Lymphoproliferative Disorders in Patients with Systemic Lupus Erythematosus

Abstract

Lymphoproliferative disorders can develop in the setting of many immunosupressive conditions, and they have been well established following solid organ transplantation or allogeneic bone marrow transplantation (Blaes & Morrison, 2010). The incidence varies, depending on the type of organ transplanted, the degree of immunosuppression, the number of episodes of acute rejection and the patient's immune status to Epstein-Barr virus. The 2008 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues defines monomorphic posttransplant lymphoproliferative disorders (PTLD) as lymphoid or plasmacytic proliferations that fulfill the criteria for one of the B-cell or T/NK-cell neoplasms recognized in immunocompetent patients. However, indolent Bcell lymphomas, such as extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), are specifically excluded from this category. Autoimmune and chronic inflammatory disorders are also associated with increased risks of non-Hodgkin lymphoma (NHL). Concretely in rheumatoid arthritis and systemic lupus erythematosus (SLE), an increased risk of malignant lymphomas has been described repeatedly, whereas the evidence is less consistent for other inflammatory disorders that display autoimmune phenomena, such as psoriasis, inflammatory bowel disorders and sarcoidosis. The risk of NHL in SLE patients is estimated to be 3to 4-fold higher (Smedby et al., 2008a). Although the incidence of PTLD is thought to be bimodal and typically related to Epstein-Barr virus in the first year after solid-organ transplantation, the relationship between Epstein-Barr virus and NHL in SLE and other autoimmune diseases is not yet well established. Because different NHL subtypes develop at different stages of lymphocyte differentiation, the incidence of specific NHL subtypes varies based on the type of autoimmune and inflammatory disorder as well as on the type and amount of autoimmune therapy. Data regarding the histology of the NHL that develops in patients with SLE suggest that these lesions derive from lymphocytes that have been exposed to antigen (Bernatsky et al., 2005a). Lymphoma development after the antigen-exposure stages of differentiation might suggest that chronic antigenic stimulation has a role in auto immunity-related lymphomas. From the lymphoma perspective, diffuse large B-cell lymphomas seem to display the most pronounced and general association with autoimmunity and inflammation, although certain specific T-cell lymphomas have been linked to distinct autoimmune conditions (e.g.