PDF(Pubmed)
Abstract：
T-follicular helper (TFH) markers are expressed in the microenvironnement of marginal zone B-cell lymphoma (MZL), and in lymphomas arising from TFH-cells, sometimes making the differential diagnosis difficult. In the skin, the \"TFH-spectrum\" is poorly defined, going from primary cutaneous lymphoproliferative disorder with small/medium CD4+ T-cells (SMLPD) to cutaneous localizations of systemic angioimmunoblastic T-cell lymphoma (cAITL), and may pass through intermediate forms (primary cutaneous T-follicular helper derived lymphoma, not otherwise specified (PCTFHL,NOS)). We retrospectively analyzed 20 MZL, 13 SMLPD, 5 PCTFHL, and 11 cAITL clinically, histologically, and molecularly, to define tools to differentiate them. Characteristics that might favor the diagnosis of MZL over SMLPD are: multiple skin nodules (p < 0.001), nodular architecture (p < 0.01), residual germinal centers with follicular dendritic cell network (p < 0.001), monotypic plasma cells (p < 0.001), and few staining with PD1 (p = 0.016) or CXCL13 (p = 0.03). PCTFHL and cAITL presented as multiple (p < 0.01) lesions, in older patients (p < 0.01), with systemic symptoms and/or biological alterations (p < 0.01). Immunophenotypic loss of T-cell markers (p < 0.001), BCL6 (p = 0.023) and/or CD10 staining (p = 0.08), and a higher proliferative index (≥ 30%, p = 0.039) favoured these diagnoses over SMLPD. Pathogenic variants were observed by genomic sequencing in 47% of MZL (TNFAIP3 (32%), EP300 (21%), NOTCH2 (16%), KMT2D (16%), CARD11 (10.5%)), 8% of SMLPD (TET2), 40% of PCTFHL (SOCS1 (20%), ARID1A (20%)) and 64% of cAITL (TET2 (63.6%), RHOA (36.4%), NOTCH1 (9%)). This study characterizes the various clinical and histological features between cutaneous lymphomas expressing TFH markers and highlights the value of the interest of screening for genomic mutations in difficult cases.
摘要：
T滤泡辅助（TFH）标记在边缘区B细胞淋巴瘤（MZL）的微环境中表达，在由TFH细胞引起的淋巴瘤中，有时使鉴别诊断困难。在皮肤上，“TFH频谱”定义不明确，从小/中CD4+T细胞的原发性皮肤淋巴增生性疾病（SMLPD）到全身性血管免疫母细胞性T细胞淋巴瘤（cAITL）的皮肤定位，并可能通过中间形式（原发性皮肤T滤泡辅助细胞衍生淋巴瘤，未指定(PCTFHL，NOS））。我们回顾性分析了20个MZL，13SMLPD,5PCTFHL,和11cAITL临床，组织学上,在分子上，定义工具来区分它们。与SMLPD相比，可能有利于诊断MZL的特征是：多个皮肤结节（p<0.001），结节结构（p<0.01），残余生发中心与滤泡树突状细胞网络（p<0.001），单型浆细胞（p<0.001），用PD1(p=0.016)或CXCL13(p=0.03)染色很少。PCTFHL和cAITL表现为多发（p<0.01）病变，在老年患者中（p<0.01），全身症状和/或生物学改变（p<0.01）。T细胞标志物的免疫表型丢失（p<0.001），BCL6（p=0.023）和/或CD10染色（p=0.08），和更高的增殖指数(≥30%，p=0.039）比SMLPD更有利于这些诊断。通过基因组测序在47%的MZL中观察到致病变异(TNFAIP3(32%)，EP300（21%），NOTCH2（16%），KMT2D（16%），CARD11（10.5%），8%的SMLPD（TET2），40%的PCTFHL(SOCS1(20%)，ARID1A（20%）和64%的cAITL（TET2（63.6%），RHOA（36.4%），NOTCH1（9%））。这项研究描述了表达TFH标记的皮肤淋巴瘤之间的各种临床和组织学特征，并强调了在困难病例中筛选基因组突变的价值。
