Lymphomas in patients with Sjögren's syndrome: review of the literature and physiopathologic hypothesis.

The occurrence of non Hodgkin's lymphoma (NHL) is the most serious complication of Sjögren's syndrome (SS). Taking the opportunity to study 16 patients with lymphoma and an underlying SS, we performed a review of literature concerning SS and lymphoma and made an hypothesis on the physiopathology of lymphoproliferation in patients with SS. Lymphomas occurring in patients with SS are in most cases low grade marginal zone lymphomas (MZL). They arise frequently in mucosal extranodal sites, not only in the salivary glands but also the stomach and the lung. These lymphomas are not associated with viruses including hepatitis C virus (HCV), Epstein-Barr virus, human herpes virus 8 or human T lymphotropic virus-I, known to be present in other types of lymphomas. Some of the translocations or mutations of oncogenes or anti-oncogenes described in other lymphomas are also detected in SS-associated lymphomas. Lymphomas complicating SS share a number of characteristics with lymphomas complicating HCV infection. We make the assumption that, in both diseases, the first event of lymphomagenesis is the chronic stimulation, on the site of the disease, of polyclonal B-cells secreting rheumatoid factor (RF). Then, these RF B-cells may become monoclonal and disseminate in other organs. The monoclonal secreted RF complexed with polyclonal IgG may cryoprecipitate. The following step would be a chromosomal abnormality (e.g. trisomy 3) which would confer to these cells a low grade B-cell lymphoma compartment. A last event (e.g. mutation of p53) could transform this low grade B-cell lymphoma into a high grade large B-cell lymphoma. If this hypothesis was correct, most of B-cell lymphomas associated with SS should have a surface immunoglobulin with RF activity and should grow through an auto-antigen driven process.