The occurrence of B cell non-Hodgkin's lymphoma is a complication of Sjögren's syndrome (SS) and, at least in some countries, of chronic hepatitis C virus (HCV) infection. Lymphomas occurring in both diseases share a number of characteristics: predominance of low grade, marginal zone histological type, frequency of mucosal localisation, possible transformation into a large B cell lymphoma, association with asymptomatic low level cryoglobulinaemia, absence of virus within lymphoma cells, but localisation of lymphomas in organs where the chronic viral infection is active in patients with HCV and where the autoimmune disease is active in patients with SS.
It is proposed that in both diseases the first event of lymphomagenesis is the chronic stimulation at the site of the disease of polyclonal B cells secreting rheumatoid factor (RF). Then, that 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 (for example, trisomy 3 or bcl-2 translocation) which would confer to these cells a low grade B cell lymphoma comportment. A last event (for example, a mutation of p53) might transform this low grade B cell lymphoma into a high grade, large B cell lymphoma. The non-random utilisation of VH and VL by SS associated lymphoma B cells and the recent demonstration that these lymphoma B cells may display RF activity support the hypothesis that these lymphomas grow through an autoantigen driven process.
The best preventive treatment of lymphoproliferations occurring in SS probably consists in decreasing the hyperactivation of autoreactive B cells when it is present, allowing the use of immunosuppressive drugs such as methotrexate or even tumour necrosis factor alpha antagonists, which in theory could favour other types of lymphoproliferation.