Atypical clinical course in pediatric Hodgkin lymphoma: Association with germline mutations in interleukin-2-inducible T-cell kinase

Background: Inherited or acquired immune dysregulation is associated with increased risk of lymphoproliferative disorders (LPDs), including classic Hodgkin lymphoma (cHL). A germline mutation in interleukin-2-inducible T-cell kinase (ITK) is described in individuals manifesting B-cell LPDs, cHL, and hemophagocytic syndromes following Epstein-Barr virus (EBV) infection. Observations: We report a novel ITK mutation in a child with EBV-associated cHL and multiple-site reactive polyclonal B-cell hyperplasia followed by relapsed cHL at another site. Following relapse, the child was successfully treated with allogeneic hematopoietic stem cell transplantation and EBV cytotoxic T cells. Conclusions: ITK-mutated T cells cause a defective antiviral immune response and the resulting immune dysregulation can lead to EBV-associated polyclonal hyperplasia with subsequent outgrowth of neoplastic B-cell clones, which in some instances may progress to LPDs, including cHL.