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Is histological diagnosis of primary liver carcinomas with fibrous stroma reproducible among experts?
  1. Gabriel Malouf (ghassan_maalouf{at}
  1. Ambroise Paré Hospital, France
    1. Bruno Falissard (falissard_b{at}
    1. Hôpital Paul Brousse, Villejuif, France
      1. Daniel Azoulay (daniel.azoulay{at}
      1. Hôpital Paul Brousse, Villejuif, France
        1. Francisco Callea (francalanci{at}
        1. Department of Pathology, Children's Hospital Bambino Gesù, Rome, Italy
          1. Linda F Ferrell (linda.ferrell{at}
          1. University of California, San Francisco, CA 94143-0102, United States
            1. Zachary D Goodman (goodman{at}
            1. Department of Hepatic and Gastrointestinal Pathology and Veterans Administration Special Reference, United States
              1. Yoshitake Hayashi (hayashi{at}
              1. First Division of Pathology, Kobe University School of Medicine, Japan
                1. Hey-Chi Hsu (heychi{at}
                1. Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
                  1. Stefan g Hubscher (s.g.hubscher{at}
                  1. Department of Pathology, University of Birmingham, Birmingham B15 2TT, United Kingdom
                    1. Masamichi Kojiro
                    1. Kurume University School of Medicine,Kurume University, Fukuoka, Japan
                      1. Irene OL N G (iolng{at}
                      1. SH Ho Foundation Research Laboratory and Jockey Club Clinical Research Centre, Hong Kong, China
                        1. Alan c Paterson (patersonac{at}
                        1. University of the Witwatersrand and National Health Services Laboratory, Johannesburg, South Africa
                          1. Michel Reynes
                          1. Paul Brousse Hospital, France
                            1. Elie-Serge Zafrani
                            1. Henri Mondor Hospital, France
                              1. Jean-François Emile (jean-francois.emile{at}
                              1. Ambroise Paré Hospital, France


                                Background: In the era of targeted therapeutics, histological typing of hepatobiliary carcinomas has major clinical implications. Little is known about the reproducibility of pathologic diagnosis of primary liver carcinomas. Therefore, our study aimed to evaluate the worldwide variation in the pathologic expert diagnoses of primary liver carcinomas with fibrous stroma in non-cirrhotic patients.

                                Methods: We selected a single set of slides from 25 tumors, which was reviewed independently by 12 pathologists with worldwide expertise in liver tumors. Reproducibility of the diagnoses was evaluated by Light's kappa, and diagnoses were clustered by multidimensional scaling. Immunohistochemistry was performed after histological review.

                                Results: The interobserver reproducibility for diagnosis of hepatocellular carcinoma subtypes and cholangiocarcinomas was poor (kappa [0.23 to 0.52]), even when the experts considered that the diagnosis required no additional stains or clinical information. Interestingly, multidimensional scaling revealed 3 main clusters of tumors; hepatocellular carcinoma with no other specifications (n=13), fibrolamellar hepatocellular carcinoma (n=3) and cholangiocarcinoma (n=9). Using immunohistochemistry, these histological clusters correlated with anti-hepatocyte and anti-cytokeratin 19 expression (P<0.001).

                                Conclusions: Our results demonstrate the poor reproducibility among experts of the pathologic diagnosis of primary liver carcinomas with fibrous stroma in non-cirrhotic patients, and highlights that the systematic use of immunohistochemistry may improve the diagnostic accuracy.

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