老年人EB病毒阳性弥漫大B细胞淋巴瘤临床病理学特点及预后分析

目的 探讨老年人EB病毒阳性（EBV＋）弥漫大B细胞淋巴瘤（DLBCL）的临床病理学特点及预后.方法 采用回顾性研究的方法 ,收集24例老年EBV＋DLBCL患者,以同期EBV-非特指型DLBCL患者为对照,分析老年EBV＋ DLBCL患者的临床病理学特点及预后.结果 24例老年EBV＋DLBCL患者肿瘤细胞形态上主要表现为单一性或多形性肿瘤细胞增生;多形性病例中常可见有地图状坏死.细胞起源免疫分型主要为非生发中心亚型,分别占91.3％（Hans分型）和100.0％（Choi分型）.CD30阳性率为55.0％,高于非特指型EBV-DLBCL（P＜ 0.001）.在总体生存时间方面,R-CHOP方案治疗的老年EBV＋DLBCL患者和＞50岁EBV-DLBCL患者的中位生存时间分别为44.2个月和29.2个月,两者差异无统计学意义（P=0.587）.结论 老年人EBV＋DLBCL肿瘤细胞形态上主要表现为单一性或多形性肿瘤性增生;多形性病例中常可见不规则坏死.CD30阳性率较高,并且主要为非生发中心B细胞亚型.R-CHOP方案治疗的老年EBV＋ DLBCL患者的总体生存时间与同年龄段非特指型EBV-DLBCL患者相近.     

老年人EB病毒阳性弥漫大B细胞淋巴瘤的研究进展

Epstein-Barr病毒(EBV)是与多种人类肿瘤的发生密切相关的DNA病毒.在2008版WHO关于淋巴造血组织肿瘤分类中,老年人EBV阳性弥漫大B细胞淋巴瘤(DLBCL)被作为非特指DLBCL的一个新的变异型,该变异型具有与其他DLBCL亚型不同的形态学和生物学特征.现对老年人EBV阳性DLBCL的病因及发病机制、临床病理特点、免疫表型、遗传学改变、诊断和鉴别诊断以及预后进行综述.     

阑尾原发性弥漫大B细胞淋巴瘤一例并文献复习

  目的　探讨阑尾弥漫大B细胞淋巴瘤（DLBCL）的临床病理特点。方法　回顾性分析收治的阑尾原发DLBCL 1例,对阑尾切除标本进行光学显微镜观察,免疫组织化学染色,并复习文献。结果　光学显微镜下见阑尾结构破坏,肿瘤组织弥漫分布,细胞呈大中心细胞样,形态介于中心母细胞和中心细胞之间。免疫组织化学染色肿瘤细胞CD20、bcl-6、CD10、CD79α及Mum1阳性,Ki-67约90 %,CK、bcl-2、CD21及ALK均阴性。结论　阑尾DLBCL少见,结合组织学形态和免疫组织化学染色有助于明确诊断及判断预后。     

EB病毒阳性老年人弥漫大B细胞淋巴瘤二例并文献复习

 目的　分析我国老年人EB病毒（EBV）阳性弥漫大B细胞淋巴瘤（DLBCL）的临床特点,提高对该病的认识。方法　报道2例老年人EBV阳性DLBCL患者临床、实验室资料及治疗经过。结果　老年人EBV阳性DLBCL高发年龄70～79岁,患者主要表现为全身淋巴结肿大,可伴结外器官受累,可出现巨脾和免疫性溶血性贫血,多伴有发热、体质量减轻等B症状,病理表现为多形性大细胞浸润,伴不同程度的反应性细胞,特别是T细胞增殖。结论　老年EBV阳性DLBCL患者肿瘤细胞CD20或CD79a阳性,EBV 编码的小RNA（EBER）阳性。疾病进展快,对标准化疗反应差。利妥昔单抗对CD20阳性病例短期有效,但疗效有限。患者的生存期短。死亡原因主要是感染所致的呼吸衰竭。     

EB病毒相关的人类免疫缺陷病毒阴性浆母细胞淋巴瘤的临床病理分析

目的 探讨人类免疫缺陷病毒（HIV）阴性且无免疫缺陷的浆母细胞淋巴瘤（PBL）的临床病理特征,提高对这组疾患的认识.方法 回顾性分析6例无免疫缺陷且HIV-PBL的组织学特点,原位杂交染色检测EB病毒（EBV）感染状态.分别采用免疫组织化学SP法及荧光原位杂交（FISH）技术检测PBL的免疫表型、EBV潜伏类型,探索myc基因的易位.结果 HIV-PBL表现为浆母细胞样或免疫母细胞样细胞的单一增生,可见瘤巨细胞及坏死;背景反应细胞少,核分裂象较多.所有病例都有EBV感染,潜伏类型为Ⅰ型（LMP1^-及EBNA2^-）.肿瘤细胞表达B细胞终末分化阶段的表型CD20^-/CD3^-/CD1386＋/Kappa＋或Lambda^＋.6例HIV-PBL均为老年患者（中位年龄69.5岁）,男女各3例;结外及口腔外侵犯率高,分别为6、5例.中位生存期为25.5个月.此外,3例患者具有免疫球蛋白重链（IgH）与myc基因易位.结论 HIV-PBL是一组独立疾患,具有无HIV感染、老年人、EBV阳性、结外及口腔外侵犯率高等特点,应与HIV＋的PBL相区别.     

血管免疫母细胞性T细胞淋巴瘤并发EB病毒阳性弥漫大B细胞淋巴瘤二例并文献复习

目的:探讨血管免疫母细胞性T细胞淋巴瘤（AITL）并发EB病毒（EBV）阳性弥漫大B细胞淋巴瘤（DLBCL）患者的临床病理特征、治疗及预后。方法:回顾性分析解放军总医院第五医学中心2例AITL并发EBV阳性DLBCL患者的临床资料,并进行文献复习。结果:例1为混合淋巴瘤（CL）患者,以低热伴全身浅表淋巴结肿大起病,右侧腋窝肿物活组织检查示AITL并发EBV阳性DLBCL,予以8个周期化疗后达不确定的完全缓解;后续应用西达本胺维持治疗,仍生存中。例2为不一致性淋巴瘤（DL）患者,以皮下结节起病,后出现浅表淋巴结进行性肿大;皮下结节病理检查诊断为DLBCL,右腹股沟淋巴结病理检查诊断为AITL;接受7个周期化疗,因合并噬血细胞综合征而死亡。结论:AITL合并EBV阳性DLBCL罕见,临床症状主要以AITL的表现为主,存在T细胞及B细胞免疫表型特征,预后差,治疗方案主要依据预后较差的淋巴瘤进行选择。     

CD30在EBV阳性弥漫性大B细胞淋巴瘤中的表达及其预后意义北大核心

目的:探讨CD30在EBV阳性弥漫性大B细胞淋巴瘤(EBV-positive diffuse large B-cell lymphoma,EBV+DLBCL)中的表达及预后意义。方法:回顾性分析322例DLBCL中EBV+DLBCL与EBV-DLBCL病例临床病理参数之间的关系,以及CD30在EBV+DLBCL中的表达及预后意义。结果:CD30在EBV+DLBCL病例中的表达多于EBV-DLBCL病例(P=0.002);EBV-DLBCL中双表达的病例多于EBV+DLBCL(P=0.044);在63例EBV+DLBCL中,CD30阳性表达多见于B症状患者(P=0.015);另外有2例EBV+DLBCL病例出现BCL6基因重排。随访139例患者中,共表达CD30和EBER的患者预后较差(P=0.002);在EBV+DLBCL中,CD30阳性提示预后更差(P=0.028)。结论:CD30在EBV+DLBCL病例中具有较高的表达率,且与患者不良预后相关,进一步为靶向药物的使用提供理论依据。     

新疆维吾尔自治区乌鲁木齐地区466例非霍奇金淋巴瘤临床病理特征分析

 目的　探讨新疆维吾尔自治区乌鲁木齐地区不同民族非霍奇金淋巴瘤（NHL）的临床病理特点。方法　收集466例NHL标本,复查HE和免疫组织化学染色结果,重新诊断、分型。结果　466例中B细胞性NHL 369例（79.2 %）,T细胞性NHL 97例（20.8 %）;结内193例（41.4 %）,结外273例（58.6 %）;最常见组织学类型为弥漫大B细胞淋巴瘤、小淋巴细胞淋巴瘤／慢性淋巴细胞白血病、黏膜相关淋巴组织结外边缘区B细胞淋巴瘤、NK／T细胞淋巴瘤、外周T细胞淋巴瘤、滤泡性淋巴瘤。维吾尔族T淋巴母细胞淋巴瘤（T-LBL）和间变性大细胞淋巴瘤（ALCL）比例分别为7.5 %（9／120）和4.2 %（5／120）,高于汉族的1.3 %（4／308）和2.3 %（7／308）（χ2＝11.276,P＝0.001;χ2＝1.137,P＝0.286）。而汉族结外NK／T细胞淋巴瘤比例为7.1 %（22／308）,高于维吾尔族的3.3 %（4／120）,差异无统计学意义（χ2＝2.196,P＝0.138）。其余各亚型在不同民族间差异皆无统计学意义（均P＞0.05）。结论　乌鲁木齐地区NHL结外发病高于结内,B细胞性淋巴瘤的发病明显高于我国内地。维吾尔族和汉族B-NHL发病构成在整体上差别不大,但是在T细胞NHL中,维吾尔族T-LBL和ALCL高于汉族,而汉族结外NK／T细胞淋巴瘤高于维吾尔族,这些差异是否与新疆维吾尔自治区的民族与地域差异有关,还需要进一步的研究证实。     

外周T细胞淋巴瘤继发弥漫大B细胞淋巴瘤一例并文献复习

目的 探讨外周T细胞淋巴瘤(PTCL)继发弥漫大B细胞淋巴瘤(DLBCL)的诊治方法.方法 报道1例PTCL继发DLBCL病例的诊治经过,分析该例患者的临床特点、治疗反应,复习文献探讨该类疾病的机制及预后.结果 患者诊断PTCL非特指型(PTCL-NOS)明确,治疗后出现以EB病毒(EBV)阴性DLBCL为表现的第二肿瘤,其临床特点及发病间隔与之前国外报道类似,可能涉及肿瘤细胞、微环境及治疗等多方面因素.该例患者初步治疗有效,有待进一步随访观察.结论 PTCL-NOS继发EBV阴性DLBCL非常罕见,发病机制和治疗效果有待进一步探索.     

免疫分型标记物和CD43在非特指弥漫性大B细胞淋巴瘤中的表达及临床意义

目的 探讨免疫分型标记物和CD43在非特指弥漫性大B细胞淋巴瘤(DLBCL NOS)中的表达及其临床意义.方法 收集120例DLBCL NOS临床病理资料进行分析.采用免疫组化法检测CD10、bcl-6、MUM-1和CD43的表达,根据Hans分型将其分为GCB型和non-GCB型.结果 120例DLBCL,NOS中GCB型和non-GCB型分别为38例和82例,Hans分型与DLBCL NOS预后无关(P＞0.05).120例DLBCL NOS中CD43阳性33例(27.5％),CD43表达与性别、临床分期和免疫分型均无关(P＞0.05),与年龄(P=0.036)和生存状态(P=0.004)有关.结论 DLBCL NOS预后差与CD43阳性表达有关,与Hans分型无关.     

非特指EBV阳性弥漫大B细胞淋巴瘤的研究进展

EB病毒(Epstein-Barr virus,EBV)感染人体后,可长期潜伏于静息记忆性或幼稚B淋巴细胞中。随着免疫系统的衰老,EBV感染者发生EBV相关恶性肿瘤的风险明显增加。非特指EBV阳性弥漫大B细胞淋巴瘤(EBV positivediffuse large B-cell lymphoma, not otherwise specified,EBV⁺DLBCL-NOS)是指发生在无已知免疫缺陷疾病或淋巴瘤病史,且肿瘤细胞核表达EBV编码RNA(EBV encoded RNA,EBER)的大B细胞淋巴瘤。流行病学研究显示,EBV⁺DLBCL-NOS主要流行于亚洲及拉丁美洲,多数患者年龄超过50岁。临床上,与EBV阴性DLBCL(EBV negative DLBCL,EBV-DLBCL)患者相比,EBV⁺DLBCL-NOS患者的临床病程更具侵袭性,初诊患者的临床分期多为晚期,且结外受累率可超过80%。老年患者通常较年轻患者的预后更差。尽管包括利妥昔单抗的免疫化疗方案可显著提高EBV-DLBCL患者的预后,EBV     

弥漫性大B细胞淋巴瘤临床病理分析

 目的　探讨弥漫性大 B细胞淋巴瘤（DLBCL）的临床病理特征、免疫表型,以提高对DLBCL的诊断水平。方法　对22例DLBCL患者进行回顾性分析,复习组织形态和临床表现,补充完善所有患者CD20、CD3、CD10、bcl-6、MUM-1、Ki-67免疫表型测定,为与其他肿瘤相鉴别,对精原细胞瘤、间变性大细胞性淋巴瘤、母细胞型套细胞淋巴瘤部分病例检测AE1／3、PLAP、CD30、ALK、CD5和CyclinD1。结果　22 例患者均为原发DLBCL,男性14例,女性8例,年龄21～71岁,平均48岁;13例结内,9例结外。生发中心细胞（CGB）型13 例（结内7例,结外6例）,非CGB（non-CGB）型9例（结内6例,结外3例）,结合临床和组织形态学17例可诊断,再结合免疫组织化学22例均可诊断。结论　DLBCL形态学、免疫表型及临床表现有一定的特征性,三者相结合能较准确诊断。     

Age-related EBV-associated B-cell lymphoproliferative disorders constitute a distinct clinicopathologic group: a study of 96 patients.

PURPOSE: We have recently reported EBV+ B-cell lymphoproliferative disorders (LPD) occurring predominantly in elderly patients, which shared features of EBV+ B-cell neoplasms arising in the immunologically deteriorated patients despite no predisposing immunodeficiency and were named as senile or age-related EBV+ B-cell LPDs. To further characterize this disease, age-related EBV+ B-cell LPDs were compared with EBV-negative diffuse large B-cell lymphomas (DLBCL). EXPERIMENTAL DESIGN: Among 1,792 large B-cell LPD cases, 96 EBV+ cases with available clinical data set were enrolled for the present study. For the control group, 107 patients aged over 40 years with EBV-negative DLBCL were selected. We compared clinicopathologic data between two groups and determined prognostic factors by univariate and multivariate analysis. RESULTS: Patients with age-related EBV+ B-cell LPDs showed a higher age distribution and aggressive clinical features or parameters than EBV-negative DLBCLs: 44% with performance status >1, 58% with serum lactate dehydrogenase level higher than normal, 49% with B symptoms, and higher involvement of skin and lung. Overall survival was thus significantly inferior in age-related EBV+ group than in DLBCLs. Univariate and multivariate analyses further identified two factors, B symptoms and age older than 70 years, independently predictive for survival. A prognostic model using these two variables well defined three risk groups: low risk (no adverse factors), intermediate risk (one factor), and high risk (two factors). CONCLUSIONS: These findings suggest that age-related EBV+ B-cell LPDs constitute a distinct group, and innovative therapeutic strategies such as EBV-targeted T-cell therapy should be developed for this uncommon disease.     

弥漫大B细胞淋巴瘤中B7-H1临床表达水平分析

目的 对弥漫大B细胞淋巴瘤(DLBCL)中B7-H1的表达水平进行分析.方法 收集DLBCL患者病理活检或手术切除的肿瘤组织标本50例,另收集瘤周正常淋巴组织标本50例作为对照.采用Western Blot法检测B7-H1在瘤周正常淋巴组织与DLBCL肿瘤组织中的表达水平;采用流式细胞仪检测瘤周正常淋巴组织与DLBCL肿瘤组织中B7-H1和调节性T细胞(Treg)的表达水平.结果 Western Blot检测结果显示,B7-H1在DLBCL肿瘤组织与瘤周正常淋巴组织中均有表达,与瘤周正常淋巴组织比较,DLBCL肿瘤组织中B7-H1的表达水平较高.HLA-DR+CD14+巨噬细胞在DLBCL肿瘤组织中表达B7-H1的比例较瘤周正常淋巴组织高(P﹤0.05).与瘤周正常淋巴组织相比较,DLBCL肿瘤组织中(包括IPI值≥2分与IPI值﹤2分)pDC、Treg、mDC与调节性T细胞(CD4+/CD8+)的比例较高(P﹤0.05).结论 B7-H1在DLBCL患者的淋巴组织中呈高表达,提示B7-H1与淋巴瘤细胞的免疫逃逸有关,从而造成了DLBCL细胞免疫平衡的失调.     

Epstein-Barr Virus Infection and Expression of B-cell Oncogenic Markers in HIV-Related Diffuse Large B-cell Lymphoma

PURPOSE: Epstein-Barr virus (EBV)-mediated lymphomagenesis in the setting of HIV infection has been widely accepted. However, little is known about how EBV impacts prognosis. We investigated the hypothesis that EBV infection is associated with expression of specific B-cell oncogenic markers in HIV-related diffuse large B-cell lymphoma (DLBCL) and examined the prognostic use of detecting EBV infection. EXPERIMENTAL DESIGN: HIV-related DLBCL cases diagnosed between 1996 and 2007 within Kaiser Permanente California were identified. Immunohistochemical staining was used to analyze the expression of selected markers that are cell-cycle regulators, B-cell activators, and antiapoptotic proteins among others. EBV infection was determined by in situ hybridization of EBV RNA. Correlations between EBV and marker expression were examined using Spearman correlation coefficient. The prognostic use of EBV status was examined in multivariable Cox model adjusting for International Prognostic Index (IPI). Receiver-operating characteristics (ROC) analysis was used to evaluate improvement in model discrimination. RESULTS: Seventy HIV-related DLBCL cases were included (31% EBV±). EBV+ tumor was associated with increased expression of BLIMP1 and CD30 and reduced expression of BCL6 and LMO2. EBV+ tumor was independently associated with elevated 2-year overall mortality [HR, 3.3; 95% confidence interval (CI), 1.6-6.6]. Area under the ROC curve showed improved model discrimination when incorporating tumor EBV status with IPI in the prediction model [0.65 vs. 0.74 (IPI only)]. CONCLUSION: Our results suggest that EBV infection was associated with expression of several tumor markers that are involved in the NF-κB pathway and that detecting tumor EBV status may have prognostic use in HIV-related DLBCLs. Clin Cancer Res; 18(17); 4702-12. ?2012 AACR.     

Age cutoff for Epstein-Barr virus-positive diffuse large B-cell lymphoma–is it necessary?

Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly (EBV+ DLBCL-e) is a molecularly distinct variant of DLBCL, characterized by a monoclonal B-cell proliferation that occurs in patients >50 years of age without a history or clinicopathologic evidence of immunodeficiency. However, patients with EBV+ DLBCL younger than 50-years-old also exist in Western countries. We evaluated the clinicopathologic, immunophenotypic and genetic features in Cacausian patients with EBV+ DLBCL who are ≤50 years of age and compared this patient group to patients who are >50 years. In patients who are ≤50 years, less frequent expression of BCL6 and a trend of more frequent expression of CD30 and pSTAT3 were found in patients with EBV+ DLBCL. In patients who are >50 years, common expression of CD30, p50, pSTAT3 and less frequent expression of BCL6 were observed. Older patients also more commonly had a poor performance status (ECOG≥2). Comparing EBV+ DLBCL patients in ≤50 years versus >50 years, both groups had similar clinicopathologic, immunophenotypic and genetic features. Gene expression profiling, microRNA profiling and treatment outcome of the younger patients with EBV+ DLBCL was not distinctive from tumors in older patients. Based on our data, we suggest that the arbitrary age cutoff for EBV+ DLBCL is unnecessary and should be eliminated in the WHO lymphoma classification scheme.     

Increased MYC expression without MYC gene translocation in patients with the diffuse large B-cell-lymphoma subtype of iatrogenic immunodeficiency-associated lymphoproliferative disorders

Post-transplant lymphoproliferative disorder (PTLD) and other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) are iatrogenic lymphoproliferative disorders (LPD) that develop in association with immunosuppressive treatment in the setting of organ transplantation and autoimmune disease, respectively. Each has a spectrum of pathologies ranging from lymphoid hyperplasia to lymphoma. To clarify the characteristics of the diffuse large B-cell lymphoma (DLBCL) subtype in a cohort of 25 patients with PTLD or OIIA-LPD from our institute, we selected 13 with a histological subtype of DLBCL, including 2 cases of PTLD and 11 of OIIA-LPD. The median patient age at diagnosis was 70 years, with a female predominance. Both PTLD cases developed after kidney transplant. Of the patients with OIIA-LPD, 10 had rheumatoid arthritis, 1 had mixed connective tissue disease, and 8 were treated using methotrexate. Both of the PTLD patients and 6 of the OIIA-LPD patients had extranodal manifestations. All patients except for one were classified as having the non-germinal center B-cell (non-GCB) subtype according to the Hans algorithm. Tissue samples from 8 patients were positive for CD30 and 8 were positive for Epstein–Barr virus (EBV)-encoded small RNA. Seven patients had MYC-positive tissue samples, but none had MYC translocation. Our study suggests that extranodal manifestations and the non-GCB subtype are common, that EBV is associated with the DLBCL subtype of PTLD and OIIA-LPD, and that anti-CD30 therapy is applicable. In addition, our patients with the DLBCL subtype of PTLD and OIIA-LPD exhibited MYC overexpression without MYC translocation, suggesting an alternative mechanism of MYC upregulation.