Diagnostic performance of a stepwise cytological algorithm for biliary malignancy in primary sclerosing cholangitis

Liver Int. 2019 Feb;39(2):382-388. doi: 10.1111/liv.14007. Epub 2018 Dec 2.


Background and aims: Detection of early cholangiocarcinoma (CCA) in primary sclerosing cholangitis (PSC) is challenging. The aim of this study was to evaluate the diagnostic accuracy of a stepwise approach to biliary brush cytology with sequential use of fluorescence in-situ hybridization (FISH) for the detection of biliary malignancy in PSC.

Method: We retrospectively studied consecutive patients with PSC who underwent biliary brushings at Karolinska University Hospital between 2009 and 2015 (n = 208). Brush samples were categorized as benign, equivocal (atypical or suspicious) and malignant. Equivocal cases were further analysed with FISH. Samples with a malignant cytology or positive FISH were considered positive. The diagnosis was determined after 12 months of follow-up.

Results: The diagnosis CCA was confirmed in 15 patients (7%), high-grade dysplasia in three patients, and low-grade dysplasia in five patients at follow-up. Using the diagnostic algorithm, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) for a diagnosis of CCA were 80% (95%CI 52%-96%), 96% (95%CI 92%-98%), 60% (95%CI 36%-81%) and 98% (95% CI 95%-100%). In patients with equivocal cytology (n = 61), the sensitivity for CCA diagnosis increased to 100% (95%CI 72%-100%) with a lower PPV of 58% (95%CI 34%-78%). The diagnostic accuracy for detection of CCA in all patients was 95% (95%CI 91%-97%).

Conclusion: Biliary brush cytology with sequential use of FISH in equivocal cases seems to be a highly predictive diagnostic test for CCA in PSC. These results support the use of FISH when cytology is equivocal for detection of biliary malignancy in PSC.

Keywords: accuracy; biliary brush cytology; biliary dysplasia; primary sclerosing cholangitis; sensitivity; specificity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Algorithms
  • Bile Duct Neoplasms / epidemiology
  • Bile Duct Neoplasms / etiology
  • Bile Duct Neoplasms / pathology*
  • Biliary Tract / pathology*
  • Biomarkers, Tumor / blood*
  • CA-19-9 Antigen / blood
  • Cholangiocarcinoma / epidemiology
  • Cholangiocarcinoma / etiology
  • Cholangiocarcinoma / pathology*
  • Cholangiopancreatography, Endoscopic Retrograde
  • Cholangitis, Sclerosing / complications
  • Cholangitis, Sclerosing / pathology*
  • Cytodiagnosis
  • Data Accuracy
  • Early Detection of Cancer / methods
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Liver Transplantation
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Retrospective Studies
  • Sweden / epidemiology
  • Young Adult


  • Biomarkers, Tumor
  • CA-19-9 Antigen