原发纵隔大B细胞淋巴瘤60例临床病理特征及预后

Clinicopathological features and prognosis of primary mediastinal large B-cell lymphoma:a series of sixty cases

目的探讨原发纵隔大B细胞淋巴瘤(PMBL)的临床病理特征及影响预后的相关因素。方法回顾性分析中日友好医院(14例)和北京协和医院(46例)2000年9月至2019年11月外检(44例)及会诊(16例)共60例PMBL的临床资料、病理形态学特征、免疫表型、免疫球蛋白基因重排及microRNA表达谱。结果60例患者中,男性23例,女性37例,年龄15~64岁(中位年龄28岁)。免疫组织化学染色表达全B细胞抗原,77.4%(24/31)的病例表达CD30,73.1%(19/26)表达CD23,45.8%(11/24)MUM1阳性,Ki-67阳性指数≥70%占90.6%(29/32);21例PMBL进行EB病毒编码的mRNA(EBER)检测,仅1例(4.8%)瘤细胞散在阳性;20例PMBL中的7例免疫球蛋白基因重排检测结果阳性(阳性率35.0%)。选取7例PMBL与9例弥漫大B细胞淋巴瘤作对照研究microRNA基因表达谱的差异,结果发现其表达差异有统计学意义的microRNA共计33个。单因素分析结果显示,血清乳酸脱氢酶(LDH)升高、临床分期Ⅲ~Ⅳ期、国际预后指数(IPI)评分≥3、未联合利妥昔单抗的化疗方案及免疫组织化学染色MUM1阳性的PMBL患者的生存率低,预后差(P<0.05);多因素分析结果显示其中联合利妥昔单抗的治疗方案是影响患者生存时间的独立预后因素(P<0.05)。结论PMBL从临床病理特征到免疫分子表型均不同于弥漫大B细胞淋巴瘤,本研究所揭示的预后因素、分子遗传学、免疫学特征丰富了对PMBL生物学的认识和理解,从而为治疗提供依据和策略。

Objective To investigate the clinicopathological features and prognostic factors of primary mediastinal large B-cell lymphoma(PMBL).Methods The clinical data of 60 patients with PMBL including 44 biopsy cases and 16 consultation cases from September 2000 to November 2019 in the Department of Pathology,China-Japan Friendship Hospital(14 cases)and Peking Union Medical College Hospital(46 cases)were enrolled.Pathologic features,immunophenotype,immunoglobulin(Ig)gene rearrangement and microRNA expression profile were retrospectively studied.Results Of the 60 patients,23 were males and 37 were females,age ranged from 15 to 64 years(median 28 years).Immunohistochemical staining showed that the tumor cells were positive for pan-B cell antigens,CD30(77.4%,24/31),CD23(73.1%,19/26),MUM1(45.8%,11/24),Ki-67 index≥70%(90.6%,29/32).EBER in situ hybridization was analyzed in 21 PMBL,only one case(4.8%)was positive.Ig gene rearrangement was performed in 20 cases,and seven were positive(35.0%).MicroRNA gene expression profiles were analyzed in seven cases of PMBL and nine cases of diffuse large B-cell lymphoma,and there were 33 microRNAs with significant difference(P<0.05).Univariate analysis indicated that the poor prognostic factors included serum lactate dehydrogenase(LDH)level,International Prognostic Index(IPI)score≥3,stagesⅢ-Ⅳ,chemotherapy not combined with rituximab and MUM1 positivity(P<0.05).Multivariate analysis showed that the treatment combined with rituximab was independently related to prognosis(P<0.05).Conclusions PMBL is different from diffuse large B-cell lymphoma in clinicopathologic features,immunophenotypic presentation and molecular features.The prognostic factors,molecular genetics and immunological characteristics reveal that this study has enriched our understanding of the biology of PMBL,thus providing evidence and strategies for treatment.