[Lymphoproliferative disorders in Sjögren's syndrome]

Sjögren's syndrome [SS] is an autoimmune disease that mainly affects the exocrine glands. B-cell lymphoproliferation is a characteristic feature of this syndrome and the lesion may range from benign to malignant.

After a systematic search of Pubmed we reviewed literature regarding the histopathology, pathophysiology and clinics of lymphoproliferation in SS.

Patients with Sjögren's syndrome [SS] have over 40-fold increased risk of the development B-cell non-Hodgkin's lymphoma. Most cases of lymphomas complicating the course of SS arise in mucosal extranodal sites, especially in the salivary gland, and are classified as low grade marginal zone B-cell lymphoma with long-term survival. The main problem in salivary lymphoproliferation in Sjögren's syndrome consists in the difficulties in the differential diagnosis of lymphoma. Genotypic studies have documented the rearrangement of immunoglobulin genes across the full spectrum of lymphoid infiltrates in the salivary gland including cases regarded as reactive lymphoepithelial sialadenitis [LESA], borderline cases with halos of monocytoid cells surrounding epimyoepithelial islets, and cases with fully developed marginal zone lymphoma [MZL]. Thus, the simple detection of B-cell clonality cannot be used as a criterion for the diagnosis of B-cell malignancy. Broad strands of monocytoid B-cells that surround and invade epimyoepithelial islets and monotypic immunoglobulin expression detected by immunohistochemistry are an essential feature for the histopathological diagnosis of MZL. The pathophysiology of lymphoma in SS remains still unknown. Viral infection, hyperstimulation of B cells, disregulation in the process of apoptosis, and unknown oncogenes are suspected to initiate the start of lymphoma. The main clinical features associated with the development of lymphoma in SS include persistent major salivary gland enlargement (> 2 months), persistent lymphadenopathy or splenomegaly, monoclonal gammapathy and type II mixed cryoglobulinemia. The treatment and prognosis of lymphoma associated with SS depend on the type and stage of lymphoma.

Patients with SS develop a variety B lymphoproliferative disorders. The nature of these must be determined by multiparameter analysis including clinical, histopathological, immunohistochemical and genotypic studies.