眼附属器弥漫大B细胞淋巴瘤的临床及病理学分析

Clinical and pathological analysis of ocular adnexal diffuse large B-cell lymphoma

目的总结眼附属器弥漫大B细胞淋巴瘤(OA-DLBCL)的临床及病理学特征。方法回顾性系列病例研究。收集天津市眼科医院2005年1月至2018年12月经组织病理学诊断为OA-DLBCL患者23例,分析患者的临床特征、影像学表现,观察OA-DLBCL组织病理学特征和免疫组织化学染色表型特征。18例患者获得随访资料,统计患者生存率;采用Kaplan-Meier方法进行生存分析,Log-rank检验分析各临床特征与患者总生存率的关系。结果 23例OA-DLBCL中男性13例,女性10例;发病年龄43~82岁,中位数为65岁;左眼14例,右眼8例,双眼1例;肿物位于眼眶14例,泪腺2例,泪腺及眼眶3例,泪囊及眼眶1例,结膜1例,结膜及眼眶1例,眼睑皮肤1例;影像学检查可见附属器或眼眶内不规则软组织密度影,MRI显示肿物信号强度与眼外肌或脑灰质接近;中心母细胞变异型21例,免疫母细胞变异型2例;生发中心B细胞样(GCB)亚型6例、非GCB亚型17例;髓细胞瘤病毒癌基因同源物及B细胞淋巴瘤蛋白2基因双表达2例,非双表达21例。18例随访患者随访时间为25~156个月,中位数为48个月。随访资料显示原发性OA-DLBCL患者5例,继发性OA-DLBCL患者13例;Ann Arbor分期ⅠE期5例,ⅢE期1例,ⅣE期12例;随访期间8例患者生存,10例患者死亡。Kaplan-Meier法分析显示患者1、3、5年总生存率分别为88.9%、71.4%和41.7%。Log-rank检验显示Ann Arbor临床分期、年龄与OA-DLBCL患者的总生存率有关(χ^(2)=7.448,8.804;均P<0.01);而性别、肿物大小、分子分型、Ki-67增殖指数和是否有骨侵犯与患者的总生存率均无关(均P>0.05)。结论 OA-DLBCL主要发病于老年群体,单眼发病率较高,眼眶为最常见的发病部位,分子分型多为非GCB亚型,Ann Arbor分期和年龄与患者的不良预后相关。

Objective To summarize the clinical and pathological characteristics of diffuse large B-cell lymphoma of ocular adnexal(OA-DLBCL).Methods A retrospective case series study.Twenty-three cases of OA-DLBCL were collected in Tianjin Eye Hospital from January 2005 to December 2018.The clinical manifestations and imaging examination results were analyzed.The pathological characteristics and immune subtypes were analyzed with hematoxylin and eosin staining and immunohistochemistry.Eighteen patients completed the follow-up.Overall survival(OS)time was from the date of diagnosis to the date of death or the final follow-up(April 30,2020).Clinical stages were analyzed by the Ann Arbor classification;Kaplan-Meier plots were used to visualize survival outcomes.The different risk groups were compared using Log-rank test.Results There were 13 males and 10 females.The median age was 65 years(range,43 to 82 years).Twenty-two patients had unilateral lymphoma(14 left eyes,8 right eyes),and one patient had bilateral lymphoma.The OA-DLBCL was in the orbit in 14 patients,in the lacrimal gland in two patients,in both the lacrimal gland and the orbit in three patients,in both the lacrimal sac and the orbit in one patient,in the conjunctiva in one patient,in both the conjunctiva and the orbit in one patient,and in the skin of eyelids in one patient.Imaging examinations showed the tumors were of irregular soft tissue density.MRI showed the tumors were close to the extraocular muscles or ectocinerea.Centroblastic morphology was present in 21 specimens,and 2 specimens had immunoblastic morphology.Six patients were of germinal center B cell-like(GCB)type,and 17 were of non-GCB type.There were 2 patients with double expression of cellular-myelocytomatosis viral oncogene and B-cell lymphoma 2.The follow-up time ranged from 25 to 156 months,and the median follow-up time was 48 months.Five of them had primary OA-DLBCL,and 13 patients had secondary OA-DLBCL.Five patients were at the Ann Arbor clinical stageⅠE,one was at stageⅢE,and 12 were at stageⅣE.During the follow-up,8 patients survived,and 10 died.The 1-,3-,and 5-year OS rates were 88.9%,71.4%and 41.7%,respectively.Log-rank analysis indicated that the Ann Arbor clinical stage and age were related to the OS of OA-DLBCL(χ^(2)=7.448,8.804;both P<0.01).The gender,tumor size,molecular typing,Ki-67 index,and bone invasion were not related to the OS of OA-DLBCL(all P>0.05).Conclusions OA-DLBCL mainly occurrs in the elderly population,unilaterally,and in the orbit.Most molecular types are non-GCB subtypes.The Ann Arbor clinical stage and age are associated with prognosis.