Garibotto Federica, Madia Francesca, Milanaccio Claudia, Verrico Antonio, Piccardo Arnoldo, Tortora Domenico, Piatelli Gianluca, Diana Maria Cristina, Capra Valeria, Garrè Maria Luisa, Rossi Andrea, Morana Giovanni
Neuro-oncology Unit, IRCCS Istituto G. Gaslini, Genova, Italy.
Laboratory of Neurogenetics and Neuroscience, IRCCS Istituto G. Gaslini, Genova, Italy.
Front Oncol. 2020 Jun 3;10:795. doi: 10.3389/fonc.2020.00795. eCollection 2020.
Pediatric neurofibromatosis type 1 (NF1) patients rarely develop aggressive central nervous system tumors. Among high-grade gliomas (HGGs), histone mutant diffuse midline gliomas (DMGs H3 K27M-mutant) have exceptionally been reported. The aim of this retrospectives single-center study was to compare the clinical behavior of DMGs H3 K27M-mutant and non-histone mutant midline HGGs in NF1 vs. non-syndromic children and to report imaging features of NF1 HGGs. We conducted a retrospective review of cerebral DMGs H3 K27M-mutant or non-histone mutant HGGs in 18 patients with or without NF1 followed at our institution between 2010 and 2018. Differences in outcomes, notably progression-free survival (PFS) and overall survival (OS), were evaluated. Two patients were identified with genetically confirmed diagnosis of NF1 and cerebral HGGs (one DMG H3 K27M-mutant and one histone wild type). Both subjects presented with midline mass lesions with imaging features of aggressive biological activity on advanced MRI or amino-acid PET. During the same time period, 16 non-NF1 patients (11 subjects with DMGs H3 K27M-mutant and 5 with non-histone mutant midline HGGs) were treated at our institution. The two patients with NF1 and HGGs presented a PFS of 3 months and an OS of 5 and 7 months. Median PFS and OS of children without NF1 were respectively 6 and 10 months in DMGs H3 K27M-mutant, and 6 and 11 months in H3 K27M wild-type tumors. Seventy-five percent of subjects with non-NF1 HGGs presented a PFS >4 months compared to 0% in NF1 patients. The 8-month OS of patients with non-NF1 HGGs was 81% compared to 0% in NF1 patients. Cerebral HGGs arising in midline structures rarely occur in pediatric patients with NF1 and present with extremely poor prognosis, worse than HGGs developing in non-NF1 patients, independent of the presence or absence of H3 K27M mutation. Imaging features of aggressive biological activity on advanced MRI or amino-acid PET imaging suggest prompt neuropathological and molecular investigations.
1型小儿神经纤维瘤病（NF1）患者很少发生侵袭性中枢神经系统肿瘤。在高级别胶质瘤（HGG）中，曾有过关于组蛋白突变型弥漫性中线胶质瘤（DMG H3 K27M突变型）的特别报道。这项回顾性单中心研究的目的是比较NF1患儿与非综合征性患儿中DMG H3 K27M突变型和非组蛋白突变型中线HGG的临床行为，并报告NF1相关HGG的影像学特征。我们对2010年至2018年在本机构接受随访的18例患有或未患有NF1的脑DMG H3 K27M突变型或非组蛋白突变型HGG患者进行了回顾性研究。评估了预后差异，尤其是无进展生存期（PFS）和总生存期（OS）。确定了2例经基因确诊为NF1且患有脑HGG的患者（1例为DMG H3 K27M突变型，1例为组蛋白野生型）。两名患者均表现为中线肿块病变，在先进的MRI或氨基酸PET上具有侵袭性生物学活性的影像学特征。在同一时期，本机构治疗了16例非NF1患者（11例为DMG H3 K27M突变型，5例为非组蛋白突变型中线HGG）。两名患有NF1和HGG的患者PFS为3个月，OS分别为5个月和7个月。无NF1患儿的DMG H3 K27M突变型的PFS和OS中位数分别为6个月和10个月，H3 K27M野生型肿瘤分别为6个月和11个月。非NF1 HGG患者中有75%的PFS>4个月，而NF1患者中这一比例为0%。非NF1 HGG患者的8个月OS率为81%，而NF1患者中这一比例为0%。发生在中线结构的脑HGG在患有NF1的小儿患者中很少见，且预后极差，比非NF1患者中发生的HGG更差，与是否存在H3 K27M突变无关。先进的MRI或氨基酸PET成像上侵袭性生物学活性的影像学特征提示应及时进行神经病理学和分子检查。
