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Journal Article
Association of lymphomatoid granulomatosis with Epstein-Barr viral infection of B lymphocytes and response to interferon-alpha 2b.
Blood 1996 June 2
Lymphomatoid granulomatosis (LyG) is an angiodestructive lymphoproliferative disorder (LPD) often involving the lungs. Its etiology is uncertain, but a number of previous studies had suggested it is a T-cell LPD associated with Epstein-Barr virus (EBV). Because of the similarity between LYG and nasal angiocentric lymphoma, the term angiocentric immunoproliferative lesion was proposed for both entities. Optimal therapy is unknown, but chemotherapy is often used. We studied four patients with LYG over a 5-year period. Biopsy samples were analyzed by immunohistochemistry, EBV in situ hybridization, and for Ig heavy-chain (IgH) gene rearrangements, Clinically, we assessed EBV serology, lymphocyte subsets, and the efficacy of interferon-alpha2b (IFN-alpha2b), All biopsy samples showed an exuberant T-cell infiltrate with scattered atypical large B cells. Double labeling showed EBV in the B cells but not T cells. Clonal IgH gene rearrangements were detected in 2 of 3 patients studied, 1 of whom had three distinct clones, and light-chain restriction showed two clones in an additional patient. All patients had positive EBV serologies. and markedly abnormal lymphocyte subsets. With 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 suggests it is related to posttransplant LPD. However, LYG and nasal angiocentric 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.
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