Roelens M, de Masson A, Ram-Wolff C, Maki G, Cayuela J-M, Marie-Cardine A, Bensussan A, Toubert A, Bagot M, Moins-Teisserenc H
Université de Paris, Paris, France.
INSERM, UMR-1160, Institut de Recherche Saint-Louis, 75010, Paris, France.
Br J Dermatol. 2020 Jun;182(6):1415-1422. doi: 10.1111/bjd.18481. Epub 2019 Oct 22.
The early diagnosis of Sézary syndrome (SS) is challenging. Loss of CD7 and CD26 expression on CD4 T cells is the currently used criterion in the initial diagnosis and staging of patients with SS.
Our aim was to evaluate the respective value of CD26, CD7 and KIR3DL2 expression on CD4 T cells and total lymphocytes at initial diagnosis of SS.
This prospective study included 254 patients with clinical features consistent with cutaneous T-cell lymphoma seen at our institution between March 2014 and February 2019. Peripheral blood analysis by flow cytometry was performed for each patient at the time of diagnosis and during follow-up. The diagnosis of SS was based on ISCL/EORTC criteria.
The presence of KIR3DL2 Sézary cells (SCs) ≥ 200 μL correlated with the diagnosis of SS, with sensitivity of 88·6% and specificity of 96·3%. All 154 patients with either inflammatory skin disease or other haematological disease had KIR3DL2 cells < 200 μL , while eight of them had CD4 CD26 T cells ≥ 1000 μL . Of five patients with SS and lymphopenia, four had CD4 CD7 T cells < 1000 μL and three had CD4 CD26 T cells < 1000 μL . However, all of them had KIR3DL2 CD4 T cells ≥ 200 μL . Among patients with available samples during evolution, all B1-staged patients with ≥ 200 μL KIR3DL2 SCs at diagnosis evolved to B2 stage within 7 months.
KIR3DL2 expression on T cells is highly specific and helps the early diagnosis of SS, especially in those patients with lymphopenia. What's already known about this topic? In the ISCL/EORTC cutaneous T-cell lymphoma (CTCL) categorization of blood involvement (B0-B2), B2 is defined as a T-cell receptor clonal rearrangement in blood, associated with high blood-smear Sézary cell (SC) count. Flow cytometry was developed to circumvent interobserver variability of SC manual counts; however, it mostly relies on detection of cells lacking CD7 and/or CD26 expression. We previously reported the reliability of KIR3DL2 as the first positive SC marker. What does this study add? Based on our analysis of 254 patients, we propose that KIR3DL2 be added to the ISCL/EORTC criteria for initial diagnosis of Sézary syndrome (SS) and B2 staging. This marker improved sensitivity of SS B2-stage CTCL diagnosis with a specificity > 95%, especially for patients with lymphopenia. We found KIR3DL2 helped early diagnosis of SS and was more reliable than CD26 in assessing blood tumour burden during therapy. What is the translational message? SC quantification is the major means of staging at initial diagnosis and monitoring blood tumour burden in a clinical trials setting. We recommend using a threshold value of KIR3DL2 SCs ≥ 200 μL or KIR3DL2 SCs/lymphocytes ≥ 10% in the diagnostic criteria of SS and propose a novel algorithm for CTCL B2 blood staging.
蕈样肉芽肿综合征（SS）的早期诊断具有挑战性。CD4 T细胞上CD7和CD26表达缺失是目前用于SS患者初始诊断和分期的标准。
我们的目的是评估在SS初始诊断时CD4 T细胞和总淋巴细胞上CD26、CD7和KIR3DL2表达的各自价值。
这项前瞻性研究纳入了2014年3月至2019年2月期间在我们机构就诊的254例具有与皮肤T细胞淋巴瘤一致临床特征的患者。在诊断时和随访期间对每位患者进行流式细胞术外周血分析。SS的诊断基于ISCL/EORTC标准。
KIR3DL2蕈样肉芽肿细胞（SCs）≥200 μL与SS诊断相关，敏感性为88.6%，特异性为96.3%。154例患有炎症性皮肤病或其他血液系统疾病的患者KIR3DL2细胞均<200 μL，其中8例患者CD4 CD26 T细胞≥1000 μL。5例SS伴淋巴细胞减少的患者中，4例CD4 CD7 T细胞<1000 μL，3例CD4 CD26 T细胞<1000 μL。然而，他们所有患者KIR3DL2 CD4 T细胞均≥200 μL。在病情进展期间有可用样本的患者中，所有诊断时KIR3DL2 SCs≥200 μL的B1期患者在7个月内进展为B2期。
T细胞上KIR3DL2表达具有高度特异性，有助于SS的早期诊断，尤其是在淋巴细胞减少的患者中。关于该主题已知的内容有哪些？在ISCL/EORTC皮肤T细胞淋巴瘤（CTCL）血液受累（B0 - B2）分类中，B2定义为血液中T细胞受体克隆重排，与高血涂片蕈样肉芽肿细胞（SC）计数相关。流式细胞术的发展是为了规避SC手工计数的观察者间变异性；然而，它主要依赖于检测缺乏CD7和/或CD26表达的细胞。我们之前报道了KIR3DL2作为首个阳性SC标志物的可靠性。本研究增加了什么内容？基于我们对254例患者的分析，我们建议将KIR3DL2添加到ISCL/EORTC蕈样肉芽肿综合征（SS）初始诊断和B2分期标准中。该标志物提高了SS B2期CTCL诊断的敏感性，特异性>95%，尤其是对于淋巴细胞减少的患者。我们发现KIR3DL2有助于SS的早期诊断，并且在评估治疗期间的血液肿瘤负担方面比CD26更可靠。转化信息是什么？SC定量是初始诊断分期和在临床试验环境中监测血液肿瘤负担的主要手段。我们建议在SS诊断标准中使用KIR3DL2 SCs≥200 μL或KIR3DL2 SCs/淋巴细胞≥10%的阈值，并提出一种用于CTCL B2血液分期的新算法。
