Age related EBV associated lymphoproliferative disorder - a spectrum of reactive lymphoid hyperplasia and lymphoma: the Western experience
Dojcinov, Stefan D × Venkataraman, Girish Pittaluga, Stefania Wlodarska, Iwona Schrager, Jeffrey A Raffeld, Mark Hills, Robert K Jaffe, Elaine S #
Blood vol:117 issue:18 pages:4726-4735
We investigated age related EBV+ B-cell lymphoproliferations (AR-EBVLPDs) in the Western population. The clinical features, histology, immunophenotype, EBER-ISH, and clonality by T-cell-receptor (TCR) and immunoglobulin (IG) PCR were categorized in 122 EBV+ lesions as follows: i) reactive lymphoid hyperplasia (RH); ii) polymorphic extranodal (Poly-E) or iii) polymorphic nodal lymphoproliferative disease (Poly-N) and iv) diffuse large B-cell lymphoma (DLBCL). Interphase FISH for IG and PAX5 gene rearrangements was performed on 17 cases of DLBCL. The overall median age was 75 (45-101; M67:F55), and 67, 79, 73, and 77 for groups i-iv. 16/21 Poly-E were classified as EBV+ mucocutaneous ulcer (EBVMCU). PCR for IG was polyclonal in RH (84%) and monoclonal in 33%, 63% and 56% of Poly-E/N and DLBCL respectively. All groups showed restricted/clonal TCR responses (27%-70%). By FISH 19% of DLBCLs showed IGH rearrangements but PAX5 was unaffected. Disease specific 5-year survival was 100%, 93%, 57% and 25% for groups i-iv, and 100% for EBVMCU. Disease volume was predictive of therapy response (p=0.0002), and pathological subtype was predictive of overall outcome (p=0.001). AR-EBVLPD is a wider disease spectrum than previously recognized, including both reactive and neoplastic LPDs. Reduction in the T-cell repertoire may contribute to decreased immune surveillance.