Ductular reaction is helpful in defining early stromal invasion, small hepatocellular carcinomas, and dysplastic nodules

Authors

  • Young Nyun Park MD, PhD,

    1. Department of Pathology and Institute of Gastroenterology, Center for Chronic Metabolic Disease, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
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  • Masamichi Kojiro MD,

    1. Department of Pathology, Kurume University School of Medicine, Kurume, Japan
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    • Participants of the Laennec Liver Pathology Society (Wilson Tsui, Paulette Bioulac-Sage, Charles Balabaud, and Alberto Quaglia) contributed cases for the study and participated in discussion of the results during the performance of the investigation and writing of the article

  • Luca Di Tommaso MD,

    1. Department of Pathology, Humanitas Clinical Institute (Italian Scientific Institute for Research Hospitalization and Health Care), University of Milan School of Medicine, Milan, Italy
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  • Amar P. Dhillon MD,

    1. Department of Histopathology, Royal Free and University College Medical School, Royal Free Campus, London, United Kingdom
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  • Fukuo Kondo MD,

    1. Department of Pathology, Funabashi Central Hospital, Funabashi, Japan
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  • Masayuki Nakano MD,

    1. Department of Pathology, Chiba Medical Center, Chiba, Japan
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  • Michiie Sakamoto MD, PhD,

    1. Department of Pathology, Keio University School of Medicine, Keio, Japan
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  • Neil D. Theise MD,

    1. Department of Medicine, Division of Digestive Diseases, Beth Israel Medical Center, New York, New York
    2. Department of Pathology, Beth Israel Medical Center, New York, New York
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    • The last 2 authors contributed equally to this paper.

  • Massimo Roncalli MD, PhD

    Corresponding author
    1. Department of Pathology, Humanitas Clinical Institute (Italian Scientific Institute for Research Hospitalization and Health Care), University of Milan School of Medicine, Milan, Italy
    • Department of Pathology, Humanitas Clinical Institute (Italian Scientific Institute for Research Hospitalization and Health Care), Via Manzoni 56, 20089 Rozzano, Italy
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    • The last 2 authors contributed equally to this paper.

    • Fax: (011) 0039-0282244791.


Abstract

BACKGROUND.

Stromal invasion is 1 of the main features used to distinguish high-grade dysplastic nodules (DNs) from well-differentiated hepatocellular carcinomas (HCCs). The authors hypothesized that ductular reaction (DR) takes place around noninvasive hepatocellular nodules but not within the stroma contiguous to invasive HCC.

METHODS.

DR/cytokeratin 7 (CK7)-positive patterns were evaluated in 105 resected small hepatic nodules according to the level of invasion. The nodules were classified histologically prior to immunostaining as noninvasive (large regenerative nodules, low-grade DNs, and high-grade DNs), minimally invasive (early HCCs with a vaguely nodular type), and overtly invasive (typical HCCs with a distinctly nodular type) in a review by expert pathologists, the current gold standard. Intranodular DR (inner DR) and DR around the nodule periphery (outer DR) were assessed separately on a semiquantitative scale from 0 to 4+.

RESULTS.

DR was 3 or 4+ in the majority of noninvasive nodules (inner DR, 81%; outer DR, 91%), whereas DR was 0 or 1+ in overtly invasive HCCs (inner DR, 96%; outer DR, 81%). Minimally invasive HCCs showed an intermediate DR pattern (2 or 3+ inner DR, 75%; 2+ outer DR, 67%). DR characteristically was absent at the stromal-invasive, leading edge of tumor cells in both minimally invasive HCCs (focal loss of DR/CK7) and overtly invasive HCCs (diffuse loss of DR/CK7). The DR patterns in 41 needle-biopsy samples were similar to the patterns observed in resected nodules.

CONCLUSIONS.

DR/CK7 immunostaining may help to identify small foci of invasion and to distinguish noninvasive, high-grade DNs from both minimally invasive and overtly invasive HCCs. Cancer 2007 © 2007 American Cancer Society.

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