Švajdler Marián, Brousil Marek, Soukup Jiří, Netuka David, Kašparová Petra, Rychlý Boris, Jirásek Tomáš, Hendrych Michal, Farcas Mihaela, Pivovarčíková Kristýna, Vaněček Tomáš, Martínek Petr, Mezencev Roman
Šikl's Department of Pathology, Faculty of Medicineand, Faculty of Medicine and University Hospital in Pilsen, Charles University, Alej Svobody 80, Pilsen, 323 00, Czech Republic.
Bioptical Laboratory, Ltd., Pilsen, Czech Republic.
Virchows Arch. 2025 May 27. doi: 10.1007/s00428-025-04110-9.
Subependymal giant cell astrocytoma (SEGA) is a World Health Organization Central Nervous System grade 1 tumor, strongly associated with tuberous sclerosis complex (TSC). Recent research indicates that Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB), regulated by microphthalmia (MiT) family transcription factors may also be modulated by loss-of-function mutations in TSC1/2. We evaluated GPNMB as a diagnostic marker of subependymal giant cell astrocytoma (SEGA). A total of 11 patients with SEGA were included in the study. The control group comprised 185 primary central nervous system tumors, including high-grade and low-grade gliomas and glioneuronal/neuronal tumors. Strong and diffuse (≥ 50% of tumor cells) GPNMB expression was present in all SEGAs. In contrast, TTF-1 expression was detected in nine SEGAs, resulting in a sensitivity of 81.8%. Among the control group, 77 cases (41.6%) were negative for GPNMB and 102 (55.1%) cases were scored as > 1% < 50% positive. Only six control tissues (3.2%) showed diffuse and strong GPNMB expression. Among the tumors with strong GPNMB expression, there were three glioblastomas (GBMs) with morphology potentially mimicking SEGA but lacking TSC1, TSC2, or MTOR mutations. Using a cutoff of diffuse (≥ 50%) and strong positivity, GPNMB demonstrated 100% sensitivity (95% confidence interval: 74.1%-100%) and 96.8% specificity (95% confidence interval: 93.1%-98.5%) for diagnosing SEGA.
室管膜下巨细胞星形细胞瘤（SEGA）是世界卫生组织中枢神经系统1级肿瘤，与结节性硬化症（TSC）密切相关。最近的研究表明，受小眼畸形（MiT）家族转录因子调控的糖蛋白非转移性黑色素瘤蛋白B（GPNMB）也可能因TSC1/2功能丧失突变而受到调节。我们评估了GPNMB作为室管膜下巨细胞星形细胞瘤（SEGA）诊断标志物的价值。该研究共纳入11例SEGA患者。对照组包括185例原发性中枢神经系统肿瘤，包括高级别和低级别胶质瘤以及神经胶质神经元/神经元肿瘤。所有SEGA均存在强且弥漫性（≥50%肿瘤细胞）的GPNMB表达。相比之下，9例SEGA检测到TTF-1表达，敏感性为81.8%。在对照组中，77例（41.6%）GPNMB阴性，102例（55.1%）评分为>1%<50%阳性。仅6例对照组织（3.2%）显示弥漫性强GPNMB表达。在GPNMB强表达的肿瘤中，有3例胶质母细胞瘤（GBM），其形态可能模仿SEGA，但缺乏TSC1、TSC2或MTOR突变。以弥漫性（≥50%）和强阳性为临界值，GPNMB诊断SEGA的敏感性为100%（95%置信区间：74.1%-100%），特异性为96.8%（95%置信区间：93.1%-98.5%）。
