青少年多形性低级别神经上皮肿瘤的临床病理及分子病理特征分析
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Research progress on the clinical pathological characteristics and molecular pathological characteristics of polymorphous low‑grade neuroepithelial tumor of the young
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    摘要:

    目的 分析青少年多形性低级别神经上皮肿瘤(PLNTY)的临床病理及分子病理特点。 方法 选取 2021 年 5 月— 2023 年 5 月于首都医科大学附属北京天坛医院接受手术治疗的 16 例 PLNTY 患者为研究对象,收集患者临床及影像学资料。采用苏木精 - 伊红染色、免疫组织化学染色及基因测序 检测肿瘤组织形态学及分子遗传学变化,电话随访及查阅影像学资料了解患者的症状改善情况、有无 放化疗及肿瘤复发情况。结果 16 例 PLNTY 患者中位发病年龄 24 岁,男女比例相当(1∶1);5 例(5/16) 呈急性起病(起病时间< 3 个月);临床症状以不同程度的癫痫发作为主;8 例(8/16)肿瘤位于颞叶,5 例 (5/16)位于顶枕叶。增强磁共振成像扫描显示,11例(11/16)无明显强化,3例(3/16)出现轻度不均匀强化, 2 例(2/16)明显不均匀强化。14 例(14/16)患者术后癫痫症状改善,其中 1 例复发。组织病理学结果显 示肿瘤呈浸润性生长,位于皮层及皮层下白质,可见多形性和少突样细胞形态,并见枝芽状细小血管, 12 例(12/16)伴钙化;其中 1 例复发再次手术切除的标本中呈现恶性转化,表现为局部细胞密度增高, 可见核分裂象、微血管增生和栅栏样坏死。16 例肿瘤免疫组织化学染色结果显示,胶质纤维酸性蛋白 (GFAP)、少突胶质细胞转录因子 2(Olig2)及 CD34 弥漫阳性,突触素呈阴性表达,其中 14 例 ki67 增殖指 数≤ 4%,恶性转化病例的 Ki67 增殖指数为 20%。7 例 PLNTY 二代测序结果显示,以BRAF或FGFR分子 变异为主,其中 3 例(3/7)存在 O6- 甲基鸟嘌呤 -DNA 甲基转移酶启动子(MGMT)甲基化;1 例原发及复发 的病例中均检测到FGFR3::TACC3融合,伴 TERT 启动子突变,且在复发病例中出现了 10 号染色体缺 失及CDK4、MDM2扩增。结论 PLNTY 好发于青少年,为一种长期癫痫相关肿瘤,多见于颞叶及顶枕 叶;肿瘤呈浸润性生长,可见多形性细胞和少突样细胞成分,CD34 弥漫阳性,分子改变以BRAF或FGFR 变异为主。大部分预后良好,术后癫痫症状改善;个别病例复发后可发生恶性转化,分子病理结果显示 FGFR3::TACC3融合并 TERT 启动子突变;临床医生需要对 PLNTY 临床病理及分子病理特征进行综合 评估并提高警惕。

    Abstract:

    Objective To explore the clinical pathological and molecular genetic characteristics of polymorphous low-grade neuroepithelial tumor of the young (PLNTY). Methods A total of 16 patients with PLNTY were recruited as research subjects, who underwent surgical treatment at Beijing Tiantan Hospital affiliated to Capital Medical University from May 2021 to May 2023. The clinical and imaging data were collected. Hematoxylin eosin staining, immunohistochemistry staining, and gene sequencing were used to detect morphological and molecular genetic changes in tumor tissue. Patients were followed up on symptom improvement, the presence of radiotherapy and chemotherapy, and tumor recurrence through telephone and imaging follow-up. Results The median age of onset was 24 years in the 16 cases of PLNTY, and the male-to-female ratio was 1∶1. Five cases (5/16) presented with acute onset (onset time < 3 months). The clinical symptoms are mainly characterized by varying degrees of epileptic seizures. Eight cases (8/16) were located in the temporal lobe, and 5 cases (5/16) were located in the parietal occipital lobe. Enhanced magnetic resonance imaging scan showed no significant enhancement in 11 cases (11/16), mild heterogeneous enhancement in 3 cases (3/16), and significant heterogeneous enhancement in 2 cases (2/16). Fourteen patients (14/16) showed improvement in postoperative epilepsy symptoms, with 1 case experiencing recurrence. The histopathological results showed that the tumor showed invasive growth, located in the cortex and subcortical white matter, with pleomorphic and oligodendrocyte like cell morphology and branching small blood vessels. Twelve cases (12/16) were accompanied by calcification. One case of recurrent resected specimen showed malignant transformation, characterized by increased local cell density, visible nuclear mitotic figures, neovascularization, and palisading necrosis. The immunohistochemical staining results of 16 cases of tumors showed diffuse positive expression of glial fibrillary acidic protein (GFAP), oligodendrocyte transcription factor 2 (Olig2), and CD34, while synaptophysin was negatively expressed. Among them, 14 cases (14/16) had a Ki67 proliferation index ≤ 4%, and the Ki67 proliferation index of malignant transformation cases was 20%. Second-generation sequencing results of 7 cases showed that BRAF or FGFR molecular mutations were predominant, with three cases (3/7) showing methylation of the O6-methylguanine-DNA methyltransferase promoter (MGMT); FGFR3::TACC3 fusion with TERT promoter mutation was detected in 1 primary and recurrent case, and chromosome 10 deletion and CDK4 and MDM2 amplification were observed in the recurrent cases. Conclusions PLNTY is common in adolescents and is a long-term epilepsy related tumor, commonly found in the temporal and parietal occipital lobes. The tumor shows invasive growth, with visible pleomorphic and oligodendrocyte cell components. CD34 is diffusely positive, and molecular changes are mainly BRAF or FGFR variants. The prognosis is mostly favorable with significant improvement in postoperative seizure symptoms. Individual cases may experience malignant transformation after recurrence, and molecular genetic results show FGFR3:: TACC3 fusion with TERT promoter mutation. It is important for clinicians to thoroughly assess clinical, pathological characteristics and molecular genetic alterations of PLNTY and be vigilant.

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邹婉婧,徐丽,苏玉金,刘震,王军梅.青少年多形性低级别神经上皮肿瘤的临床病理及分子病理特征分析[J].神经疾病与精神卫生,2024,(5).
DOI :10.3969/j. issn.1009-6574.2024.05.006.

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  • 在线发布日期: 2024-05-31