Malignancy Risk in Systemic Lupus: Recent Research and Ongoing Challenges

What is the magnitude of cancer risk in systemic lupus erythematosus (SLE) compared to the general population? Recent data confirmed a slight increased risk in SLE for all cancers combined, as well as a moderate increased risk of lung cancer, and a strikingly increased risk for hematological malignancies. The hematological cancer type most clearly elevated in SLE is non-Hodgkin's lymphoma (NHL); Hodgkin's lymphoma appears to be increased as well. In SLE, the most commonly identified NHL subtype is diffuse large B-cell lymphoma. Recent analyses suggest that lymphoma in autoimmune rheumatic diseases, including SLE, often presents extra-nodally and/or in advanced stages. Some data suggest that mortality risk in SLE patients with NHL has a bimodal pattern, with a number of patients succumbing early on, and the remainder experiencing fairly good survival rates. Key issues remaining under study relate to the links between cancer risk, clinical features, and medication exposures. New data suggest that disease-related factors may be as or more important, compared to other exposures such as immunosuppressive therapy. The challenge of establishing the independent influences of medication exposures versus disease activity on the risk of malignancy in SLE remains. Work in progress should shed light on these very important issues.