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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. [ABSTRACT FROM AUTHOR]

Simple Summary: FGFR3::TACC3 fusion is a driver, potentially targetable, alteration detected in approximately 4% of diffuse gliomas. Diffuse gliomas with FGFR3::TACC3 fusion (F3T3 gliomas) and high-grade histological features harbor molecular stigmata and the DNA methylation profile of glioblastoma, though they are associated with slightly longer patient survival. Histologically low-grade F3T3 gliomas are molecularly heterogeneous and likely comprise three epigenetic groups. One includes tumors, exclusive to adults, displaying genetic and epigenetic features of glioblastoma and potentially representing precursors of high-grade gliomas. The second group lacks the molecular features of glioblastoma and has an epigenetic profile similar to that of dysembryoplastic neuroepithelial tumors. Finally, tumors in the third group are epigenetically close to gangliogliomas. Owing to their genetic and epigenetic heterogeneity, F3T3 gliomas do not represent a distinct nosological entity. Further research is needed to clarify the prognosis, refine the grading, and determine the optimal treatment approaches for these tumors. FGFR3::TACC3 fusion is a driver, potentially targetable, genetic alteration identified in approximately 4% of high-grade diffuse gliomas and rare cases with low-grade histology. Herein, we review the genetic and epigenetic features of these tumors and highlight the challenges in their classification and grading. Diffuse gliomas with FGFR3::TACC3 fusion display unique histopathological and molecular features, including an oligodendroglioma-like appearance, calcifications, and CD34 extravascular immunoreactivity. High-grade tumors exhibit molecular alterations and a DNA methylation profile typical of glioblastoma, suggesting that they may represent a subtype clinically characterized by a slightly better prognosis. Tumors with low-grade morphology are genetically and epigenetically heterogeneous. Some, exclusive to adults, have molecular alterations typical of glioblastoma, although most do not match any methylation classes, using version 12.5 of the Heidelberg classifier. Another group, which mostly affects children or adolescents, lacks the molecular features of glioblastoma and has a DNA methylation profile similar to that of low-grade glioneuronal tumors. In conclusion, diffuse gliomas with FGFR3::TACC3 fusion do not constitute a distinct nosological entity, owing to their genetic and epigenetic diversity. Further studies are warranted to clarify the biological aggressiveness of tumors with low-grade histology to refine the grading and determine the optimal treatment strategy. [ABSTRACT FROM AUTHOR]

This article discusses the case of a 31-year-old woman who presented with symptoms of headache, dizziness, and phosphenes. Magnetic resonance imaging (MRI) revealed a well-circumscribed mass in the left cerebellar hemisphere. The tumor was diagnosed as a cerebellar liponeurocytoma, a rare and slow-growing tumor that occurs in the cerebellum. The article highlights the diagnostic challenges of distinguishing cerebellar liponeurocytoma from other tumors, such as medulloblastoma, and emphasizes the importance of thorough examination and analysis of histological and immunohistochemical features for accurate diagnosis. The study concludes that cerebellar liponeurocytoma has distinct genetic and epigenetic features that can aid in diagnosis, and that the identification of lipomatous foci is crucial for distinguishing this tumor from other similar tumors. [Extracted from the article]