血管免疫母细胞性T细胞淋巴瘤临床-病理-分子遗传学改变与预后相关性分析

目的 血管免疫母细胞性T细胞淋巴瘤(angioimmunoblatic T-cell lymphoma,AITL)是一种侵袭性淋巴瘤,本研究探讨AITL的临床病理特征、与EB病毒相关性及分子遗传学改变,并分析相关预后因素.方法 选取2003-01-03-2012-12-31新疆医科大学第一附属医院有详细临床病理资料的16例AITL患者石蜡样本,EnVision法进行CXCL13、PD-1、CD10和Bcl-6免疫标记;原位杂交技术检测肿瘤EB病毒编码mRNA表达情况;荧光原位杂交技术检测肿瘤组织中Bcl-2、Bcl-6和C-MYC基因异常情况,并对所有患者进行随访.结果 16例患者,男11例(68.8％),女5例(31.2％),男女比例2.2∶1.中位年龄65.5岁.75.0％(12/16)患者国际预后指标(international prognostic indicators,IPI)评分为中高危,56.3％(9/16)患者血清乳酸脱氢酶(lactic dehydrogenase,LDH)异常,20％(2/10)患者存在骨髓侵犯,81.3％(13/16)患者临床分期为ⅢB期及以上;免疫组织化学染色结果示,CXCL13、PD-1、CD10、Bcl-6阳性率分别为93.8％(15/16,95％CI为70％～100％)、75.0％(12/16,95％CI为48％～93％)、50.0％(8/16,95％CI为25％～75％)和81.3％(13/16,95％CI为54％～96％);AITL显示特征性的CD23和CD21滤泡树突状细胞网增生,阳性率均为87.5％(14/16,95％CI为62％～98％);原位杂交:EBER阳性率为56.3％(9/16,95％CI为30％～80％);FISH检测结果示,10例AITL患者Bcl-2/IgH、Bcl-6、C-myc检测均为阴性;术后电话随访,自病理确诊之日起开始计算生存期,15例患者有随访结果.随访1～84个月,全组中位生存期为17个月;其中5例在1年内死亡,1年生存率为66.7％(5/15),总共6例患者死亡,占全组的40.0％(6/15).单因素分析显示,年龄≥65岁、IPI评分高危组、LDH水平异常、临床病理分期ⅢB～Ⅳ期患者预后较差.结论 AITL好发于老年患者,具有高度侵袭性,预后差,CXCL13、PD-1、CD10、Bcl-6可作为一个免疫组化套餐,在该肿瘤的诊断具有重要作用,临床病理分期、IPI评分、LDH水平是影响预后的重要因素.

Clinicopathologic and molecular genetic abnormalitis of angioimmunoblatic T-cell lymphoma and their association with prognosis

OBJECTIVE Angioimmunoblatic T-cell lymphoma (AITL) is an invasive lymphoma.To explore clinicopathologic,and molecular genetic correlation with EB virus and analysis of the related prognostic factors of the AITL.METHODS Get paraffin samples of the 16 cases AITL with the detailed clinico-pathologic information were studied using immunohistochemical EnVision method for CXCL13,PD-1,CD10,Bcl-6 immunolabeling.We detected the expression of EBER mRNA with in situ hybridization and the Bcl-2,Bcl-6 and C-myc gene abnormalities with interphase fluorescence in situ hybridization,and follow-up for all patients.RESULTS Sixteen cases including 11 male cases (68.8％) and 5 female cases (31.2％),the sex ratio was 2.2 ∶ 1,the age ranged from 38-78 years old and median age was 65.5 years.AITL typically prestend with advanced stage,enlargement of the body and some lymph nodes,fever,splenomegaly and rash,some accompanied by polyclonal hypergammaglobulinemia,75.0％ (12/16) were high-risk/high-risk with International Prognosis Index (IPI),66.3 ％ (9/16) presented abnormalities with lactate dehydrogenase (LDH),20％ (2/10) patients had bone marrow involvement,81.3％ (13/16) patients with clinical stage Ⅲ B period and above.Immunophenotype analysis showed neoplastic cells expressed the following markers:CXCL13 (positive rate 93.8％,15/16),PD-1 (positive rate75.0％,12/16),CD10 (positive rate 50.0％,8/16),Bcl-6 (positive rate 81.3％,13/16),CD21 (positive rate 87.5％,14/16),CD23 (positive rate 87.5％,14/16),EBER (positive rate 56.3％,9/16).The genetic alterations of Bcl-2,Bcl-6 and C-MYC was not found using FISH technique,respectively.Postoperative follow-up with telephone,starting from the date of the pathological diagnosis of survival,15 patients had follow-up results,followup of 1-84 months,the median survival time was 17 months (1-84 months);5 cases died within a year,one year survival rate was 66.7％ (5/15),All data was used for statistical analysis.6 cases died (mortality rate 40.0％,6/15).Univariate analysis showed that:the age ≥65 years,IPI score risk group,LDH level exception and clinical stage Ⅲ B-Ⅳ,the prognosis of patients was poor,all statistical data analysis.CONCLUSIONS The AITL is generally more common in eld erly patients,with an advanced stage and a poor prognosis;CXCL13,PD-1,CD10,Bcl-6 plays an important role in the diagnosis of the tumor.Clinical staging,IPI score and LDH levels are important prognostic factors.