移植后淋巴组织增殖性疾病11例临床病理分析

Posttransplant lymphoproliferative disorders:a clinicopathological analysis of 11 cases

目的分析移植后淋巴组织增殖性疾病(PTLD)的临床病理学特点,提高其诊断水平。方法收集2008年1月至2018年1月河南省人民医院、北京大学医学部及北京大学第三医院收治的11例PTLD患者资料,采用免疫组织化学染色、EB病毒原位杂交、荧光原位杂交及基因测序等方法,回顾性分析PTLD患者的病理学特点及预后相关指标等。结果11例PTLD患者,男性9例,女性2例,中位年龄18岁(3~34岁)。9例造血干细胞移植发生PTLD的中位时间为移植后4个月(2~24个月),2例实质器官移植患者分别在移植后6、13个月出现PTLD。淋巴结是最常见的发病部位(9例),另外发生在肝脏和鼻咽部各1例。3例为多形性移植后淋巴组织增殖性疾病(P-PTLD),8例为单形性移植后淋巴组织增殖性疾病(M-PTLD),所有患者EB病毒检测均为阳性。8例M-PTLD均为弥漫大B细胞淋巴瘤(DLBCL),荧光原位杂交检测bcl-2、myc、IGH及A20基因,仅1例存在IGH基因断裂,其余均未获得相关异常。5例PTLD患者(包括4例M-PTLD和1例P-PTLD)进行了Ig基因克隆性分析,4例M-PTLD均存在克隆性重排,1例P-PTLD未获得克隆性重排。单因素分析显示年龄≤18岁与不良预后有关(P=0.040)。结论PTLD病理形态多样,均存在EB病毒感染,基因重排可辅助诊断。

Objective To analyze the clinicopathological features of the posttransplant lymphoproliferative disorders(PTLD)and to improve the diagnostic levels.Methods The clinical data of 11 patients diagnosed with PTLD between January 2008 and January 2018 from Henan Provincial People's Hospital,Peking University Science Center and the Affiliated Third Hospital of Peking University were collected.The clinicopathological features and the potential prognostic predictors were retrospectively analyzed by using immunohistochemical staining,EB virus in situ hybridization,fluorescence in situ hybridization and gene sequencing.Results There were 9 males and 2 females in 11 PTLD patients,and the median age of the total patients was 18 years old(3-34 years old).The median time of 9 cases who underwent hematopoietic stem cell transplantation developing PTLD was 4 months(2-24 months)after the transplantation.The other 2 cases undergoing solid organ transplantation(SOT)occurred PTLD after 6 months and 13 months,respectively.The lymph node was the most common site to be involved(9 cases),1 case occurred in liver and 1 case occurred in nasopharynx site.Among 11 patients,3 cases were classified as polymorphic PTLD(P-PTLD)and the other 8 cases were monomorphic PTLD(M-PTLD).EB virus of all cases was positive,and 8 cases of M-PTLD were classified as diffuse large B-cell lymphoma(DLBCL).Fluorescence in situ hybridization was used to detect bcl-2,myc,IGH and A20 gene,and only one case had the gene break of IGH,while other cases didn't find any other abnormalities.Ig gene clone analysis was made in 5 patients with PTLD,including 4 cases of M-PTLD with gene rearrangement and 1 case of P-PTLD without gene rearrangement.Univariate analysis showed that age(≤18 years old)was associated with poor prognosis(P=0.040).Conclusions The clinicopathologic features of PTLD are various and infected by EB virus.Gene rearrangement can help the diagnosis.