Significance of KRAS mutation testing in biliary brushing cytology specimens: A 10-year retrospective review

Biliary strictures can be caused by benign and malignant conditions. A biliary duct brushing diagnosis can be challenging because of low cellularity and overlapping morphology among different entities, leading to a variable reported sensitivity. This study aimed to assess the value of KRAS mutation testing in adding cytological diagnosis of biliary duct brushings.

With institutional review board approval, biliary duct brushing cytology specimens were collected from 269 patients with extrahepatic biliary stenosis between August 2011 and July 2021. The results of cytology and KRAS mutational analyses were evaluated in view of corresponding cytology examination and histopathological/clinical follow-up.

KRAS mutations were identified in 50 of 269 biliary stricture brushing cases (19%). Among the cases with available follow-up, 72% (34 of 47) of biliary brushings had confirmed malignancy when there were KRAS mutations. The overall specificity and sensitivity of KRAS mutation testing was 92% and 36%, respectively. KRAS mutation was significantly more enriched in pancreatic duct adenocarcinoma than in cholangiocarcinoma (66% vs 5%, P < .001). The absolute risk of malignancy was 3%, 28%, and 71%, respectively, in negative, atypical, and suspicious cytological diagnostic categories and the risks increased to 14%, 68%, and 95% in corresponding categories with KRAS mutation.

Our results suggested that KRAS mutational analysis can be considered supplementary to cytology diagnosis of biliary duct brushing for patients with extrahepatic biliary stenosis in clinical practice.