Suspicious brush cytology is an indication for liver transplantation evaluation in primary sclerosing cholangitis

Abstract

Aim: To investigate markers for high-grade dysplasia for the optimal timing of liver transplantation in patients with primary sclerosing cholangitis (PSC).

Methods: Earlier data support a dysplasia-carcinoma sequence, even low- to high-grade dysplasia, in PSC-associated cholangiocarcinoma (CCA). Surveillance using endoscopic retrograde cholangiography (ERC) and brush cytology aims to detect cases of biliary dysplasia, and liver transplantation is an option in cases with suspicion of malignancy in brushing. This study investigated markers to identify patients with high-grade biliary dysplasia for optimal timing in early liver transplantation. Patients undergoing surveillance using ERC and brush cytology during 2008-2014 and who were diagnosed with biliary dysplasia in explanted liver or CCA until February 2016 were included in the study. Demographic data, cholangiography findings, laboratory values, cytological morphology and DNA ploidy were analysed.

Results: Thirty PSC patients had biliary neoplasia in the explanted liver during the study period. Sixteen of these patients had low-grade dysplasia, 10 patients had high-grade dysplasia, and 4 patients had CCA. Fifteen PSC patients diagnosed with CCA were not transplanted. Patients with low-grade dysplasia were younger. Alkaline phosphatase or carcinoembryonic antigen values did not differ between groups during surveillance, but carbohydrate antigen 19-9 was higher in CCA patients. No difference in PSC duration, ERC scores, suspicious cytology, or ploidy analysis was found between groups. No difference was observed between fibrosis stage in explanted livers. Low- and high-grade dysplasia could not be differentiated before liver transplantation based on liver enzymes, tumour markers, ERC scores, brush cytology or DNA ploidy.

Conclusion: Repeated suspicion of neoplasia in brush cytology should be an indication for evaluations of liver transplantation prior to the development of CCA.

Keywords: Biliary dysplasia; Brush cytology; Cholangiocarcinoma; Endoscopic retrograde cholangiography.

Figure 1

Representative examples of bile duct brushings. A: Benign brush cytology with inflammatory atypia; B: Brush cytology with suspicion of malignancy; C: Malignant brush cytology. Patient was diagnosed with cholangiocarcinoma.

Figure 2

Histology from explanted livers diagnosed with biliary neoplasia. A: Bile duct from explanted liver with low-grade dysplasia; B: Bile duct from explanted liver with high-grade dysplasia; C: Cholangiocarcinoma from explanted liver.