Ohshima K, Suzumiya J, Sugihara M, Nagafuchi S, Ohga S, Kikuchi M
Department of Pathology, School of Medicine, Fukuoka University, Japan.
Pathol Int. 1998 Dec;48(12):934-43. doi: 10.1111/j.1440-1827.1998.tb03864.x.
Chronic active Epstein-Barr virus (CAEBV) infection has been previously reported to be sometimes associated with an aggressive clinical course. However, the role of EBV in the CAEBV is not well clarified. A retrospective study was performed on nine adult and five child patients (eight males and six females). Histologically, at first admission, the presence of neoplastic lesions could not be confirmed. The lymph nodes in half of all cases revealed paracortical hyperplasia with transformed lymphocytes (hyperplastic type). Half of the cases showed non-suppurative necrosis and an increased number of histiocytes with phagocytosis (histiocytic type). Activated histiocytes with lymphokine positivity were frequently detected in the histiocytic type. In the phenotypical study, 10 of the examined 11 cases showed increased numbers of natural killer (NK) cells and/or CD8-positive T lymphocytes. In situ hybridization (ISH) showed EBV-infected lymphoid cells, but the number of EBV-infected cells varied. Double-labeling immunochemistry/ISH demonstrated EBV-infected T cells, including NK cells, but not B cells. In addition, three cases showed a monoclonal dissemination of EBV terminal repetitive sequence (TR), and two cases showed oligoclonal dissemination. From those findings, monoclonal, oligoclonal and polyclonal populations of EBV-infected T or NK cells were considered to be present in CAEBV states. During the clinical course, 12 of the 14 cases died within 5 years. Six cases died from EBV-associated hematopoietic tumors (histiocytic tumor, T cell lymphoma, B cell lymphoma, plasmacytoma, and NK cell leukemia); one from non-EBV-associated acute myelogenous leukemia, and five due to hemophagocytic syndrome. The examined EBV-associated hematopoietic tumors showed monoclonal EBV terminal repetitive sequences. There is a possibility that the monoclonal dissemination of EBV-infected cells develops from oligoclonal or polyclonal EBV-infected cells. And active histiocytes with lymphokine positivity were frequently detected in the cases with histologically histiocytic type. These findings seem to be related with the causes of death due to hemophagocytic syndrome.
既往报道慢性活动性EB病毒（CAEBV）感染有时与侵袭性临床病程相关。然而，EB病毒在CAEBV中的作用尚未完全阐明。对9例成年患者和5例儿童患者（8例男性和6例女性）进行了一项回顾性研究。组织学上，首次入院时无法确认肿瘤性病变的存在。所有病例中有一半的淋巴结显示副皮质增生伴转化淋巴细胞（增生型）。一半的病例表现为非化脓性坏死和吞噬组织细胞数量增加（组织细胞型）。在组织细胞型中经常检测到具有淋巴因子阳性的活化组织细胞。在表型研究中，11例受检病例中有10例显示自然杀伤（NK）细胞和/或CD8阳性T淋巴细胞数量增加。原位杂交（ISH）显示EB病毒感染的淋巴细胞，但EB病毒感染细胞的数量各不相同。双标记免疫化学/ISH显示EB病毒感染的T细胞，包括NK细胞，但未显示B细胞。此外，3例显示EB病毒末端重复序列（TR）的单克隆播散，2例显示寡克隆播散。基于这些发现，认为在CAEBV状态下存在EB病毒感染的T或NK细胞的单克隆、寡克隆和多克隆群体。在临床病程中，14例患者中有12例在5年内死亡。6例死于EB病毒相关的造血系统肿瘤（组织细胞肿瘤、T细胞淋巴瘤、B细胞淋巴瘤、浆细胞瘤和NK细胞白血病）；1例死于非EB病毒相关的急性髓性白血病，5例死于噬血细胞综合征。所检查的EB病毒相关造血系统肿瘤显示单克隆EB病毒末端重复序列。EB病毒感染细胞的单克隆播散有可能从寡克隆或多克隆EB病毒感染细胞发展而来。并且在组织学为组织细胞型的病例中经常检测到具有淋巴因子阳性的活化组织细胞。这些发现似乎与噬血细胞综合征导致的死亡原因有关。
