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Am J Surg Pathol. 2006 Dec;30(12):1604-12.

Impact of Epstein-Barr virus in monomorphic B-cell posttransplant lymphoproliferative disorders: a histogenetic study.

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  • 1Department of Pathology, Division of Hematopathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.


The heterogeneity of the posttransplant lymphoproliferative disorders (PTLDs) is well recognized. However, in contrast to other immunodeficiency-associated lymphomas or diffuse large B-cell lymphomas in general, studies of the histogenetic spectrum of the large category of monomorphic B-cell cases have been more limited, produced conflicting results, and have paid little attention to the impact of Epstein-Barr virus (EBV). Therefore, 30 monomorphic B-cell PTLD from 27 patients were analyzed using EBER in situ hybridization for EBV and a panel of antibodies directed against CD20, CD3/bcl-6, CD10, MUM-1/IRF4, CD138, and bcl-2. The results were correlated with the histopathologic features and clinical outcome. All PTLD were CD20 with 23% CD10, 53% bcl-6, 67% MUM-1/IRF4, 13% CD138, 83% bcl-2 and 67% EBV. 30% of the PTLD had a germinal center (GC) profile (CD10, bcl-6, MUM-1/IRF4, CD138), 53% a "late GC/early post-GC" profile (CD10, bcl-6, MUM-1/IRF4, CD138), 13% a post-GC profile (CD10, bcl-6, MUM-1/IRF4, CD138) and 3% an indeterminate profile (all markers negative). EBV positivity was associated with MUM-1/IRF4 expression (P=0.005) and with a non-GC phenotype (P=0.01). All CD138 cases were EBV. The cases with a GC phenotype were the most likely to resemble transformed GC cells (P=0.023). No statistically significant survival differences could be documented between those with a GC versus non-GC phenotype. These results highlight the broad histogenetic spectrum of monomorphic B-cell PTLD. They demonstrate the association of EBV positivity with a non-GC phenotype and suggest that EBV PTLD are more like lymphomas that arise in immunocompetent individuals. The lack of a demonstrable correlation with survival may relate to the relatively small number of cases studied.

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