间变型少突胶质细胞瘤发生中枢神经系统以外转移：附1例经验及文献回顾  

Occipital anaplastic oligodendroglioma with multiple organ metastases after a short clinical course：a case report and literature review

作　　者：李军钊 贺世明[1] 张治国[1] 巩丽[3] 金天博[4] 崔光彬[5] 高立[1] 梁娜[1] 高国栋[1] 李刚[1] 

机构地区：[1]第四军医大学唐都医院神经外科,陕西西安710038 [2]第四军医大学学员旅,陕西西安710038 [3]第四军医大学唐都医院病理科,陕西西安710038 [4]西北大学生命科学学院,陕西西安710069 [5]第四军医大学唐都医院放射科,陕西西安710038

出　　处：《转化医学电子杂志》2014年第6期1-12,共12页E-Journal of Translational Medicine

基　　金：国家自然科学基金（81272776）;中国抗癌协会神经肿瘤专业委员会神经肿瘤研究基金（CSN0-2013-MSD014）;陕西省科技攻关项目（2012K13-01-13;2011K12-47）;吴阶平医学基金会临床科研专项资助基金（320.6750.12161）;第四军医大学唐都医院精英人才培育资助计划资助项目（2010年＆2013年）;第四军医大学唐都医院新技术新业务项目（2012年） 致谢：本文得益于与中山大学附属肿瘤医院陈忠平教授、第四军医大学基础医学院病理教研室李青教授、天津医科大学总医院于士柱教授、杨学军教授的多次讨论.

摘　　要：目的：通常认为脑胶质瘤（包括高级别脑胶质瘤）不会发生中枢神经系统（CNS）以外的转移．然而，少突胶质细胞瘤（OGD）不会在CNS以外转移这一观念已经在发生改变．方法：本文对1例间变型OGD患者发生CNS以外转移的病例进行了报道．该OGD患者术后13月被证实，明确地发生了多个淋巴结、骨髓以及多处骨（包括双侧髂骨、右侧股骨以及多个椎体）转移．该例患者进行了1p与19q染色体缺失、MGMT基因启动子甲基化状态以及PTEN 基因外显子突变的检测．对PubMed收录文献进行检索、对比，检索关键词分别为 Extracranial，Extraneural，Oligodendroglioma，Oligodendroglio-mas，Metastatic，Metastasis，Metastases，对上述关键词进行多种组合．结果：患者骨髓穿刺活检提示，明确发生了肿瘤骨髓转移．免疫组织化学染色诊断确立了本例临床诊断，系间变型OGD伴CNS以外转移．检测显示，上述肿瘤组织均未发生1 p与19q缺失，发生了MGMT 基因启动子甲基化及PTEN 基因第2号外显子第234号编码子G→A的颠换．检索显示，1951年至今见诸文献的 OGD 发生 CNS 以外转移的病例已有60例，本文报道的系第61例．这61例患者中，OGD共侵犯110处部位，其中最经常侵犯的部位依次是骨与骨髓（n =47；42．7％）、淋巴结（n =22；20．0％）、肝（n =7；6．4％）、头皮（n=6；5．5％）、肺（n=6；5．5％）、胸膜（n=4；3．6％）、胸壁（n=3；2．7％）、髂腰肌（n=2；1．8％）、软组织（n=2；1．8％）以及腮腺（n=2；1．8％）．结论：OGD的CNS以外转移尽管发生率较低，但的确发生．OGD最经常侵犯的部位是骨与骨髓．检测1p与19q缺失、MGMT 基因启动子甲基化状态及PTEN基因外显子突变可能有助于筛选出OGD中可能发生CNS以外转移的类型．AIM：It is generally believed that malignant gliomas never metastasize outside the central nervous system.Oligoden-drogliomas （OGDs）are characterized by multiple recurrences and extracranial spread is rare,especially distant metastases.However,the notion that OGD cells cannot spread outside the central nervous system is being challenged.METHODS：Herein we describe in detail the clinical story of one patient with anaplastic OGD,which metastasized to many lymph nodes,bone marrow, and bones （bilateral iliac,right acetabulum,and multi-vertebral bodies）.Genetic analyses included detection of the 1p and 19q chromosomal arms,methylation status of the MGMT （O-6-methyl-guanine-DNA methyltransferase）promoter,and PTEN （phospha-tase and tensin homolog）exon mutations.A search of worldwide literature was conducted for reports of metastatic OGDs using NC-BI-PubMed,with the keywords “extracranial”,“extraneural”,“oligo dendroglioma”,“oligodendrogliomas”,“metastatic”,“metastasis”,and “metastases”,in different combinations.The reference lists of the subsequently selected journals were also reviewed.RESULTS：An open biopsy of the infiltrated bones in our patient revealed that malignant cells had replaced the patient＇s marrow.Moreover,the diagnosis of multiple-organ metastases of anaplastic OGD was confirmed based on immunohistochemical staining.Genetic analyses showed that the tumors originated from previously resected brain lesions.None of the metastatic lesions had the 1p and 19q deletions that are common in OGD,but hypermethylation of MGMT promoter was detected,and a G→A transversion at codon 234 of PTEN exon 2.Review of the literature yielded 60 reports of metastatic OGDs from 195 1 to the pres-ent,which with our patient makes 6 1 cases.Concerning these 6 1 patients,there were 1 10 infiltrated sites correlated closely with primary OGDs.The most frequent metastatic sites were bone and bone marrow （n =47;42.7%）, lymph nodes （n =22;20.0%）,liver （n=7;6.4%）,scalp （n =6;

关 键 词：胶质瘤 少突胶质细胞瘤 颅外转移 解剖 1p/19q 染色体缺失 遗传分析 

分 类 号：R739.41[医药卫生—肿瘤]