Other Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders with a T- or NK-cell phenotype

Abstract

Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPDs) with a T- or NK-cell phenotype are markedly rare, with only a limited number of cases having been reported thus far. Methotrexate (MTX) is the most common agent used for OIIA-LPD patients, and 43 cases of MTX-associated T-LPDs (MTX T-LPDs) and five cases of MTX-associated NK/T-LPDs (MTX NK-LPDs) have been described. In addition to MTX T-LPDs and MTX NK/T-LPDs, T-LPD and NK/T-LPDs have been reported in patients receiving other immunosuppressive agents such as thiopurines, TNF antagonists, and cyclosporine. Hepatosplenic T-cell lymphoma (HSTL) is specifically associated with iatrogenic immunodeficiency, and 10% of HSTL cases develop in patients receiving thiopurines and/or TNF antagonists for inflammatory bowel disease (IBD). In this review, we focused on MTX T-LPD, MTX NK/T-LPD, and HSTL in patients with IBD. These T- and NK/T-cell associated OIIA-LPDs are the most common in daily medical practice.

Keywords: T or NK/T-cell lymphoma; hepatosplenic T-cell lymphoma; inflammatory bowel disease; methotrexate; other iatrogenic immunodeficiency-associated lymphoproliferative disorder.

Fig. 1

Histological and immunohistochemical features of angioimmunoblastic T-cell lymphoma-type methotrexate-associated T-cell lymphoproliferative disorder (MTX-AITL). MTX-AITL had diffuse and polymorphous infiltration of small- to medium-sized lymphocytes accompanied by the proliferation of high endothelial venules. Small- to medium-sized lymphocytes were characterized by clear cytoplasm (A: HE x 200, B: HE x 400). Immunohistochemically, the tumor cells were positive for PD1 (C: PD1 x 200). Scattered EBV-infected B cells were detected in the background (D: EBER x 200).

Fig. 2

Histological and immunohistochemical features of EBV⁺CD8⁺ cytotoxic T-cell lymphoma (CTL)-type methotrexate-associated T-cell lymphoproliferative disorder. The EBV⁺CD8⁺ CTL type was characterized by the infiltration of medium-sized atypical lymphocytes (A: HE x 400). Immunohistochemically, tumor cells were positive for CD8 (B: HE x 400), TIA-1 (C: HE x 400), and EBER (D: EBER x 400).

Fig. 3

Histological and immunohistochemical features of hepatosplenic T-cell lymphoma. The tumor cells were small to medium in size with pale cytoplasm (A: HE x 400). The liver exhibited predominant sinusoidal infiltration (B: HE x 200). Immunohistochemically, most cases were positive for CD3 (C: CD3 x 400) and TIA-1 (D: TIA-1 x 400). The photographs in Figure 3 were kindly provided by Dr. Ohshima, Kurume University.