Non-Hodgkin lymphomas (NHL) account for approximately 6-7% of pediatric cancers and their incidence increases with age. Patients with PIDDs show a higher susceptibility to hematopoietic malignancies, in particular to NHL. Recently new gene defects responsible for PIDDs with lymphoproliferation as a key clinical sign have been identified. Our goal is to investigate possible immune-mediated mechanisms underlying malignant lymphoproliferation in children who did not show other typical symptoms of PIDDs.
We retrospectively selected and reviewed the clinical history of eight patients with NHL (6 Burkitt lymphoma, 2 large B cell lymphoma and 1 lymphoblastic T cell lymphoma). Immunophenotyping and exome analysis of known PIDDs genes were performed after lymphoma remission.
Six out of eight patients showed a mild hypogammaglobulinemia at time of presentation, not noticed before. Moreover, one patient had history of recurrent respiratory infections, one of hematologic autoimmunity and two of eight were EBV-positive at diagnosis. Preliminary results show an aberrant B cell phenotype in four patients; exome analysis reveals a novel heterozygous genetic variation in IKZF1 gene in one patient with Burkitt lymphoma and autoimmune cytopenia was identified. Concerning the remaining patients, further studies are ongoing.
A detailed review of clinical history of pediatric patients affected from NHL as well as an impaired immunophenotyping can be important indicators of immune-mediated disorder underlying lymphoproliferation and helpful signs of possible PIDDs that should promptly be investigated by genetic analysis. This will allow an appropriate diagnosis and disease management.