Anghileri Elena, Castiglione Melina, Nunziata Raffaele, Boffano Carlo, Nazzi Vittoria, Acerbi Francesco, Finocchiaro Gaetano, Eoli Marica
Neurosurg Rev. 2016 Jan;39(1):37-45; discussion 45-6. doi: 10.1007/s10143-015-0656-9. Epub 2015 Jul 28.
Glioblastoma (GBM) are high-grade gliomas that severely impact on overall survival (OS). GBM cell motility and the breakdown of the blood-brain barrier could favor GBM cell communication with the systemic circulation. In spite of this, extracranial GBM metastases are rare. Here, we describe two YKL-40-positive GBM patients with extra-CNS (central nervous system) metastases, and we present a meta-analysis of 94 cases. The analysis concluded that extra-CNS metastases occurred 8.5 months after first GBM diagnosis and OS was 12 months; surgical GBM excision was associated at a longer interval to extra-CNS metastasis than biopsy only, and even longer if followed by radiotherapy and chemotherapy. Both our case reports were adult males who developed extra-CNS, YKL-40-positive metastases at lymph nodes, lung and subcutaneous sites, after 86 and 24 months from initial diagnosis of GBM. At first GBM local recurrence, they were treated with bevacizumab (BV), an anti-vascular endothelial growth factor antibody. They died after 4 and 1 month from the occurrence of metastases. Both cases expressed YKL-40 and lacked EGFR amplification, suggesting a mesenchymal phenotype, and maintained such profile at extra-CNS recurrence; they did not show MGMT promoter methylation, IDH1/2 mutations, or c-Met upregulation. Our two cases and the meta-analysis support the idea that prolonged survival of GBM patients increases the probability of GBM cells shedding to lymphatic and hematic system. Interestingly, the present two cases showed the features of mesenchymal profile, usually related with worst prognosis that was maintained in extracranial metastases.
胶质母细胞瘤（GBM）是高级别胶质瘤，严重影响总生存期（OS）。GBM细胞的运动性以及血脑屏障的破坏可能有利于GBM细胞与体循环进行交流。尽管如此，颅外GBM转移却很少见。在此，我们描述了两名发生中枢神经系统（CNS）外转移的YKL-40阳性GBM患者，并对94例病例进行了荟萃分析。分析得出，CNS外转移发生在首次诊断GBM后8.5个月，总生存期为12个月；与仅进行活检相比，手术切除GBM与CNS外转移的间隔时间更长，如果随后进行放疗和化疗则间隔时间更长。我们的两个病例报告均为成年男性，在GBM初始诊断86个月和24个月后，在淋巴结、肺和皮下部位发生了CNS外、YKL-40阳性转移。在首次GBM局部复发时，他们接受了贝伐单抗（BV）治疗，这是一种抗血管内皮生长因子抗体。他们在转移发生后4个月和1个月死亡。两例均表达YKL-40且缺乏表皮生长因子受体（EGFR）扩增，提示为间充质表型，并且在CNS外复发时保持这种特征；它们未显示O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子甲基化、异柠檬酸脱氢酶1/2（IDH1/2）突变或c-Met上调。我们的两个病例以及荟萃分析支持这样一种观点，即GBM患者生存期延长会增加GBM细胞进入淋巴和血液系统的可能性。有趣的是，目前这两个病例表现出间充质特征，通常与预后最差相关，且在颅外转移中保持这一特征。
