Recurrent Follicular Lymphoma Unmasking Common Variable Immunodeficiency: A Case Report and Review of Immunologic Links

Non-Hodgkin follicular lymphoma (NHFL) is a common indolent B-cell lymphoma. Immunodeficiency, particularly common variable immunodeficiency (CVID), has been increasingly recognized as a predisposing factor for lymphoproliferative disorders due to impaired immune surveillance. CVID is characterized by defective B-cell differentiation, hypogammaglobulinemia, and impaired antibody responses, often resulting in recurrent infections, autoimmune manifestations, and malignancy. Up to 8-10% of patients with CVID develop lymphoma, predominantly NHL. We report a case of a 68-year-old female with a history of NHFL, initially diagnosed during evaluation for left upper quadrant pain and retroperitoneal adenopathy. Biopsy confirmed follicular lymphoma. She was treated with rituximab and achieved remission. Nearly 20 years later, she relapsed with a chest wall mass, confirmed as follicular lymphoma. Following successful rituximab induction and maintenance therapy, she was diagnosed with CVID, based on persistent hypogammaglobulinemia-IgG 245 mg/dL (normal: 700-1600 mg/dL), IgA 58 mg/dL (normal: 70-400 mg/dL), IgM 18 mg/dL (normal: 40-230 mg/dL)-and an impaired response to vaccination. She was subsequently started on intravenous immunoglobulin therapy. This case highlights the rare but clinically significant association between recurrent NHL and underlying CVID. While lymphoma is a recognized complication of CVID, diagnosis of CVID may be delayed when lymphoma precedes overt immunodeficiency. Given the critical role of the immune system in tumor surveillance, immune dysfunction in CVID likely contributes to both lymphoma development and recurrence. Since lymphoma may be the initial manifestation of CVID, routine screening for primary immunodeficiencies in patients with recurrent or atypical lymphoma presentations-especially in the presence of recurrent infections or autoimmune features-is crucial. Likewise, vigilant surveillance for lymphoma in patients with CVID is warranted. Long-term immunoglobulin replacement therapy in CVID reduces infectious complications, improves survival, and enhances quality of life. By stabilizing immune function and decreasing chronic antigenic stimulation, immunoglobulin therapy may also lower the risk of malignancy, although further studies are needed to confirm a direct protective effect against lymphoma. This case underscores the importance of recognizing the association between CVID and non-Hodgkin's lymphoma. Understanding this interplay should prompt a lower threshold for evaluating one condition when the other is diagnosed. Early identification and treatment of either CVID or NHL can enable more timely interventions, reduce complications, and potentially improve long-term clinical outcomes.