Marginal Zone Lymphoma, Immune Dysregulation, and High-Grade Transformation

Marginal zone lymphoma (MZL) is a low-grade B-cell lymphoma, which includes mucosa-associated lymphoid tissue lymphoma, splenic MZL, and nodal MZL. Of these, mucosa-associated lymphoid tissue lymphoma is the most frequent. While all 3 subtypes are typically indolent, a subset undergoes transformation to an aggressive B-cell lymphoma resulting in treatment challenges and a worse prognosis. We present a patient with systemic lupus erythematosus and Sjögren disease who developed MZL while on cyclophosphamide and steroids for treatment of her autoimmune disease. Her MZL was associated with a relatively indolent initial course. Unfortunately, her systemic lupus erythematosus continued to progress, and she ultimately required a renal transplant for end-stage renal disease due to lupus nephritis. At transplant, her MZL was thought to be in remission, but shortly thereafter, she developed an enlarging neck mass. A biopsy demonstrated background MZL with focal transformation to diffuse large B-cell lymphoma. Evidence is emerging that the underlying biology of a subset of MZL based on mutational profile, gene expression, and/or cytogenetic factors may affect the risk of transformation. Immune status has not been linked to progression, but chronic inflammation and immune dysregulation in the setting of chronic infection or autoimmune disease may underlie MZL development. In addition, iatrogenic immunosuppression for solid organ transplant or acquired immunodeficiency in the setting of human immunodeficiency virus may also result in increased risk or unusual presentations of MZL. This article features a case-based approach to explore factors related to MZL progression in a patient with a complex history of autoimmunity and immune suppression.