Clinical, immunologic, and molecular factors predicting lymphoma development in Sjogren's syndrome patients

Among autoimmune diseases, Sjogren's syndrome (SS) displays the highest incidence of non-Hodgkin lymphoma (NHL) development with the salivary extranodal marginal zone B cell lymphomas being the most common type. The majority of SS-associated NHLs are characterized by localized stage, indolent clinical course, and recurrence in other extranodal sites. Although the transition from a chronic inflammatory condition to malignant lymphoma is a multistep process yet poorly understood, there is increasing evidence that chronic antigenic stimulation by an exoantigen or autoantigens plays an essential role in the development of SS associated lymphoproliferation. Additional molecular oncogenic events such as microsatellite instability, loss of the B cell cycle control, and the forced overproduction of specific B cell biologic stimulators seem to contribute to the emergence and progression of the malignant overgrowth. Among the clinical and serological parameters that have been associated with lymphoma development in SS patients, the presence of palpable purpura, low C4, and mixed monoclonal cryoglobulinemia constitute the main predictive markers, and patients displaying these risk factors should be monitored closely.