Objective: To examine the relationship between autoimmunity and extranodal lymphocytic infiltrates in different lymphoproliferative disorders with immunoglobulin alterations.
Subjects and design: A clinical review combined with a retrospective cohort study of 380 patients, 28 with monoclonal gammopathy of undetermined significance, three with common variable immunodeficiency, 147 with chronic lymphocytic leukaemia, 57 with Waldenström's macroglobulinaemia and 145 with non-Hodgkin's malignant lymphoma.
Setting: A university hospital and The State Serum Institute in Copenhagen.
Intervention: Clinical examination of each patient with special attention to chronic inflammatory and autoimmune manifestations. Biopsies were taken from non-infectious infiltrates, some of which were additionally tested with PCR analysis for gene rearrangements. Serological screening with a test battery for various autoantibodies was used in combination with techniques for the detection of M-components and monoclonal B-cell proliferation.
Main outcome measures: Clinical and/or serological autoimmune manifestations, M-component and other immunoglobulin alterations, and inflammatory tissue changes were studied in patients with chronic inflammatory, polyclonal or oligoclonal pseudolymphomas and in monoclonal, malignant extranodal lymphomas.
Results: In 380 consecutive patients, 49 (12.9%) had extranodal manifestations, of whom 47 also had autoimmune manifestations. Nearly half of the 47 patients had more than one autoimmune manifestation. There was a strong correlation between clinical signs and corresponding autoantibodies such as anti-SSA and -SSB antibodies in Sjögren's syndrome (10 cases), antithyroid peroxidase antibodies in thyroiditis and Graves' disease (10 cases), and parietal cell antibodies in gastric ulcers with maltoma (12 cases). Clinical and serological signs of autoimmunity correlated strongly with female sex (34, 72% women; and 13, 28% men) and with immunoglobulin alterations.
Conclusions: To our knowledge this is the first systematic review of B-lymphoproliferative and autoimmune disorders indicating that pseudolymphoma and malignant lymphomas, including maltomas, may develop in the context of a permanent autoantigenic drive.