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WHO Classification of Tumours
Combined hepatocellular carcinoma and cholangiocarcinoma
Liver and intrahepatic bile ducts


Definition

A tumour containing unequivocal, intimately mixed elements of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (ChC). This tumour should be distinguished from separate HCC and ChC arising in the same liver
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Goodman ZD, Ishak KG, Langloss JM, Sesterhenn IA, Rabin L (1985)
Combined hepatocellular-cholangiocarcinoma. A histologic and immunohistochemical study.
Cancer 55: 124-35



. Such tumours may be separated or intermixed (“collision tumour”). This tumour type comprises < 1% of all liver carcinomas.

> Histological types
Combined hepatocellular-cholangiocarcinoma, classical type
Subtypes with stem-cell features:
1) Combined hepatocellular-cholangiocellular carcinoma with stem-cell features, typical subtype
2) Combined hepatocellular-cholangiocarcinoma with stem-cell features, intermediate-cell subtype
3) Combined hepatocellular-cholangiocarcinoma with stem-cell features, cholangiolocellular type

The prognosis for patients with combined hepatocellular-cholangiocarcinoma without stem cell features is thought to be worse than for pure HCC

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Kassahun WT, Hauss J (2008)
Management of combined hepatocellular and cholangiocarcinoma.
Int J Clin Pract 62: 1271-8



. Prognosis for combined hepatocellular-cholangiocarcinoma with stem-cell features is unknown, with conflicting evidence based on small series and numbers of patients
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Ding SJ, Li Y, Tan YX, Jiang MR, Tian B, Liu YK, Shao XX, Ye SL, Wu JR, Zeng R, Wang HY, Tang ZY, Xia QC (2004)
From proteomic analysis to clinical significance: overexpression of cytokeratin 19 correlates with hepatocellular carcinoma metastasis.
Mol Cell Proteomics 3: 73-81




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Kim H, Park C, Han KH, Choi J, Kim YB, Kim JK, Park YN (2004)
Primary liver carcinoma of intermediate (hepatocyte-cholangiocyte) phenotype.
J Hepatol 40: 298-304




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Komuta M, Spee B, Vander Borght S, De Vos R, Verslype C, Aerts R, Yano H, Suzuki T, Matsuda M, Fujii H, Desmet VJ, Kojiro M, Roskams T (2008)
Clinicopathological study on cholangiolocellular carcinoma suggesting hepatic progenitor cell origin.
Hepatology 47: 1544-56




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Okamura D, Ohtsuka M, Kimura F, Shimizu H, Yoshidome H, Kato A, Miyazaki M (2008)
Ezrin expression is associated with hepatocellular carcinoma possibly derived from progenitor cells and early recurrence after surgical resection.
Mod Pathol 21: 847-55




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Qin LX, Tang ZY (2004)
Recent progress in predictive biomarkers for metastatic recurrence of human hepatocellular carcinoma: a review of the literature.
J Cancer Res Clin Oncol 130: 497-513




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Theise ND, Yao JL, Harada K, Hytiroglou P, Portmann B, Thung SN, Tsui W, Ohta H, Nakanuma Y (2003)
Hepatic 'stem cell' malignancies in adults: four cases.
Histopathology 43: 263-71




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Uenishi T, Kubo S, Yamamoto T, Shuto T, Ogawa M, Tanaka H, Tanaka S, Kaneda K, Hirohashi K (2003)
Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence.
Cancer Sci 94: 851-7




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Yamashita T, Forgues M, Wang W, Kim JW, Ye Q, Jia H, Budhu A, Zanetti KA, Chen Y, Qin LX, Tang ZY, Wang XW (2008)
EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma.
Cancer Res 68: 1451-61



. Long-term follow-up of larger cohorts of strictly categorized tumours is needed to adequately define the clinical and biological behaviour of all the combined variants
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Bosman FT, Carneiro F, Hruban RH, Theise ND (Eds.)
WHO Classification of Tumours of the Digestive System.
4th Edition
International Agency for Research on Cancer: Lyon 2010



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