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

Abstract

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.

Keywords: 6-Mercaptopurine; Autoimmune disorders; Azathioprine; Immunosuppression; Inflammatory bowel disease.

Figure 1

Bone marrow involvement by hepatosplenic T-cell lymphoma (HSTCL). A. The bone marrow shows 80% cellularity with trilineage hematopoiesis. (hematoxylin and eosin stain, x400, Case 4). B. Immunohistochemistry for the CD3 highlights lymphoma cells with an interstitial and sinusoidal pattern. (CD3 immunohistochemistry with hematoxylin counterstain, x400, Case 4). C. Histologic section of spleen shows expansion of the red pulp by small to intermediate-size lymphoma cells (hematoxylin and eosin stain, x100, Case 5). D. CD3 immunohistochemical stain of spleen highlights the neoplastic cells infiltrating sinusoids (CD3 immunohistochemistry with hematoxylin counterstain, x400, Case 5).

Figure 2

Venn diagram of therapy patients with HSTCL received for their underlying immune disorders. A total of 51 (89%) patients received immunosuppressive drugs and 31 (54%) received both immunosuppressive drugs and TNF-α inhibitors; 1 patient (2%) received TNF-α inhibitors only, and 5 patients (9%) received neither immunosuppressive drugs nor TNF-α inhibitors.