We thank Drs. Cardinale et al.1 for the interest in our study.2 In our study, we focused on the “histopathological diversity” in intrahepatic cholangiocellular carcinomas (ICCs). We compared the different tumor types with the different cells lining the biliary tree as possible cells of origin; pure mucin-producing ICC (muc-ICC) can originate from mucin-producing cholangiocytes lining large bile duct versus ICC with histological diversity (mixed-ICC) can originate from the most peripheral biliary branches including hepatic progenitor cells (HPCs), which are capable of differentiating into either hepatocytes or cholangiocytes. As cancer is in general a monoclonal entity, we conclude that recognizing histopathological diversity in ICC could be a sign of HPC-derived ICCs. Therefore, we completely agree with the comment concerning HPCs-derived tumors. However, concerning muc-ICCs, we did not investigate the correlation between muc-ICCs and peribiliary glands (PBGs), and the possible origin of the intraductal papillary neoplasm of the bile duct. To clarify these issues, further studies in a larger series of tumors are required. Therefore, we invite the authors to investigate this hypothesis further in a collaborative effort.
Mina Komuta M.D., Ph.D.*, Tania Roskams M.D., Ph.D.*, * Department of Morphology and Molecular Pathology, University Hospitals Leuven, Leuven, Belgium.