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Aspects of liver pathology in adult patients with MDR3/ABCB4 gene mutations

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Abstract

The aims of this study were to describe the histological liver lesions in adult patients with MDR3/ ABCB4 mutation and to study the usefulness of MDR3 immunostaining as a diagnostic tool. All adult patients from our institution with an MDR3/ABCB4 mutation and a liver histology were included (n = 13). Eleven patients had a single heterozygous gene mutation and two patients had two heterozygous mutations. Two patients had no liver lesions. Eight patients had a mild ductular reaction and portal fibrosis. One patient had a few fibrous septa and two patients had biliary cirrhosis. In three cases intraductal lipid crystals were identified. Two patients had biliary fibroobliterative lesions with no sclerosing cholangitis on cholangiography. Biliary dysplasia was identified in hepatectomy specimens from two patients, one of whom developed an intrahepatic cholangiocarcinoma. One patient with biliary cirrhosis developed a hepatocellular carcinoma. MDR3 immunostainings performed on formalin-fixed paraffin-embedded sections showed a strong canalicular staining in all patients except in one. To conclude, the predominant histological features were ductular reaction with no or mild fibrosis without cholangitis. Liver lesions previously unreported in association with MDR3/ABCB4 gene mutations (biliary dysplasia, cholangiocarcinoma, small duct sclerosing cholangitis) were also found. Lipid crystals in bile ducts may be suggestive of MDR3/ABCB4 mutation. MDR3 immunostaining on formalin-fixed paraffin-embedded sections does not seem to be sensitive for the diagnosis of heterozygous MDR3/ABCB4 mutations.

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Authors and Affiliations

  1. Service d’Anatomie Pathologique, APHP, Hôpital St Antoine, 75012, Paris, France

    Dominique Wendum & Jean-François Fléjou

  2. Service de Biochimie, APHP, Hôpital St Antoine, 75012, Paris, France

    Véronique Barbu

  3. Service d’Hépatologie, APHP, Hôpital St Antoine, 75012, Paris, France

    Olivier Rosmorduc & Raoul Poupon

  4. Service d’imagerie médicale, APHP, Hôpital St Antoine, 75012, Paris, France

    Lionel Arrivé

  5. Université Pierre et Marie Curie, UPMC, Univ Paris06, 75005, Paris, France

    Dominique Wendum, Véronique Barbu, Olivier Rosmorduc, Lionel Arrivé, Jean-François Fléjou & Raoul Poupon

  6. INSERM, UMR_S938, CdR Saint-Antoine, 75012, Paris, France

    Dominique Wendum, Véronique Barbu & Olivier Rosmorduc

  7. Service d’Anatomie et Cytologie Pathologiques, Hôpital St Antoine, 184, rue du Faubourg St Antoine, 75571, Paris Cedex 12, France

    Dominique Wendum

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  1. Dominique Wendum
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  2. Véronique Barbu
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  3. Olivier Rosmorduc
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  5. Jean-François Fléjou
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  6. Raoul Poupon
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Correspondence to Dominique Wendum.

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Wendum, D., Barbu, V., Rosmorduc, O. et al. Aspects of liver pathology in adult patients with MDR3/ABCB4 gene mutations. Virchows Arch 460, 291–298 (2012). https://doi.org/10.1007/s00428-012-1202-6

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  • DOI: https://doi.org/10.1007/s00428-012-1202-6

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