Hepatosplenic T-cell lymphoma arising in patients with immunodysregulatory disorders: a study of 7 patients who did not receive tumor necrosis factor-α inhibitor therapy and literature review.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive extranodal T-cell lymphoma that can arise in patients with underlying immune disorders. Others have suggested that tumor necrosis factor (TNF)-α inhibitor therapy for immune disorders increases the risk of HSTCL. To assess for a potential relationship between HSTCL and the use of TNF-α inhibitors, we searched for patients with HSTCL and underlying immune disorders at our institution. We identified 7 patients with a median age of 38 years. Five patients had Crohn disease, 1 ulcerative colitis, and 1 rheumatoid arthritis. In 6 patients, medication history for the immune disorder was available: 6 patients received 6-mercaptopurine or azathioprine, and 2 patients received steroids; no patients received TNF-α inhibitors. In all 7 patients, the histologic, immunophenotypic, and cytogenetic findings were similar to cases of HSTCL that arise in immunocompetent patients. We reviewed the literature and identified 60 patients with immune disorders who subsequently developed HSTCL. These patients were treated with immunosuppressive drugs in 89%, TNF-α inhibitors in 56%, and both therapies in 54%, and 1 (2%) patient was treated with TNF-α inhibitors only. Our cohort and literature review indicates that TNF-α inhibitor therapy is not essential for the development of HSTCL in patients with immunodysregulatory disorders, and implies that immunosuppressive drugs or other factors (eg, genetic predisposition, chronic antigenic stimulation) may be more critical in the pathogenesis in this context. Although these data are observational, they have implications for the use of TNF-α inhibitors in patients with inflammatory bowel disease and other immunodysregulatory disorders.