Publication Date:
2015-12-03
Description:
Introduction: While immunosuppression for solid organ transplant is associated with an increased risk of lymphoproliferative disease (LPD), this has been more difficult to establish in autoimmune disorders, even though patients are often treated with similar agents. One reason is that autoimmune disease may elevate baseline LPD risk. However, associations have been shown with certain rare types of LPD; most strikingly hepatosplenic lymphoma, now known to occur as a consequence of anti-TNF-alpha therapy in young men with inflammatory bowel disease (IBD) (J Ped Gast Nutr. 2007; 44:265-7). We have noticed a rise in the incidence of another rare lymphoma in autoimmune disease patients: primary central nervous system (PCNS) LPD. Six cases have been diagnosed at our institution since 2010, with none before that dating back to onset of electronic records in 1986. All of these patients were taking mycophenolate mofetil (MMF) and/or thiopurines. A similar rise in reported cases has been seen in the literature (Fig 1) with suggestion of but no direct association with drug treatment shown. We systematically investigated this trend. Methods: We searched our pathology database to identify all LPD cases diagnosed over a 28-year period in patients treated for autoimmune disease as well as all similar cases involving the CNS reported in the literature over the past 40 years. Statistical analyses were performed using the Fisher's exact test. Results: We identified 44 cases of LPD arising in patients treated for autoimmune disease, including 6 with PCNS disease (Table 1). Of LPDs in patients on anti-TNF-alpha agents, 4/5 had a T-cell phenotype, and 3 had IBD. By contrast, in patients who developed LPD while taking methotrexate, the majority for rheumatoid arthritis, only 1/18 had a T-cell phenotype. Instead they were categorized as polymorphous, Hodgkin or large B-cell morphologies, which were frequently EBV-positive (67%), but never involved the brain (0/18). The LPDs arising in patients on MMF and/or thiopurines showed a similar morphologic profile but were more likely to involve the CNS. In particular, MMF was significantly associated with PCNS compared to non-CNS disease (p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
Permalink