原发性皮肤CD4+小/中型多形性T细胞淋巴增生性疾病（PC-SMTLD）被认为是一种具有争议性的皮肤疾病，被纳入皮肤T细胞淋巴瘤组，最常表现为孤立的结节和/或斑块，并具有特定的头颈偏好。由于PC-SMTLD和假性淋巴瘤（PL）之间存在较大的重叠，鉴别诊断通常具有挑战性。在多种癌症中，包括全身淋巴瘤，DNA的5位点甲基化和细胞内5-羟甲基胞嘧啶（5-hmC）水平的降低是一个关键的表观遗传事件。然而，它在皮肤淋巴瘤中的研究很少。作者旨在探讨差异5-hmC免疫染色作为鉴别PC-SMTLD和PL的有用标记的作用。在PL和PC-SMTLD中进行了免疫组化和免疫荧光分析的回顾性病例系列研究。结果显示，与PL相比，PC-SMTLD中5-hmC核染色显著减少（p < 0.0001）。通过半定量等级整合，在两个研究组中的最终5-hmC评分上存在统计学差异。5-hmC与CD4的免疫荧光共染色显示，在PC-SMTLD的CD4+淋巴细胞中5-hmC减少。研究样本规模较小。在CD4+淋巴细胞中5-hmC的免疫反应性极具推测性，支持其为PL的良性过程。此外，PC-SMTLD中5-hmC核染色的降低表明其淋巴增生状态，并有助于与PL进行鉴别诊断。 版权所有 © 2023 Sociedade Brasileira de Dermatologia. Elsevier España, S.L.U. 发表。版权所有。

Primary cutaneous CD4+ small/medium-sized pleomorphic T-Cell lymphoproliferative disorder (PC-SMTLD) has been considered as a controversial dermatological disease that has been included in cutaneous T-cell lymphoma group, presenting most commonly as a solitary nodule and/or plaque with a specific and characteristic head and neck predilection. Due to the considerable overlap between PC-SMTLD and pseudolymphoma (PL), the differential diagnosis is often challenging. Methylation of DNA at position 5 of cytosine, and the subsequent reduction in intracellular 5-hydroxymethylcytosine (5-hmC) levels, is a key epigenetic event in several cancers, including systemic lymphomas. However, it has rarely been studied in cutaneous lymphomas.The authors aimed to explore the role of differential 5-hmC immunostaining as a useful marker to distinguish PC-SMTLD from PL.Retrospective case series study with immunohistochemical and immunofluorescence analysis of 5-hmC was performed in PL and PC-SMTLD.Significant decrease of 5-hmC nuclear staining was observed in PC-SMTLD when compared with PL (p < 0.0001). By semi-quantitative grade integration, there were statistical differences in the final 5-hmC scores in the two study groups. The IF co-staining of 5-hmC with CD4 revealed a decrease of 5-hmC in CD4+ lymphocytes of PC-SMTLD.The small clinical sample size of the study.The immunorreactivity of 5-hmC in CD4+ lymphocytes was highly suggestive of a benign process as PL. Furthermore, the decrease of 5-hmC nuclear staining in PC-SMTLD indicated its lymphoproliferative status and helped to make the differential diagnosis with PL.Copyright © 2023 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.