS mutations in pancreatic cyst FNAs are highly specific for both IPMNs and MCNs; however, this has not been examined prospectively in the clinical setting.
Design: A total of 518 pancreatic cyst FNAs were submitted for KRAS codons 12 and 13 mutational analyses between 2007 and 2012. In all cases, samples were submitted by the endoscopist due to uncertainty as to whether a pancreatic cyst represented either an IPMN or MCN. Of the 518 specimens, 505 (97%) were satisfactory for molecular analysis. Cytopathology slides as well as subsequent surgical resection material were also reviewed.
Results: KRAS mutational analysis was performed on 505 pancreatic cyst FNAs from 448 patients. Patients ranged in age from 17 to 90 years (mean, 63.7 years) and were predominantly female (77%). Pancreatic cysts were relatively evenly distributed throughout the pancreas and ranged in size from 0.6 to 10.1 cm (mean, 2.2 cm). Mutations in KRAS were detected in 197 of 505 (39%) FNAs. Although sufficient for molecular studies, 268 of 505 (53%) specimens were either less than optimal (37.8%) or unsatisfactory (15.2%) for cytopathologic diagnosis. Surgical follow-up information was available for 98 of 448 (22%) patients and corresponded to 41 KRAS-mutated and 57 KRAS wild-type cysts. Of 57 resected IPMNs, KRAS mutations had an overall specificity of 95% and overall sensitivity of 68%. In contrast, KRAS mutations were neither specific nor sensitive for MCNs with 1 of 14 cases harboring a KRAS mutation.
Conclusions: Although the sensitivity was low, KRAS mutations in pancreatic cyst FNAs was highly specific for IPMNs. However, contrary to published reports, KRAS mutations were inadequate in identifying MCNs. Future molecular studies including other fluid markers are required to improve the detection and classification of pancreatic mucinous neoplasms.
Tuesday, March 5, 2013 1:45 PM
Proffered Papers: Section F, Tuesday Afternoon