Transformation in mycosis fungoides: the role of methotrexate

Large cell transformation in patients with mycosis fungoides (MF) has been well reported in the literature. Although the risk factors have not been clearly elucidated, advanced stage seems to be associated with a higher incidence of transformation. Because MF is a rare disorder, little is known about the influence of other factors such as immunosuppressive therapy in the occurrence of transformation.

We questioned the role of methotrexate (MTX) in the transformation of MF to large cell lymphoma (LCL).

We identified all patients with MF who were registered in our cutaneous lymphoma database. Transformation was defined by the presence of large cells exceeding 25% of the infiltrate in at least one skin biopsy. In one patient, we followed the histologic, immunophenotypic, and genotypic changes taking place as transformation occurred.

A total of 134 patients with MF were identified. Of 21 patients who received MTX, 3 transformed, and of the 113 patients in the non-MTX group, only 2 transformed. The incidence of transformation in the patients who received MTX was significantly higher than in those who did not receive the drug (14.3% vs. 1.8%; p = 0.03). This significance was maintained, even after controlling for stage and sex. For one patient who transformed, we demonstrated an identical dominant T-cell clone in all skin specimens, including the large cell lymphoma.

Our results demonstrate a significant association between MTX exposure and transformation to LCL in patients with MF. In light of the small sample size, short followup of patients, and the inherent tendency of mycosis fungoides to transform, the role for MTX in transformation is unproven and needs to be confirmed in a multicenter study.