Zhu Yi, Carabenciov Darin D, Johnson Derek R, Trejo-Lopez Jorge A, Nguyen Aivi T, Raghunathan Aditya, Lanzino Giuseppe, Ida Cristiane M, Zepeda-Mendoza Cinthya J, Dasari Surendra, Russler-Germain Emilie, Dahiya Sonika, Quezado Martha, Aldape Kenneth, Giannini Caterina
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Brain Pathol. 2025 Jul;35(4):e13326. doi: 10.1111/bpa.13326. Epub 2024 Dec 18.
Adult primary leptomeningeal gliomatosis (PLG) is a rare, rapidly progressive and fatal disease characterized by prominent leptomeningeal infiltration by a glial tumor without an identifiable parenchymal mass. The molecular profile of adult PLG has not been well-characterized. We report the clinical, pathological, and molecular findings of six adult PLG patients (five males and one female), median age 58 years. All cases exhibited pathological leptomeningeal enhancement at presentation. Leptomeningeal biopsy was diagnostic in five (of six) cases, revealing infiltration by an astrocytic glioma with mitotic activity, lacking microvascular proliferation or necrosis. One case was diagnosed at autopsy. All tumors were IDH-wildtype, with five harboring TERT promoter mutations. Additional mutations identified were PTEN in one case, TP53 in two cases, and NF1 in two cases. A chromosome profile with +7/-10 was found in four cases, whereas the remaining two showed either chromosome 7 or 7p gain only. Four cases showed chromosome 9p loss with CDKN2A/B homozygous deletion, one case showed hemizygous CDKN2A/B loss, and one case showed intact chromosome 9 and CDK4/GLI1 amplification. DNA methylation profiling was performed in four cases and revealed a match to glioblastoma (GBM) family and mesenchymal typical class with high confidence scores in two cases; the other two cases showed only suggestive combined scores for GBM family and mesenchymal atypical class. The molecular profile of all cases closely aligned with that of adult-type GBM, IDH-wildtype, CNS WHO grade 4. All patients succumbed to the disease. In five cases with extensive leptomeningeal disease at diagnosis, the course was rapid, with median survival of 24 days following palliative care. Only one case, with relatively localized disease at diagnosis, received chemoradiation therapy and survived 535 days, raising the possibility that early diagnosis and timely treatment could improve outcome. A detailed list of previously reported cases is provided in a supplementary table.
成人原发性软脑膜胶质瘤病（PLG）是一种罕见、进展迅速且致命的疾病，其特征是胶质肿瘤显著浸润软脑膜，而无明确的实质肿块。成人PLG的分子特征尚未得到充分描述。我们报告了6例成人PLG患者（5例男性和1例女性）的临床、病理和分子学发现，中位年龄58岁。所有病例在初诊时均表现出病理性软脑膜强化。软脑膜活检在6例中的5例具有诊断价值，显示为有丝分裂活性的星形胶质细胞瘤浸润，无微血管增生或坏死。1例在尸检时确诊。所有肿瘤均为异柠檬酸脱氢酶（IDH）野生型，其中5例存在端粒酶逆转录酶（TERT）启动子突变。另外鉴定出的突变包括1例中的磷酸酶和张力蛋白同源物（PTEN）、2例中的肿瘤蛋白p53（TP53）以及2例中的神经纤维瘤病1型（NF1）。4例发现有+7/-10的染色体谱，而其余2例仅显示7号染色体或7p增益。4例显示9号染色体短臂缺失伴细胞周期蛋白依赖性激酶抑制剂2A/2B（CDKN2A/B）纯合缺失，1例显示CDKN2A/B半合子缺失，1例显示9号染色体完整且细胞周期蛋白依赖性激酶4/胶质瘤相关癌基因同源物1（CDK4/GLI1）扩增。对4例进行了DNA甲基化分析，其中2例显示与胶质母细胞瘤（GBM）家族和间充质典型类别高度匹配；另外2例仅显示GBM家族和间充质非典型类别的提示性综合评分。所有病例的分子特征与成人型GBM、IDH野生型、世界卫生组织（WHO）中枢神经系统4级密切一致。所有患者均死于该疾病。在诊断时伴有广泛软脑膜疾病的5例患者中，病程进展迅速，姑息治疗后的中位生存期为24天。仅1例在诊断时疾病相对局限，接受了放化疗，存活了535天，这增加了早期诊断和及时治疗可能改善预后的可能性。补充表中提供了先前报道病例的详细列表。
