ReviewThe American Journal of dermatopathology2025
Primary Cutaneous Methotrexate-Associated T-Cell Lymphoproliferative Disorder in the Setting of Autoimmune Disease: A Case Series and Review of the Literature.
Review in The American Journal of dermatopathology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
abstractMethotrexate (MTX), an antimetabolite targeting certain autoimmune conditions and various hematologic malignancies, has been associated with iatrogenic lymphoproliferative disease (LPD) primarily of B-cell lineage. Less commonly are T-cell neoplasms where primary skin involvement is considered rare. Three cases were encountered in the medical practice of one of the authors. The patients ranged in age from 38 years to 99 years (2 women and 1 man) with 2 having rheumatoid arthritis and 1 having ankylosing spondylitis. All 3 patients received MTX. The cases included subcutaneous peripheral T-cell lymphoma not otherwise specified (NOS) (1 patient), mycosis fungoides (1 patient), and a primary aggressive epidermotropic cytotoxic T-cell lymphoma (1 patient) that proved to be fatal. One patient had spontaneous regression following MTX withdrawal; she later developed a recurrence while off MTX. Two patients died, 1 of unrelated causes and 1 of lymphoma. Seven previously reported cases included subcutaneous panniculitis-like T-cell lymphoma (2 cases), primary cutaneous CD4+ LPD (2 cases), peripheral T-cell lymphoma (NOS) (1 case), anaplastic large cell lymphoma (1 case), and peripheral T-cell lymphoma localized to fat (1 case). Regression without recurrence occurred in 6 of the 7 patients with MTX withdrawal. The patients were on the MTX for an average of 4 years and had a median age of 61 years with a slight dominance of men over women. Three of the 7 cases showed Epstein-Barr encoding region (EBER) positivity while the 3 cases reported in this series were negative. MTX-associated T-cell LPD involves older patients on long-term MTX where EBER positivity is more frequent than extracutaneous MTX-associated T-cell LPD. A spectrum of classic forms of CTCL is seen with subcutaneous involvement representing a significant percentage of cases. Regression with MTX withdrawal occurs although not in every case.
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