Hodgkin lymphoma: a review of pathological features and recent advances in pathogenesis
Hodgkin lymphoma: a review of pathological features and recent advances in pathogenesis
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DOI：
10.1016/j.pathol.2019.09.005
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发表时间：
2020-01-01
期刊：
影响因子：
4.5
通讯作者：
Chang, Kung-Chao
中科院分区：
文献类型：
--
作者：
Piris, Miguel A.;Medeiros, L. Jeffrey;Chang, Kung-Chao
霍奇金淋巴瘤(HL)由结节淋巴细胞为主的霍奇金淋巴瘤和经典型的霍奇金淋巴瘤两种不同的病理实体组成，后者分为四种亚型。与大多数其他人类淋巴瘤不同，在炎症背景下，肿瘤细胞通常占肿瘤体积的不到10%。在这些淋巴瘤中，肿瘤细胞是肿瘤成分的主要组成部分。几乎所有病例中的HL肿瘤细胞都是B细胞系(PAX5+)。HL通常影响患有局部结节疾病的年轻患者，其临床行为通常是惰性的。患者对化疗的反应良好，治愈率为80%-90%，最近发现PD-L1的表达，这是一个免疫检查点，为一些复发和/或难治性HL患者提供了免疫治疗。HL神秘的RS细胞以其丰富的细胞质和具有特征的双叶核而独特，具有嗜酸性的突出核仁，使人看起来像猫头鹰眼。H细胞是单核变异体。病毒包涵体样形态是发现经典HL与EB病毒(EBV)之间联系的线索。然而，这种关联在不同的地理区域和病理亚型中是不同的，并与年龄(>；60岁)和社会经济状况相关，表明环境因素可能参与了HL的发病。病毒相关的内质网(ER)应激也可能与HRS细胞特有的形态特征有关。内质网应激可诱导胞质细胞周期蛋白A异常表达，导致核超二倍体。细胞周期蛋白A的异常表达通常与HL的HRS细胞形态有关，可能是通过EBV潜伏膜蛋白1(LMP1)信号转导。遮盖素也可能在多核RS细胞的形态发生中起作用。此外，EBV阳性和阴性的HL细胞表达存活信号，但不表达ER应激的死亡信号，EBV-LMP1基因转染增加了HL细胞系生存信号的表达。这些数据提示，存活的内质网应激可能参与了HL的发病。
Hodgkin lymphoma (HL) is composed of two distinct pathological entities, nodular lymphocyte predominant HL and classic HL, the latter with four subtypes. In contrast with most other human lymphomas, in which the neoplastic cells are a major population of the tumour constituents, the neoplastic 'Hodgkin (H) and Reed-Sternberg (RS)' cells usually account for less than 10% of tumour bulk against an inflammatory background. The neoplastic cells of HL are of B-cell lineage (PAX5+) in virtually all cases. HL usually affects young patients with a localised nodal disease and its clinical behaviour is typically indolent. Patients respond well to chemotherapy with cure rates of 80-90% and the recent finding of PD-L1 expression, an immune checkpoint, warrants the use of immunotherapy for some patients with recurrent and/or refractory HL.The enigmatic RS cells of HL are unique in their abundant cytoplasm and characteristic bilobed nuclei with eosinophilic prominent nucleoli, imparting an 'owl-eye' appearance. H cells are mononuclear variants. The viral inclusion-like morphology was a clue on the way to discovering an association between classic HL and Epstein-Barr virus (EBV). However, this association is variable in different geographic regions and in pathological subtypes, and correlates with older age (>60 years) and socioeconomic status, indicating that environmental factors are likely involved in HL pathogenesis. Virus-associated endoplasmic reticulum (ER) stress also may contribute to mechanisms underlying the characteristic morphological features of HRS cells. ER stress has been found to induce aberrant, cytoplasmic cyclin A expression, leading to nuclear hyperdiploidy. Aberrant expression of cyclin A is commonly associated with HRS cell morphology in HL, probably through EBV-latent membrane protein-1 (LMP1) signalling. Shelterin also may play a role in the morphogenesis of multinucleated RS cells. In addition, EBV-positive and -negative HL cases express survival, but not death signals of ER stress at similar levels and EBV-LMP1 transfection increases expression of survival signals in HL cell lines. These data suggest that surviving ER stress may be involved in HL pathogenesis.