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Presence of natural killer‐cell clones with variable proliferative capacity in chronic active Epstein–Barr virus infection

Chronic active Epstein–Barr virus infection (CAEBV) is a syndrome that takes diverse clinical courses and is often associated with lymphoproliferative disorders of T / natural killer (NK)‐cell lineage. We describe a patient with CAEBV associated with persistent pharyngeal ulcer, and with subsequent nasal T/NK‐cell lymphoma in her neck lymph nodes and nasopharynx. Immunophenotyping of lymphoid cells showed that the lineage of Epstein–Barr virus (EBV)‐positive cells in the patient was of NK‐cell origin. By means of high‐dose recombinant interleukin‐2, we established an EBV‐positive cell line of NK‐cell lineage from her peripheral blood. Southern blot analysis for the number of terminal repeat sequences of EBV detected three NK‐cell clones in the patient’s lymph node. One of these clones was identical to the established cell line but was not observed in the pharyngeal ulcer, while the other two clones were present in the pharyngeal ulcer. These results suggest that the patient had expansion of the three NK‐cell clones, one of which had proliferative capacity in vitro and was involved in the formation of the lymphoma. Moreover, the results suggest that the proliferative capacity of EBV‐positive cells can be variable even in a single patient, and this variability may explain the clinical diversity in CAEBV.