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Intrahepatic cholangiocarcinoma, second in incidence to hepatocellular carcinoma among the primary liver carcinomas, has an even more dismal prognosis. Intrahepatic cholangiocarcinoma is difficult to diagnose at an early stage of development and advances aggressively, with widespread metastases. Molecular genetic features of intrahepatic cholangiocarcinoma have been partially elucidated, although the specific genetic lesions and molecular processes that drive its development, progression, and metastasis are still obscure. Evidence has accumulated from many sources suggesting that cholangiocarcinoma and hepatocellular carcinoma are components of a spectrum of primary liver carcinomas, including poorly and aberrantly differentiated varieties. Primary liver carcinomas arise from cells in different stages of development that encompass the entire lineage of liver epithelial cells generated from hepatoblasts and/or adult liver stem cells, and share critical genomic aberrations and phenotypes with these progenitor cells. [ABSTRACT FROM AUTHOR]