title: Aspects of liver pathology in adult patients with MDR3/ABCB4 gene mutations.
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.
authors.affiliation: Service d'Anatomie Pathologique, APHP, Hôpital St Antoine, 75012 Paris, France. dominique.wendum@sat.aphp.fr
authors.forename: Dominique
authors.initials: D
authors.lastname: Wendum
authors.forename: Véronique
authors.initials: V
authors.lastname: Barbu
authors.forename: Olivier
authors.initials: O
authors.lastname: Rosmorduc
authors.forename: Lionel
authors.initials: L
authors.lastname: Arrivé
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Fléjou
authors.forename: Raoul
authors.initials: R
authors.lastname: Poupon
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008107:Liver Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016612:Paraffin Embedding; D016707:Tissue Fixation; D055815:Young Adult
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D015415:Biomarkers; C095122:multidrug resistance protein 3