Department of Pathology and Laboratory Medicine, University of Vermont Larner College of Medicine, 89 Beaumont Avenue, Burlington, VT 05405, USA; Department of Pathology, Stanford University School of Medicine, 291 Campus Drive, Stanford, CA 94305, USA.
Department of Pathology, Stanford University School of Medicine, 291 Campus Drive, Stanford, CA 94305, USA.
Ann Diagn Pathol. 2024 Jun;70:152286. doi: 10.1016/j.anndiagpath.2024.152286. Epub 2024 Feb 29.
Epstein-Barr virus (EBV) is responsible for many B cell lymphoproliferative disorders (LPD) spanning subclinical infection to immunodeficiency-related neoplasms. EBV establishes a latent infection in the host B cell as defined histologically by the expression of EBV latent membrane proteins and nuclear antigens. Herein, we characterize the latency patterns of immunodeficiency-related neoplasms including post-transplant lymphoproliferative disorders (PTLD) and therapy-related LPD (formerly iatrogenic) with latent membrane protein-1 (LMP-1) and EBV nuclear antigen-2 (EBNA-2) immunohistochemistry. The latency pattern was correlated with immunodeficiency and dysregulation (IDD) status and time from transplant procedure. 38 cases of EBV+ PTLD in comparison to 27 cases of classic Hodgkin lymphoma (CHL) and diffuse large B cell lymphoma (DLBCL) arising in either the therapy-related immunodeficiency setting (n = 12) or without an identified immunodeficiency (n = 15) were evaluated for EBV-encoded small RNAs by in situ hybridization (EBER-ISH) and for LMP-1 and EBNA-2 by immunohistochemistry. A full spectrum of EBV latency patterns was observed across PTLD in contrast to CHL and DLBCL arising in the therapy-related immunodeficiency setting. Polymorphic-PTLD (12 of 16 cases, 75 %) and DLBCL-PTLD (9 of 11 cases, 82 %) showed the greatest proportion of cases with latency III pattern. Whereas, EBV+ CHL in an immunocompetent patient showed exclusively latency II pattern (13 of 13 cases, 100 %). The majority of EBV+ PTLD occurred by three years of transplant procedure date and were enriched for latency III pattern (21 of 22 cases, 95 %). Immunohistochemical identification of EBV latency by LMP-1 and EBNA-2 can help classify PTLD in comparison to other EBV+ B cell LPD and lymphomas arising in therapy-related immunodeficiency and non-immunodeficiency settings.
爱泼斯坦-巴尔病毒（EBV）可引起多种 B 细胞淋巴增殖性疾病（LPD），从亚临床感染到免疫缺陷相关肿瘤均有涉及。EBV 在宿主 B 细胞中建立潜伏感染，这在组织学上可通过 EBV 潜伏膜蛋白和核抗原的表达来定义。在此，我们通过免疫组织化学方法分析了与免疫缺陷相关的肿瘤（包括移植后淋巴组织增生性疾病（PTLD）和治疗相关的 LPD（以前称为医源性））的潜伏模式，这些肿瘤的潜伏模式与潜伏膜蛋白-1（LMP-1）和 EBV 核抗原-2（EBNA-2）有关。我们还将潜伏模式与免疫缺陷和失调（IDD）状态以及从移植手术到现在的时间进行了相关性分析。我们评估了 38 例 EBV+PTLD、27 例经典霍奇金淋巴瘤（CHL）和弥漫性大 B 细胞淋巴瘤（DLBCL）病例，这些病例分别发生在治疗相关免疫缺陷背景下（n=12）或无明确免疫缺陷背景下（n=15），并通过原位杂交（EBER-ISH）评估 EBV 编码的小 RNA，通过免疫组织化学评估 LMP-1 和 EBNA-2。与发生在治疗相关免疫缺陷背景下的 CHL 和 DLBCL 相比，PTLD 中观察到了 EBV 潜伏期的全谱。多态性-PTLD（16 例中的 12 例，75%）和 DLBCL-PTLD（11 例中的 9 例，82%）显示出 III 型潜伏模式的比例最高。而在免疫功能正常的患者中，EBV+CHL 仅表现出 II 型潜伏模式（13 例中的 13 例，100%）。大多数 EBV+PTLD 发生在移植后 3 年内，且 III 型潜伏模式比例较高（22 例中的 21 例，95%）。通过 LMP-1 和 EBNA-2 的免疫组织化学鉴定 EBV 潜伏期有助于将 PTLD 与其他 EBV+B 细胞 LPD 和发生在治疗相关免疫缺陷和非免疫缺陷背景下的淋巴瘤进行分类。
