摘要
目的探讨具有毛细胞样特征的高级别星形细胞瘤(high-grade astrocytoma with piloid features,HGAP)临床病理学及分子遗传学特征。方法收集首都医科大学附属北京天坛医院神经病理中心2023年8月至2024年10月经组织病理学和甲基化聚类分析确诊的7例HGAP的临床及影像学资料,分析其组织学及分子遗传学特征。结果7例患者男性4例,女性3例;诊断中位年龄为37(34,51)岁。患者临床症状与肿瘤发病部位相关。病变部位4例位于小脑、2例发生于幕上大脑半球、1例累及脊髓。影像学特征:磁共振成像显示其中6例患者呈囊实性病变,增强扫描可见轻度或不均匀强化,边界相对模糊不清。病理学特征:肿瘤组织学形态表现多样,级别广泛,5例为低级别的毛细胞样星形细胞瘤形态,浸润性生长;2例呈高级别的胶质母细胞瘤样组织学特征,局部含多形性黄色星形细胞瘤样和少许毛细胞样成分。免疫组织化学染色所有病例胶质纤维酸性蛋白(GFAP)和Olig2均弥漫阳性,4例ATRX部分或完全缺失,Ki-67阳性指数2%~40%不等。分子检测特点:二代测序肿瘤细胞存在MAPK通路基因变异,和/或CDKN2A/B的纯合性缺失,和/或ATRX突变;其中3例含有以上3类分子的遗传变异,1例为MAPK变异和CDKN2A/B的纯合性缺失,1例为MAPK变异和ATRX突变,1例仅有MAPK突变,1例未检测到任何分子改变;DNA甲基化聚类分析7例病例HGAP模型预测中位评分为0.94(0.85~0.99),其中5例MGMT启动子呈高甲基化。随访结果:术后4例患者行放疗和替莫唑胺同步治疗,3例未行治疗;至末次随访,7例均存活,其中2例复发病变,1例带瘤生存。结论HGAP好发于成人,组织形态学与级别较广泛,以毛细胞样星形细胞瘤和胶质母细胞瘤样组织特征多见,确诊依赖于甲基化聚类分析;大多数肿瘤存在MAPK信号通路基因变异,伴CDKN2A/B的纯合性缺失和/或ATRX突变;生物学行为不良,影像学和组织学具有一定迷惑性,需临床医师综合考虑以提升诊断意识、防止漏诊。
Objective To investigate the clinicopathological and molecular genetic features of high-grade astrocytomas with piloid features(HGAP).Methods Clinical,histopathological and imaging data of 7 cases of HGAP diagnosed at the Neuropathology Center of Beijing Tiantan Hospital,Beijing,China from August 2023 to October 2024 were collected.The histopathological and molecular features for each case were analyzed.Results Among the seven patients there were 4 males and 3 females,with the median age of 37(34,51)years.Patients exhibited various clinical symptoms and signs depending on the tumor′s location.Four tumors were located in the cerebellum,2 in the supratentorial region,and 1 in the spinal cord.Magnetic resonance imaging showed that 6 of the 7 patients had cystic and solid lesions,with focal or nodular enhancement and relatively unclear boundaries.Histopathological features had a diverse morphological spectrum and extensive grading.Five cases displayed a pilocytic astrocytoma-like appearance with infiltrative growth patterns,while two cases presented glioblastoma-like morphology,containing locally anaplastic pleomorphic xanthoastrocytoma with minor pilocytic components.All tumors were diffusely positive for GFAP and Olig2,while 4 tumors exhibited partial or complete loss of ATRX.The Ki-67 proliferation index ranged from 2%to 40%.Next-generation sequencing showed that tumor cells most commonly harbored MAPK pathway gene mutations,and/or homozygous deletions of CDKN2A/B,and/or ATRX mutations.Among the 7 HGAP models,3 cases showed the three types of molecular genetic variations,1 case showed MAPK mutations and homozygous deletions of CDKN2A/B,1 case had MAPK mutations and ATRX mutations,1 case had only MAPK mutations,and 1 case showed no detectable molecular changes.DNA methylation clustering analyses showed that the median model prediction score was 0.94(range,0.85-0.99)for the 7 HGAP models.Five cases showed the MGMT promoter hypermethylation.Four patients received radiotherapy and concomitant temozolomide treatment after surgery,while three patients received no known treatments.At the last follow-up,seven patients were alive without any tumor,two patients had recurrence,and one patient was alive with the tumor.Conclusions HGAP is relatively rare and predominantly occurs in adults.It has a wide histopathological spectrum and various histological grades,characterized by piloid astrocytoma-like and glioblastoma-like histological features.Its diagnosis relies on methylation clustering analysis.Most tumors harbor gene alterations in the MAPK signaling pathway,along with homozygous deletions of CDKN2A/B or ATRX mutations.The biological behavior is typically aggressive,while imaging and histological findings can be misleading.Therefore,clinicians need to increase their diagnostic awareness of this tumor and prevent missed diagnoses.
作者
邹婉婧
柴睿超
徐丽
孙婷
刘震
刘朝霞
常青
Zou Wanjing;Chai Ruichao;Xu Li;Sun Ting;Liu Zhen;Liu Zhaoxia;Chang Qing(Center of Neuropathology,Beijing Tiantan Hospital,Capital Medical University/Beijing Institute of Neurosurgery,Beijing 100070,China;Department of Neuroimaging,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China;Department of Neurosurgery,Shunyi Hospital,Beijing 101300,China)
出处
《中华病理学杂志》
北大核心
2025年第8期805-811,共7页
Chinese Journal of Pathology
