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Epstein-Barr virus (EBV)-positive diffuse large B cell lymphoma (DLBCL) is known for distinct clinical features. This disease was formerly designated as EBV-positive DLBCL of the elderly, but the restriction to elderly patients has been removed, and the World Health Organization classification revised 4th edition lists EBV-positive DLBCL, not otherwise specified (NOS). The frequency of EBV-positive DLBCL among DLCBL is about 2.5–14.0%, with higher incidence among East Asians. Most cases occur in patients aged over 50 years old with male predominance. The clinical characteristics of EBV-positive DLBCL, compared to those with EBV-negative DLBCL, include association with older age, more advanced clinical stage, a higher rate of extranodal involvement, and worse performance status. It is usually treated with R-CHOP, consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. EBV-positive DLBCL shows an inferior prognosis with R-CHOP as compared with EBV-negative DLBCL. Furthermore, high EBV-DNA load and positivity of EBV-encoded RNA in biopsy specimens are associated with a worse prognosis.
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