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Two types of candidate stem\/progenitor cells of the biliary tree are postulated to exist at the peribiliary glands for large bile ducts and at the canals of Hering for small ducts and hepatocytes. According to the recent observations, <jats:styled-content style=\"fixed-case\">ICC<\/jats:styled-content>s can be subclassified into two types: tumors involving the large bile ducts comparable in size to the intrahepatic second branches and composed of a tubular or papillary component with tall columnar epithelium, and tumors involving the smaller duct than segmental branches and composed of small tubules with cuboidal epithelium. Perihilar large duct type <jats:styled-content style=\"fixed-case\">ICC<\/jats:styled-content>s can be interpreted as arising from large bile duct type <jats:styled-content style=\"fixed-case\">ICC<\/jats:styled-content>s, and peripheral small duct type <jats:styled-content style=\"fixed-case\">ICC<\/jats:styled-content>s may arise from small bile duct type or ductular type <jats:styled-content style=\"fixed-case\">ICC<\/jats:styled-content>s. Chronic biliary inflammation induces neoplastic change of the large bile ducts and thereby progression to the perihilar large duct type <jats:styled-content style=\"fixed-case\">ICC<\/jats:styled-content>, which can be grossly classified into periductal filtrating type <jats:styled-content style=\"fixed-case\">ICC<\/jats:styled-content> and intraductal growth type <jats:styled-content style=\"fixed-case\">ICC<\/jats:styled-content>, while chronic hepatitis or cirrhosis induces mass\u2010forming peripheral small duct type <jats:styled-content style=\"fixed-case\">ICC<\/jats:styled-content>. The different morphological and molecular features, including stromal components and tumor vasculature, support the hypothesis that perihilar large duct type <jats:styled-content style=\"fixed-case\">ICC<\/jats:styled-content>s and peripheral small duct type <jats:styled-content style=\"fixed-case\">ICC<\/jats:styled-content>s arise from different backgrounds, have different carcinogenetic pathways, and exhibit different biologic behaviors.<\/jats:p>","DOI":"10.1002\/jhbp.154","type":"journal-article","created":{"date-parts":[[2014,9,2]],"date-time":"2014-09-02T09:05:53Z","timestamp":1409648753000},"page":"94-100","source":"Crossref","is-referenced-by-count":200,"title":["Pathogenesis and classification of intrahepatic cholangiocarcinoma: different characters of perihilar large duct type versus peripheral small duct type"],"prefix":"10.1002","volume":"22","author":[{"given":"Shinichi","family":"Aishima","sequence":"first","affiliation":[{"name":"Pathology and Microbiology Faculty of 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