细胞毒性外周 T 细胞淋巴瘤和 EBV 阳性 T/NK 细胞淋巴增生性疾病:新出现的概念、最新进展,以及克隆性造血的推测作用。2022 年 EA4HP/SH 淋巴瘤研讨会报告。
Cytotoxic peripheral T-cell lymphomas and EBV-positive T/NK-cell lymphoproliferative diseases: emerging concepts, recent advances, and the putative role of clonal hematopoiesis. A report of the 2022 EA4HP/SH lymphoma workshop.
机构信息
Department of Pathology, Hospital Universitari de Bellvitge-IDIBELL, Feixa Llarga s/n, L'Hospitalet de Llobregat, 08907, Barcelona, Spain.
Department of Pathology, Hautepierre, University Hospital Strasbourg, Strasbourg, France.
出版信息
Virchows Arch. 2023 Sep;483(3):333-348. doi: 10.1007/s00428-023-03616-4. Epub 2023 Aug 30.
Cytotoxic peripheral T-cell lymphomas and EBV-positive T/NK-cell lymphoproliferative diseases were discussed at the 2022 European Association for Haematopathology/Society for Hematopathology lymphoma workshop held in Florence, Italy. This session focused on (i) primary nodal EBV-positive T and NK-cell lymphomas (primary nodal-EBV-TNKL), (ii) extranodal EBV-positive T/NK lymphoproliferative diseases (LPD) in children and adults, (iii) cytotoxic peripheral T-cell lymphomas, NOS (cPTCL-NOS), EBV-negative, and (iv) miscellaneous cases. Primary nodal-EBV-TNKL is a newly recognized entity which is rare, aggressive, and associated with underlying immune deficiency/immune dysregulation. All cases presented with lymphadenopathy but some demonstrated involvement of tonsil/Waldeyer's ring and extranodal sites. The majority of tumors are of T-cell lineage, and the most frequent mutations involve the epigenetic modifier genes, such as TET2 and DNMT3A, and JAK-STAT genes. A spectrum of EBV-positive T/NK LPD involving extranodal sites were discussed and highlight the diagnostic challenge with primary nodal-EBV-TNKL when these extranodal EBV-positive T/NK LPD cases demonstrate predominant nodal disease either at presentation or during disease progression from chronic active EBV disease. The majority of cPTCL-NOS demonstrated the TBX21 phenotype. Some cases had a background of immunosuppression or immune dysregulation. Interestingly, an unexpected association of cPTCL-NOS, EBV-positive and negative, with TFH lymphomas/LPDs was observed in the workshop cases. Similar to a published literature, the genetic landscape of cPTCL-NOS from the workshop showed frequent mutations in epigenetic modifiers, including TET2 and DNMT3A, suggesting a role of clonal hematopoiesis in the disease pathogenesis.
在意大利佛罗伦萨举行的 2022 年欧洲血液病理学协会/血液病理学协会淋巴瘤研讨会上,讨论了细胞毒性外周 T 细胞淋巴瘤和 EBV 阳性 T/NK 细胞淋巴增生性疾病。本次会议重点讨论了:(i)原发性结外 EBV 阳性 T 和 NK 细胞淋巴瘤(原发性结外-EBV-TNKL),(ii)儿童和成人的结外 EBV 阳性 T/NK 淋巴增生性疾病(LPD),(iii)细胞毒性外周 T 细胞淋巴瘤,NOS(cPTCL-NOS),EBV 阴性,和(iv)其他病例。原发性结外-EBV-TNKL 是一种新认识的实体,具有侵袭性,与潜在的免疫缺陷/免疫失调有关。所有病例均表现为淋巴结病,但有些病例还存在扁桃体/咽淋巴环和结外部位的受累。大多数肿瘤为 T 细胞谱系,最常见的突变涉及表观遗传修饰基因,如 TET2 和 DNMT3A 以及 JAK-STAT 基因。讨论了一系列涉及结外部位的 EBV 阳性 T/NK LPD,并强调了当这些 EBV 阳性 T/NK LPD 病例在表现时或在慢性活动性 EBV 疾病进展为疾病时,主要表现为结外疾病时,原发性结外-EBV-TNKL 存在诊断挑战。大多数 cPTCL-NOS 表现出 TBX21 表型。一些病例存在免疫抑制或免疫失调的背景。有趣的是,在研讨会上观察到 cPTCL-NOS、EBV 阳性和阴性与 TFH 淋巴瘤/LPD 之间存在意外关联。与已发表的文献相似,研讨会中 cPTCL-NOS 的遗传景观显示表观遗传修饰物(包括 TET2 和 DNMT3A)的频繁突变,提示克隆性造血在疾病发病机制中的作用。