Supplementary Material for: Improved diagnosis of glioblastoma, IDH-wildtype, metastasis through molecular and DNA methylation profiling: Two case reports

Glioblastoma, the most common primary malignant brain tumor in adults, accounts for approximately 50% of primary malignant brain tumors. Extracranial metastases are extremely rare, affecting <0.5% of patients. This article describes two cases where Next-Generation Sequencing and DNA methylation profiling, confirmed extracranial metastases of glioblastoma, IDH-WT. The first case involves a 77-year-old man who developed lung and liver mass within months of diagnosis. While both biopsies revealed undifferentiated malignant tumor, identical genetic mutations on the lung biopsy and DNA methylation profiling on the liver biopsy confirmed glioblastoma metastases. The second case details a 75-year-old women diagnosed with glioblastoma, IDH-WT who presented diffuse bone infiltration. Bone marrow aspirate and bone marrow biopsy associated with NGS and methylation profiling confirmed glioblastoma metastasis. Both patients succumbed within 8 months. These cases underscore the importance of molecular diagnostics in identifying glioblastoma metastases and guiding treatment, particularly in rare presentations involving extracranial spread.

胶质母细胞瘤（Glioblastoma）是成人最常见的原发性恶性脑肿瘤，约占原发性恶性脑肿瘤总数的50%。颅外转移极为罕见，受累患者比例不足0.5%。本文报道两例经下一代测序（Next-Generation Sequencing）与DNA甲基化谱分析（DNA methylation profiling）证实的异柠檬酸脱氢酶野生型（IDH-WT）胶质母细胞瘤颅外转移病例。首例患者为77岁男性，确诊后数月内出现肺部与肝脏占位。尽管两次活检均提示为未分化恶性肿瘤，但肺部活检检出的一致性基因突变与肝脏活检的DNA甲基化谱分析结果，证实病灶为胶质母细胞瘤转移灶。第二例为75岁女性，确诊为异柠檬酸脱氢酶野生型胶质母细胞瘤后出现弥漫性骨浸润。骨髓穿刺与骨髓活检结合下一代测序及甲基化谱分析，证实病灶为胶质母细胞瘤转移灶。两名患者均在确诊后8个月内离世。上述病例凸显了分子诊断在识别胶质母细胞瘤转移灶、指导临床治疗中的重要价值，尤其针对罕见的颅外扩散表现病例。