EB病毒阳性淋巴组织增殖性疾病13例临床与病理特征

Clinical and pathological features of 13 children with Epstein-Barr virus-positive lymphoproliferative diseas

的探讨儿童EB病毒阳性淋巴组织增殖性疾病（EBV＋LPD）的临床表现、病毒学特征、组织病理学特点和临床转归。方法对北京儿童医院感染内科2011年1月至2016年12月收治的13例组织病理学确诊的儿童EBV＋LPD的临床资料及随访情况进行回顾性病例总结。结果13例患儿中，男5例、女8例。中位年龄6.0岁（范围1.3-15.0岁）。从发病到诊断的中位时间为3个月（1-24个月）。13例均有发热，9例肝脾淋巴结肿大，4例仅有淋巴结肿大；7例外周血细胞降低，7例肺受累，3例中枢神经系统受累，3例心脏受累，3例肠道受累，2例皮肤受累，腹部包块1例。13例均行全血EB病毒-DNA检查，拷贝数1×108/L-1×1011/L。病理学检查：6例为淋巴结病理，2例为皮肤病理，肺、回肠黏膜、肝脏、腹腔肿物、骨髓组织病理各1例；13例中9例为系统性EB病毒阳性T细胞淋巴组织增殖性疾病（EBV＋T-LPD），2例为种痘样水疱病（HV），2例为EB病毒阳性弥漫性大B细胞淋巴瘤（EBV＋ DLBCL）。对13例患儿分别随访至出院后2 d-65个月，9例系统性EBV＋T-LPD，其中1例短期内死亡，1例进展为T细胞淋巴瘤死亡，2例行造血干细胞移植痊愈，1例行噬血细胞综合征2004方案化疗后痊愈，4例病情尚稳定；2例HV患儿1例发展为种HV样淋巴瘤死亡，另外1例仍有症状；2例EBV＋ DLBCL，1例出院后短期死亡，1例化疗后病情稳定。结论儿童EBV＋LPD常见表现为慢性反复发热、淋巴结、肝脾肿大，另外可累及肺、中枢神经系统、肠道、皮肤等脏器；对于慢性反复不明原因发热伴有淋巴结和（或）肝脾肿大的，伴全血EB病毒-DNA载量持续显著增高时，应警惕EBV＋LPD，尽早行增殖病灶组织活检明确诊断；本病预后差，部分进展为淋巴瘤，造血干细胞移植治疗有效。

ObjectiveTo summarize the clinical characteristics, virological and histopathological features, clinical outcome of Epstein-Barr virus-positive lymphoproliferative disease （EBV＋LPD） in children.MethodsThe clinical and follow-up data of 13 children histopathologically diagnosed as EBV＋LPD in the Department of Infectious Disease of Beijing Children＇s Hospital between January 2011 and December 2016 were summarized.ResultsOf the 13 patients, 5 were males and 8 females. The median age of disease onset was 6.0 years （range 1.3 to 15.0 years）. The median duration between disease onset and diagnosis was 3 months （range 1 to 24 months）. All the 13 patients had fever, 9 cases had hepatosplenomegaly and lymphoadenopathy, 4 cases had only lymphoadenopathy, 7 cases had reduced peripheral blood cells, 7 cases had lung involvement, 3 cases had central nervous system involvement, 3 cases had cardiac involvement, 3 cases had intestinal involvement, 2 cases had skin involvement and 1 case had abdominal mass. All the 13 patients underwent whole blood EBV-DNA PCR examination and the copies ranged from 1×108/L to 1×1011/L. Pathology of lymph node confirmed 6 cases, skin pathology confirmed 2 cases, lung pathology, ileum mucosa pathology, liver pathology, abdominal mass pathology and bone marrow pathology confirmed 1 case each. Among 13 patients, 9 cases presented with EBV-positive T cell lymphoproliferative disease（EBV＋ T-LPD）, 2 cases with hydroa vacciniforme （HV） and 2 cases with EBV-positive diffuse large B-cell lymphoma （EBV＋ DLBCL） . All the patients were followed up for 2 days to 65 months after discharge. Among 9 cases of EBV＋T-LPD, 1 case died in a short time, 1 case died after evolved to T-cell lymphoma, 2 cases recovered after hematopoietic stem cell transplantation, 1 case recovered after the chemotherapy of hemophagocytic lymphohistiocytosis（HLH） 2004 protocol and 4 cases were stable now. Of 2 cases of HV patients, 1 case died after evolved to HV like lymphoma and the other still have symptoms. Among 2 cases of EBV＋ DLBCL, 1 case died shortly after discharge and the other was still stable after chemotherapy. ConclusionsChronic recurrent fever, lymphadenopathy and hepatosplenomegaly are the most common clinical manifestations in children with EBV＋LPD. Involvement of lung, central nervous system, intestinal tract, skin and other organs are also involved frequently. For children with chronic fever of unknown cause and accompanied by lymphadenopathy and （or） hepatosplenomegaly, EBV ＋ LPD should be considered highly when the whole blood EBV-DNA load continues to increase significantly, early biopsy of the proliferative lesion should be performed to make a definite diagnosis. The prognosis of EBV ＋ LPD is poor, and some evolve to lymphoma, hematopoietic stem cell transplantation is an effective way to treat this disease.