间变性大细胞性T细胞性淋巴瘤中EB病毒检测及CD56的表达

目的：研究间变性大细胞性Ｔ细胞性淋巴瘤ＥＢ病毒表达情况及其与ＣＤ５６阳性表达间的关系。方法：采用免疫组织化学ＬＳＡＢ法检测１５例ＡＬＴＣＬ中Ｋｉ－１及ＣＤ５６的表达,并用原位杂交法检测其ＥＢＥＲｓ。结果：１５例ＡＬＴＣＬ中Ｋｉ－１均阳性（１００％）,５例ＣＤ５６阳性（３３．３％）,９例ＥＢＥＲＳ阳性。其中,３例ＡＬＴＣＬ中ＥＢＥＲＳ和ＣＤ５６共同阳性。结论：ＡＬＴＣＬ的发生同ＥＢ病毒感染有一定关系     

皮下脂膜炎样T细胞淋巴瘤的细胞毒颗粒相关蛋白TIA—1的表达及 …

目的 认识皮下脂膜炎样Ｔ细胞淋巴瘤（ＳＰＴＣＬ）的临床和病理特点。研究细胞毒颗粒相关蛋白ＴＬＡ－１在ＳＰＴＣＬ中的表达及与Ｅｐｓｔｅｉｎ－Ｂａｒｒ（ＥＢ）病毒感染的关系。方法 和ＴＩＡ－１、ＣＤ４５ＲＯ、ＣＤ３、ＣＤ２０和ＣＤ６８等抗体作免疫组织化学ＡＢＣ法染色应用ＥＢＥＲ１／２原位杂交检测ＥＢ病的潜伏感染。结果 １７例ＳＰＴＣＬ男女之比１：１．１．中位发病年龄２４岁,主要表现为下肢、躯干无症状性     

细胞毒颗粒相关蛋白TIA-1在鼻NK/T细胞淋巴瘤及淋巴增生组织中的表达

目的 观察２７例鼻ＮＫ／Ｔ细胞淋巴瘤之瘤细胞表达细胞毒颗粒相关蛋白ＴＩＡ－１的情况及其与该肿瘤的免疫表型,基因型及ＥＢ病毒感染的关系。方法 采用ＳＰ法免疫组织化学染色,选用的抗体有：ＴＬＡ－１,ＣＤ５６,ＣＤ３ε,ＣＤ４５ＲＯ,ＣＤ８和ＣＤ２０等;聚合酶链反应,作ＴＣＲγ链及免疫球蛋白ＪＨ链基因重排,ＥＢＥＲ１／２原位杂交及与ＴＬＡ－１和ＣＤ８等的双标记染色,还与１０例鼻咽淋巴增生病例进行了比较。     

T细胞性淋巴瘤组织CD56的检测及其与EB病毒的关系

目的探讨Ｔ细胞性淋巴瘤（ＴＣＬ）中ＣＤ５６的表达情况及ＣＤ５６阳性表达同爱波斯坦－巴尔病毒（ＥｐｓｔｅｉｎＢａｒＶｉｒｕｓ,ＥＢＶ）感染的关系。方法对４６例ＴＣＬ进行ＣＤ５６的免疫组织化学ＬＳＡＢ法检测及ＥＢＥＲｓ的原位杂交检测。结果（１）４６例ＴＣＬ中８例ＣＤ５６阳性（１７．４％）,其中鼻腔、咽部和口腔阳性率最高（５／１７例,２９．４％）。弥漫性大细胞型淋巴瘤ＣＤ５６阳性率最高（６／１６例,３７．５％）。（２）４６例ＴＣＬ中２４例ＥＢＥＲｓ阳性（５２．２％）。（３）８例ＣＤ５６阳性病例中,４例ＥＢＥＲｓ阳性。结论ＣＤ５６的表达同ＴＣＬ发生部位和类型有一定关系。ＣＤ５６阳性表达与ＥＢ病毒感染未发现相关性     

大细胞间变型T细胞淋巴瘤与EBV关系

目的：研究大细胞间变形Ｔ细胞淋巴瘤（ＡＬＣ－ＴＣＬ）与ＥＢＶ之间的关系，方法：应用免疫组织化学，聚合酶锭反应和ＲＮＡ原位杂交方法检测ＥＢＶ－ＤＮＡ的序列和ＥＢＶ编码ＲＮＡ。结果：检测的７例ＡＬＣ－ＴＣＬ，其中４例显示ＥＢＶ－ＤＮＡ和Ｅ－ＢＥＲ１／２阳性，两种检测方法的阳性率均为５７．１％（４／７），结论：ＡＬＣ－ＴＣＬ的发病与ＥＢＶ的感染的关系较密切。     

共刺激对T细胞功能和细胞因子格局的作用

利用Ｂ７－１单抗和环孢素Ａ处理ＡＰＣ：Ｔ细胞反应系统,探讨了Ｂ７／ＣＤ２８芡刺激对Ｔ细胞增殖及细胞因子产生的影响,并用ＲＴ－ＰＣＲ方法分析了细胞因子基因格局的改变。结果表明Ｂ７－１单抗可抑制特异性抗原诱导的Ｔ细胞增殖和ＩＬ－２的产生,Ｂ７－１单抗瑟ＣｓＡ联用可阻断Ｔ细胞增殖和ＩＬ－２产生。Ｂ７－１单抗绎ＩＬ－４的产生未显示明显的影响,而Ｂ７－１单抗与ＣｓＡ联用ＩＬ－４仍可检测到。     

磷脂抗体阳性红斑狼疮患者周围血T细胞受体基因表达初探

目的：初步探讨ＳＬＥ患者周围血Ｔ细胞受体Ｖβ基因是否存在偏移。方法：应用荧光ＰＣＲ定量方法对ＨＬＡ－ＤＲＢ１＾＊０８０３／ＤＱＡ１＊０１０３的抗磷脂抗体阳性ＳＬＥ患者４例,病人对照干燥综合征（ＳＳ）１例,正常对照３例进行周围血ＴＣＲ－Ｖβ的分析。结果;健康者和病人对照的ＴＣＲ仅少数Ｖβ有轻微增高表达。１例非活动性ＳＬＥ患者与对照组相仿,但３例活动性ＳＬＥ５的ＴＣＲ－Ｖβ基因谱呈多克隆激活,其中２例     

McAb共激活T细胞介导肝癌细胞前后的膜分子与TCRVβ基因的表达

Ｔ淋巴细胞活化是一个涉及多种膜表面分子和受体以及一系列相关多肽的复杂过程，为了使Ｔ细胞发挥更好的识别和杀伤癌细胞的功能，采用抗ＣＤ３、ＣＤ２８、ＣＤ８０（Ｂ７１）、ＣＤ２、ＣＤ５８ＭｃＡｂ分别刺激健康人ＰＢＬｓ后作用肝癌细胞，对作用前后ＰＢＬｓ用ＦＡＣＳ进行表型分析，结果发现：作用后ＣＤ３和ＣＤ８分子表达比作用前明显增高，而ＣＤ４分子无显著变化，同时基因家族采用ＲＴＰＣＲＳｏｕｔｈｅｒｎ印迹分析ＴＣＲＶβ基因１～２０亚家族表达水平与特征，健康人ＰＢＬｓ分别加入ＩＬ２、ＰＨＡ、抗ＣＤ３和ＣＤ３＋ＣＤ２８、ＣＤ２８＋ＣＤ８０、ＣＤ２＋ＣＤ５８作用肝癌细胞（ＢＥＬ７４０２）前表达水平平均约为５％，作用ＢＥＬ７４０２后表达水平约为１３％～２５％，其特征为Ｖβ７增高，这提示在癌抗原的参与下ＭｃＡｂ共刺激的Ｔ细胞活化，ＴＣＲ接受ＡＰＣ相应抗原的刺激，具有该ＴＣＲ的淋巴细胞迅速增殖而成为针对抗原的Ｔ细胞克隆，发挥其识别和杀伤癌细胞的作用，这将为肿瘤生物治疗的研究提供分子免疫学依据。     

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     

血管免疫母细胞性淋巴结病及血管免疫母细胞性T细胞淋巴瘤

为了深入调查血管免疫母细胞性淋巴结病（ＡＩＬＤ）和血管免疫母细胞性Ｔ细胞淋巴瘤（ＡＩＴＬ）的临床病理、病变性质诸方面，采用了免疫组化和聚合酶链反应（ＰＣＲ）等方法对５例进行了分析。该５例患者均有全身淋巴结肿大（但直径多小于１ｃｍ），肝脾肿大、发热和多项血液指标改变。ＡＩＴＬ时在ＡＩＬＤ病变背景上出现异型的透明Ｔ细胞浸润为诊断和鉴别依据。５例中４例行ＴＣＲ－β重排分析均呈现克隆性改变。并对４例埃泼斯坦－巴尔病毒（ＥＢＶ）感染情况进行分析，其中３例ＥＢＶＤＮＡ阳性。认为ＡＩＬＤ可能是一种与ＥＢＶ感染相关的瘤前病变，发展为淋巴瘤的比例较高。     

EB病毒相关与不相关的肠道T细胞淋巴瘤临床病理研究

目的：探讨EB病毒相关与不相关的肠道T细胞淋巴瘤的临床病理特征、免疫分型和肿瘤细胞属性。方法：运用EBER1／2原位杂交检测EB病毒感染,采用免疫组化检测32例肠肠道原发T细胞淋巴瘤的免疫表型以及LMP－1、TIA－1、bcl-2和CD21的表达。结果：（1）27例（84．4％）为EB病毒相关淋巴瘤,其中11例（40．75）表达LMP－1。（2）32例瘤细胞均表达CD45RO,CD8＋。4例（12．5％）,CD4＋8例（25．0％）,CD56＋9例（28．1％）,17例（53．7％）为CD4－、CD8－、CD56－。TIA－1＋31例（96．9％）。无1例表达bcl2-,CD21。形态上28例为多形性中一大细胞性,单形性中等大细胞性和多形性各2例。临床上多见于青壮年男性,以腹痛、便血、发热、体重下降为主要症状,预后较差（中位生存期1．7月）。（3）EB病毒相关与相关者出现便血和发热以及CD3,CD8、CD56的表达方面差异有显著性。结论：在我国,绝大多数肠道T细胞淋巴瘤为EB病毒相关,具有特殊临床病理表现和免疫表型。其肿瘤细胞源自不同T细胞亚群（包括细胞毒性T细胞）或者NK细胞。     

淋巴结细胞毒性自然杀伤/T细胞淋巴瘤

目的 探讨淋巴结细胞毒性自然杀伤（NK/T）细胞淋巴瘤的临床病理学特征。方法 对5例淋巴结细胞毒性NK/T细胞淋巴瘤作临床病理观察及随访、用ISAB法做免疫表型分析（CD35RO、CD8、CD56、CD30、CD20、TIA-1）及EBER1/2原位杂交检测。结果 淋巴结细胞毒性NK/T细胞淋巴瘤的瘤 理组织学特点为：（1）淋巴结结构明显破坏并被瘤细胞所取代：（2）瘤细胞呈多形性;（3）我数肿瘤细胞表达淋巴细胞分化抗原。5例中CD45RO阳性的有4例,其中3例瘤细胞同时呈CD56阳性;1例为无标记细胞性;所有病例的TIA-1和EBER均为阳性。结论 淋巴结细胞毒性NK/T细胞淋巴瘤有特征性的形态改变和免疫表型。提示肿瘤进展及预后不良。     

Prevalence of Epstein-Barr virus in non-Hodgkin's lymphomas in central region of Tunisia

The purpose of this study was to evaluate the prevalence of EBV in non-Hodgkin's lymphomas occuring in non-immunocopromised patients in Tunisia through a series of 126 cases. EBV was investigated by EBER oligonucleotide in situ hybridization (ISH) and LMP1-immunohistochemistry. Serological study of EBV has been performed before therapy in 28 patients. EBV was detected in tumor cells by ISH in 28/126 (22.2%) cases. Variable proportions of tumor cells were positive. LMP1 was identified in only 8 cases. EBV was more frequently observed in T-cell lymphomas (9/24 patients; 37.5%) than in B-cell lymphomas (19/102 patients; 18.6%) (p=0.04). There was a strong relationship between EBV and small intestine lymphomas (6/8 patients; 75%) and T/NK nasal type lymphomas (3/3 patients; 100%). EBV serological reactivation was noted in 7/13 patients in clinical stages III/IV and in only 1/10 patients in stages I/II (p=0.03). In conclusion, the prevalence of EBV in Tunisian non-Hodgkin's lymphomas is low but variable depending on the histological type and anatomical location with a predilection for small intestine and nasal lymphomas.     

Epstein-Barr virus infection and its gene expression in gastric lymphoma of mucosa-associated lymphoid tissue

The role of Epstein-Barr virus (EBV) in the pathogenesis of gastric lymphoma of mucosa-associated lymphoid tissue (MALT) has not been well understood. The aim of the study was to investigate EBV infection and its gene expression in this tumor in order to understand its role in the pathogenesis. EBV infection was screened by in situ hybridization for EBV-encoded nonpolyadenylated RNA (EBER ISH) in 79 cases of gastric MALT lymphoma of nonimmunocompromised patients. The expression of EBV proteins [LMP1 (latent membrane protein 1), EBNA2 (EBV nuclear antigen 2), ZEBRA (switch protein encoded by BZLF1 gene)] was studied by immunohistochemistry in EBER-positive cases. EBV was detected with EBER ISH in 15 (19%) of the 79 cases. EBV was found in virtually all tumor cells in 2 cases of high-grade MALT lymphoma (2.5%) (EBV-associated), and was found only in occasional large or small lymphoid cells in 13 cases (16.5%). False positive EBER signal was detected in the mucinous glandular epithelial cells of gastric antrum with FITC-labeled oligonucleotide probe but not with digoxigenin or ³⁵S-labeled riboprobes. Type II latency (EBER+LMP1+ EBNA2-) was detected in both EBV-associated cases. Type III latency (EBER+LMP1+EBNA2+) was also identified in one EBV-associated case besides latency II. Double labeling showed coexpression of LMP1 and EBNA2 in a small number of tumor cells, indicating the presence of type III latency in single cell level. In cases with only occasional EBER-positive large or small lymphoid cells, LMP1 and EBNA2 were not detected. ZEBRA was negative in all the cases. These findings suggest that EBV may contribute to the pathogenesis of a small proportion of high-grade MALT lymphoma, where virtually all tumor cells harbored EBV and the oncogenic viral protein LMP1 was expressed. Moreover, latency III of EBV infection may exist in nonimmunocompromised patient. J. Med. Virol. 56:342–350, 1998 . © 1998 Wiley-Liss, Inc.     

脾脏非霍奇金淋巴瘤的临床病理特征及其与免疫表型的关系

目的 探讨脾脏非霍奇金淋巴瘤（NHL）的临床病理特征及其与瘤细胞属性的关系。方法 复习19例NHL的临床病理资料、进行随访、并用SP法行CD45RO、CD20及髓过氧化物酶等免疫组织化学染色,对CD45RO阳性的病例加作CD8、CD56、TLA-1、CD68免疫表型检测和EBER原位杂交。结果 （1）19例均有脾脏肿大,其中52.6%(10/19)有脾脏占位病变,（2）73.7%(14/19)为B细胞性,滤泡型5例,经济危弥漫型9例;中心母细胞性8例,中心母细胞/中心细胞性3例,小细胞性4例,10例原发脾脏NHL均为B细胞性;（3）26.3%(5/19)为外周T细胞性,大细胞性4例,小细胞性1例;TLA-1阳性3例,其中CD8阳性和CD56阳性各1例,且均为EBNER1/2阳性,余1例为CD8、CD56、EBER均阴性;均为继发脾脏NHL;（4）73.7%(14/19)有随访,9例生存者中有8例为原发脾脏NHL,生存时间为8个月-10年不等;5例死亡病例均为继发脾脏NHL,生存时间为2-6个月不等。结论 脾脏NHL的临床病理表现与瘤细胞的属性有一定关系。原发脾脏NHL的预后明显优于继发脾脏NHL,对原发脾脏NHL的诊断应从严把握。     

Histological and immunophenotypic profile of nasal NK/T cell lymphomas from Peru: high prevalence of p53 overexpression.

Nasal NK/T-cell lymphoma is a unique form of lymphoma highly associated with Epstein-Barr virus (EBV). These lymphomas are rare in Western populations and much more prevalent in some Asian and Latin American countries. Although there are several sizable studies from Asian countries, the same is not true from South America. The aim of this study was to analyze a series of 32 cases of nasal T-cell lymphoma from Peru and to further extend the characterization of this disease. Immunohistochemistry was performed on paraffin sections using the following antibodies: CD20 (L26), CD45RO, CD3, Ki67, CD57, CD56, TIA-1, bcl-2, and p53. The presence of EBV was investigated with immunohistochemical analysis for latent membrane protein (LMP)-1 and in situ hybridization using an antisense riboprobe to EBER 1. The 32 patients included 18 men and 14 women (M:F ratio, 1.2:1), with a median age of 43 years (11 to 72). Three categories were identified: (1) Nasal NK/T cell lymphomas (28 cases): The morphology ranged from small or medium-sized cells to large transformed cells. Necrosis was present in 86% of the cases, and angioinvasion was seen in 36% of the cases. All cases were positive for CD45RO, CD3, and for TIA-1. CD56 was positive in 21 of 27 cases (78%), and CD57 was negative in all cases. EBER 1 positivity was identified in most of the tumor cells in 27 of 28 cases (96%), including the six cases in which CD56 was negative. Overexpression of p53 was detected in 24 cases (86%). (2) Blastic NK cell lymphoma (1 case): The neoplastic cells resembled those of lymphoblastic lymphoma. CD56 and CD45RO were positive; TIA-1, TdT, and EBER-1 were negative. (3) Peripheral T-cell lymphoma (PTCL) unspecified (3 cases): CD56, TIA-1, and EBER-1 were negative. Nasal lymphomas from Peru with a T cell phenotype are predominantly EBV-associated NK/T cell lymphomas, similar to those described in Asian countries. The expression of CD56, TIA-1, and EBER-1, in combination, are very useful markers for the diagnosis of nasal NK/T cell lymphoma in paraffin-embedded tissue. The differential diagnosis of T-cell lymphomas in the nasal region should include rare cases of PTCL unspecified and the blastic variant of NK cell lymphoma. P53 is overexpressed in 86% of the cases. The significance of this finding with regard to clinical behavior and prognosis remains to be determined.     

American Registry of Pathology Expert Opinions: Immunohistochemical evaluation of classic Hodgkin lymphoma

The diagnosis of classic Hodgkin lymphoma requires immunohistochemical confirmation in most cases and one can argue for these studies as standard-of-care in the diagnostic workup. The authors propose a panel of studies for primary identification of CHL to include: CD3, CD20, CD15, CD30 and PAX5. When pattern discordances are identified, additional assessment is recommended. In the case of overexpression of B lineage markers by Hodgkin/Reed-Sternberg cells, or a differential diagnosis that includes large B-cell lymphoma or variants, additional markers recommended are: CD45, OCT2, BOB1, CD79a and MUM1/IRF4. If primary mediastinal large B cell lymphoma is considered in the differential diagnosis, suggested additional markers include: P63, CD23, CD45 and CD79a. When considering a differential diagnosis that includes anaplastic large cell lymphoma we suggest: ALK, CD45, pan T cell antigens (such as CD2, CD5, CD7, and CD43), and cytotoxic markers (granzyme, perforin, and TIA1). If peripheral T cell lymphoma or T cell lymphomas of follicular helper origin are considered in the differential diagnosis, the following panel is recommended: pan T cell antigens, CD4, CD8, one or more follicular dendritic cell markers, and assessment for Epstein-Barr virus (EBV) infection, preferably EBV encoded RNA (EBER) as assessed by in situ hybridization When the differential diagnosis includes nodular lymphocyte predominant Hodgkin lymphoma, recommended additional studies include OCT2, CD21 and/or CD23, PD1, and assessment for EBV infection. The authors recognize that these panels may not be adequate to completely characterize other lymphomas, but these panels will usually be sufficient to distinguish classic Hodgkin lymphoma from other lymphoma types.     

Evidence for lytic infection by Epstein-Barr virus in mucosal lymphocytes instead of nasopharyngeal epithelial cells in normal individuals.

Normal nasopharyngeal tissues from 23 individuals who died of causes unrelated to the upper respiratory system and had no evidence of Epstein-Barr virus (EBV)-related diseases were studied using in situ hybridisation (ISH) and immunohistochemistry for the detection of EBV RNA and expression of EBV proteins, respectively. ISH using ³⁵S-labelled riboprobe for EBV EBER RNA showed occasional to a few EBER + lymphocytes in the stroma of nasopharyngeal mucosa in 14/16 cases with available paraffin-embedded tissues. In addition, very rare intraep-ithelial EBER+ lymphocytes were also detected in 3/16 cases. However, in none of these cases was EBER detected in the epithelial cells. Similar results were obtained using a nonradioactive ISH method for EBER (Dako). In 3/23 cases, im-munostaining using monoclonal antibodies for EBV proteins on cryostat sections showed occasional cells in the stroma expressing EBV nuclear antigen 2 (EBNA2), latent membrane protein-1 (LMP), and switch protein encoded by BZLF1 gene (ZEBRA) in two cases and only very rare LMP+ and ZEBRA+ cells in one other case. Double immuno-staining combining alkaline phosphatase anti-alkaline phosphatase (APAAP) for CD markers and indirect immunofluorescence for LMP showed that the LMP+ cells were either CD19+ or less frequently CD3+, but none were CD68+. These results show that both B and T lymphocytes harbouring EBV can be found in the normal nasopharyngeal tissues. Interestingly, EBV proteins associated with lytic viral replication—diffuse early antigen (EA-D), viral capsid antigen (VCA), or membrane antigen (MA)—were also detected in rare cells in the stroma in one case, and in another case only one MA+ cell was detected. These results provide evidence for a lytic type of infection by EBV in the normal nasopharynx involving a very small proportion of stromal lymphocytes and support the view that nasopharyngeal lymphocytes can act as a reservoir for EBV in normal individuals. © 1995 Wiley-Liss, Inc.     

High frequency of Epstein–Barr virus in Chinese peripheral T-cell lymphoma

Forty-two cases of Chinese T-cell lymphoma were studied for expression of Epstein–Barr virus (EBV) encoded RNA (EBER-1) and EBV latent membrane protein-1 (LMP-1) using in situ hybridization and immunohistochemistry, respectively. EBV was detected in tumour cells in 24/39 peripheral T-cell lymphomas (62%), comprising 18/27 pleomorphic, medium and large cell lymphomas (67%), 4/6 angioimmunoblastic lymphadenopathy-like lymphomas (67%), 2/2 Lennert's lymphomas, 0/2 anaplastic large cell lymphomas, and 0/2 T-zone lymphomas. EBV was not found in three T-lymphoblastic lymphomas. EBV was associated with 12/24 nodal (50%) compared with 12/15 extranodal (80%) peripheral T-cell lymphomas. In EBV positive nodal lymphomas, 9/12 cases (75%) contained less than 10% EBER positive tumour cells. In EBV positive extranodal lymphomas, 9/11 cases (82%) showed EBV gene expression in more than 50% of the tumour cells, and in five of these almost all tumour cells were positive. Lymphomas of the nasopharynx (mainly midline granuloma-type) showed EBER-1 expression in nearly all tumour cells. LMP-1 was detected in 19/23 EBER positive peripheral T-cell lymphomas (83%). Our results show that EBV is strongly associated with peripheral T-cell lymphomas in Chinese. An important role for the virus is suggested in lymphomas of the nasopharynx. The significance of EBV in T-cell lymphomas that contain only a minor population of virally infected tumour cells is currently unclear.