肠道T细胞淋巴瘤的预后分析

目的 了解我国肠道T细胞淋巴瘤（ITCL）的预后情况,探讨不同临床病理因素和EB病毒基因产物对其预后的影响,以期寻找确切的预后指标。方法 收集42例ITCL,运用免疫组织化学LSAB法染色观察CD4、CD8、CD45RO、CD56、TA-1和EB病毒潜伏膜蛋白（LMP-1）的表达,采用聚合酶链反应（PCR）检测TCR-γ基因重排扩增,运用EBER1/2原位杂交检测EB病毒感染。收集全部42例ITCL的临床资料并进行随访。应用SPSS10.0软件分析临床病理、免疫表型及EB病毒基因产物各项指标与治疗及生存率曲线的关系。结果 （1）42例ITCL中有随访结果者29例（69%）。存活6例,最长存活时间156个月（13年）。死亡23例,其中复发4例,存活时间0.3-24.3个月,存活时间中位数3.0个月,1年生存率和2年生存率分别为30%和22%。（2）在病灶为单发或多发,患者是否出现发热、便血、肠穿孔、淋巴结转移等临床表现,肿瘤细胞是否表达CD4、CD8、CD56、LMP-1,有无TCR-γ基因重排、手术治疗后是否并化疗或放疗等其他治疗方法各因素中,除TCR-γ基因重排（P=0.0078,）和不同的治疗方法（P=0.0250）外,其他各因素与预后不相关。（3）没有发现有意义的预后因素。结论 肠道T细胞淋巴瘤临床进程凶猛、预后差的特殊表现可能归因于其肿瘤细胞的细胞毒性细胞属性以及肿瘤发生发展过程中病毒病因学的影响。     

肠道T细胞淋巴瘤中的EB病毒感染和T细胞内抗原1的表达

目的 探讨ＥＢ病毒感染在肠道Ｔ细胞淋巴瘤发病中的意义。方法 用ＥＢＥＲ１／２原位杂交及三步ＡＢＣ法免疫组织化学染色技术,观察２４例肠道Ｔ淋巴瘤患者中ＥＢ病毒感染及Ｑ细胞内抗原（ＴＩＡ－１）抗原表达情况,选用的抗体有ＴＬＡ－１,ＬＭＰ－１,ＣＤ３,ＣＤ２０,ＣＤ３０和ＣＤ４５ＲＯ等。     

肠道淋巴瘤与EB病毒相关性研究

目的：探讨EB病毒（Epstein-Barr virus,EBV)感染在肠道淋巴瘤发病中的意义。方法：采用EBV的DNA原位杂交及S－P法免疫组化技术（第一抗体为EBV、CD3、CD20、CD43、CD45、CD45RO、CD74等），观察24例肠道淋巴瘤患者（8例肠病相关T细胞淋巴瘤、16例黏膜相关淋巴组织B细胞淋巴瘤）EBV感染情况。以20例慢性结肠炎作为对照。结果：患者年龄21－92岁（平均52．8岁），男女之比为3．8：1。临床上均以腹痛、腹胀或便血就诊。组织病理学：T细胞淋巴瘤细胞多形性、核大，不规则，嗜血管性及大片坏死；B细胞淋巴瘤细胞中等大小，多呈圆形、椭圆形、胞质较少淡染，核稍大，核分裂象多见，可见“淋巴上皮病变”。24例淋巴瘤中检出（原位杂交及免疫组化）EBV－DNA 14例（检出率为58．3％），其中T细胞淋巴瘤EBV的检出率为75％，B细胞淋巴瘤EBV的检出率为50％（P＜0．01）。结论：肠道淋巴瘤的发生与EBV的感染有明显的相关性。     

淋巴母细胞性T细胞淋巴瘤与EB病毒的关系

目的：探讨淋巴母细胞性Ｔ细胞淋巴瘤与ＥＢ病毒的关系。方法：收集９例淋巴母细胞性Ｔ细胞淋巴瘤进行ＥＢ病毒检测，用免疫组织化学ＡＢＣ法证实其肿瘤细胞本质；用聚合酶链反应检测ＥＢ病毒特征性ＤＮＡ序列（ＥＢＶ ＤＮＡ）；用ＲＮＡ原位杂交法检测ＥＢ病毒编码的ＲＮＡ（ＥＢＥＲ１／２）。结果：９例淋巴母细胞性Ｔ细胞淋巴瘤，ＥＢＶ ＤＮＡ阳性７例（７７．８％），ＥＢＥＲ１／２阳性６例（６６．７％）。结论：淋巴母细     

血管内NK细胞淋巴瘤的临床病理分析

目的探讨血管内NK细胞淋巴瘤(IVNKL)的临床病理特征及预后特点,以提高对这一罕见疾病的认识。方法采用HE、免疫组织化学染色（EliVision法）和原位杂交技术,结合临床资料对2例IVNKL进行分析,对文献中的7例及该组2例患者进行临床病理学特征分析和预后比较。结果2例患者分别为68岁女性和22岁男性,均表现为躯干和四肢皮疹伴发热,皮肤活检结果符合典型的血管内淋巴瘤,免疫表型证实为NK细胞来源,即CD3、CD56、颗粒酶B和EBV编码的小RNA探针(EBER)阳性。2例患者均于确诊2个月后死亡。汇总文献,9例患者中男4例,女5例,平均年龄45.7岁,中位数47岁,红斑皮疹是最常见的临床表现,7例患者病程中出现多系统受累,3例中枢神经系统受累。随访时间2～17个月,9例中6例死亡,中位生存时间为9个月,1年生存率为(35.6±18.6)％。多系统受累患者的死亡率( 6/7)略高于单纯皮疹者(0/2),但差异无统计学意义(P =0.083)。结论IVNKL是一种罕见疾病,确诊需要依据典型组织学特点,并结合免疫表型分析和EBER原位杂交检测。该病预后较差,需尽早确诊、及时治疗,以避免多系统受累。     

鼻NK/T细胞淋巴瘤--15年研究报道

目的 :探讨鼻NK/T细胞淋巴瘤 (原诊断为“中线恶性网织细胞增生症”)的临床病理及免疫表型特征、病变性质及其与EB病毒感染的关系。方法 :过去 15年中对近 2 0 0例“中线恶网”病例做了一系列研究 ,包括临床病理分析、LSAB法免疫组化染色作免疫表型分析、用PCR技术作T细胞受体β和γ链基因重排及EBV DNA检测、EBER原位杂交和原位末端标记DNA片段技术检测细胞凋亡。结果 :①鼻NK/T细胞淋巴瘤有特征性临床及病理形态学表现 ;②瘤细胞表达CD3ε:89 8% ;CD45RO :81 2 % ;CD5 6 :81 2 % ;TIA 1:10 0 %。不表达B淋巴细胞和组织细胞分化抗原 ;③TCR β链基因重排检出率为85 7% ,TCR γ链基因重排检出率为 94 45 % ;④EBV DNA检出率为 6 7 86 % ;EBER原位杂交阳性率为 90 6 3% ;⑤肿瘤组织中的凋亡细胞与Ki 6 7 呈明显正相关 (P <0 0 0 6 3) ,Ki 6 7 细胞数量变化与患者的平均生存期有明显关系 (P <0 0 2 )。结论 :“中线恶网”实为EB病毒相关、细胞毒性NK/T细胞淋巴瘤。     

不同亚型T细胞淋巴瘤与EB病毒的关系

目的 :探讨不同组织学类型T细胞淋巴瘤 (TCL)与EBV感染的关系。方法 :对 83例 (6种类型 )TCL进行研究 ,包括低度恶性 30例 (其中小多形 2 1例、小淋巴细胞性 9例 ) ,高度恶性 5 3例 (其中大 /中多形 31例、淋巴母细胞性 9例、间变性大细胞性 7例、透明细胞性 6例 )。采用PCR检测EBV特征性的DNA序列 (EBV DNA)和ISH法检测EBV编码的RNA(EBER 1/2 )。结果 :每种类型TCL均有EBV的阳性表达 ,低度恶性组与高度恶性组之间EBER 1/ 2表达率差别有显著性 (P <0 0 5 )。结论 :各种类型TCL的发生发展均与EBV感染有关 ,但高度恶性组EBER 1/ 2的表达比低度恶性组更显著。     

肠病型肠道T细胞淋巴瘤临床病理分析

目的通过分析小肠肠病型肠道T细胞淋巴瘤(enter-opathytype Tcell lymphoma,ETCL)患者的临床表现、病理改变,提高临床医师和病理医师对ETCL的认识,以期改善患者的生存率。方法回顾分析2005年2月～2009年7月收治的2例ETCL患者的临床和组织病理学表现;采用免疫组化方法标记CD45RO、CD3、CK、CD20、CD45、CD79α、Pax-5、CD56。结果 2例ETCL患者均有肠病史,确诊后2例均存活但一般情况差。病变均发生于小肠,1例为回肠多发性溃疡性病变,1例为空肠肠穿孔。肿瘤细胞为多形性T细胞,组织学形态为多形性淋巴细胞弥散分布,以血管中心性浸润,淋巴上皮病变,大片或多灶性坏死为特征。2例患者肿瘤组织CD45RO、CD3、CD45、CD56均为阳性。结论 ETCL临床症状多无特异性,病程发展迅猛,预后差,病损肠管表现为多发性溃疡,以穿孔为首发症状者应多取材,避免漏诊。结合免疫组织化学,早期诊治提高患者生存率。     

EB病毒潜伏感染在不同位T细胞淋巴瘤中的表达

探讨不同部位Ｔ细胞淋巴瘤与ＥＢ病毒感染的关系。方法对１００例不同部位的ＴＭＬ，采用原位杂交法检测肿瘤细胞ＥＢＶ编码的ＲＮＡ。结果（１）１００例中ＥＢＥＲ１／２检出率４８％，结内ＴＬ检出率３０％，结外ＴＭＬ检出率６０％，结内，结外ＥＢＶ检率差异有非常显著意义。     

流式细胞术在弥漫性大B细胞淋巴瘤伴大量T细胞反应病理诊断中的应用

目的探讨流式细胞免疫分型技术在弥漫大B细胞淋巴瘤伴大量T细胞反应病例诊断中的应用价值。方法对3例弥漫大B细胞淋巴瘤伴大量T细胞反应病例病理形态、免疫组织化学染色及流式细胞免疫分型进行回顾性分析。结果例1：在CIM5-SSC（Side Scatter,侧向散射角）点图上可见CD45阳性细胞明显分2群,强阳性细胞由T细胞和B细胞共同组成,但以T细胞为主,其中B细胞为免疫球蛋白轻链非限制性表达。而CD45弱阳性细胞基本都是B细胞,且为免疫球蛋白轻链入限制性表达。例2：在CD45-SSC点图中可见CD45阳性细胞因SSC大小不同而分2群,SSC较小的细胞群为T、B细胞混合存在,SSC较大,相当于单核细胞位置的细胞群主要为B细胞,且为免疫球蛋白轻链K限制性表达;例3：再作CD19／κ／CD20,CD19／λ／CD20三重标记发现部分CD19阳性细胞CD20阴性,该群细胞呈κ限制性表达。结论通过多参数、多组合流式细胞免疫分型技术可以从抗原表达减弱或增强、抗原丢失、是否表达非B系抗原、FSC（前向散射光）和（或）SSC的变化以及是否有表达不成熟B细胞的抗原6个方面将肿瘤性B细胞与反应性细胞区分开。     

鼻腔和鼻咽非霍奇金淋巴瘤EB病毒潜伏膜蛋白表达

目的；探讨鼻咽癌高发区人群鼻咽／鼻腔原发非霍奇金淋巴瘤（ＮＨＬ）与ＥＢ病毒（ＥＢＶ）感染的关系，方法：对４１例鼻咽和鼻腔ＮＨＬ进行免疫细胞学分型以及ＥＢＶ潜伏膜蛋白（ＬＭＰ１）检测。结果：发现（１）鼻咽／鼻腔ＮＨＬ的ＬＭＰ１检出率为４８．８％（２０／４１），（２）鼻咽ＮＨＬ的ＬＭＰ１检出率３７．９％（１１／２９），鼻腔７５％（９／１２），（３）Ｔ细胞性淋巴瘤ＬＭＰ１检出率６０％（１５／２５），Ｂ细     

唾腺淋巴上皮样癌与EBV的相关性

目的 探讨唾腺淋巴上皮样癌与EB病毒的关系及病理诊断价值。方法 采用PCR法检测唾腺淋巴上皮样癌组织中EB病毒，免疫组织化学检测EB病毒潜伏膜蛋白1(latent membrane protein-1)的蛋白表达。结果 PCR检测EBV／IR3区域DNA阳性率为81．8％(9／11)，免疫组化检测EB病毒LMP-1阳性表达率54．5％(6／11)；EB病毒和LMP-1蛋白表达同时检出率为45％(5／11)。结论 唾腺淋巴上皮样癌的发生、发展与EB病毒感染密切相关，PCR检测石蜡包埋组织中的EB病毒具有操作简单、灵敏度高等优点。     

Detection of Epstein Barr virus in an hepatic leiomyomatous neoplasm in an adult human immunodeficiency virus 1-infected patient

We report the first case of a human immunodeficiency virus (HIV)-related primary hepatic leiomyoma in an adult patient. The diagnosis was made at autopsy and confirmed by immunohistochemistry. Epstein Barr virus (EBV) was identified in tumour cells by in situ hybridization. Review of the literature revealed 13 cases of visceral myogenic tumours occuring in acquired immunodeficiency syndrome children, and only 2 cases in adults. One was a spinal epidural leiomyoma, the other multiple smooth muscle tumours of the colon and adrenal gland. This is the first report of EBV in smooth muscle neoplastic cells in an HIV-infected adult patient.     

Characteristics of Epstein-Barr virus isolated from the malignant lymphomas in Korea

Epstein-Barr virus (EBV) is a common herpes virus linked to a variety of human neoplasms. In this study, the EBV detection was identified with the paraffin-embedded tissues from 62 non-Hodgkin's lymphomas, 20 Hodgkin's lymphomas, and 48 non-neoplastic tonsils, using PCR for EBNA-1 and EBER-1 mRNA in situ hybridization for EBER-1 mRNA. The isolates were analyzed for type 1/2, variants C/D and F/f, and LMP-1 30 bp deletion. EBV was isolated in 31 of 48 (66%) non-neoplastic tonsils, 24 of 42 (57%) B cell lymphomas, in 15 of 20 (75%) T cell lymphomas, and 17 of 20 (85%) Hodgkin's lymphomas. These viruses were classified as type 1 for 81% of non-neoplastic tonsils, 95% of B cell lymphomas, 93% of T cell lymphomas, and 73% of Hodgkin's diseases. Both type 1 and 2 viruses were isolated in one non-neoplastic tonsil and 3 Hodgkin's diseases. Type C virus was predominant in non-neoplastic tonsils (77%) and B cell lymphomas (75%), while type D virus was common in T cell lymphomas (71%) and Hodgkin's diseases (73%) (P < 0.05). Majority of the viruses detected in non-neoplastic tonsils (93%) and malignant lymphomas (91%) were "F" prototype. LMP-1 30 bp deletion was found in high frequency in both non-neoplastic tonsils (92%) and malignant lymphomas (86%). In conclusion, most of EBV found in Korea was type 1, and "DF" genotype was more frequent in T cell lymphomas and Hodgkin's diseases than in non-neoplastic tonsils and B cell lymphomas. LMP-1 30 bp deletion did not seem to be associated with malignant lymphomas.     

Valganciclovir suppressed Epstein Barr virus reactivation during immunosuppression with alemtuzumab

BackgroundReactivation of latent herpes viruses occurs with immunosuppression. Alemtuzumab is an antibody targeting CD52, which is expressed on all B- and T-cells. Treatment with alemtuzumab leads to profound T-cell suppression, and reactivation of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) occurs. Valganciclovir is used as an anti-CMV prophylaxis during alemtuzumab therapy.ObjectiveTo determine if EBV reactivation is decreased with valganciclovir prophylaxis.Study designPlasma EBV DNA was serially quantified by quantitative polymerase chain reaction with a World Health Organization EBV standard in patients receiving alemtuzumab therapy with valganciclovir as anti-CMV prophylaxis.ResultsTwenty-nine patients were studied. A total of 258 samples were quantified, at a median of 7 (3–25) specimens per patient. Twenty-four patients never had any quantifiable EBV DNA. Five patients (17%) developed EBV reactivation. Two patients had EBV reactivation at very low levels of about 10³ IU/mL, 3–4 logs lower than those typically found in post-transplant lymphoproliferative diseases. Three patients had EBV reactivation at higher levels of 10⁴ IU/mL, which only occurred after two courses of alemtuzumab were administered. EBV reactivation subsided spontaneously in four cases. One patient developed EBV-positive Hodgkin lymphoma, but he had also received previously another potent T-cell suppressing drug fludarabine.ConclusionValganciclovir suppressed EBV reactivation during alemtuzumab therapy. It might be a useful prophylaxis in immunocompromized patient populations at high risk of EBV reactivation.     

Epstein-Barr病毒壳抗原的纯化及其在检查血清抗体中的应用

为了建立纯化Ｅｐｓｔｅｉｎ－Ｂａｒｒ（ＥＢ）病毒壳抗原（ＥＢＶ－ＶＣＡ）的方法，用于酶联免疫吸附试验（ＥＬＩＳＡ）检测人血清中的相关抗体，我们用重组昆虫病毒在感染的ｓｆ９细胞中表达ＥＢＶ－ＶＣＡ。感染的细胞经裂解后，层析纯化表达产物。用纯化的ＶＣＡ作为抗原包被ＥＬＩＳＡ板或硝基纤维膜，检查血清中ＶＣＡ／ＩｇＡ和ＶＣＡ／ＩｇＧ抗体，为ＥＢＶ感染的检测和ＮＰＣ的诊断发展了一个敏感、特异和简便的方法。     

Epstein-Bar病毒潜伏膜蛋白在喉癌组织中的表达

为了探讨Ｅｐｓｔｅｉｎ－Ｂａｒ病毒在喉鳞癌细胞中的表达情况，对９０例喉鳞癌组织进行了Ｅｐ－ｓｔｅｉｎ－Ｂａｒｒ病毒潜伏膜蛋白（ＥＢＶ－ＬＭＰ－１）的检测，结果显示，ＬＭＰ－１主要定位于细胞膜和细胞浆内，９０例喉鳞癌中ＬＭＰ－１阳性者４１例，阳性检出率为４５．５％，其中低分化鳞癌阳性率为４４％（１２／２７），中分化鳞癌为５２％（２５／４８），高分化鳞癌为２６．６％（４／１５）。提示，ＥＢ病毒不仅存在于低分化喉鳞癌中，也存在于高分化鳞癌中，喉癌的发生可能与ＥＢ病毒感染有关。     

Prognostic significance of CD20 expression and Epstein‐Barr virus (EBV) association in classical Hodgkin lymphoma in Japan: A clinicopathologic study

To investigate the clinicopathological significance of CD20 expression and Epstein‐Barr virus (EBV) association in Hodgkin and Reed–Sterberg cells of classical Hodgkin lymphoma (CHL), CD20 expression and EBV positivity (by EBER in situ hybridization) were investigated in 389 CHL patients in Japan. They included 74 CD20‐positive cases (19%) and 315 CD20‐negative cases (81%). CD20‐positive cases showed significantly older age at onset (P = 0.018) and higher association with EBV (P = 0.002). Multivariate analysis identified EBV‐positivity (but not CD20‐positivity), presence of B symptoms, thrombocytopenia, elevated serum lactate dehydrogenase and performance status >1 as poor prognostic factors for overall survival (OS). We constructed a new prognostic model with these five factors classifying patients into three groups: low risk, 0–1 adverse factor; intermediate risk, 2–3 factors; high risk, 4–5 factors. This prognostic model could stratify the prognosis of CHL patients (P < 0.0001). For 144 patients (58%) classified into the low‐risk group, the 5‐year OS was 91%. For 92 patients (37%) in the intermediate group, the 5‐year OS was 66%; for 11 patients (5%) in the high‐risk group, the 5‐year OS was 36%. In conclusion, EBV is identified as an independent poor prognostic factor for CHL patients. Therefore, examination of EBV association in CHL is recommended as routine pathologic practice especially in countries where EBV infection prevails.