Nocco Sarah, Magro Cynthia
Dermatology, New York Presbyterian/ Weill Cornell Medicine, New York, NY; and.
Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY.
Am J Dermatopathol. 2025 Feb 1;47(2):145-152. doi: 10.1097/DAD.0000000000002905.
Methotrexate (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.
甲氨蝶呤（MTX）是一种抗代谢药物，用于治疗某些自身免疫性疾病和各种血液系统恶性肿瘤，它与主要为B细胞谱系的医源性淋巴增殖性疾病（LPD）有关。T细胞肿瘤较少见，其中原发性皮肤受累被认为罕见。本文作者之一在医疗实践中遇到了3例。患者年龄在38岁至99岁之间（2名女性和1名男性），2例患有类风湿性关节炎，1例患有强直性脊柱炎。所有3例患者均接受了MTX治疗。这些病例包括皮下未另行特指的外周T细胞淋巴瘤（NOS）（1例）、蕈样肉芽肿（1例）和1例原发性侵袭性亲表皮细胞毒性T细胞淋巴瘤（1例），后者被证明是致命的。1例患者在停用MTX后自发缓解；她后来在未使用MTX时复发。2例患者死亡，1例死于无关原因，1例死于淋巴瘤。先前报道的7例病例包括皮下脂膜炎样T细胞淋巴瘤（2例）、原发性皮肤CD4 + LPD（2例）、外周T细胞淋巴瘤（NOS）（1例）、间变性大细胞淋巴瘤（1例）和局限于脂肪的外周T细胞淋巴瘤（1例）。7例患者中有6例在停用MTX后缓解且未复发。患者平均使用MTX 4年，中位年龄为61岁，男性略多于女性。7例病例中有3例显示爱泼斯坦 - 巴尔编码区（EBER）阳性，而本系列报道的3例为阴性。MTX相关的T细胞LPD累及长期使用MTX的老年患者，其中EBER阳性比皮肤外MTX相关的T细胞LPD更常见。可见一系列经典形式的皮肤T细胞淋巴瘤，其中皮下受累占相当比例的病例。尽管并非每个病例都如此，但停用MTX后会出现缓解。
