ASSOCIATION OF LYMPHOMATOID GRANULOMATOSIS WITH EPSTEIN-BARR VIRAL-INFECTION OF B-LYMPHOCYTES AND RESPONSE TO INTERFERON-ALPHA-2B

Lymphomatoid granulomatosis (LYG) is an angiodestructive lymphoprolife rative disorder (LPD) often involving the lungs. Its etiology is uncer tain, but a number of previous studies had suggested it is a T-cell LP D associated with Epstein-Barr virus (EBV). Because of the similarity between LYG and nasal angiocentric lymphoma, the term angiocentric imm unoproliferative lesion was proposed for both entities. Optimal therap y is unknown, but chemotherapy is often used. We studied four patients with LYG over a 5-year period. Biopsy samples were analyzed by immuno histochemistry, EBV in situ hybridization, and for Ig heavy-chain (IgH ) gene rearrangements. Clinically, we assessed EBV serology, lymphocyt e subsets, and the efficacy of interferon-alpha 2b (IFN-alpha 2b). All biopsy samples showed an exuberant T-cell infiltrate with scattered a typical large B cells. Double labeling showed EBV in the B cells but n ot T cells. Clonal IgH gene rearrangements were detected in 2 of 3 pat ients studied, 1 of whom had three distinct clones, and light-chain re striction showed two clones in an additional patient. All patients had positive EBV serologies and markedly abnormal lymphocyte subsets. Wit h IFN, 3 patients are alive and disease free at 36, 43, and 60 months; 1 patient achieved a partial response for 16 months but discontinued therapy and died with lymphoma. These results indicate that LYG is a T -cell-rich EBV-associated B-cell LPD in which the infiltrating T cells are numerous but reactive. IgH gene rearrangements may be polyclonal, monoclonal, or oligoclonal. Its association with immune defects sugge sts it is related to posttransplant LPD. However, LYG and nasal angioc entric lymphoma are distinct entities and should no longer be included together under the term angiocentric immunoproliferative lesion. IFN is effective therapy and should be studied further. (C) 1996 by The Am erican Society of Hematology.