High incidence of Epstein–Barr virus (EBV)‐positive Hodgkin lymphoma and Hodgkin lymphoma‐like B‐cell lymphoproliferations with EBV latency profile 2 in children with interleukin‐2‐inducible T‐cell kinase deficiency

Aims Interleukin-2-inducible T-cell kinase (ITK) deficiency is an inherited T-cell deficiency characterized by the development of Epstein–Barr virus (EBV)-associated lymphoproliferations. We aimed to describe the histopathological features of lymphoproliferative processes arising in ITK deficiency, and to compare them with lymphoproliferations in otherwise immunocompromised patients. Methods and results We revised the histopathological diagnoses of 12 biopsies of lymphoproliferations from seven ITK-deficient children according to the World Health Organization criteria, and determined the EBV latency types and lytic activity by staining for EBV-encoded small RNA, latent membrane protein 1, EBV nuclear antigen 2, and ZEBRA. We found polymorphic and borderline polymorphic to monomorphic B-cell lymphoproliferations with variable contents in large cells (five cases), a Hodgkin-like B-cell proliferation (one case), and classic mixed-cellularity Hodgkin lymphoma (six cases). All cases (12/12) were EBV-positive. The Hodgkin lymphoma-like and Hodgkin lymphoma, and all but one polymorphic B-cell lymphoproliferation, showed EBV latency type 2, as observed in classic EBV-positive Hodgkin lymphoma. Conclusions The 100% EBV association, the high percentage of EBV-positive classic Hodgkin lymphoma and Hodgkin-like B-cell proliferations and the predominance of EBV latency type 2 even in polymorphic lesions are the main features of lymphoproliferations in patients with ITK deficiency, and suggest a unique pathomechanism of lymphomagenesis in this T-cell immunodeficiency.