传染性单核细胞增多症5例中EBNA2表达研究

EBNA2 Expression Research of 5 Cases of Infectious Mononucleosis

摘要: 目的：探讨EBNA2在传染性单核细胞增多症(infectious mononucleosis, IM)的诊断价值和表达模式。方法：收集陕西省人民医院2017年3月至2022年8月诊断的IM 5例，另选择2例EB病毒相关淋巴组织增殖性疾病(EBV-associated lymphoproliferative diseases, EBV + LPD)作为对照，回顾性分析其临床表现，组织形态，免疫表型，EBNA2表达情况及治疗和预后的情况。结果：患者男性1例，女性4例，中位年龄16岁，临床表现多以病毒感染相关的发热，扁桃体肿大，淋巴结肿大为主要症状。5例均有扁桃体肿大，颈部淋巴结肿大，1例伴有脾大。5例均符合IM的临床诊断标准，2例EBV + LPD病例符合系统性慢性活动性EBV感染(Chronic Active Epstein-Barr Virus Disease, CAEBV)同时合并嗜血细胞性淋巴组织细胞增生症(hemophagocytic lymphohistiocytosis, HLH)的诊断标准。组织形态表现：在4例IM中淋巴结或者扁桃体中淋巴组织结构基本存在，滤泡散在分布，间区淋巴细胞显著增生，免疫母细胞样大细胞增多，并见较多胞浆丰富中等大小细胞以及浆细胞，形成谱系。在1例IM和2例CAEBV中淋巴结结构破坏，未见明显滤泡，免疫母细胞样大细胞呈片分布。原位杂交5例均EBER阳性。EBNA2在4例IM中阳性。在1例脾大和凝血功能异常的IM中阴性，在2例CAEBV合并HLH中阴性。EBNA2的表达模式分为2种：第一种是部分表达，阳性指数较高，以生发中心为主，第二种是散在表达在淋巴组织中，阳性率较低，与生发中心没有明确关系。治疗多采用休息，抗病毒治疗，抗生素的使用，糖皮质激素等综合治疗。本组病例随访时间：7~72个月，IM患者，均未复发，预后良好。结论：EBNA2在大部分IM中阳性，同时在CAEBV中阴性表达。IM中EBNA2阳性提示EBV初次感染，EBNA2阳性可以用来鉴别IM与EBV + LPD。

Abstract: Purpose: To investigate the diagnostic value and the expression pattern of EBNA2 in infectious mononucleosis (IM). Methods: 5 cases of IM from March 2017 to August 2022 at Shaanxi provincial people’s hospital were collected. 2 cases of EBV-associated lymphoproliferative diseases (EBV + LPD) at Shaanxi provincial people’s hospital were collected as a control. The clinical data, histomorphology, immunophenotype, expression of EBNA2, treatment and the prognosis were an-alyzed retrospectively. Results: There were 1 male and 4 female patients, with the median age of 16 years. The most common initial symptoms were acute fever, pharyngitis and cervical lym-phadenopathy. Antiadoncus and cervical lymphadenopathy were involved in 5 cases. Splenomegaly was seen in 1 case. All of 5 cases meet the clinical diagnostic criteria of IM, and 2 cases meet the diagnostic criteria of Chronic Active Epstein-Barr Virus Diseases (CAEBV) with hemophagocytic lymphohistiocytosis (HLH). Microscopically, in the cases with IM, the tonsil and lymph nodes show basically preservation of the architecture with regressive follicles and the expanded interfollicular, which was polymorphic with some relatively large cells, medium-sized cells and plasma cells. But in the cases with CAEBV, the tonsil and lymph nodes architecture were completely effaced by interfollicular proliferation of large-sized monotonous lymphoid cells with immunoblastic cytomorphology. All of 5 cases were positive in EBER. EBNA2 was positive in 4 cases of IM. On the other hand, EBNA2 was negative in 2 cases of CAEBV with HLH and 1 case of IM with Splenomegaly and the disorder of the coagulation function. 2 distinct EBNA2 expression patterns can be recognized in IM: One that was mainly positive in the germinal center with high positive index and one that was scattered positive in the lymphoid tissue with low positive index. The patients with IM were usually treated with comprehensive therapy including rest, antiviral therapy, antibiotic therapy, glucocorticoids therapy etc. During the 7~72 month’s follow-up period, the prognosis was good in the IM. Conclusions: EBNA2 is mostly positive in IM, negative in EBV + LPD. And EBNA2 positive expression in IM indicates the primary infection of EBV, which could distinguish IM from EBV + LPD.