EBV Reactivation Syndromes in Adults without Known Immunodeficiency
JA Schrager, S Pittaluga, M Raffeld, ES Jaffe. NCI, Bethesda, MD
Background: EBV-related B-cell lymphoproliferative diseases (LPDs) constitute a broad spectrum. Recent studies have identified EBV+ B-cell lymphomas in the elderly. We wished to identify possible precursors of EBV+ B-cell lymphoma, and to characterize the phenotype, genotype, and possible relationship of these cases to classical Hodgkin lymphoma (CHL) .
Design: 116 benign or malignant EBV+ B-LPDs were identified in a 7 yr period. Pts with known lymphoma, autoimmune disesease, or immunodeficiency were excluded. Cases were analyzed for histological features, immunophenotype (CD20, CD79a, cIg, MUM1, CD30, CD15), EBER in situ, and TCR and IgH gene rearrangement by PCR. Cases were classified as 1) hyperplasia with inc. EBV+ cells (RH); 2) nodal or 3) extranodal polymorphic EBV+ B-cell lymphoma (N-polylym/E-polylym); 4) nodal EBV+ DLBCL including plasmablastic lymphoma (PBL).
Results: RH was diagnosed in 28; median age 67(45-93); M=F. All cases tested were polyclonal by IgH PCR. T-cell clonality or a restricted TCR pattern was seen in 3. Features included preserved architecture, spectrum in cell size of EBV+ cells with frequent localization to germinal centers. Most patients had self-limited disease. 1 patient progressed to N-polylym in 1 year. There were 38 N-polylym; median age 73(30-94); 18M:20F. Most patients had generalized LNs. IgH PCR was clonal in 22/33(66%); TCR was clonal in 22%; 33% showed a restricted pattern and TCR was polyclonal in 44%. EBV+ cells exhibited a range in cell size. Cells were positive for CD79a, MUM1, and CD30 but often negative for CD20. Clinical progression was common. There were 35 E-polylym; median age 76 (55-101); 21M:14F. Most common sites were oral cavity, including gingiva, tongue, and lips (13); tonsil or nasopharynx (7); adrenal gland (4); GI tract (3). 58% of cases tested were monoclonal by IgH PCR. A clonal or restricted TCR pattern was seen in 17%. Hodgkin-like (HRS) cells were common. Immunotype showed CD79a+, CD20 variable, MUM1+, CD30+. HRS-like cells expressing CD30 and CD15 were seen in 5 cases in sites unusual for CHL (oral cavity, skin, adrenal). There were 11 nodal DLBCL and 4 PBL in nodal or extranodal sites; median age 77; M=F).
Conclusions: RH with increased EBV+ cells is frequent in the elderly, but is rarely a precursor to EBV+ B-cell lymphoma. Most EBV+ B-cell LPDs are extranodal, resemble those seen in the post-transplant setting, and may contain CD30+/CD15+ cells mimicking CHL. IgH PCR is usually clonal, but clonal T-cell populations are often seen and may reflect an antigen-driven response in an immunosenescent host.
Monday, March 9, 2009 11:45 AM
Platform Session: Section D, Monday Morning