Nodal T Follicular Helper Cell Lymphoma With Epstein–Barr Virus‐Positive Neoplastic T Cells Derived From Clonal Hematopoiesis

Introduction Nodal T follicular helper cell lymphoma (nTFHL) with Epstein–Barr virus (EBV)‐positive neoplastic T cells is rare. Methods We report a woman with nTFHL and analyzed EBV‐infected cells using an immunobead‐based method and assessed somatic mutations in lymphoma and lymphoma‐uninvolved bone marrow by targeted sequencing. Results EBV DNA was enriched in the CD4‐positive fraction containing neoplastic T cells. Shared TET2 mutation was identified in both lymphoma and bone marrow, whereas additional TET2 and RHOA G17V mutations were restricted to the lymphoma. Conclusion These findings support a stepwise model of EBV‐positive nTFHL arising from TET2 ‐mutated clonal hematopoiesis with subsequent acquisition of a RHOA mutation. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission.