成人EB病毒相关T/NK细胞淋巴组织增殖性疾病临床及实验特征

本研究分析成人EB病毒相关的T/NK细胞淋巴组织增殖性疾病(EBV+T/NK-LPD)的临床及实验室检查特征,探讨成人EBV+T/NK-LPD早期诊断和临床预后。对2005年至2012年间在我院诊断的19例EBV+T/NK-LPD患者临床病理资料进行回顾性分析。结果表明:男11例,女8例,中位年龄32岁(20-70岁);起病至确诊时间平均3.5个月,中位生存时间为2.5个月;持续不明原因发热、肝脾大、肝功能损害、间质性肺炎为常见首发表现;血细胞减少出现在18例患者中,所有患者具有β2-MG、LDH、TNF、IL-6水平升高及血EBV-DNA阳性(中位拷贝数>106);骨髓细胞形态表现为异常大颗粒淋巴细胞、组织细胞增多或伴噬血现象;骨髓流式细胞检查易见CD5、CD7缺失的T/NK淋巴细胞;骨髓活检显示,10例患者可见异常淋巴细胞间质浸润,6例可见少量大细胞成灶性浸润;骨髓免疫组织化学检测表明,异常细胞表达为CD3+CD56+NK细胞2例,CD3+CD8+T细胞11例,CD3+CD4+细胞3例;全部病例表达细胞胞质内抗原(TIA-1)和EBER;3例淋巴结活检病理主要为反应性增生。全部患者死于进行性的多器官功能衰竭。结论:成人EBV+T/NK-LPD以发热和肝脾大为主要临床表现,实验室检查以外周血EBV-DNA持续升高、EB病毒感染T/NK淋巴细胞组织浸润并有多器官进行性损伤的炎症反应综合征,临床多数预后不良,上述特征性临床表现及实验室检查有助于成人EBV+T/NK-LPD的及时诊断。

Clinical Features and Laboratory Findings of Adult Epstein-Barr Virus Associated T/NK Lymphoproliferative Disease

The aim of this study was to analyze the clinical features and laboratory findings of adult Epstein-Barr virus associated T/NK cell lymphoproliferative disease（EBV＋T/NK-LPD）and to investigate the early diagnosis and prognosis of EBV＋T/NK-LPD.The clinical data of 19 adult patients with EBV＋T/NK-LPD were retrospectively analyzed.The results indicated that there were 11 males and 8 females.The median age was 32 years（range：20-70 years）.The average duration from onset of symptoms to diagnosis was 3.5 months.The median survival time was 2.5 months.Unkown fever,hepatosplenomegaly,liver dysfunction and interstitial pneumonia were the main clinical features.High levels of β2-MG、LDH、TNF、IL-6 and significantly increased EBV-DNA level（median level〉10^6 copies/ml） were occurred in all the patients.Cytopenia was seen in 18 cases.Morphologically,atypical large granular lymphocytes and hemophagocytosis were common in bone marrow smears.Deletion of CD5 or CD7 were frequently observed in T/NK lymphocytes in bone marrow cells by flow cytometry.Bone marrow biopsy showed atypical lymphocyte interstitial infiltrated in 10 cases,while a few large cells infiltrated in 6 cases.Immunohistochemistry showed the expression of CD3^＋CD56^＋ were seen in 2 cases,CD3^＋CD8^＋ in 11 cases and CD3^＋CD4^＋ in 3 cases.TIA-1 and EBER were positive in all biopsy specimens.Three cases underwent biopsy of lymphonodes showed reactive proliferations of lymphocytes.All the patients died of multiorgan failure.It is concluded that the fever,hepatosplenomegaly are the most common clinical features in adult EBV＋T/NK-LPD,the bone marrow infiltration of EBV-infected T/NK lymphocytes and significantly increased EBV-DNA level can be observed in all cases,the clinical outcome of this disease is poor,these clinical and experimental features can be served as a reliable marker for the timely diagnosis of adult EBV＋T/NK-LPD.