Davide Mulone, Andrea Mafficini, Evelina Miele, Francesco Sala, Valeria Barresi
{"title":"Solitary subependymal giant cell astrocytoma lacking TSC1/2 mutations and TTF-1 expression: A potential diagnostic pitfall.","authors":"Davide Mulone, Andrea Mafficini, Evelina Miele, Francesco Sala, Valeria Barresi","doi":"10.1111/neup.13013","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":""},"PeriodicalIF":1.3000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuropathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/neup.13013","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
Neuropathology is an international journal sponsored by the Japanese Society of Neuropathology and publishes peer-reviewed original papers dealing with all aspects of human and experimental neuropathology and related fields of research. The Journal aims to promote the international exchange of results and encourages authors from all countries to submit papers in the following categories: Original Articles, Case Reports, Short Communications, Occasional Reviews, Editorials and Letters to the Editor. All articles are peer-reviewed by at least two researchers expert in the field of the submitted paper.