A coded histologic study of hepatic graft-versus-host disease after human bone marrow transplantation

Authors

  • Howard M. Shulman M.D.,

    Corresponding author
    1. Departments of Pathology, Medicine and Biostatistics, Fred Hutchinson Cancer Research Center, Virginia Mason Hospital, Veterans Administration Medical Center, and the University of Washington School of Medicine, Seattle, Washington 98108
    • Department of Pathology, Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, Washington 98104
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  • Pankaj Sharma,

    1. Departments of Pathology, Medicine and Biostatistics, Fred Hutchinson Cancer Research Center, Virginia Mason Hospital, Veterans Administration Medical Center, and the University of Washington School of Medicine, Seattle, Washington 98108
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  • Deborah Amos,

    1. Departments of Pathology, Medicine and Biostatistics, Fred Hutchinson Cancer Research Center, Virginia Mason Hospital, Veterans Administration Medical Center, and the University of Washington School of Medicine, Seattle, Washington 98108
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  • L. Frederick Fenster,

    1. Departments of Pathology, Medicine and Biostatistics, Fred Hutchinson Cancer Research Center, Virginia Mason Hospital, Veterans Administration Medical Center, and the University of Washington School of Medicine, Seattle, Washington 98108
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  • George B. McDonald

    1. Departments of Pathology, Medicine and Biostatistics, Fred Hutchinson Cancer Research Center, Virginia Mason Hospital, Veterans Administration Medical Center, and the University of Washington School of Medicine, Seattle, Washington 98108
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Abstract

We tested the hypothesis that liver histology from patients with graft-versus-host disease could be distinguished from other common liver diseases. Liver biopsies from 33 allogeneic marrow transplant recipients with acute and chronic graft-versus-host disease and 37 nontransplant liver disease patients without graft-versus-host disease were recut, restained and coded for blind review.

Analysis of individual histologic features showed significantly more cytologic aberration of bile duct epithelium and more cholestasis among biopsies with graft-versus-host disease when compared to biopsies without graft-versus-host disease (p ≤ 0.05). The duration of graft-versus-host preceding the biopsy influenced the histologic features. Biopsies before Day 35 showed frequent acidophilic bodies but infrequent bile duct changes. Biopsies from Days 35 to 90 posttransplant had more frequent bile duct exocytosis and disruption, and biopsies from patients with chronic graft-versus-host disease (beyond Day 90) showed more frequent portal fibrosis and bile duct dropout.

Pattern assessment of coded biopsies showed that a histologic diagnosis of graft-versus-host disease had a positive predictive value of 86%, a sensitivity of 66% and a specificity of 91%. False-negative diagnoses occurred most frequently in biopsies obtained less than 4 weeks posttransplant, usually because bile duct abnormalities were not present. False-positive diagnoses of graft-versus-host disease occurred in nongraft-versus-host disease biopsies with periportal inflammation and proliferated bile ducts. However, biopsies of chronic graft-versus-host disease had more frequent dropout and disruption of bile duct epithelium than did biopsies of acute or chronic hepatitis.

We conclude that a histologic diagnosis of hepatic graft-versus-host disease is likely to be correct if histology shows abnormal bile duct epithelium and cholestasis. While distinction between chronic graft-versus-host disease and non-A, non-B viral hepatitis is imprecise, cytologically atypical and destructive bile duct features favor chronic graft-versus-host disease.

The histologic appearance of graft-versus-host disease is similar to that of primary biliary cirrhosis.

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