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  • Title: Posttransplant lymphoproliferative disorder in pediatric bone marrow transplant recipients: disseminated disease of donor origin demonstrated by fluorescence in situ hybridization.
    Author: Lones MA, Lopez-Terrada D, Shintaku IP, Rosenthal J, Said JW.
    Journal: Arch Pathol Lab Med; 1998 Aug; 122(8):708-14. PubMed ID: 9701332.
    Abstract:
    BACKGROUND: Posttransplant lymphoproliferative disorders in bone marrow transplantation are typically rapidly progressive and fatal B-cell lymphoid proliferations associated with Epstein-Barr virus, and are mostly of donor origin. We report three pediatric bone marrow transplant cases in which posttransplant lymphoproliferative disorder was diagnosed at postmortem examination. Epstein-Barr virus in these cases was identified by a combined in situ hybridization-immunoperoxidase technique and donor origin was identified by fluorescence in situ hybridization. METHODS: Tissues obtained from postmortem examination were evaluated by light microscopy, immunohistochemistry, combined in situ hybridization-immunoperoxidase technique with Epstein-Barr virus-encoded RNA probe, and fluorescence in situ hybridization with X and Y centromeric probes. RESULTS: Three pediatric patients underwent sex-mismatched, T-cell-depleted bone marrow transplants complicated by graft versus host disease, rapidly progressive multiple organ failure, and postmortem diagnosis of posttransplant lymphoproliferative disorder. Histologic examination and immunohistochemistry studies demonstrated immunoblastic lymphoma (one case) or polymorphic B-cell lymphoma (two cases). In all cases, Epstein-Barr virus-encoded RNA was detected by a combined in situ hybridization-immunoperoxidase technique. Fluorescence in situ hybridization for X and Y chromosomes in paraffin sections demonstrated donor origin in two cases (one case was indeterminate). CONCLUSION: Fluorescence in situ hybridization was used to prove donor derivation of Epstein-Barr virus-associated posttransplant lymphoproliferative disorders in pediatric bone marrow transplant recipients. Many features of posttransplant lymphoproliferative disorders in pediatric bone marrow transplant recipients are very similar to adult cases, although a higher proportion of children appear to be diagnosed postmortem and have a fatal outcome.
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