Ohno T, Miyake N, Hada S, Hirose Y, Imura A, Hori T, Uchiyama T, Saiga T, Mizumoto T, Furukawa H
Department of Internal Medicine, Ohtsu Red Cross Hospital, Nagara, Japan.
Cancer. 1998 May 15;82(10):1963-72.
The recent recognition of the association of Epstein-Barr virus (EBV) with T-cell/natural killer cell (T/NK-cell) lymphoma has documented that particular types of EBV-containing T/NK-cell lymphoma are frequently complicated by hemophagocytic syndrome (HPS). This observation suggests that both EBV and proliferating T/NK-lymphoma cells play significant roles in the development of HPS. Cytokines released from neoplastic T cells are presumed to account for the activation of macrophages, which is followed by a complex cascade of cytokine production, resulting in full-blown HPS. Five patients with B-cell lymphoma complicated by HPS were studied for elevated serum cytokines, the association of EBV, and CD25 expression of lymphoma cells; the aim of this study was to verify whether the mechanisms of HPS development hypothesized for T/NK-cell lymphoma also operate in B-cell lymphoma.
Sera were analyzed for the presence of inflammatory and immunoregulatory cytokines. Flow cytometry, immunohistology (IH), in situ hybridization (ISH), polymerase chain reaction (PCR), and Southern blot analysis were performed using bone marrow aspirates, biopsy specimens, and autopsy specimens.
Immunophenotypic and Southern blot studies verified that the lymphoma cells of all five patients were of B-cell lineage. Bone marrow aspirates demonstrated histiocytosis with extensive hemophagocytic activity. Marked elevation of serum cytokines and expression of CD25 were observed in all five patients. However, the results of PCR, ISH using EBER1 probe, and IH for latent membrane protein indicated that these lymphoma cells were free of EBV infection.
In patients with B-cell lymphoma, EBV infection is not necessarily required for the initiation of HPS. In this article, the pathogenesis of HPS assumed to be operative in B-cell lymphoma is discussed with reference to T/NK-cell lymphoma complicated by HPS.
最近对爱泼斯坦 - 巴尔病毒（EBV）与T细胞/自然杀伤细胞（T/NK细胞）淋巴瘤关联的认识表明，特定类型的含EBV的T/NK细胞淋巴瘤常并发噬血细胞综合征（HPS）。这一观察结果提示，EBV和增殖的T/NK淋巴瘤细胞在HPS的发生发展中均起重要作用。肿瘤性T细胞释放的细胞因子被认为是巨噬细胞激活的原因，随后是一系列复杂的细胞因子产生级联反应，导致典型的HPS。对5例并发HPS的B细胞淋巴瘤患者进行了血清细胞因子升高情况、EBV关联以及淋巴瘤细胞CD25表达的研究；本研究的目的是验证针对T/NK细胞淋巴瘤所假设的HPS发生机制是否也适用于B细胞淋巴瘤。
分析血清中炎性和免疫调节细胞因子的存在情况。使用骨髓穿刺液、活检标本和尸检标本进行流式细胞术、免疫组织学（IH）、原位杂交（ISH）、聚合酶链反应（PCR）和Southern印迹分析。
免疫表型和Southern印迹研究证实，所有5例患者的淋巴瘤细胞均为B细胞系。骨髓穿刺液显示组织细胞增多并伴有广泛的噬血活性。所有5例患者均观察到血清细胞因子显著升高和CD25表达。然而，PCR结果、使用EBER1探针的ISH以及潜伏膜蛋白的IH结果表明，这些淋巴瘤细胞未感染EBV。
在B细胞淋巴瘤患者中，HPS的发生不一定需要EBV感染。本文参照并发HPS的T/NK细胞淋巴瘤讨论了假定在B细胞淋巴瘤中起作用的HPS发病机制。
