Background: K-ras mutations in endobiliary brush cytology are an early event in carcinogenesis and justify a suspicion of malignancy in patients with extrahepatic biliary stenosis. However, K-ras mutations have been detected in specimens obtained by brushing of clinically benign extrahepatic biliary stenosis. The aim of this study was to determine whether these findings represent an early or false-positive diagnosis of cancer. Methods: Cytologic specimens were obtained by brushing in 312 consecutive patients with extrahepatic biliary stenosis. Mutations in the K-ras oncogene were detected by an enriched polymerase chain reaction and allele-specific oligonucleotide hybridization assay. Eight patients with a K-ras mutation and a clinically benign extrahepatic biliary stenosis were followed. Results: After a median follow-up of 65 months, 6 of the 8 patients were alive without evidence of malignancy. One patient died of congestive heart failure. The other patient died 60 months after the specimen was obtained, possibly because of chronic pancreatitis, although previously there had been suspicion of malignancy. Biopsy specimens from the papilla were negative for neoplasia and the K-ras analysis harbored the same mutation as previously found in the brush specimen. Conclusion: Based on long-term follow-up, the K-ras mutations in all 8 patients with a clinically benign extrahepatic biliary stenosis must be considered as confirmed false-positives. Nevertheless, a false-positive result is infrequent. Therefore, patients with a positive K-ras mutation in biliary cytologic specimens obtained by brushing still require careful, continuing follow-up.
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