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Immunohistochemical Markers on Needle Biopsies Are Helpful for the Diagnosis of Focal Nodular Hyperplasia and Hepatocellular Adenoma Subtypes

Bioulac-Sage, Paulette MD*,†; Cubel, Gaelle BSc; Taouji, Saïd PhD; Scoazec, Jean-Yves MD, PhD; Leteurtre, Emmanuelle MD§,∥,¶; Paradis, Valérie MD, PhD#; Sturm, Nathalie MD**; Van Nhieu, Jeanne Tran MD††; Wendum, Dominique MD‡‡; Bancel, Brigitte MD§§; Ramos, Jeanne MD∥∥; Paraf, François MD¶¶; Saint Paul, Marie Christine MD##; Michalak, Sophie MD***; Fabre, Monique MD†††; Guettier, Catherine MD‡‡‡; Le Bail, Brigitte MD, PhD*,†; Zucman-Rossi, Jessica MD, PhD§§§,∥∥∥,¶¶¶; Balabaud, Charles MD

The American Journal of Surgical Pathology: November 2012 - Volume 36 - Issue 11 - p 1691–1699
doi: 10.1097/PAS.0b013e3182653ece
Original Articles

Phenotypic identification of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) subtypes using immunohistochemical markers has been developed from their molecular characteristics. Our objective was to evaluate the sensitivity of these markers in the definitive diagnosis of these lesions by core needle biopsies. A total of 239 needle biopsies paired with their surgical resection specimen (group A) or without an associated resection specimen (group B) were reviewed. Using a step-by-step algorithm after standard staining, appropriate immunostaining analyses were performed to determine the certainty of diagnosis of FNH, HNF1α-inactivated HCA, inflammatory HCA, β-catenin-activated HCA, or unclassified HCA. The diagnosis of FNH was certain or probable on routine stains in 53% of needle biopsies of group A, whereas after glutamine synthetase staining, the diagnosis was certain in 86.7% as compared with 100% on the corresponding surgical specimen (P=0.04). In needle biopsies of group A, the diagnosis of HCA was certain on routine stains in 58.6% as compared with 94.3% on surgical specimens. After specific immunostaining, diagnosis was established on biopsies with 74.3% certainty, including all HCA subtypes, with similar distribution in surgical specimens. For each “certain diagnosis” paired diagnostic test (biopsy and surgical specimen), a positive correlation was observed (P<0.001). No significant difference was observed between groups A and B for FNH (P=0.714) or for HCA subtypes (P=0.750). Compared with surgical specimens, immunohistochemical analysis performed on biopsies allowed the discrimination of FNH from HCA and the identification of HCA subtypes with good performance.

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*Department of Pathology, CHU Bordeaux, Hôpital Pellegrin

Inserm U1053, Université Bordeaux Segalen, Bordeaux

Department of Pathology, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon

§§Department of Pathology, CHU Lyon-Nord, Hôpital Croix rousse, Lyon

§Institut de Pathologie, CHRU Lille

Inserm, UMR 837

Université Lille Nord de France, Lille

#Department of Pathology, Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, Clichy

**Department of Pathology, CHU Grenoble, Hôpital Albert Michallon, Grenoble

††Department of Pathology, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil

‡‡Department of Pathology, Assistance Publique-Hôpitaux de Paris, Hôpital St-Antoine

§§§Inserm, U674, Génomique fonctionnelle des tumeurs solides

∥∥∥Université Paris Descartes, Faculté de médecine

¶¶¶Department of Oncology, Assistance Publique-Hôpitaux de Paris, HEGP, Paris

∥∥Department of Pathology, CHU Montpellier, Hopital Gui de Chauliac, Montpellier

¶¶Department of Pathology, CHU Dupuytren, Limoges

##Department of Pathology, CHU Nice, Hôpital Pasteur, Nice

***Department of Pathology, CHU Angers, Angers

†††Department of Pathology, Institut Gustave Roussy

‡‡‡Department of Pathology, Assistance Publique-Hôpitaux de Paris, Hopital Paul Brousse, Villejuif, France

Conflicts of Interest and Source of Funding: Supported by grants from the Société Nationale Française de Gastroentérologie (Fonds de Recherche 2006) and Association pour la Recherche sur le Cancer (grant 3194). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Paulette Bioulac-Sage, MD, Department of Pathology, Hôpital Pellegrin, Place Amélie Raba Léon, CHU Bordeaux, 33076 Bordeaux, France (e-mail:

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© 2012 Lippincott Williams & Wilkins, Inc.