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.     

富于PD-1阳性T细胞的滤泡间弥漫大B细胞淋巴瘤1例临床病理分析

目的探讨富于PD-1阳性T细胞的滤泡间弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)的临床病理学和免疫表型特征及鉴别诊断。方法应用HE和免疫组化染色、EBER原位杂交及基因克隆性重排技术检测1例罕见的富于PD-1阳性T细胞的滤泡间DLBCL,并复习相关文献。结果镜下见淋巴结内增生的淋巴滤泡散在分布,滤泡间区增宽明显伴多形性细胞浸润,包括异型的中心母细胞和免疫母细胞样大细胞、小淋巴样细胞、嗜酸性粒细胞和组织细胞。免疫表型:滤泡间区异型大细胞CD20、PAX5、MUM1一致强阳性表达,CD3、CD5、CD10、BCL-6、CD30和CD15均阴性,背景小淋巴样细胞多为PD-1阳性的T细胞。此外,EBER原位杂交阴性,免疫球蛋白基因重排示B细胞单克隆性增生,T细胞受体基因未见单克隆性重排。结论滤泡间DLBCL,特别是伴有PD-1阳性的T细胞背景,其诊断具有挑战性。认识DLBCL这一罕见生长方式很重要,需与包括反应性免疫母细胞增生性疾病、血管免疫母细胞性T细胞淋巴瘤、滤泡间霍奇金淋巴瘤和其它富于PD-1阳性T细胞的大B细胞淋巴瘤等类似病变鉴别。     

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。     

原发性皮肤间变性大细胞淋巴瘤临床病理分析

目的 探讨原发性皮肤间变性大细胞淋巴瘤(C-ALCL)的临床病理特征、免疫表型及预后.方法 分析8例C-ALCL的临床病理资料,复习HE切片,进行T淋巴细胞、B淋巴细胞、活化淋巴细胞和细胞毒性等16种标记的免疫组织化学染色,原位杂交检测EB病毒.结果 8例中男3例,女5例,中位年龄49.5岁.临床上以皮肤无症状的单个红色结节、肿块为主要表现,组织学上肿瘤细胞在真皮与皮下脂肪内大片状、弥漫性浸润.瘤细胞以大细胞为主,异形性明显.8例C-ALCL的瘤细胞CD30阳性细胞数均大于75%.瘤细胞均表达1～3个T细胞标记(CD3、CD5或CD45RO)及1～3个细胞毒性标记[T细胞内抗原(TIA)-1、颗粒酶B或穿孔素].表达白细胞共同抗原(LCA)为8例、CIM为5例、CD8为1例、间变性淋巴瘤激酶(ALK)-1为1例、上皮细胞膜抗原(EMA)为3例,均不表达CD15、CD20、CK和HMB45.EBER 1/2原位杂交均为阴性.获随访的6例中5例存活,1例死亡(死因不详).结论 C-ALCL有独特的临床病理表现和免疫表型,预后较好.EB病毒与C-ALCL可能无明确的相关性.     

混合性经典型霍奇金淋巴瘤合并T细胞淋巴瘤一例

混合性淋巴瘤是指两种不同类型的淋巴瘤同时发生。该例患者男性,44岁,因无意中发现左颈部肿物入院,彩超提示左颈部4 cm大小肿物。镜下见弥漫小淋巴细胞间散在核大异型细胞。免疫组织化学显示散在核大细胞CD15、CD30、MUM1、PAX5等标记阳性,EB病毒编码的小RNA(EBER)显色原位杂交(CISH)检测显示核大细胞阳性,符合经典型霍奇金淋巴瘤。免疫组织化学显示背景小淋巴细胞CD3、CD2、CD7等标志物阳性,EBER CISH检测显示部分细胞阳性,T细胞受体基因检测提示2个位点单克隆重排,符合T细胞淋巴瘤。混合性淋巴瘤治疗不同于普通的淋巴瘤,需要综合制定化疗方案。     

传染性单核细胞增多症的临床病理及EB病毒定位性研究

目的 研究传染性单核细胞增多症(IM)的临床特征、病理特点、免疫表型和EB病毒原位感染特征,以提高对IM的认识和诊断水平.方法 采用HE染色以及免疫组织化学、原位杂交技术,结合临床资料分析,对15例IM进行了临床病理、免疫表型和EB病毒感染的研究.结果 (1)IM多见于儿童和青年人(中位年龄18岁),起病急,常有发热(12例),伴浅表淋巴结肿大,多数在短期内痊愈.(2)病变以T区增生为主,斑驳状改变常见,细胞混杂,种类多样,可见B细胞分化谱(活化淋巴样母细胞、免疫母细胞、浆样细胞、浆细胞),包膜不厚,间质不多.(3)病变中以CD3阳性的小T淋巴细胞为主,部分活化的淋巴样母细胞和免疫母细胞表达CD20和CD30,信号强弱不等,散在分布.(4)所有病例都有EB病毒编码的小RNA(EBER)阳性细胞,数量多少不一(10～100个/HPF),大中小淋巴细胞均可阳性,主要分布在T区,也见于套区、初级滤泡和生发中心内.结论 进一步确认了IM是EB病毒引起的一种急性自限性淋巴组织增生性疾病.IM在临床、病理、免疫表型和EB病毒感染方面都具有特点,只有综合考虑这4方面的信息才能减少错误,做出更准确的诊断.     

血管免疫母细胞性T细胞淋巴瘤的形态及免疫表型研究

目的 研究血管免疫母细胞性T细胞淋巴瘤(AITL)形态学特点、特异性标志物,并探讨AITL中滤泡树突状细胞网的增生状况及其起源.方法 对29例AITL行bcl-6、CD10、CXCL13、CD21染色(EliVision法)及bcl-6/CD3、CD10/CD21及CD10/CD20双重染色,并选取外周T细胞淋巴瘤,非特殊类型(PTL-U);结外NK/T细胞淋巴瘤,鼻型;间变性大细胞淋巴瘤(ALCL);肠病性T细胞淋巴瘤(ETTL);皮下脂膜炎性T细胞淋巴瘤及淋巴结反应性增生作为对照.结果 (1)22例(75.9%)AITL表达CD10,对照组除1例PTL-U外均阴性;24例(82.8%)AITL表达CXCL13,所有PTL-u均阴性;而AITL中bcl-6的表达情况和PTL-u及反应性增生病例有一定程度的交叉.(2)29例AITL显示特征性的CD21阳性滤泡树突状细胞网增生,4例具有明显生发中心的病例,2例显示增生的滤泡树突状细胞网覆盖并超过生发中心.结论 AITL具有典型的形态学变化,CD10和CXCL13是AITL特异性标志物,而bcl-6不具有特异性;AITL中增生的滤泡树突状细胞网可能部分起源于生发中心.     

淋巴瘤样丘疹病临床病理分析

目的 探讨淋巴瘤样丘疹病(LyP)的临床病理特征、免疫表型及预后.方法 分析13例LyP的临床病理资料,用LSAB法、EliVision法行T淋巴细胞、B淋巴细胞、活化淋巴细胞和细胞毒性等12种免疫组织化学标记,原位杂交检测EB病毒.结果 13例LyP中男6例,女7例,平均年龄26.4岁,皮损多表现为四肢、躯干无症状的多发性丘疹、结节.组织学分型:A型6例,B型1例,c型6例,主要在真皮与皮下脂肪组织内浸润,主要浸润方式分别为楔形、带状及片状、结节状.13例中8例有瘤细胞亲表皮现象;1例B型无大瘤细胞,余12例的大瘤细胞均表达CD30.13例瘤细胞均表达2～3个T细胞标记(CD3、CD5或CD45RO)及1～3个细胞毒性标记[T细胞胞质内抗原(TIA)-1、粒酶B或穿孔素];13例均表达CD4、4例表达CD8、1例表达CD15、1例表达CD20(局灶阳性),均不表达间变性淋巴瘤激酶(ALK)-1.亲表皮之瘤细胞多为CD3~+、CD4~+、CD8~-表型.13例中1例EBER1/2原位杂交阳性.获随访的12例均存活.结论 LyP有独特的临床病理表现和免疫表型,预后较好.A型和C型中亲表皮的瘤细胞均为核扭曲、深染,似覃样霉菌病细胞,推测其与CD30~+大瘤细胞可能来源于不同的克隆群体有关.EB病毒与LyP可能无明确的相关性.     

Ig/TCR基因重排分析联合EBER原位杂交检测在原发性胃肠道淋巴瘤诊断中的应用

目的 探讨Ig/TCR基因重排分析联合EBER原位杂交检测在原发性胃肠道淋巴瘤(gastrointestinal lymphomas,GIL)中的诊断价值.方法 选取常规石蜡包埋的GIL病理标本35例(包括成熟B淋巴细胞肿瘤29例,成熟T淋巴细胞和NK细胞肿瘤6例),淋巴结反应性增生病变10例,提取DNA,应用BIOMED-2引物系统进行Ig/TCR基因重排的克隆性分析,并采用原位杂交方法检测EB病毒编码的小RNA(EBER).结果 35例GIL中,共检测出34例克隆性重排.其中29例成熟B细胞淋巴瘤均扩增出Ig克隆性重排,敏感性为100%,且联合应用IgH与IgK引物Ig单克隆性重排的检出率最高;6例成熟T淋巴细胞和NK细胞肿瘤中5例扩增出TCR克隆性重排,敏感性为83.3%;10例淋巴结反应性增生病例均未检测到Ig及TCR克隆性重排条带,其检测特异性为100%.29例成熟B细胞淋巴瘤及10例淋巴结反应性增生组织经EBER原位杂交检测均为阴性,6例成熟T淋巴细胞和NK细胞肿瘤中2例EBER原位杂交检测阳性,且均为鼻型NK/T细胞淋巴瘤.结论 BIOMED-2标准化的基因重排分析系统检测石蜡包埋组织中Ig基因和TCR基因克隆性重排的敏感性和特异性均很高,对GIL的诊断和鉴别诊断具有重要的临床应用价值,EBER原位杂交检测对基因克隆性重排阴性的淋巴瘤也具有一定的辅助诊断作用.     

淋巴组织良性病变和淋巴瘤中SHP-1蛋白的表达及意义

目的探讨淋巴组织良性病变和淋巴瘤的SHP-1蛋白表达及其意义。方法应用免疫组化SP方法检测111例不同类型淋巴瘤和27例淋巴组织良性病变。结果(1)SHP-1的正常表达部位在淋巴结和扁桃体生发中心的套区和边缘区及部分的滤泡间区,脾脏主要在边缘区及部分动脉周围淋巴鞘;在淋巴瘤中残留的淋巴组织和反应性成分也可表达;淋巴瘤的SHP-1蛋白表达比良性病变弱。(2)SHP-1在淋巴瘤中的阳性表达率(36·04%,40/111)远低于良性病变的阳性表达率(100%,27/27),包括霍奇金淋巴瘤(62·5%,5/8)、B细胞非霍奇金淋巴瘤(37·68%,26/69)、T细胞非霍奇金淋巴瘤(26·47%,9/34);不同亚型淋巴瘤表达上有差异,其阳性表达率分别是:黏膜相关淋巴瘤(12·5%,2/16),弥漫性大B细胞淋巴瘤50%(11/22),滤泡性淋巴瘤42·11%(8/19),大细胞间变性淋巴瘤中有80%(4/5),NK/T细胞淋巴瘤16·67%(1/6),前驱T淋巴母细胞淋巴瘤14·29%(1/7),外周T细胞淋巴瘤0(0/7)。(3)滤泡性淋巴瘤的表达方式有:肿瘤性滤泡有阳性表达;肿瘤性滤泡无表达,滤泡周围也是阴性。结论(1)SHP-1在淋巴瘤鉴别诊断中有参考意义,尤其适合滤泡反应性增生的良性病变和滤泡性淋巴瘤的鉴别。(2)SHP-1蛋白的缺失与淋巴瘤的发生、发展密切相关,是重要的抑癌基因。     

成年人系统性EB病毒阳性T/NK细胞淋巴组织增殖性疾病的临床病理研究

目的 探讨成年人系统性EB病毒阳性T/NK细胞淋巴组织增殖性疾病(ASEBV+ T/NK-LPD)的临床病理特征、免疫表型和EBV感染特征,以提高对其的认识及诊断水平.方法 经过HE染色观察并采用免疫组织化学、原位杂交及基因重排技术,结合临床资料,对20例ASEBV+ T/NK-LPD患者病理资料进行回顾性研究,并进行随访.结果 (1)男15例,女5例,中位年龄34岁;起病至确诊时间平均8.7个月;主要临床表现有发热(18/20)、肝脾大(18/20)、淋巴结肿大(17/20);17例随访中11例死亡,平均生存时间2.9个月.(2)组织病理学特点:淋巴结T区明显增宽至弥漫成片,淋巴滤泡不同程度地减少或消失.病变中细胞种类多样至相对单一,以中小淋巴细胞增多为主,大细胞散在其中.淋巴细胞多数异型性不明显,少数轻或中度异型.6例被膜增厚,9例可见局灶或片状坏死及核碎;3例可见噬血细胞现象;另外,肝、脾、肠黏膜、扁桃体和骨髓主要表现为轻至中度异型淋巴细胞浸润.(3)免疫表型特点:20例都表现出T细胞明显多于B细胞,很多细胞表达颗粒酶B或T细胞胞质内抗原(TIA)-1,仅1例CD56阳性.14例CD4/CD8检测病例中8例以CD8阳性细胞为主,5例以CD4阳性细胞为主,1例CD8和CD4阳性数量相当.(4)全部病例EBER均阳性.阳性细胞最多的区域数量在30～300个/HPF,绝大多数病例中EBER阳性细胞包括大、中、小淋巴细胞,主要分布在扩大的T区.(5)TCR基因重排显示该病细胞群体中既有多克隆(4/7)也有单克隆(3/7).结论 ASEBV+T/NK-LPD呈亚急性或慢性经过,主要表现为反复发热伴淋巴结及肝脾大;淋巴结以T区扩大和轻中度异型淋巴细胞浸润为主;EBV感染的细胞毒性T细胞构成病变主体.它是一种危及生命的疾病,患者往往死于器官衰竭和出血.

Abstract：

Objective To study the clinicopathologic features, immunophenotype, clonality and Epstein-Barr virus (EBV) status of systemic EBV-positive T/NK-cell lymphoproliferative disease in adults (ASEBV + T/NK-LPD). Methods Twenty cases of ASEBV + T/NK-LPD were analyzed retrospectively with histopathologic review, immunohistochemistry and in-situ hybridization for EBV-encoded RNA (EBER).The follow-up data were collected. Results There were altogether 15 males and 5 females. The median age of the patients was 34 years. The average duration from onset of symptoms to diagnosis was 8. 7 months.Fever (18/20), hepatosplenomegaly (18/20) and lymphadenopathy (17/20) were the main clinical manifestations. Eleven of the 17 patients died during follow-up, with a mean survival of 2. 9 months.Histologically, there was obvious expansion of T zone of the involved lymph nodes, associated with diminished lymphoid follicles. The interfollicular areas were widened and infiltrated by small to median-sized lymphoid cells which showed only mild atypia. Scattered large lymphoid cells were not uncommon. The nodal capsule was thickened in 6 cases. Focal necrosis was seen in 9 cases. Sinus histiocytic proliferation with erythrophagocytosis was observed in 3 cases. In addition, there were mild atypical lymphoid cells infiltrate into the liver, spleen, intestinal mucosa and bone marrow. Immunohistochemical study and in-situ hybridization showed that the EBER-positive cells were of T-cell lineage, with CD3 expression. They were also positive for cytotoxic molecules (granzyme B or TIA-I) . Only 1 case was CD56 positive. A predominance of CD8-positive cells was demonstrated in 8 of the 14 cases studied, while CD4-positive cells predominated in the remaining 5 cases. One case showed similar proportion of CD8 and CD4-positive cells.The number of EBER-positive cells ranged from 30 to more than 300 per high-power fields. These EBERpositive cells were of small to large size and located mainly in the expanded T zone and occasionally in the germinal centers. Three of the 7 cases exhibited clonal rearrangement of T-cell receptor gamma gene, while the other 4 cases exhibited polyclonal rearrangement of T-cell receptor gamma gene. Conclusions ASEBV +T/NK-LPD is a systemic disease with a subacute or chronic clinical course. Most patients suffer from relapsing fever, lymphadenopathy and hepatosplenomegaly. The disease is characterized by proliferation of EBV-infected cytotoxic T cells. The T zone of the involved lymph nodes shows expansion by mildly atypical lymphoid cells. The disease is associated with poor clinical outcome and can be life-threatening. The patients often die of multiorgan failure and bleeding.     

Distribution and phenotype of Epstein-Barr virus-infected cells in human pharyngeal tonsils.

Although Epstein-Barr virus (EBV) is often found in human tonsils, it remains to be precisely determined in what cells and microenvironment the virus is present. Although generally regarded as a B lymphotropic virus, EBV is associated with non-B-cell tumors, for example, NK/T-cell lymphoma, carcinoma, and leiomyosarcoma. To provide a basis for understanding the origin and biology of EBV-infected non-B cells, the immunophenotype of all EBV-infected cells in reactive human tonsils was determined by subjecting tonsil sections to dual/triple EBER in situ hybridization and immunohistochemistry with monoclonal antibodies to T cells (CD3, CD4, CD8, CCR3), B cells (CD20), plasma cells (CD138), natural killer (NK) cells (PEN5), and epithelial cells (cytokeratin), as well as frozen section immunostaining with antibodies to EBV latent proteins EBNA1, EBNA2, LMP1, and EBV early protein BZLF1. Most tonsils contained nearly equal numbers of EBNA1- and LMP1-positive cells (latency program) while only a few contained EBNA2-positive cells (growth program). More than 1000 EBER-positive cells from six tonsils were detected in the interfollicular zone (59%), tonsillar crypts (26%), and follicles (15%). Most (82%) EBER-positive cells are CD20-positive B cells, 7% are CD3-positive T cells, and 11% are cells of indeterminate lineage, often with plasmacytoid morphology. However, no EBER-positive plasma cells were identified. Rare EBER-positive NK cells and EBER/BZLF1-positive epithelial cells were identified. The direct demonstration of EBV within rare T cells, NK cells, and epithelial cells in reactive human tonsils provide a basis for further understanding of the origin of EBV-associated tumors of non-B-cell type.     

An adult case of systemic Epstein-Barr virus-positive T/natural killer-cell lymphoproliferative disorder with good outcome

Epstein-Barr virus-positive T/natural killer (NK)-cell lymphoproliferative disorder (EBV+T/NK LPD) encompasses a heterogeneous group of disorders that have a common feature with excessive lymphoid proliferation of mainly T cells and/or NK cells. This disease is rare, predominantly affects children and young adults, and associated with high mortality. Herein, we report a case of EBV+T/NK LPD that occurred in an old woman with good outcome. The patient presented with fever, splenomegaly, and pancytopenia. Computed tomography (CT) scan of the abdomen showed splenomegaly. The clinical impression was a malignant tumor of spleen, so splenectomy was performed. Microscopically, the architecture of the spleen was preserved. The white pulp Malpighian corpuscles were atrophied. The red pulp showed intact sinusoids and pulp cords with increased cellular infiltrate. The proliferating lymphoid cells were mostly small lymphoid cells with minimal or no nuclear atypia, mixed with rare medium-sized or large cells. Immunohistochemical study and in-situ hybridization showed that the EBER-positive lymphoid cells were positive for CD3 and CD56. They were also positive for cytotoxic molecules, such as T-cell restricted intracellular antigen (TIA1), granzyme B. The case exhibited polyclonal rearrangement of T-cell receptor gene (TCR) by polymerase chain reaction (PCR) studies. Without radiotherapy and chemotherapy, the patient is alive and well with no evidence of disease 25 months after surgery.     

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。     

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.     

鼻咽原发性腺样囊性癌及其与EB病毒感染的关系

目的 探讨鼻咽癌高发的广州地区鼻咽原发性腺样囊性癌的临床病理特征及其与EB病毒感染的关系。方法 对17例鼻咽原发性腺样囊性癌进行临床资料分析。除HE、阿辛蓝及过碘酸Schiff(PAS)常规染色外,采用标记链酶素卵白素生物素(LSAB)免疫组织化学法检测一系列上皮性标志物、CD21和EB病毒编码的潜伏膜蛋白(LMP)1的表达。采用原位杂交法检测EB病毒编码的小RNAs(EBER)。用巢式聚合酶链反应(PCR)法检测EB病毒DNA W片段。结果 17例鼻咽原发性腺样囊性癌患者的男女之比为7：10,年龄30-63岁,中位年龄46岁。17例中14例的肿物呈明显局部侵袭性生长,病变属T3或T4期,仅1例有同侧颈淋巴结转移。大部分肿瘤细胞呈基底细胞样,核小而深染、仅有少许胞质;细胞之间常可见伊红染色同质性或黏液样物质;16例可见筛孔状的特征性结构。鼻咽原发性腺样囊性癌均表达广谱细胞角蛋白和上皮膜抗原。9例(9／17)可见少数癌细胞呈EBER阳性,采用巢式PCR法同时检测到这9例活检组织192bp的EB病毒W片段阳性带,EBER阳性癌细胞的病例中,5例的癌细胞表达LMPI;其中3例的肿瘤间质中又可见少数EBER阳性的浸润性淋巴细胞。所有17例的癌细胞,包括EBER阳性的癌细胞均不表达CD21。结论 鼻咽原发性腺样囊性癌患者以女性为多见。肿瘤生长呈明显的侵袭性,常侵犯鼻咽及其周围组织。鼻咽原发性腺样囊性癌与EB病毒感染的关系并不密切。     

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。     

儿童腹腔非霍奇金B细胞淋巴瘤的临床病理及免疫表型分析

目的 探讨儿童腹腔原发性非霍奇金B细胞淋巴瘤的临床病理、免疫表型与EBER特征及其病理诊断和鉴别诊断.方法 按WHO(2008年)淋巴瘤分类标准分析74例儿童腹腔原发性非霍奇金B细胞淋巴瘤的临床病理资料,制备组织芯片,进行免疫组织化学SP法染色,EBER原位杂交和c-myc基因荧光原位杂交,观察CD20、CD79a、CD3、CD10、bcl-6、MUM1、bcl-2、CD43、CD38和Ki-67蛋白的表达和EBER表达特征,并区分伯基特淋巴瘤(BL)、弥漫性大B细胞淋巴瘤(DLBCL)和介于BL和DLBCL之间的不能分类的B细胞淋巴瘤(DLBCL/BL)病理类型,在DLBCL中再区分其生发中心B细胞型(GCB)和非生发中心B细胞型(non-GCB)的分化特征.结果 儿童腹腔非霍奇金B细胞淋巴瘤中BL为65例(87.8%),DLBCL为4例(5.4%),DLBCL/BL为5例(6.8%).临床以腹痛、腹部包块、肠梗阻及肠套叠为主要发病症状.BL免疫组织化学表达CD20(65例)、CD79a(65例)、CD10(63例)、bcl-6(62例)、MUM1(15例)、CD43(46例)和CD38(63例);不表达CD3、bcl-2;27例(41.6%)EBER阳性;54例(93.0%)c-myc基因位点断裂.DLBCL免疫组织化学表达CD20(4例)、CD79a(4例)、CD10(3例)、bcl-6(2例)、MUM1(2例)、bcl-2(3例)、CD43(2例)、CD38(2例);不表达CD3;其中2例GCB,2例non-GCB;EBER阴性;1例c-myc基因位点断裂.DLBCL/BL免疫组织化学表达CD20(5例)、CD79a(5例)、CD10(5例)、bcl-6(4例)、MUM1(3例)、CD43(5例)、CD38(3例),不表达CD3和bcl-2;4例EBER阴性;3例c-myc基因位点断裂.结论 儿童腹腔非霍奇金B细胞淋巴瘤具有侵袭性生长的特点,以BL为主要病理类型.临床以腹痛、腹部包块、肠梗阻及肠套叠为主要发病症状,主要累及回盲部肠组织及周围系膜淋巴结,病理形态、免疫表型、EBER、c-myc基因的检测对BL、DLBC及DLBCL/BL淋巴瘤的诊断和鉴别诊断有重要作用.