Methotrexate-associated lymphoproliferative disorders mimicking angioimmunoblastic T-cell lymphoma

Patients affected by autoimmune diseases (rheumatoid arthritis (RA), psoriasis, and dermatomyositis) treated with methotrexate (MTX) develop lymphoproliferative disorders (LPDs). These cases have been reported to be diffuse large B-cell lymphoma, Hodgkin lymphoma, or polymorphous post-transplant LPDs. However, angioimmunoblastic T-cell lymphoma (AITL) is extremely rare in the medical literature. In this report, we describe three cases of RA patients who developed MTX-associated LPDs resembling AITL. They developed systemic lymph node swelling after initiation of MTX. The affected lymph nodes showed the histological finding of AITL: polymorphous infiltrates, mainly T-cells and arborizing high endothelial venules. Two cases showed a predominance of CD4-positive cells in proliferative T-cells, whereas the third case showed CD8-positive cells. CD10 was negative in all cases. RNA in situ hybridization of Epstein-Barr virus (EBV) demonstrated EBV-positive B-cells to be scattered in two cases, but not in one case. The lymphoadenopathy spontaneously regressed with cessation of MTX in all three cases, but one case recurred. These are interesting cases of MTX-associated LPDs mimicking AITL, and cessation of MTX is the only cure for patients with MTX-associated LPDs resembling AITL.