外周 T 细胞淋巴瘤 (PTCL) 包含一组异质的胸腺后 T 细胞淋巴瘤，有 30 多种不同的亚型，与不同的临床病理特征相关。不幸的是，主要 PTCL 亚型的总体生存率很低，并且几十年来都没有改善，因此改善诊断、治疗和临床结果迫切需要满足临床需求。诊断通常具有挑战性，需要对临床、形态学和免疫表型特征进行组合评估。由于肿瘤间和肿瘤内巨大的异质性、有限的组织可用性以及缺乏真正的 T 淋巴瘤细胞系或遗传可靠的动物模型，PTCL 病理学很难研究。转录组分析和基因组测序的应用显着加速了新生物标志物、分子特征和遗传病变的发现，其中一些发现已被纳入修订后的 WHO 或 ICC 分类中。全基因组研究揭示了 PTCL 实体的突变情况和转录组谱，将细胞起源定义为 T 细胞淋巴瘤生物学的主要决定因素，并允许细化具有生物学和临床意义的实体以进行精准治疗。在这篇综述中，我们优先讨论常见的淋巴结 PTCL 亚型以及两种病毒相关的 T 或 T/NK 淋巴瘤。我们简要回顾了与 PTCL 发病机制和生物学相关的正常 T 细胞发育、分化和 T 细胞受体信号传导。本综述将有助于更好地了解不同 PTCL 实体的生物学知识，以及它们的分层，以进行更多研究和目标导向的临床试验。版权所有 © 2024 美国血液学会。

Peripheral T-cell lymphomas (PTCLs) encompass a heterogeneous group of post-thymic T-cell lymphomas with more than 30 distinct subtypes associated with varied clinicopathological features. Unfortunately, the overall survival of the major PTCL subtypes is dismal and has not improved for decades, thus there is an urgent unmet clinical need to improve diagnosis, therapies, and clinical outcomes. The diagnosis is often challenging requiring a combinatorial evaluation of clinical, morphologic, and immunophenotypic features. PTCL pathobiology is difficult to investigate due to enormous inter- and intra-tumor heterogeneity, limited tissue availability, and the paucity of authentic T-lymphoma cell lines or genetically faithful animal models. The application of transcriptomic profiling and genomic sequencing has markedly accelerated the discovery of new biomarkers, molecular signatures, and genetic lesions and some of the discoveries have been included in the revised WHO or ICC classification. Genome-wide investigations have revealed the mutational landscape and transcriptomic profiles of PTCL entities, defined the cell-of-origin as a major determinant of T-cell lymphoma biology, and allowed for the refinement of biologically and clinically meaningful entities for precision therapy. In this review, we prioritize the discussion on common nodal PTCL subtypes together with two virus associated T or T/NK lymphomas. We succinctly review normal T-cell development, differentiation, and T-cell receptor signaling as they relate to PTCL pathogenesis and biology. This review will facilitate a better biological understanding of the different PTCL entities, and their stratification for additional studies and target-directed clinical trials.Copyright © 2024 American Society of Hematology.