C型凝集素样自然杀伤(NK)细胞受体在结外鼻型NK/T细胞淋巴瘤中表达及意义

目的 探讨C型凝集素样自然杀伤(NK)细胞受体CD94和NKG2在结外鼻型NK/T细胞淋巴瘤中的表达及意义.方法 运用逆转录聚合酶链反应(RT-PCR)检测C型凝集素样NK细胞受体CD94和NKG2在经组织形态、免疫组织化学、EB病毒原位杂交及T细胞受体PCR克隆性重排分析确诊的21例结外鼻型NK/T细胞淋巴瘤以及对照组同部位B细胞淋巴瘤8例、淋巴结外周T细胞淋巴瘤(PTCL)10例、脾脏5例、胸腺5例和慢性炎性鼻黏膜5例组织中的表达情况并进行随访.结果 21例结外鼻型NK/T细胞淋巴瘤具有典型的形态学改变,表达CD3ε、CD56和细胞毒蛋白,TCR重排阴性,20例EB病毒阳性;RT-PCR扩增结果显示,在21例结外鼻型NK/T细胞淋巴瘤中,18例(85.7%)CD94呈阳性表达;NKG2总阳性率为95.2%(20/21),各亚基表达阳性率依次为NKG2A/2B(85.7%)、NKG2D(61.9%)、NKG2F(14.3%)、NKG2C,/2E(4.8%).对照组中PTCL和B细胞淋巴瘤均不表达CD94和NKG2,仅2例脾脏和2例慢性炎性鼻黏膜组织表达CD94,1例脾脏组织表达NKG2A/2B,1例胸腺组织表达NKG2D.CD94和NKG2在结外鼻型NK/T细胞淋巴瘤中的表达与T细胞淋巴瘤和B细胞淋巴瘤比较,差异均有统计学意义(P均<0.01).CD94和NKG2同时表达于17例结外鼻型NK/T细胞淋巴瘤,共表达率为81.0%(17/21).结论 CD94和NKG2在结外鼻型NK/T细胞淋巴瘤中呈特异性和顺序性表达,提示多数病例肿瘤细胞处于活化和功能NK细胞阶段.对这些分子的检测有可能成为NK细胞源性淋巴瘤诊断的重要手段.     

结外鼻型NK/T细胞淋巴瘤中EB病毒潜伏膜蛋白1基因30 bp碱基缺失的检测意义及其与预后的关系

目的 比较结外鼻型NK／T细胞淋巴瘤和鼻咽部慢性炎症和扁桃体炎中EB病毒潜伏膜蛋白（LMP）1基因30bp碱基缺失的检出率,初步探讨结外鼻型NK／T细胞淋巴瘤中LMP1缺失型的检出意义及其与预后的关系。方法 通过聚合酶链反应（PCR）检测55例结外鼻型NK／T细胞淋巴瘤和19例鼻咽部慢性炎症和扁桃体炎中EB病毒LMP1基因30bp的缺失情况,结合随访资料进行分析。结果 结外鼻型NK／T细胞淋巴瘤中LMP1野生型和野生为主型9例,LMP1缺失型和缺失为主型46例;鼻咽部慢性炎症和扁桃体炎中LMP1缺失型和缺失为主型16例。LMP1缺失型和缺失为主型的检出率在NK／T细胞淋巴瘤与鼻咽部慢性炎症和扁桃体炎病例间差异无统计学意义（P〉0．05）。结外鼻型NK／T细胞淋巴瘤中LMP1野生型和野生为主型病例比缺失型和缺失为主型病例预后好。结论 不能简单地将LMP1缺失型作为结外鼻型NK／T细胞淋巴瘤的致病因素,但也不能完全否定其促进该淋巴瘤演进的作用。     

LAT和CD99在T淋巴母细胞淋巴瘤中的表达及意义

目的 探讨LAT和CD99在T淋巴母细胞淋巴瘤(precursor T lymphoblastic lymphoma,T-LBL)中表达的价值.方法 对37例T-LBL应用免疫组织化学EnVision二步法进行LAT和CD99标记.同时选取15例其他病例作为对照:3例B淋巴母细胞淋巴瘤,4例非特殊类型外周T细胞淋巴瘤,3例结外鼻型NK/T细胞淋巴瘤,5例淋巴结反应性增生.结果 37例T-LBL均表达LAT和CD99;4例外周T细胞淋巴瘤及3例鼻型结外NK/T细胞淋巴瘤弥漫表达LAT,不表达CD99;3例B淋巴母细胞淋巴瘤均表达CD99,但不表达LAT;5例反应性增牛淋巴结的T细胞区LAT阳性,淋巴结皮、髓质区均不表达CD99.结论 联合检测LAT和CD99有助于T-LBL的诊断和鉴别诊断.     

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。     

963例成熟T和自然杀伤细胞/T细胞淋巴瘤的临床病理特征分析

目的 观察广东地区不同类型成熟T和自然杀伤(NK)细胞/T细胞淋巴瘤及其亚型的临床病理特点.方法 按WHO(2008版)标准重新评估广东地区2002-2006年1137例成熟T和NK/T细胞淋巴瘤患者.由多名血液病理医师复查,补做必要的免疫组织化学染色及原位杂交.结果 963例确诊为成熟T和NK/T细胞淋巴瘤,占同期所有淋巴瘤20.1%(963/4801),发生于结内319例(33.1%),结外644例(66.9%);非特殊型外周T细胞淋巴瘤293例(30.4%);结外鼻型NK/T细胞淋巴瘤281例(29.2%);间变性大细胞淋巴瘤(ALCL)198例(20.6%);血管免疫母细胞性T细胞淋巴瘤(AILT)46例(4.8%).男女比为1.99:1,发病中位年龄为44岁.非特殊型外周T细胞淋巴瘤好发于55～64岁;结外鼻型NK/T细胞淋巴瘤好发于25～54岁;间变性淋巴瘤激酶(ALK)阳性ALCL多见于年轻人而阴性多见于中老年人;AIIJT好发于65～74岁.结论 广东地区成熟T和 NK/T细胞淋巴瘤多见于结外,好发于男性,总体发病与年龄增长无明显关系,但具体类型有不同的年龄侧重群;常见的类型依次为非特殊型外周T细胞淋巴瘤、结外鼻型NK/T细胞淋巴瘤及ALCL;EB病毒感染与NK/T细胞淋巴瘤关系密切.     

鼻NK/T细胞淋巴瘤瘤细胞分化状态的探讨

目的 探讨鼻自然杀伤(NK)／T细胞淋巴瘤肿瘤细胞的分化状态。方法 收集已确诊的88例鼻NK／T细胞淋巴瘤的临床资料。免疫组织化学染色选用的抗体有：T细胞分化抗原(CD3ε、CD5、CD1a)、NK细胞相关抗原(CD56、CD57),还有CD34和CD38抗原。结果(1)病变部位以鼻腔最常见,其次为咽部,主要体征为溃疡或黏膜糜烂。本组88例鼻NK／T细胞淋巴瘤中有62例(70．5％)之瘤细胞呈弥漫性增生和浸润,瘤细胞中等大小者有71例(80．7％);(2)88例NK／T细胞淋巴瘤中,T细胞标记CD3ε阳性者78例(88．6％),CD5阳性者56例(63．6％),NK细胞标记CD56阳性者25例(28．4％);CD57、CD1a、CD34和CD38均为阴性。结论 鼻NK／T细胞淋巴瘤瘤细胞的分化可能已超越前体细胞阶段,但尚未达到成熟T淋巴细胞或NK细胞阶段。     

142例结外NK/T细胞淋巴瘤免疫组织化学分析

目的:探讨结外NK/T细胞淋巴瘤(extranodal NK/T-cell lymphoma,ENKTL)的免疫组织化学特征.方法:回顾性分析142例ENKTL的免疫组织化学结果及EBER原位杂交结果,并用PCR方法检测1例ENKTL的TCR基因重排.结果:ENKTL免疫组织化学阳性率CD2为87.9％(116/132),CD3为99.3％(141/142),CD5为33.3％(44/132),CD7为74.7％(74/99),CD4为30.2％(13/43),CD8为35.9％(14/39),CD56为92.9％(132/142),TIA-1为100％(132/132),颗粒酶B为99％(111/112),穿孔素为100％(6/6),CD30为40.9％(36/88),PDGFRA为51.9％(28/54),CMYC为53.7％(29/54),Ki-67指数50％～90％,中位数为80％.EBER原位杂交阳性率为100％(142/142).TCR基因重排结果阴性.结论:结外NK/T细胞淋巴瘤存在较为特征性的免疫组织化学表型,并且EBER原位杂交呈阳性.     

原发性中枢神经系统淋巴瘤的临床病理、免疫表型及其与EB病毒相关性研究

目的：观察原发性中枢神经系统淋巴瘤（PCNSL）的临床病理、免疫表型及其与EB病毒的关系。方法：搜集25例PCNSL的临床资料并随访,应用单克隆抗体UCHL－1、L26、k、λ胶质纤维酸性蛋白（GFAP）和CS1－4行免疫组织化学染色,EB病毒寡核苷酸探针（EBER1／2）原位杂交,研究其免疫表型和EB病毒感染情况。结果：25例PCNSL均为B细胞淋巴瘤,EBER1／2原位杂交25例中仅2例（8％）出现阳性。结论：本组PCNSL均为B细胞激性。且与EB病毒呈低相关性。     

非霍奇金B细胞淋巴瘤369例病理形态观察--2001年世界卫生组织淋巴组织肿瘤新分类应用体会

目的探讨非霍奇金B细胞淋巴瘤(B—NHL)的病理形态和免疫表型在B—NHL诊断中的价值,评价2001版世界卫生组织(WHO)淋巴瘤分类的可行性。方法依据2001版WHO淋巴瘤分类,应用HE、免疫组织化学(LSAB法)和原位杂交技术对369例B—NHL重新诊断分型。结果369例B—NHL确定了11个类型,未观察到毛细胞白血病和B-前淋巴细胞白血病,其中最常见的3个类型依次是：弥漫大B细胞淋巴瘤(189例,51．2％),黏膜相关淋巴组织结外边缘区细胞淋巴瘤(55例,14．9％),滤泡淋巴瘤(39例,10．6％)。发生于淋巴结者占42．8％(158例),结外为57．2％(211例)。单纯HE形态诊断对比形态结合免疫表型的诊断结果,符合率达80％,免疫组织化学可将B—NHI。的诊断正确率提高近20％。结论病理形态是淋巴瘤诊断的基础,免疫表型在诊断和分型中起重要作用,二者与临床特征结合可使绝大多数淋巴瘤得到明确诊断。2001版WHO淋巴瘤分类具有较强的实用性。     

双侧肾上腺原发性NK/T细胞淋巴瘤1例并文献复习

目的探讨肾上腺原发性NK/T细胞淋巴瘤(NK/T cell lymphoma)的临床病理学特征、免疫表型、分子表型、诊断及鉴别诊断、治疗及预后。方法回顾性分析1例NK/T细胞淋巴瘤的临床病理学特征、影像学资料、免疫表型、治疗及预后,并复习相关文献。结果患者女性,68岁,肾上腺双侧巨大实性占位。镜下正常肾上腺固有结构消失,瘤细胞呈弥漫性片状分布,以小圆蓝细胞为主,核分裂象多见。免疫表型:瘤细胞表达TIA-1、Granzyme B、CD56、CD2、CD3,Ki-67增殖指数为90%,EBER原位杂交结果阳性,符合肾上腺原发性NK/T细胞淋巴瘤。结论肾上腺淋巴瘤少见,其中以继发性多见,原发性罕见。病理类型为NK/T细胞淋巴瘤则更为罕见,其治疗以手术联合放、化疗为主,预后差。熟悉NK/T细胞淋巴瘤的临床病理特征及免疫表型,EBV的存在与否,结合临床病史,有助于正确诊断。     

Expression of killer cell inhibitory receptors is restricted to true NK cell lymphomas and a subset of intestinal enteropathy-type T cell lymphomas with a cytotoxic phenotype

BACKGROUND/AIMS: Killer inhibitory receptors (KIR) have a modulating effect on the cytotoxic functions of natural killer (NK) cells and T cells. Because lymphoma cells often have the same receptors as their non-neoplastic counterparts, this study investigated the expression of KIR on well defined groups of NK and T cell lymphomas, with and without a cytotoxic phenotype, from different sites of origin. METHODS: Nine CD56+/CD3- NK cell lymphomas, 29 CD3+/CD56- T cell lymphomas with a cytotoxic phenotype, and 19 T cell lymphomas without a cytotoxic phenotype were stained for KIR using monoclonal antibodies specific for CD94, CD158a, and CD158b. In addition, the expression of KIR was studied on normal lymphoid tissues. RESULTS: KIR expression was seen in five of nine true NK cell lymphomas including three of four nasal, one of four cutaneous, and one of one intestinal lymphoma nasal type. Double staining for CD56 and CD94 in normal lymphoid tissues revealed that KIR was predominantly expressed by CD56+ NK cells and sporadically on CD8+ T cells. Moreover, enteropathy-type T cell lymphomas with a cytotoxic phenotype showed KIR expression (three cases expressing CD94 and one case expressing CD158a). All nodal and extranodal nonintestinal T cell lymphomas with or without a cytotoxic phenotype lacked expression of KIR. CONCLUSIONS: These results show that KIR expression is restricted to CD56+/CD3- true NK cell lymphomas originating from the nose, gut, and skin, as well as in a subset of extranodal T cell lymphomas originating from the small intestine, which possessed a cytotoxic phenotype. Thus, the presence of KIR on NK/T cell lymphomas seems to mimic the distribution of KIR found on NK and T cells in normal lymphoid tissue.     

Immunoreactivity of CD99 in non-Hodgkin's lymphoma: unexpected frequent expression in ALK-positive anaplastic large cell lymphoma

To verify the spectrum of CD99-expressing lymphoid malignancy, an immunohistochemical study for CD99 was carried out in 182 cases of non-Hodgkin's lymphoma, including 21 lymphoblastic lymphomas, 11 small lymphocytic lymphomas, 9 mantle cell lymphomas, 12 follicular lymphomas, 37 diffuse large B cell lymphomas, 18 Burkitt's lymphomas, 28 NK/T-cell lymphomas, 8 angioimmunoblastic T-cell lymphomas, 23 peripheral T-cell lymphomas, unspecified, and 15 systemic anaplastic large cell lymphomas. CD99 was positive in all T-lymphoblastic lymphomas and in 60% of B-lymphoblastic lymphomas. Majority of T and NK cell lymphomas were negative for CD99, except anaplastic large cell lymphomas (ALCLs). Eight of 15 cases (54%) of ALCLs reacted with anti CD99 antibody. Seven of 10 (70%) ALK positive ALCLs expressed CD99, whereas only 1 of 5 (20%) ALK negative ALCLs were positive. Of the mature B-cell lymphomas, 5.4% (2/37) of diffuse large B cell lymphomas and 11.1% (2/18) of Burkitt's lymphomas expressed CD99. In conclusion, CD99 is infrequently expressed in mature B and T cell lymphomas, except ALK-positive ALCL. High expression of CD99 in ALK-positive ALCL is unexpected finding and its biologic and clinical significances have yet to be clarified.     

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.     

Classification of cell lineage and anatomical site, and prognosis of extranodal T-cell lymphoma – natural killer cell, cytotoxic T lymphocyte, and non-NK/CTL types

Due to their minority among the non-Hodgkin lymphomas, classification of extranodal T-cell lymphomas, including those of the natural killer (NK) cell type, has long been controversial and unclear, and the clinical outcome is not well clarified. Recently, new well-defined disease entities have been described based on tumor cell biology combined with anatomical site, clinical features, Epstein-Barr virus (EBV) status, and cell lineage as determined by immunophenotype and genotype. Cytological features are usually not specific, and there are no morphologic correlates with the classification of extranodal T/NK-cell lymphomas. From a human T-cell lymphotropic virus type 1 (HTLV-1) endemic area in Japan, we report here the analysis of 144 cases of extranodal T-cell lymphoma, from which fresh tissues were available. As the clinicopathological features were known, we simply reclassified the cases according to cell lineage and anatomical site. The extranodal T-cell lymphomas were classified into three types on the basis of cell lineage: (1) natural killer cell (NK) type [sCD3-, CD56+, T-cell receptor gene (TCR) germline], (2) cytotoxic T lymphocyte (CTL) type [sCD3+, TIA-1+, TCR rearranged, CD8+/-, CD4-/+], and (3) non-NK/CTL type [sCD3+, TIA-1-, TCR rearranged, CD4+/-, CD8-/+]. In addition to cell lineage, the anatomical site and clinical features were added for subclassification. NK type tumors (35 cases) included the lymphoblastic type, nasal/nasal-type NK lymphoma, and NK leukemia. The CTL type (46 cases) included anaplastic large cell lymphoma (ALCL), cutaneous type, intestinal, gamma delta T-cell type, and an unspecified type. The non-NK/CTL type (63 cases) included adult T-cell leukemia/lymphoma (ATLL), mycosis fungoides (MF), and an unspecified type. With the exception of ATLL and MF, most extranodal T-cell lymphomas had a cytotoxic phenotype of NK type or CTL type and were often associated with EBV infection. MF and the unspecified type within the non-NK/CTL tumors, with the exception of ATLL, had a favorable prognosis. However, NK and CTL types, with the exception of ALCL, were associated with a poor prognosis. Our results indicate that anatomical site and cell lineage are useful predictors of clinical outcomes of extranodal T-cell lymphomas.     

Peripheral T cell and natural killer (NK) T cell lymphomas: a clinicopathological study from a single Australian centre

McKelvie P A, Thompson P A & Tam C S
(2012) Histopathology  61, 212–233 Peripheral T cell and natural killer (NK) T cell lymphomas: a clinicopathological study from a single Australian centre Aims: Using pathological and clinical review, to identify all cases diagnosed as peripheral T cell and natural killer (NK) T cell lymphoma over 10 years from one metropolitan Australian hospital. Methods and results: Subtyping was performed using World Health Organization (WHO) 2008 criteria and a comprehensive immunohistochemical panel. Clinical data including follow‐up were obtained. There were 47 cases, including 11 peripheral T cell lymphomas, not otherwise specified (NOS), nine extranodal NK T cell lymphomas, nasal type (eight nasal), eight primary cutaneous anaplastic large cell lymphomas, seven angioimmunoblastic T cell lymphomas, three anaplastic lymphoma kinase (ALK)‐positive anaplastic large cell lymphomas, four ALK‐negative anaplastic large cell lymphomas, three enteropathic T cell lymphomas and two subcutaneous panniculitis‐like T cell lymphomas. Follow‐up of 46 of 47 cases (median time 45 months) revealed that 50% (23 of 46) of patients died. Five‐year survival rates were: peripheral T cell lymphoma, NOS 39%; angioimmunoblastic T cell, 43%; nasal NK T 67%; ALK‐negative anaplastic large cell lymphoma 67% (at 2 years); ALK⁺ anaplastic large cell lymphoma 33%; subcutaneous panniculitis‐like T cell lymphomas 100%; primary cutaneous anaplastic large cell lymphoma 86%; and enteropathic T cell lymphoma 33% (at 1 year). One patient with Lennert lymphoma suffered four late cutaneous relapses. Conclusions: This first Australian clinicopathological series of peripheral T cell and NK T cell lymphoma shows epidemiological and survival data similar to those for Europe and North America.     

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。