Impact of Epstein-Barr virus in monomorphic B-cell posttransplant lymphoproliferative disorders: a histogenetic study.
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.
Johnson
Lawrence R
LR
Department of Pathology, Division of Hematopathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Nalesnik
Michael A
MA
Swerdlow
Steven H
SH
D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D015415:Biomarkers / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D016867:Immunocompromised Host; D017403:In Situ Hybridization; D008232:Lymphoproliferative Disorders / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects*; D011183:Postoperative Complications; D012367:RNA, Viral / Q000032:analysis; D015996:Survival Rate
D015415:Biomarkers; C099537:Epstein-Barr virus encoded RNA 1; D012367:RNA, Viral