B Cell Expansion and Neoplasia in Sjögren’s Syndrome

Sjogren’s syndrome (SS) is a progressive systemic autoimmune disease causing chronic inflammation of the salivary, lacrimal, and other glands and B cell hyperactivity leading to the production of autoantibodies, such as anti-Ro (SS-A), La (SS-B), and rheumatoid factor (RF), and a 40-fold increased risk of extranodal B cell lymphoma arising in the inflamed salivary glands, especially the parotid glands. Although most of the cells infiltrating the salivary glands are T cells, B cells and plasma cells within the inflammatory infiltrates may undergo benign or malignant expansions. A variety of B cell lymphoproliferative processes are seen, both benign (e.g., lymphocytic interstitial pneumonitis) and malignant (e.g., marginal zone lymphoma, diffuse large B cell lymphoma, and follicular lymphoma). Many of the B cell lymphomas produce RF with restricted usage of somatically mutated heavy-chain genes. We discuss the pathogenesis of B cell lymphomas in SS as well as their higher frequency in primary compared with secondary SS. Finally, we review clinical aspects of lymphoid neogenesis in SS, including the risk factors, diagnostic considerations, and therapeutic options.