Methotrexate-associated B-cell Lymphoproliferative Disorders Presenting in the Skin A Clinicopathologic and Immunophenotypical Study of 10 Cases
Methotrexate-associated B-cell Lymphoproliferative Disorders Presenting in the Skin A Clinicopathologic and Immunophenotypical Study of 10 Cases
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DOI：
10.1097/pas.0000000000000225
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发表时间：
2014-07-01
影响因子：
5.6
通讯作者：
Jansen, Patty M.
中科院分区：
文献类型：
--
作者：
Koens, Lianne;Senff, Nancy J.;Jansen, Patty M.
甲氨蝶呤（MTX）相关的B细胞淋巴组织增生性疾病（B-LPD）可能首先出现在皮肤，但其临床病理特征仍然不明确。与原发性皮肤滤泡中心淋巴瘤和原发性皮肤弥漫性大B细胞淋巴瘤，腿型（PCLBCL-LT）的鉴别很重要，因为MTX相关的B-LPD在MTX治疗停止后可能会自发消退。在本研究中，10例MTX相关的B-LPD患者首次出现在皮肤，包括5 EBV+和5 EBV-的情况下，临床病理和表型特征进行了研究。6例患者有皮肤局限性疾病。临床上，取消MTX治疗导致4例完全缓解，另2例部分缓解。5年疾病特异性生存率为90%。MTX相关B-LPD与原发性皮肤滤泡中心淋巴瘤的不同之处在于存在溃疡和/或全身皮肤病变，浸润由中心母细胞/免疫母细胞而不是大的中心细胞组成，CD 79 a染色减少，大多数情况下表达BCL 2、IRF 4和FOXP 1。EBV+ MTX相关B-LPD与PCLBCL-LT的不同之处在于存在溃疡性皮肤病变、显著的肿瘤细胞多态性、CD 79 a染色减少以及CD 30和EBV的表达。EBV-病例显示与PCLBCL-LT的形态学和免疫表型相似，但在5例病例中的4例中表现为全身性皮肤病变。本研究的结果显示，相当大比例的患者仅停用MTX后，临床结局相对较好，疾病自发消退，强调了在考虑对MTX相关皮肤B-LPD患者进行更积极的治疗之前，谨慎观望政策的重要性。
Methotrexate (MTX)-associated B-cell lymphoproliferative disorders (B-LPD) may first present in the skin, but their clinicopathologic features are still ill defined. Differentiation from primary cutaneous follicle center lymphoma and primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) is important, as MTX-associated B-LPD may show spontaneous regression after withdrawal of MTX therapy. In the present study, the clinicopathologic and phenotypical features of 10 patients with MTX-associated B-LPD first presenting in the skin, including 5 EBV+ and 5 EBV- cases, were investigated. Six patients had skin-limited disease. Clinically, abrogation of MTX therapy resulted in a complete response in 4 cases and a partial response in another 2. The 5-year disease-specific survival was 90%. MTX-associated B-LPD differed from primary cutaneous follicle center lymphoma by the presence of ulcerating and/or generalized skin lesions, an infiltrate composed of centroblasts/immunoblasts rather than large centrocytes, reduced staining for CD79a, and expression of BCL2, IRF4, and FOXP1 in most cases. EBV+ MTX-associated B-LPD differed from PCLBCL-LT by the presence ulcerative skin lesions, marked tumor cell polymorphism, reduced staining for CD79a, and expression of CD30 and EBV. EBV- cases showed morphologic and immunophenotypical similarities to PCLBCL-LT but differed by presentation with generalized skin lesions in 4 of 5 cases. The results of this study, showing a relatively good clinical outcome and spontaneous disease regression after only withdrawal of MTX in a considerable proportion of patients, underscores the importance of a careful wait-and-see policy before considering more aggressive therapies in patients with MTX-associated B-LPD of the skin.