Bile duct adenoma may be a precursor lesion of small duct type intrahepatic cholangiocarcinoma

Background/aims Precursor lesions of small duct type intrahepatic cholangiocarcinoma (small duct iCCA) have not been clarified so far. We hypothesised that precursor lesions may be frequently distributed in the background liver of small duct iCCA. Methods and results We determined by histology the presence of bile duct adenomas and von Meyenburg complexes as candidate precursor lesions in the background liver of small duct iCCA, with other primary liver carcinomas as control. Subjects included 28 patients with small duct iCCA, 29 with large duct iCCAs, 60 with combined hepatocellular-cholangiocarcinoma (Comb) and 40 with hepatocellular carcinoma (HCC). The prevalence of bile duct adenomas in the background liver was significantly higher in small duct iCCA (35.7%) compared to other primary liver carcinomas (Comb, 4.9%; 10%, HCC) (P < 0.01). The prevalence of bile duct adenomas was significantly associated with the presence of von Meyenburg complexes and ductal plate malformation-like patterns in small duct iCCAs and Combs. Von Meyenburg complexes were detected in 11 small duct iCCA (39.3%), five large duct iCCAs (17.2%), 10 Comb (16.4%) and 13 HCC (33.3%), respectively (P > 0.05). Small duct iCCAs showed altered expression of ARID1A (46.4%), p53 (39.3%), PBRM1 (14.3%), IMP3 (85.7%) and EZH2 (82.1%), whereas these markers were negative in bile duct adenomas. Conclusion Bile duct adenomas may be precursor lesions of small duct iCCAs. Alteration of ARID1A, p53 or PBRM1 may be involved in the carcinogenesis of small duct iCCAs.

Automated summary

The prevalence of bile duct adenomas in the background liver was significantly higher in small duct iCCA compared to other primary liver carcinomas, suggesting they may be precursor lesions. Alterations in ARID1A, p53, and PBRM1 genes may be involved in the carcinogenesis of small duct iCCA.