Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by reduced levels of immunoglobulins and impaired antibody responses, leading to recurrent infections, autoimmunity, and an increased risk of malignancies. One of the most well-recognized genetic causes of CVID is mutations in the NFKB1 gene, which plays a crucial role in immune regulation. NFKB1 mutation is associated not only with primary immunodeficiencies (PIDs) but also with an increased risk of lymphoproliferative disorders.
This case report describes a 16-year-old patient with CVID due to NFKB1 mutation, who later developed Epstein-Barr virus (EBV)-negative Burkitt lymphoma (BL).
The patient was born to non-consanguineous parents of Tunisian origin. Her early childhood was unremarkable until she began experiencing recurrent upper respiratory tract infections associated with hypogammaglobulinemia. Given these findings and a significant family history of primary humoral immunodeficiency, her father having been diagnosed with CVID at the age of 33 and started on immunoglobulin replacement therapy, an underlying immunodeficiency was suspected. Further genetic analysis confirmed a NFKB1 mutation. She was initiated on immunoglobulin replacement therapy along with antibiotic prophylaxis. At the age of 16 years, she developed an aggressive non-EBV-induced Burkitt lymphoma (BL), which was confirmed through histopathology and immunohistochemistry.
This case underscores the complex interplay between genetic immunodeficiencies and oncogenesis, emphasizing the need for vigilant surveillance in patients with CVID. The absence of EBV in this case highlights alternative pathways of lymphomagenesis, particularly in the context of impaired NF-κB signalling. Multidisciplinary management is crucial for early detection and optimal treatment of malignancies in immunodeficient patients.
