中枢神经系统血管内淋巴瘤1例临床分析并文献复习

Clinical analysis of a case with central nervous system-intravascular lymphoma and literature review

目的探讨中枢神经系统(CNS)-血管内淋巴瘤(IVL)患者的临床特点、实验室检查结果及诊治方法,并进行相关文献复习。方法选择2021年12月19日成都市第二人民医院神经外科收治的1例54岁CNS-IVL男性患者为研究对象。采用回顾性分析方法,对其既往病史,临床表现,实验室检查、影像学检查、宏基因二代测序(mNGS)结果等临床资料进行分析。依据临床特征和相关检查结果,对患者进行诊断和治疗。本研究以"血管内淋巴瘤""弥漫大B细胞淋巴瘤""脊髓内出血""中枢神经系统""脊髓""intravascular lymphoma""diffuse large B-cell lymphoma""intraspinal hemorrhage""central nervous system""spinal cord"为中、英文关键词,检索中国知网数据库、万方数据知识服务平台及PubMed数据库中相关文献,总结与本研究累及脊髓CNS-IVL患者相关疾病的诊治资料。文献检索时间为建库至2022年3月1日。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求,并与患者及患者家属签署临床研究知情同意书。结果①本例患者因"左上肢麻木、无力10 d"入院。既往有结核性脑膜炎、病毒性脑膜炎、肝功能不全、重症肺炎及红皮病病史。②入院时本例患者血常规检查结果示,白细胞计数(WBC)、中性粒细胞百分数、红细胞计数、血红蛋白(Hb)值、血小板计数分别为5.4×10^(9)/L、72.5%、3.02×10^(12)/L、87 g/L、49×10^(9)/L。腹部彩色多普勒超声检查结果示,脾轻度增大。头部MRI、磁共振血管成像(MRA)、磁敏感加权成像(SWI)检查结果示,双侧额叶、左侧顶叶、基底节区腔隙性脑梗死及缺血灶;脑萎缩,脑白质脱髓鞘改变;颅内动脉走行、侧支循环正常;右侧颞叶及侧脑室旁少许微出血灶。脊柱MRI检查结果示,颈段脊髓明显水肿,其内见斑片状低信号影,考虑脊髓内出血。患者接受颈段脊椎全椎板入路髓内病损切除和椎板复位内固定手术治疗。术后病变组织活组织检查结果示,退变坏死组织,伴出血,淋巴瘤细胞血管腔内浸润,部分聚集在血管壁周围和血液凝块中。免疫组织化学检查结果示,B细胞抗原CD20(+)、CD79a(+)、配对盒蛋白(PAX)-5(+)、血管内皮细胞抗原CD34(+)。原位杂交组织化学检查结果示,EB病毒编码小RNA(EBER)(阳性,约为90%)。③根据患者的临床特征和相关检查结果,本例患者被诊断为CNS-IVL。由于本例患者存在严重的多系统损害病史,患者未进行化疗等专科治疗。因CNS-IVL病情恶化,2022年1月14日患者死亡。④根据本研究设定的文献检索策略,共纳入10篇英文文献,报道10例累及脊髓CNS-IVL患者,加上本例患者共计11例患者。本组累及脊髓CNS-IVL患者,早期容易被误诊为脊髓炎或者脊髓梗死,其中经病灶活组织检查确诊3例,皮肤活组织检查确诊4例,尸检确诊4例。提高早期确诊率及采用CHOP(环磷酰胺+多柔比星+长春新碱+泼尼松)或R-CHOP(利妥昔单抗+CHOP)方案治疗,有利于改善患者预后。结论CNS-IVL以脑膜炎起病进展性累及脊髓的病例少见。对于脑脊液EB病毒(EBV)感染呈阳性的患者,需进行CNS-IVL相关检查。

Objective To investigate the clinical characteristics,laboratory findings,diagnosis and treatment of patients with central nervous system(CNS)-intravascular lymphoma(IVL),and review the related literature.Methods On December 19,2021,a case of a 54 year-old male patient with CNS-IVL admitted to Neurosurgery Department of Chengdu Second People′s Hospital was selected as the study subject.A retrospective analysis method was used to analyze the patient′s clinical data such as medical history,clinical manifestations,laboratory tests,imaging examinations,metagenomic next-generation sequencing(mNGS)results.Diagnose and treatment of this patient based on clinical manifestations and related examination results.China National Knowledge Infrastructure database,Wanfang Data Knowledge Service Platform and PubMed database were searched using"intravascular lymphoma","diffuse large B-cell lymphoma","intraspinal hemorrhage","central nervous system","spinal cord"as Chinese and English keywords.Diagnosis and treatment data of CNS-IVL involving spinal cord was summarized.The time for literature retrieval was from inception of the database to March 1,2022.Procedure followed in this study was in line with requirements of the World Medical Association Declaration of Helsinki revised in 2013,and informed consent of clinical research was signed with the patient and his family members.Results①This patient was admitted due to"numbness and weakness in the left upper limb for 10 d".Previous history of the patient included tuberculous meningitis,viral meningitis,liver dysfunction,severe pneumonia and erythroderma.②At the time of admission,blood routine test results of this patient showed that white blood cell count(WBC),neutrophil percentage,red blood cell count,hemoglobin(Hb)value,platelet count were 5.4×10^(9)/L,72.5%,3.02×10^(12)/L,87 g/L,49×10^(9)/L,respectively.Abdominal color Doppler ultrasound shows mild enlargement of the spleen.Results of cranial MRI,magnetic resonance angiography(MRA),and susceptibility weighted imaging(SWI)showed lacunar cerebral infarction and ischemic focus in the bilateral frontal lobe,left parietal lobe,basal ganglia,and cerebral atrophy,demyelination of white matter.Intracranial artery runs and collateral circulation is normal.A few micro hemorrhage foci were near the right temporal lobe and lateral ventricles.MRI results of spine showed significant swelling of the cervical spinal cord with abnormal signals,indicating consideration of intramedullary hemorrhage.This patient underwent a intramedullary lesion resection,lamina reduction and internal fixation of cervical spine through whole lamina approach.Biopsy of pathological tissue after operation showed that degenerated and necrotic tissue,accompanied by hemorrhage,lymphoma cells infiltrated into the vascular cavity,and some of them gathered around the vascular wall and in blood clots.Immunohistochemical results showed that B cell antigens CD20(+),CD79a(+),paired box protein(PAX)-5(+),and vascular endothelial CD34(+).Epstein-Barr virus-encoded small RNA(EBER)in situ hybridization was positive with about 90%.③According to clinical features and related examination result,the final diagnosis was CNS-IVL.Due to severe multisystem damage in medical history,the patient did not receive specialized treatment,such as chemotherapy.Due to the deterioration of CNS-IVL condition,the patient died on January 14,2022.④According to the literature retrieval strategy set in this study,a total of 10 articles were included,involving 11 patients with CNS-IVL involving spinal cord included this case in this study.CNS-IVL patients involving the spinal cord in this group are easily misdiagnosed as myelitis or spinal cord infarction in the early stage.Among them,3 cases were confirmed by lesion biopsy,4 cases were confirmed by skin biopsy,and 4 cases were confirmed by autopsy.Improving the early diagnosis rate and followed by either a regimen with cyclophosphamide,vincristine,doxorubicin,and prednisone(CHOP)or R-CHOP(rituximab+CHOP)will be beneficial for improving the prognosis of patients.Conclusions CNS-IVL with meningitis onset and progressive involvement of the spinal cord is relatively rare.Patients with Epstein-Barr virus(EBV)positive cerebrospinal fluid should be test for CNS-IVL.