胃T细胞淋巴瘤临床病理观察

目的 探讨胃T细胞淋巴瘤的临床病理学特点.方法 收集7例胃T细胞淋巴瘤病例标本,对其进行了临床病理分析、免疫组织化学检测、EBER原位杂交检测及T细胞受体(TCR)基因重排检测.结果 7例病例中6例为男性,1例为女性,平均发病年龄为45岁.6例可获得资料的病例中,1例有长期腹泻史,5例有低蛋白血症.组织学上,7例标本中,有5例表现为肿瘤细胞体积较大而不一致,2例表现为大小一致的中等细胞.1例病例可见肿瘤细胞浸润腺上皮.所有病例的肿瘤组织均不表达CD20及CD79a.7例病例中,各有6例表达CD3及T细胞胞质内抗原,各有4例表达CD5、βF-1及CD30,有3例表达CDM,各有1例病例表达CD8、CD56、问变性淋巴瘤激酶及粒酶B.7例病例肿瘤细胞EBER原位杂交检测均为阴性且都存在TCR基因克隆性重排.结论 胃T细胞淋巴瘤是一种少见的恶性淋巴瘤,具有独特的临床病理特点.     

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.     

皮下脂膜炎样T细胞淋巴瘤的免疫表型、基因重排检测及其在诊断中的意义

目的 探讨免疫表型和基因重排检测在皮下脂膜炎样T细胞淋巴瘤(SPTL)的诊断和鉴别诊断中的意义.方法 参照2005年世界卫生组织-欧洲癌症研究与治疗组织(WHO-EORTC)皮肤淋巴瘤分类标准收集20例SPTL.采用10种抗原标记进行免疫表型检测,运用PCR技术检测TCRγ、IgH基因重排,并用EB病毒编码的小RNA1/2(EBER1/2)原位杂交检测EB病毒感染.结果 (1)本组病例中男9例、女11例,平均年龄29.5岁;(2)所有病例的瘤细胞均表达1个或多个T细胞分化抗原(CD2、CD3或CD45RO),18/19病例表达BF1,18/20病例表达CD8,20/20、16/20病例分别表达细胞毒颗粒相关蛋白TIA-1、颗粒酶B,瘤细胞不表达CD4、CD20和CD56;(3)16/20病例检出TcRγ基因重排,未检出IgH基因重排;(4)5/20病例EBERl/2原位杂交阳性.结论 SPTL的瘤细胞具有克隆性TCR基因重排,综合临床病理、免疫表型及基因重排检测有助于本病确诊.     

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。     

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。     

韦氏环伴滤泡辅助T细胞表型并异常表达CD20的外周T细胞淋巴瘤1例并文献复习

目的 探讨韦氏环伴滤泡辅助T细胞表型的外周T细胞淋巴瘤(Waldeyer’s ring peripheral T-cell lymphoma with T-follicular helper phenotype, wPTCL-TFH)临床病理学、遗传学特征及预后。方法 收集1例wPTCL-TFH临床资料,对其病变组织行HE、免疫组化染色、EBER原位杂交及TCR基因重排检测,应用一代测序法检测IDH2 Exon4基因突变情况,并复习相关文献。结果 患者女性,61岁,临床表现为咽痛、消瘦,无其他发热、盗汗等B症状。组织学表现为扁桃体实质内小-中等大淋巴细胞弥漫浸润。免疫表型：肿瘤细胞表达全T细胞标志物及滤泡辅助T细胞标志物：CD10、BCL6和PD-1,弥漫表达CD20,部分表达CD30(约10%);TCR基因单克隆性重排,IDH2基因未见突变。采用R-CHOP方案化疗6个周期,随访7个月,患者无瘤生存。结论 wPTCL-TFH异常表达CD20者临床罕见,化疗中加入利妥昔单抗可能对CD20异常表达wPTCL-TFH有效,仍需更多的病例进一步证实。     

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.     

皮下脂膜炎性T细胞性淋巴瘤的临床特征及分子生物学特点

目的：对皮下脂膜炎性T细胞淋巴瘤(SPTCL)的临床特征、病理、免疫表型及分子生物学特点进行研究。方法：临床观察及实验室、病理检查研究SPTCL的临床、病理特点，免疫表型通过LCA、CD3、UCIL、L26单抗进行石蜡免疫过氧化物酶染色、用αβTCR、γδTCR抗体进行冷冻切片免疫过氧化物酶的染色，用识别Vδ^1、Vδ^2的抗体进行γδTCR亚型分析，PCR检测SPTCL患者TCR基因重排。结果：7例SPTCL患者均有皮下结节、高热、体重下降，5例出现嗜血细胞综合征，7例SPTCL患者均有电介质、酸碱平衡失调及酶学检查的异常。7例SPTCL患者的病理均在脂肪组织内见大量异型淋巴细胞浸润，均表达LCA、CD3、UCHL，不表达L26。4例SPTCL患者中有3例表达γTCR，1例表达αβTCR，3例γδTCR患者均表达Vδ^2 ，4例有3例出现TCRγ基因重排。结论：SPTCL大多病情严重，肿瘤细胞来源于T细胞系的皮肤淋巴细胞组织相关的Vδ^2 细胞，可以出现TCRγ基因重排。     

原发性皮肤γδT细胞淋巴瘤2例临床病理分析

目的探讨原发性皮肤γδT细胞淋巴瘤(primary cutaneous gamma-delta T-cell lymphoma,PCGDTCL)的临床病理特征,以提高对该病的认识及诊断水平。方法分析2例PCGDTCL的临床表现、病理学形态特征、免疫表型及基因检测结果,并结合文献复习。结果 2例患者均以皮肤病变起病,肿瘤细胞表达T细胞标记和细胞毒性标记,不表达髓系、B细胞特异性标记;EBV原位杂交EBER阴性;基因克隆性重排结果为TCRγ阳性。结论 PCGDTCL是一种少见的皮肤恶性肿瘤,临床表现缺乏特异性,明确诊断依赖于病理活检及TCR基因重排结果。     

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.     

CXCL13、CD10和bcl-6在血管免疫母细胞性T细胞淋巴瘤的诊断及鉴别诊断中的作用

目的 探讨CXCL13、CD10、bcl-6等标志物在血管免疫母细胞性T细胞淋巴瘤(AITL)的诊断和鉴别诊断中的作用.方法 对四川大学华西医院病理科1990年1月至2008年1月诊断的115例AITL、30例非特指外周T细胞淋巴瘤(PTCL,NOS)和30例以副皮质区增生为主的反应性增生(RH)进行回顾性分析.按2008版WHO关于淋巴造血组织肿瘤分类进行组织学分型,采用9种抗原标志物的免疫组织化学(SP法)染色及TCR-γ基因重排检测.结果 (1)7.8%(9/115)的AITL、6.7%(2/30)的PTCL,NOS和83.3%(25/30)的RH病例观察到生发中心;98.3%(113/115)的AITL、63.3%(19/30)的FTCL,NOS和76.7%(23/30)的RH病例观察到显著血管增生.(2)CXCL13、CD10、bcl-6在RH病例的表达局限在生发中心,在AITL的表达率分别为96.5%(111/115)、50.4%(58/115)和78.3%(90/115),在PTCL,NOS的表达率分别为26.7%(8/30)、3.3%(1/30)和3.3%(1/30),以上三个标记在两种淋巴瘤的表达率差异均具有统计学意义.115例AITL病例均见到滤泡外不规则分布的CD21阳性的滤泡树突状细胞网(FDC).TCR-γ基因克隆性重排在AITL中检出率为83%(83/100).结论 AITL是一种来源于生发中心辅助性T细胞(TFH)的高度侵袭性肿瘤,CXCL13、CD10、bcl-6是AITL诊断和鉴别诊断有用标志物.     

Peripheral T-cell lymphoma with a nodular growth pattern

Peripheral T-cell lymphomas (PTCL) with nodular growth patterns are very rare, with only 17 cases reported previously. Here, we report a case of PTCL with a nodular growth pattern. The patient was an 81-year-old Japanese woman who complained of malaise, fever and generalized lymph node swelling. Cervical lymph node biopsy was performed, and histological examination revealed proliferation of medium- to large-sized atypical lymphoid cells with indented to irregular nuclei, distinct nucleoli and clear cytoplasm. The nodular growth pattern of the lymphoma cells was obvious. On immunohistochemistry, the atypical lymphoid cells proved to be of T-helper cell origin (CD2+CD3CD4+CD5+CD7+ CD8-CD10-CD25-CD30-CD57-). Polymerase chain reaction analysis of the T-cell receptor gamma-chain revealed a monoclonal rearrangement band. This unusual growth pattern should be distinguished among PTCL, as such cases could be confused with reactive nodular hyperplasia, nodular lymphoma, mantle cell lymphoma and marginal zone lymphoma with nodular colonization.     

Follicular variant of peripheral T-cell lymphoma mimicking follicular lymphoma: a case report with a review of the Literature

Peripheral T-cell lymphoma (PTCL) with a follicular growth pattern is very rare. Herein, a case of follicular variant of PTCL in a 50-year-old man who complained of tonsillar and generalized lymph node swelling is reported. The resected tonsil revealed a vague nodular growth pattern of atypical cells, medium to large in size, with abundant pale cytoplasm. The lymphoma cells were CD3(+) CD4(+) CD5(+) CD8(-) CD10(+) CD56(-) CD57(-) BCL6(+) PD-1(+) CXCL13(+) and were associated with a meshwork of CD21(+) follicular dendritic cells. Molecular studies revealed clonal rearrangement of the T-cell receptor gamma chain gene but not of the immunoglobulin gene. Cytogenetic analysis disclosed a complex abnormality in 18 of 20 cells with the exclusion of t(5; 9). These findings suggest that the present case is a follicular variant of PTCL derived from follicular T-helper cells.     

Genomic profiling of peripheral T-cell lymphoma, unspecified, and anaplastic large T-cell lymphoma delineates novel recurrent chromosomal alterations

To characterize genetic alterations in peripheral T-cell lymphoma, not otherwise specified (PTCL NOS), and anaplastic large T-cell lymphoma (ALCL), 42 PTCL NOS and 37 ALCL [17 anaplastic large cell kinase (ALK)-negative ALCL, 9 ALK-positive ALCL, 11 cutaneous ALCL] were analyzed by comparative genomic hybridization. Among 36 de novo PTCL NOS, recurrent chromosomal losses were found on chromosomes 13q (minimally overlapping region 13q21, 36% of cases), 6q and 9p (6q21 and 9p21-pter, in 31% of cases each), 10q and 12q (10q23-24 and 12q21-q22, in 28% of cases each), and 5q (5q21, 25% of cases). Recurrent gains were found on chromosome 7q22-qter (31% of cases). In 11 PTCL NOS, high-level amplifications were observed, among them 3 cases with amplification of 12p13 that was restricted to cytotoxic PTCL NOS. Whereas cutaneous ALCL and ALK-positive ALCL showed few recurrent chromosomal imbalances, ALK-negative ALCL displayed recurrent chromosomal gains of 1q (1q41-qter, 46%), and losses of 6q (6q21, 31%) and 13q (13q21-q22, 23%). Losses of chromosomes 5q, 10q, and 12q characterized a group of noncytotoxic nodal CD5+ peripheral T-cell lymphomas. The genetics of PTCL NOS and ALK-negative ALCL differ from other T-NHLs characterized genetically so far, among them enteropathy-type T-cell lymphoma, T-cell prolymphocytic leukemia, and adult T-cell lymphoma/leukemia.     

The application of antigen receptor gene rearrangement of BIOMED-2 in the pathologic diagnosis of 348 cases with non-Hodgkin lymphoma in a single institution in Southwest of China

ObjectiveTo explore the clinical value of immunoglobulin (Ig) and T cell receptor (TCR) gene rearrangement in the diagnosis of non-Hodgkin lymphoma.MethodsUsing the standardized BIOMED-2 multiplex PCR strategy to detect IgH, IgK and TCR in 272 cases of mature B-cell lymphoma, 55 cases of mature T-cell lymphoma, 21 cases of extranodal NK/ T-cell lymphoma, nasal type, and 20 cases of lymphoid tissue reactive hyperplasia.ResultsAmong all mature B-cell lymphomas, the sensitivity of Ig gene rearrangement was 91.18% (248/272), IgH and IgK gene rearrangement was 76.47% (208/272) and 75.00% (204/272), respectively, meanwhile the sensitivity of TCRγ rearrangement was 3.68% (10/272). In the 55 cases of mature T-cell lymphoma, the sensitivity of the detection of TCRγ was 76.36% (44/55), at the same time the sensitivity of Ig gene rearrangement was 14.55% (8/55), IgH and IgK gene rearrangement was 7.27% (4/55) and 12.73% (7/55), respectively. In 21 cases of extranodal NK/T cell lymphoma, nasal type, and 20 cases of reactive lymphoid hyperplasia, no gene rearrangement was found in the samples of IgH, IgK and TCR. The sensitivity of gene rearrangement in Ig/TCR in B and T-cell lymphoma was significantly different from that in the control group (P < 0.05).ConclusionThe Ig/TCR gene rearrangement of BIOMED-2 multiplex PCR strategy has important auxiliary value in the diagnosis of B/T-cell non-Hodgkin lymphoma respectively, however, a few B-cell lymphomas may company TCR gene rearrangement as well as a few T-cell lymphomas may accompany Ig gene rearrangement, it must be comprehensively judged with the combination of morphology, immunohistochemistry and clinical features.     

T-cell receptor variable (V) gene usage by lymphoid populations in T-cell lymphoma.

A panel of monoclonal antibodies specific for TcR V gene families was used to study TcR V region expression in 28 cases of malignant and reactive T-cell expansions including four cases of mixed cellularity Hodgkin's disease (HD) and five reactive cases. TcR V beta 5 gene products were represented in three cases of lymphoblastic malignancy (V beta 5.1, V beta 5.2) and two cases of peripheral T-cell lymphoma (PTCL) (V beta 5.1). In the PTCL cases, the expanded family was found in the absence of clonal TcR gene rearrangements and in one of these cases with Ig JH and Ck clonal gene rearrangements consistent with the presence of a phenotypically and histologically undetectable clonal B-cell population. In a third PTCL case not investigated for genotype, the TCR V alpha 12 family was overrepresented. Expanded TcR V alpha 2 and V beta 5.1 families were identified in HD and V beta 8 and V beta 5.2/V beta 5.3 families in a reactive lymph node and CD3 and CD8-positive blood lymphocytosis respectively. Further study of PTCL and related entities are needed to establish whether expanded TcR families are common in those cases that fail to exhibit clonal TcR gene rearrangement.