儿童系统性EB病毒阳性T细胞淋巴组织增殖性疾病的临床病理观察

目的 探讨儿童系统性EB病毒阳性T细胞淋巴组织增殖性疾病(CSEBV+T-LPD)的临床病理特征、诊断及鉴别诊断要点.方法 经过HE染色观察并采用免疫组织化学、原位杂交技术,结合临床资料,对30例CSEBV+T-LPD病例进行回顾性研究,并进行随访.结果 (1)CSEBV+T-LPD,男19例,女11例,中位年龄9岁;起病至确诊的时间平均14个月;主要临床表现有发热(96.7%),淋巴结增大(83.3%),肝脾肿大(66.7%),常见皮肤损害包括蚊虫叮咬超敏反应(13.3%)和皮疹(20.0%);20例随访患者中6例死亡,4例发展为淋巴瘤.(2)组织病理特点:淋巴结表现为T区扩大,淋巴滤泡缩小、减少甚至消失;病变主要为中小淋巴细胞以及多少不等的组织细胞,大细胞散在其中,轻至中度异型;21例淋巴结的间质及小血管增多,11例包膜增厚;另外,肝、脾和皮肤主要表现为轻至中度异形淋巴细胞浸润;3例可见噬血细胞现象.(3)免疫表型特点:病变中的中小淋巴细胞表达CD3、粒酶B和T细胞胞质内抗原(TIA-1);8例检测病例中7例表达CD8,1例主要表达CIM,也表达CD8;15例检测了CD56,2例阳性并已进展为NK/T细胞淋巴瘤,其余13例阴性.(4)30例均检测出EB病毒编码的小RNA(EBER)阳性细胞,数量5～500个/HPF;EBER在各种淋巴细胞中均阳性,9例以中至大淋巴细胞阳性为主,其余主要是中小淋巴细胞阳性;主要分布在T区,也见于套区、初级滤泡和生发中心内.结论 中国存在CSEBV+T-LPD;主要发生于儿童和青少年,病程为亚急性或慢性伴反复发热;此病为系统性病变,主要累及淋巴结和肝脾,也可累及皮肤,淋巴结以T区扩大和轻中度异形淋巴细胞浸润为主要形式;EB病毒感染的细胞毒性T细胞构成病变主体;是一种危及生命的疾病,患者往往死于严重并发症或进展为恶性淋巴瘤;应综合考虑临床、病理、免疫表形和EB病毒感染4方面信息以获得准确诊断.

Clinicopathologic features of systemic EBV-positive T-cell lymphoproliferative disease of childhood

Objective To study the clinicopathologic features,diagnosis and differential diagnosis of systemic Epstein-Barr virus(EBV)-positive T-cell lymphoproliferative disease of childhood(CSEBV+ T-LPD).Methods Thirty cases of CSEBV* T-LPD were retrospectively studied by light microscopy,immunohistochemistry and in-situ hybridization for EBV-encoded RNA(EBER).The clinical information and follow-up data were analyzed.Results Nineteen of the 30 patients were males and 11 females.The median age of disease onset was 9 years(range=1.5 to 32 years).The average duration between disease onset and diagnosis was 14 months.The major clinical manifestations were fever(96.7%),lymphadenopathy(83.3%)and hepatosplenomegaly(66.7%).Cutaneous manifestations were not uncommon,which included hypersensitivity to mosquito bite(13.3%)and skin rash(20.0%).Six of the 20 patients died on follow up.Histologically,the lymph nodes showed expansion of T zone,with diminished or effaced lymphoid follicles.The lymphoid cells were of small to medium size.Scattered large lymphoid cells were also identified in the expanded T zone.Furthermore,the liver and spleen showed mild to marked sinusoidal infiltration.In some cases,various degrees of sinus histiocytosis with erythrophagocytosis were present Skin biopsies showed mild to marked degree of lymphocytes infiltration in dermis.Immunohistochemical study and in-situ hybridization showed that the EBER-positive cells were of T lineage and CD3 positive.They also expressed cytotoxic molecules granzyme B and TIA-1.Seven of the 8 cases examined were CD8 positive,while the remaining case was mainly CD4 positive.Thirteen of 15 cases were shown to be CD56 negative.The number of EBER-positive cells ranged from 5 to more than 500 per highpower field.These cells included small to large lymphoid cells located mostly in the expanded T zone and sometimes in the germinal centers.Nine of the 30 cases,which consisted mainly of medium to large-sized lymphoid cells,were also EBER positive.Conclusions Systemic EBV-positive T-cell lymphoproliferative disease of childhood occurs most often in children and young adults,with a median age of 9 years.It has a subacute or chronic clinical course.Most of the patients have evidence of systemic disease,often with lymph node,liver,spleen and skin involvement It carries a poor clinical outcome and can be life-threatening.The disease is characterized by a clonal proliferation of EBV-infected T cells with cytotoxic immunophenotype.Definitive diagnosis requires correlation between clinical,pathologic and ancillary investigation findings.