Mulone Davide, Mafficini Andrea, Miele Evelina, Sala Francesco, Barresi Valeria
Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
Dipartimento di Ingegneria per la Medicina di Innovazione, University of Verona, Verona, Italy.
Neuropathology. 2025 Apr;45(2):167-173. doi: 10.1111/neup.13013. Epub 2024 Nov 4.
Subependymal giant cell astrocytoma (SEGA) is a rare, low-grade glioma typically associated with tuberous sclerosis (TS) and mutations in the TSC1 or TSC2 genes. It is characterized by an intraventricular location, an expansive growth pattern, and the expression of glial and neural markers. TTF-1 expression is considered a sensitive marker of SEGA, likely reflecting its origin from progenitor cells in the caudothalamic groove. We report a case of SEGA with unusual immunohistochemical and molecular features in a 20-year-old man with no signs or family history of TS. The tumor was located in the anterior horn of the right ventricle and obstructed the foramen of Monro. Histologically, it exhibited an expansive growth pattern and was composed of cells with ovoid nuclei and abundant eosinophilic cytoplasm. Immunohistochemically, the tumor cells were positive for GFAP and S-100 protein, weakly positive for SOX2, focally positive for synaptophysin, and negative for TTF-1, neurofilament protein, NeuN, EMA, chromogranin, and BCOR. Scattered OLIG2-positive neoplastic cells were also observed. Molecular analysis revealed no pathogenic mutations or copy number variations in the analyzed 174 genes, including TSC1/2, except for a variant of unknown significance in BAP1. The histopathological features and immunohistochemical profile suggested SEGA, despite the absence of TTF-1 expression and TSC1/2 mutations. The diagnosis was confirmed by DNA methylation profiling, which assigned the tumor to the methylation class "subependymal giant cell astrocytoma with TSC1/TSC2 alterations" with a calibrated score of 0.95. This case highlights the potential diagnostic pitfall of SEGA lacking TTF-1 expression and emphasizes the importance of considering this entity in the differential diagnosis of intraventricular tumors, even in the absence of TS and characteristic molecular alterations. The existence of TTF-1 negative SEGAs reveals that these tumors might also derive from TTF-1 negative cells in the subpendymal region.
室管膜下巨细胞星形细胞瘤（SEGA）是一种罕见的低级别胶质瘤，通常与结节性硬化症（TS）以及TSC1或TSC2基因突变相关。其特征为位于脑室内、呈膨胀性生长模式，并表达胶质和神经标志物。甲状腺转录因子-1（TTF-1）表达被认为是SEGA的一个敏感标志物，可能反映其起源于丘脑尾侧沟的祖细胞。我们报告一例20岁男性的SEGA病例，该病例具有不寻常的免疫组化和分子特征，且无TS的体征或家族史。肿瘤位于右心室前角，阻塞了孟氏孔。组织学上，它呈膨胀性生长模式，由具有卵圆形核和丰富嗜酸性细胞质的细胞组成。免疫组化方面，肿瘤细胞GFAP和S-100蛋白阳性，SOX2弱阳性，突触素局灶性阳性，而TTF-1、神经丝蛋白、NeuN、EMA、嗜铬粒蛋白和BCOR阴性。还观察到散在的OLIG2阳性肿瘤细胞。分子分析显示，在所分析的174个基因中，包括TSC1/2，除了BAP1中有一个意义不明的变异外，未发现致病突变或拷贝数变异。尽管缺乏TTF-1表达和TSC1/2突变，但组织病理学特征和免疫组化谱提示为SEGA。DNA甲基化谱分析确诊了该诊断，将肿瘤归为甲基化类别“伴有TSC1/TSC2改变的室管膜下巨细胞星形细胞瘤”，校准分数为0.95。该病例突出了缺乏TTF-1表达的SEGA潜在的诊断陷阱，并强调了即使在没有TS和特征性分子改变的情况下，在脑室内肿瘤的鉴别诊断中考虑这一实体的重要性。TTF-1阴性SEGA的存在表明这些肿瘤也可能起源于室管膜下区域的TTF-1阴性细胞。
