Malignancy in autoimmune diseases.

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Abstract
Association between antecedent autoimmune diseases and malignancy, including lympho-proliferative disorders (LPD), has been reported in generalized autoimmune diseases such as systemic lupus erythematosus (SLE), dermatomyositis (DM) and rheumatoid arthritis (RA), and also in organ-specific autoimmune diseases such as Sjögren's syndrome (SS) and chronic thyroiditis. In this paper, LPD were summarized for DM, SLE, RA and SS, and some etiologic factors were considered. In surveying previous Japanese literature on the topic, it was revealed that LPD occur frequently in DM similar to various types of cancer. The period between the occurrence of cancer and DM is usually within 12 months, suggesting that the etiologic factor may differ between cancer and LPD in DM. Sixty one cases (20.0%) of monoclonal non-malignant LPD were observed among our 306 patients with SS. Fifteen cases (5.0%) of malignant LPD such as malignant lymphomas (13 cases) and Waldenström's macroglobulinemias (2 cases) were also seen among our SS patients. The activation of rheumatoid factor genes such as Humkv 325 and Vg was considered as one of the triggering factors to advance LPD from the benign to malignant state. A high amount of the bcl-2 protein expression was detected in lymphoepithelial lesions of salivary glands in patients with SS, suggesting that the activation of this gene plays an important role in the progression of the lesion from benign to malignant LPD. Accumulation of many genetic abnormalities including bcl-2 and p 53 genes by chronic stimulation of T and B cells at the site of the autoimmune reaction may be important in the high occurrence of LPD in patients with autoimmune diseases.

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