Diffuse large B-cell淋巴瘤（DLBCL）携带Epstein-Barr病毒（EBV）主要发生在具有免疫缺陷或老年患者中，但也报道了免疫正常的年轻患者。作者研究了这些三组患者中EBV阳性DLBCL的病理差异。共纳入了57例EBV阳性DLBCL患者进行研究；其中16例患有免疫缺陷，10例为年轻患者（年龄小于50岁），31例为老年患者（50岁及以上）。在甲醛固定、石蜡包埋样本上进行CD8、CD68、PD-L1和EB病毒核抗原2的免疫染色和基于面板的下一代测序。免疫组化发现49名患者中有21名患者具有EB病毒核抗原2的阳性表达。每组中CD8阳性和CD68阳性免疫细胞浸润和PD-L1表达程度没有显著差异。年轻患者外部淋巴结病变更为常见（p = .021）。在突变分析中，具有最高突变频率的基因是PCLO（n = 14），TET2（n = 10）和LILRB1（n = 10）。对于TET2基因，所有10个突变都发生在老年患者中（p = .007）。与验证队列相比，TET2和LILRB1在EBV阳性患者中的突变频率均高于EBV阴性患者。在三个不同年龄和免疫状态组中发生的EBV阳性DLBCL表现出相似的病理特征。值得注意的是，TET2和LILRB1突变的高频率特征在老年患者中更明显。需要进一步研究以确定TET2和LILRB1突变在EBV阳性DLBCL发生中与免疫衰老的发展角色。©2023年美国癌症协会。

Diffuse large B-cell lymphoma (DLBCL) harboring Epstein-Barr virus (EBV) primarily occurs in patients who have underlying immunodeficiency or in elderly patients but is also reported in young, immunocompetent patients. The authors investigated the pathologic differences in EBV-positive DLBCL in these three groups of patients.In total, 57 patients with EBV-positive DLBCL were included in the study; of these, 16 patients had associated immunodeficiency, 10 were young (younger than 50 years), and 31 were elderly (aged 50 years or older). Immunostaining for CD8, CD68, PD-L1, and EBV nuclear antigen 2, and panel-based next-generation sequencing was performed on formalin-fixed, paraffin-embedded blocks.Immunohistochemistry revealed EBV nuclear antigen 2 positivity in 21 of the 49 patients. The degree of CD8-positive and CD68-positive immune cell infiltration and PD-L1 expression did not differ significantly in each group. Extranodal site involvement was more common in young patients (p = .021). In mutational analysis, the genes with the highest mutation frequency were PCLO (n = 14), TET2 (n = 10), and LILRB1 (n = 10). For the TET2 gene, all 10 mutations were found in elderly patients (p = .007). Compared with a validation cohort, both TET2 and LILRB1 showed a higher mutation frequency in EBV-positive patients than in EBV-negative patients.EBV-positive DLBCL occurring in three different age and immune status groups showed similar pathologic characteristics. Notably, a high frequency of TET2 and LILRB1 mutations was characteristic of this disease in elderly patients. Further studies are needed to determine the role of TET2 and LILRB1 mutations in the development of EBV-positive DLBCL along with immune senescence.Epstein-Barr virus-positive diffuse large B-cell lymphoma occurring in three different groups (immunodeficiency-associated, young, and elderly) showed similar pathologic characteristics. The frequency of TET2 and LILRB1 mutations was high in elderly patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma.© 2023 American Cancer Society.