Immunomodulator agent-related lymphoproliferative disorders

Abstract

The recent development of inhibitors of key immune response proteins has revolutionized the therapy of autoimmune diseases; these immunomodulator agents include monoclonal antibodies and receptor antagonists. However, as with all therapies, these new agents are not without side effects and complications. In particular, anti-tumor necrosis factor alpha (TNFa) agents have been reported to be associated with an increased incidence of lymphoproliferative disorders, infections, and vasculitis. We evaluated the clinicopathological features of 18 cases of immunomodulator agent-related lymphoproliferative disorders (IAR-LPD) from several institutions. These included 6 cases of B-cell lymphoma, 2 cases of T-cell lymphoma, 3 cases of classical Hodgkin lymphoma, and 7 atypical lymphoid proliferations that did not fulfill diagnostic criteria for lymphoma; two of the latter regressed after discontinuation of the immunomodulator agent therapy. All eight lymphoma patients with available information had also received prior chemotherapy (methotrexate or 6-mercaptopurine). EBV was strongly associated with the B-cell and classical Hodgkin lymphomas. This case series illustrates that a broad range of lymphoid proliferations can occur after immunomodulator agent therapy and that these immunomodulator agent-related lymphoproliferative disorders have considerable overlap with other well-defined lymphoproliferative diseases associated with iatrogenic immunosuppression. Further study is warranted to evaluate how these therapies interact with other immunosuppressive agents and the underlying abnormal immune system to enhance the development of lymphomas and atypical lymphoid proliferations.

Reactive Tonsillar Enlargement Showing Strong 18F-Fdg Uptake During the Follow-Up of Follicular Lymphoma

“…In lymphoma patients, unfortunately, false-positive results are possible, because an infection, inflammation, hypermetabolic brown fat surrounding lymph nodes or reactive process producing strong 18 F-FDG uptake might be present [2,[5][6][7][8]. In these cases, and not uncommonly after chemotherapy, reactive enlargement of the lymph nodes, tonsils, and thymus gland can be detected [8][9][10][11][12]. Thus, to accurately interpret FDG-PET/CT images, one must be fully familiar with the variable patterns and intensities of uptake and with the frequencies of physiologic and nonphysiologic uptake [13,14].…”

Malignancies and anti-TNF therapy in rheumatoid arthritis: a single-center observational cohort study

“…These lymphomas can be seen as i mmunomodulator agent-related lymphoproliferative disorders. Regression of lymphoproliferative disease after discontinuation of anti-TNF-therapy has been described in case reports [31]. The same is seen in Methotrexate-related lymphoproliferative disorders in patients who did not receive anti-TNF therapy.…”

Unusual Case of Idiopathic Membranous Later Developing Non-Hodgkin’s Lymphoma

“…The immunomodulators can exhaust cytotoxic T lymphocytes and induce an imbalance in the control of EBV infection thus giving EBV associated B Cell lymphoma [8] [9]. We have not assessed EBV status in our patient, though our 90% general population is IgM positive for EBV (unpublished data).…”