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.     

27例血管免疫母细胞性T细胞淋巴瘤的免疫表型分析

目的：分析27例血管免疫母细胞性T细胞淋巴瘤(angioimmunoblastic T-cell lymphoma,AITL)的免疫表型,重点探讨CXCL-13、PD-1、CD10、bcl-6在其诊断中的作用,其中3例CD30阳性病理的诊断意义及问题。方法：收集黄石市第二医院病理科2009年1月至2015年7月间诊断的27例血管免疫母细胞性T细胞淋巴瘤,对其进行常规形态学和免疫学表型分析,观察对预后的影响。结果：27例血管免疫母细胞性T细胞淋巴瘤中,免疫组织化学表达阳性：CD3(27/27)、CXCL13(27/27)、PD-1(27/27)、CD10(20/27)、bcl-6(23/27)其中有3例CD30散在阳性(3/27),CD20(0/27),CD4和CD8阳性细胞混合组中,20例CD4阳性细胞占优势,5例CD8阳性细胞占优势,1例CD4、CD8全阴性,1例CD4、CD8全阳性。CD21滤泡树突细胞阳性,并显示明显的围绕血管特征,同时也提示在肿瘤中均存在滤泡树突网。结论：AITL是一种来源生发中心辅助性T细胞的高度侵袭性肿瘤。CXCL13PD-1CD10bcl-6在诊断中为有用标记物,四种联合应用更能提示诊断。本组3例AITL中存在CD30阳性细胞除鉴别诊断外,其临床意义有待研究。     

血管免疫母细胞性T细胞淋巴瘤骨髓/外周血瘤细胞免疫表型分析

血管免疫母细胞性T细胞淋巴瘤(AITL)是一类以异形T淋巴细胞增生伴显著血管增生,以及滤泡树突状细胞增生为主要表现,为一类来源于成熟T细胞的淋巴瘤[1].过去AITL瘤细胞形态学诊断缺乏特异性的鉴别特征,而近来AITL瘤细胞CD10[2]和CXCL13表达意义的发现为AITL的诊断提供了有力的支持,为了更深入了解AITL瘤细胞的免疫表型特征及发病机制,我们利用流式细胞术分析AITL患者骨髓及外周血有核细胞表面CD分子标志,期望获得更多信息.     

外周细胞淋巴瘤中TET2和DNMT3A的表达及意义

目的探讨TET2和DNMT3A在外周T细胞淋巴瘤(peripheral T-cell lymphoma,PTCL)中的表达及其与PTCL免疫表型的关系。方法应用CD3、CD4、CD10、BCL-6、CXCL-13、CD30、ALK免疫标记将PTCL分为血管免疫母细胞性T细胞淋巴瘤(angioimmu-noblastic Tcelll ymphoma,AITL)、外周T细胞淋巴瘤,非特指(peripheral T-cell lymphoma,not otherwise specified,PTCL-NOS)、ALK阳性的间变性大细胞淋巴瘤(ALK+ anaplastic large cell lymphoma,ALK~+ ALCL)和ALK阴性的间变性大细胞淋巴瘤(ALK-anaplastic large cell lymphoma,ALK~- ALCL)4种类型。应用免疫组化法检测PTCL组织中TET2和DNMT3A的表达。结果 89例PTCL中,AITL 36例,PTCL-NOS 26例,ALK~- ALCL 18例,ALK~+ ALCL 9例。在AITL组织中,TET2胞质表达和DNMT3A胞质及胞核表达的高表达率均高于PTCL-NOS和ALCL,差异有统计学意义(P均0.05)。TET2胞质表达和DNMT3A胞质及胞核表达在AITL中均呈正相关(P0.05)。结论 TET2和DNMT3A可以作为诊断AITL的分子标志物,为AITL的明确诊断提供新策略。     

血管免疫母细胞性T细胞淋巴瘤侵犯骨髓相关病理特征分析

目的 探讨血管免疫母细胞性T细胞淋巴瘤(angioimmunoblastic T cell lymphoma, AITL)侵犯骨髓的病理特征。方法 回顾性分析32例AITL侵犯骨髓的临床病理特征,采用免疫组化EnVision法和流式细胞术检测AITL相关免疫标记,通过T系基因重排分析T细胞克隆性。结果 肿瘤细胞浸润模式主要以结节状(20/32,62.5%)、间质性或小簇状(10/32,31.3%)为主,结节成分较杂,可呈“肉芽肿样改变”;肿瘤细胞主要为小至中等大小淋巴细胞,异型不明显,少数病例可出现明显浆细胞增生。19例行免疫组化染色,CD4阳性T细胞较少,平均为8.4%;滤泡辅助T细胞(T follicular helper cells, TFH)相关免疫组化标记阳性率分别为：CD10(7/14,50.0%)、BCL6(6/19,31.6%)、PD-1(13/19,68.4%)、CXCL13(13/19,68.4%),大部分病例肿瘤细胞PD-1和CXCL13同时阳性,且阳性细胞数量较少(均<1%)。24例行流式细胞术检测,其中22例均一致性表达胞质CD3(cCD3)、CD5、C...     

bcl-10蛋白异常表达对黏膜相关淋巴组织结外边缘区B细胞淋巴瘤的诊断价值

目的探讨bcl-10蛋白表达对黏膜相关淋巴组织结外边缘区B细胞淋巴瘤（MALT淋巴瘤）的诊断价值。方法收集140例不同部位的MALT淋巴瘤,包括胃38例、眼眶35例、肠16例、皮肤15例、涎腺15例、肺14例、甲状腺3例、其他部位4例。对照：10例扁桃体反应性滤泡增生（RFH）、5例眼眶的淋巴组织增生和143例非MALT淋巴瘤、不同类型的非霍奇金淋巴瘤（NHL）,包括20例NK／T细胞淋巴瘤、20例滤泡性淋巴瘤（FL）、20例间变性大细胞淋巴瘤（ALCL）、20例淋巴结内弥漫大B细胞淋巴瘤（DLBCL）、10例原发胃DLBCL、13例淋巴结边缘区淋巴瘤（NMZL）、12例套细胞淋巴瘤（MCL）、11例脾脏边缘区淋巴瘤（SMZL）、6例血管免疫母细胞性T细胞淋巴瘤（AITL）、6例外周T细胞淋巴瘤（PTCL）、3例B．小淋巴细胞淋巴瘤（B-SLL）、1例淋巴浆细胞性淋巴瘤（LPL）和1例浆细胞瘤。免疫组织化学EnVision法检测bcl-10蛋白;免疫组织化学双标记法检测CD20与bcl-10的共表达。结果在扁桃体RFH中,bel-10蛋白呈中等强度表达于生发中心B细胞质中,套细胞不表达,边缘区细胞和副皮质区T细胞呈弱表达。在眼眶淋巴组织增生中,2例bel-10阴性,3例主要呈淋巴滤泡生发中心B细胞质阳性,与扁桃体RFH的表达类似。在非MALT淋巴瘤的其他类型NHL中,除3例（3／10）原发胃DLBCL呈胞核阳性外,其余均未见胞核表达;在不同NHL中的胞质阳性分别为：结内（12／20）和胃（7／10）DLBCL、FL和ALCL（16／20）、PTCL（5／6）、AILT（6／6）、NMZL（13／13）、SMZL（11／11）、B-SLL（3／3）和浆细胞瘤（1／1）,11例MCL呈胞质可疑阳性,20例NK／T细胞淋巴瘤和1例LPL阴性;在部分淋巴瘤中可见肿瘤性细胞表达而反应性小淋巴细胞不表达：MALT淋巴瘤之bcl-10的总表达率为92．1％（129／140）,其中54．3％（76／140）胞质阳性,37．9％（53／140）胞核阳性;但不同部位之胞核阳性率有所不同。在MALT淋巴瘤中,bcl-10蛋白核强表达最常见于眼眶（25．7％,9／35）;除出现异常bcl-10胞核表达外,约20％有反应性滤泡的病例呈生发中心失表达。双标记显示bcl-10阳性细胞为CD20阳性细胞,但CD20阳性细胞多于bcl-10阳性细胞。结论（1）淋巴细胞增生性病变中bcl-10蛋白普遍表达,细胞质表达可出现在多数NHL和反应性增生中,但在淋巴瘤中呈肿瘤细胞表达而反应性细胞不表达,提示bcl-10异常可能与部分淋巴瘤的形成有关;（2）细胞核内bcl-10异常表达主要见于MALT淋巴瘤;眼眶、肺等部位的胞核强阳性和生发中心阴性的特殊模式,对MALT淋巴瘤的诊断及其与反应性病变的鉴别诊断有一定辅助意义。     

血管免疫母细胞性T细胞淋巴瘤累及胃肠道的临床病理学特征分析

目的探讨血管免疫母细胞性T细胞淋巴瘤(AITL)累及胃肠道的临床病理学特点、诊断及预后。方法收集郑州大学第一附属医院2021年9月诊断的1例肠道活检的AITL, 复习临床特点, 行HE染色、免疫组织化学、EB病毒编码的RNA(EBER)原位杂交、T细胞受体(TCR)基因重排(BIOMED2法)及二代测序检测1 166个基因, 并复习总结文献中报道的AITL累及胃肠道的特征。结果患者女, 53岁, 肠镜示回盲部至直肠多发结节状、息肉样隆起;HE示典型AITL的形态, 肿瘤主要浸润黏膜固有层, 局部侵及黏膜下层, 未见固有腺体侵犯及黏膜表面溃疡;免疫组织化学:肿瘤细胞表达T系标志物(CD3、CD4、CD5)及滤泡辅助T细胞标志物(PD-1及CXCL13), CD21示滤泡树突状细胞网增生紊乱, Ki-67阳性指数约40%;EBER原位杂交见散在细胞阳性;二代测序检测发现3组融合基因:EIF4E3-FOXP1、RP11-434C1.1-ETV6、RP11-380O24.1-SRGAP3。随访2个月, 患者化疗1个疗程后因肠出血死亡。结论胃肠道部位AITL罕见, 常为淋巴结AITL累及所致, ...     

弥漫性生长为主的滤泡性淋巴瘤伴1p36缺失8例临床病理学分析

目的探讨弥漫性生长为主的滤泡性淋巴瘤(DFL)伴1p36缺失的临床病理特点。方法收集2017年1月至2023年1月首都医科大学附属北京友谊医院(5例)和河南省肿瘤医院(3例)诊断为DFL伴1p36缺失病例的临床资料并随访, 总结形态学特点, 进行免疫标记和荧光原位杂交检测, 结合文献和诊断经验进行讨论。结果 8例患者, 男性5例, 女性3例, 中位年龄67岁, 以腹股沟淋巴结肿大为主要特点。本组8例病理形态学基本类似, 表现为正常淋巴结结构破坏, 肿瘤以弥漫生长的中心样细胞增生为主, 伴或不伴局灶滤泡性结构为特征。瘤细胞表达CD10和/或bcl-6等生发中心标志物, 荧光原位杂交检测示1p36缺失但无bcl-2易位。结论 DFL伴1p36缺失是一组少见的滤泡性淋巴瘤亚型, 病理学特点与其他类型的滤泡性淋巴瘤和低级别B细胞淋巴瘤存在一定程度的重叠;准确诊断需要结合临床特点、病理形态、免疫组织化学和相关分子检测进行综合判断。     

儿童散发性伯基特淋巴瘤的分子遗传学特征分析

目的 研究儿童散发性伯基特淋巴瘤(BL)的分子遗传学特征及其诊断和鉴别诊断.方法 对64例儿童BL和6例儿童弥漫性大B细胞淋巴瘤(DLBCL)进行免疫组织化学染色(SP法)和荧光原位杂交(FISH)技术检测c-myc、bcl-2、bcl-6、IgH、myc/lgH及bcl-2/IgH基因重排的情况.根据细胞起源分类分为生发中心组(GC组)、生发中心晚期组(late-GC组)、生发中心后组(post-GC组).结果 BL表达CD20(64例)、CD10(63例)、bcl-6(62例)、MUM1(15例)、bcl-2(0例).GC组49例(76.6%)、late-GC组14例(21.9%)、post-GC组1例(1.6%).c-myc基因断裂54例(93.1%);IgH基因断裂48例(82.8%);c-myc与IgH基因同时断裂并myc/IgH基因易位46例(85.2%);c-myc基因断裂、IgH和myc/IgH基因正常4例(7.4%);c-myc、IgH和myc/IgH基因均正常4例(7.4%);bcl-2基因正常61例(100%);bcl-6基因正常59例,1例断裂并扩增具有BL的病理形态和免疫表型特征,同时具有c-myc基因断裂,将病理诊断修改为介于DLBCL和BL之间的未分类的B细胞淋巴瘤(DLBCL/BL).6例DLBCL中c-myc基因断裂2例;2例bcl-6基因扩增,其中1例伴c-myc基因断裂;无bcl-2/IgH基因重排.结论 儿童散发性BL大多数来源于生发中心B细胞,c-myc基因的断裂是其主要分子遗传学改变.应用FISH进行多基因的检测,有助于提高儿童BL的诊断和鉴别诊断水平.     

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.     

Clinicopathologic analysis of peripheral T-cell lymphoma, follicular variant, and comparison with angioimmunoblastic T-cell lymphoma: Bcl-6 expression might affect progression between these disorders

We examined clinicopathologic findings in 17 cases of peripheral T-cell lymphoma, follicular variant (f-PTCL), and compared these findings with angioimmunoblastic T-cell lymphoma (AITL) to determine whether they were identical to the spectrum of changes seen in AITL and how each of the findings in f-PTCL were related to the characteristics of AITL. Almost all f-PTCL cases showed pathologic characteristics of AITL and immunohistochemical positivities in lymphoma cells for CD4, CD10, Bcl-6, PD-1, and CXCL13. Except for pathologic characteristics, clinicopathologic findings in f-PTCL had few significant differences from AITL. The positive rate for Bcl-6 expression in neoplastic cells was significantly associated with the frequency of polymorphic infiltrates, vascular proliferation, B-immunoblasts, clear cells, Epstein-Barr virus-positive lymphocytes, hepatosplenomegaly, and skin rash. Our study confirmed the continuity between f-PTCL and AITL. Moreover, Bcl-6 expression in f-PTCL was statistically associated with the characteristics of AITL.     

Peripheral T-cell lymphoma with extensive dendritic cell network mimicking follicular dendritic cell tumor: a case report with pathologic, immunophenotypic, and molecular findings

Peripheral T-cell lymphoma (PTCL) with a nodular pattern of growth is uncommon and may be misdiagnosed initially as a B-cell lymphoma or reactive process. We report a case of a rapidly growing PTCL with a distinctly nodular pattern in an axillary lymph node from an 89-year-old man. Immunohistochemical stains for CD21, CD23, and CD35 highlighted an extensive dendritic cell network that imparted the nodular appearance and, in addition, was associated intimately with the neoplastic cells. The neoplastic cells otherwise had an immunophenotype similar to previously reported cases of PTCL with a nodular pattern and germinal center origin (CD3+, CD4+, CD5+, bcl-6+, CD31+, subset CD10+, subset CXCL13+, and subset CD79a+). Molecular studies confirm a clonal T-cell receptor g gene rearrangement. This case emphasizes unusual morphologic features in a PTCL that may be mistaken for follicular lymphoma or a tumor of follicular dendritic cell origin.     

Distinguishing angioimmunoblastic T-cell lymphoma from peripheral T-cell lymphoma, unspecified, using morphology, immunophenotype and molecular genetics

AIMS: To identify distinguishing histological, immunophenotypic and molecular genetic features between angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma (PTL). METHODS: Nodal T-cell lymphomas examined (n =137), included AITL (n = 89), PTL (n = 22), anaplastic large cell lymphoma (n = 16) and 'AITL/PTL indeterminate' (n = 10) with overlapping features between AITL and PTL, showing morphology typical of AITL but lacking follicular dendritic cell expansion. Immunohistochemistry for CD3, CD20, CD21 and CD10, in situ hybridization for Epstein-Barr virus encoded RNA (EBER) and polymerase chain reaction for T-cell and B-cell clonality analysis were performed. RESULTS: Of the AITLs, 74/89 showed typical morphology, whereas 15/89 showed hyperplastic follicles. AITL and 'AITL/PTL indeterminate' showed a polymorphous infiltrate and prominent vascularity in all cases. In both groups, CD10 was present in the majority and clear cells and EBER positivity were specific (but not universal) features lacking in PTL. Detection of T-cell clonality was significantly higher in AITL (90%) compared with PTLu (59%). CONCLUSION: Clear cells and EBV infection (when present) are useful distinguishing features and CD10 a sensitive and specific marker of AITL. Hyperplastic follicles are present in a significant minority of AITL. AITL/PTL indeterminate probably falls within the spectrum of AITL rather than PTL.     

The usefulness of flow cytometric CD10 detection in the differential diagnosis of peripheral T-cell lymphomas

We studied the histologic and multiparameter flow cytometry (MFC) features of 12 cases of angioimmunoblastic T-cell lymphoma (AITL), 13 of mature T-cell lymphoma, and 25 control cases of reactive lymphoid hyperplasia to evaluate the role of CD10 in the differential diagnosis of peripheral T-cell lymphomas (PTCLs). A characteristic immunophenotypic profile (CD2+/CD4+) with recurrent phenotypic aberrancies (eg, CD3 and CD7 loss) was identified in most AITL cases; MFC documented CD10 coexpression on T cells in 10 (83%). Mature T-cell lymphoma showed a more heterogeneous altered immunophenotypic pattern, and 2 cases of PTCL, unspecified, had clear evidence of aberrant CD10 expression on T cells. A small physiologic CD3+/CD4+/CD10+ T-cell population was detected by MFC in all control cases tested (range, 0.28%-4.71%), suggesting that a normal subset of peripheral CD10+ T cells exists. CD10 was a highly sensitive but incompletely specific phenotypic marker for diagnosing AITL; the differential diagnosis of PTCL, unspecified, must be related with traditional histologic features. A small number of CD10+ T cells in reactive lymph nodes suggests that this subpopulation may be the normal counterpart of neoplastic T cells in AITL. The biologic role of CD10+ T cells should be studied further.     

Angioimmunoblastic T-cell lymphoma in Taiwan shows a frequent gain of ITK gene

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral T-cell lymphoma (PTCL) of follicular helper T-cell origin and is rare in Taiwan. There are overlapping features of AITL and peripheral T-cell lymphoma with a follicular growth pattern (PTCL-F). Around one fifth of PTCL-F exhibits t(5;9)(q33;q22)/ITK-SYK chromosomal translocation, which is essentially absent in AITL. We retrospectively investigated 35 cases of AITL from Taiwan with histopathology review, immunohistochemistry, in situ hybridization for Epstein-Barr virus (EBV) and fluorescence in situ hybridization (FISH) for t(5;9)(q33;q22)/ITK-SYK and correlated the results with overall survival. Twenty-six cases of not otherwise specified PTCL (PTCL-NOS) were also examined by FISH for comparison. Most AITL patients were male (69%) and elderly (median age at 67 years) with frequent bone marrow involvement (53%), high Ann Arbor stages (77%), and elevated serum lactate dehydrogenase (68%). Most cases (80%) showed a typical CD4+/CD8- phenotype and in 90% cases there were scattered EBV-positive B-cells (less than 10% cells). None of these cases showed t(5;9)(q33;q22)/ITK-SYK translocation by FISH. Gain of ITK and SYK gene was identified in 38% and 14% tumors, respectively, but both were not associated with overall survival. Performance status < 2 was associated with a better outcome but not the other clinicopathological factors. All PTCL-NOS cases were negative for ITK-SYK translocation with similar rates (38% and 12%, respectively) of gains at ITK and SYK loci as that of AITL. In this so far the largest series of AITL from Taiwan, we reported the clinicopathological features and FISH findings on ITK and SYK genes. We confirmed the absence of t(5;9)(q33;q22)/ITK-SYK translocation, which may serve as an additional differential diagnostic tool from PTCL-F when present. PTCL-NOS shared a similar pattern of ITK and SYK gains with AITL. More studies are warranted to elucidate the roles of SYK and ITK and other genes in the lymphomagenesis of AITL in Taiwan.     

T细胞淋巴瘤1和CD44蛋白在Burkitt淋巴瘤中的表达及其诊断价值

目的 探讨T细胞淋巴瘤1(TCL1)和CD44蛋白在Burkitt淋巴瘤中的表达及其诊断价值.方法 在石蜡包埋的实验组25例Burkitt淋巴瘤和对照组25例非特指弥漫性大B细胞淋巴瘤(DLBCL)中采用免疫组织化学EnVision法检测CD44、TCLl以及CD10、bel-2、bcl-6、c-myc、Ki-67等常用抗体表达情况.结果 Burkitt淋巴瘤中瘤细胞96%(24例)呈TCL1阳性,仅4%(1例)CD44阳性;88%(22例)CD10阳性、92%(23例)bcl-6和c-myc阳性,仅4%(1例)bcl-2阳性;Ki-67增殖指数为95%～100%.非特指DLBCL中仅16%(4例)TCL1弱阳性,84%(21例)CD44阳性、32%(8例)CD10阳性、72%(18例)bcl-6和bcl-2阳性、c-myc均阴性,Ki-67增殖指数40%～90%.结论 当形态和免疫表型不典型时,TCL1和CD44两种蛋白的检测有助于提高Burkitt淋巴瘤的确诊率及其与DLBCL的鉴别诊断.