Brain tumors are increasingly understood as having components of a development organization in which malignant cells leverage neural progenitor programs, lineage hierarchies, and circuit interactions that normally shape the developing brain. This review examines how these principles inform the biology of ependymoma and gliomas across the age spectrum, including H3 K27-altered diffuse midline glioma, H3 G34-mutant diffuse hemispheric glioma, IDH-mutant glioma, and glioblastoma. We highlight how tumor identity reflects developmental timing, regional context, and cell-of-origin competence, while also emphasizing that malignant cells can acquire plasticity beyond their normal counterparts. Across entities, single-cell, spatial, lineage-tracing, and organoid studies reveal progenitor-like compartments that sustain tumor growth, generate heterogeneous malignant states, and interact dynamically with the neural and immune microenvironment. Cancer neuroscience further extends this developmental framework by showing that neuronal activity, synaptic input, and neuromodulatory signaling can regulate tumor proliferation, migration, epigenetic state, and therapeutic response. Together, these findings argue that brain tumors should be viewed not as disorganized cellular masses but as aberrant developmental systems. Defining the developmental dependencies and circuit vulnerabilities of malignant progenitor states may enable more precise therapies that target tumor biology while preserving essential brain function.

Tumors of the central nervous system harboring alterations of BCOR comprise a heterogeneous and evolving group of neoplasms. CNS tumors with BCOR internal tandem duplication are recognized as a distinct WHO entity, whereas tumors harboring EP300/CREBBP::BCOR/BCORL1 fusions represent an emerging and less clearly defined group with overlapping but non-identical morphologic and immunophenotypic features. We report a 42-year-old man with a supratentorial high-grade CNS neoplasm initially interpreted as a glial tumor with features suggestive of supratentorial anaplastic ependymoma. Histologically, the tumor showed marked intratumoral heterogeneity, with expansile/circumscribed ependymoma-like areas containing prominent perivascular pseudorosettes, and infiltrative high-grade areas with glioblastoma-like features, including extensive necrosis, marked microvascular proliferation, brisk mitotic activity and a Ki-67 index reaching approximately 70%. Immunohistochemistry showed GFAP negativity in the ependymoma-like areas and GFAP positivity in the high-grade glioblastoma-like component. OLIG2 was negative, EMA showed dot-like/paranuclear staining, and BCOR demonstrated moderate diffuse nuclear expression. RNA-based targeted sequencing identified reciprocal EP300::BCOR and BCOR::EP300 fusion junctions. FISH demonstrated homozygous CDKN2A/B deletion and 1q32 gain, findings subsequently supported by DNA-based copy-number analysis within an aneuploid profile. No reportable SNV or indel alterations of established diagnostic significance were identified. DNA methylation profiling was not performed. Accordingly, the integrated diagnostic interpretation was based on morphology, immunophenotype and RNA-based fusion detection, without methylation-class confirmation. This case expands the recognized morphologic and immunophenotypic spectrum of CNS tumors with EP300::BCOR fusion and highlights the diagnostic value of fusion testing in ependymoma-like supratentorial tumors with additional high-grade glioma-like features.

The diagnosis and classification of central nervous system (CNS) tumors has undergone a paradigm shift over the past decade, evolving from a purely histology-based approach to an integrated framework that incorporates molecular and epigenetic features. This review summarizes recent updates in key genomic and epigenomic biomarkers across major CNS tumor categories, with a focus on their diagnostic, prognostic, and therapeutic implications. DNA methylation profiling has emerged as a valuable tool for tumor classification, subgrouping, and grading, complementing traditional histopathologic assessment. Across diffuse gliomas, newly characterized molecular alterations have refined grading criteria and clarified the boundaries between tumor types, including important caveats about the use of individual molecular features as sole diagnostic criteria. In ependymomas, medulloblastomas, atypical teratoid/rhabdoid tumors, meningiomas, pineal tumors, and embryonal tumors, methylation profiling now defines biologically and clinically meaningful subgroups that inform risk stratification and treatment selection. The emerging recognition of mismatch repair-deficient gliomas and fusion-driven tumor entities further underscores the expanding complexity of CNS tumor taxonomy. As molecular technologies continue to advance, the integration of genomic, epigenomic, histopathologic, and clinical data will be essential to improving diagnostic precision, guiding therapy, and ultimately enhancing patient outcomes.

Dysphagia is a frequent postoperative complication in children undergoing surgery for posterior fossa tumors (PFTs), yet early swallowing trajectories remain insufficiently characterized despite the growing focus on functional outcomes in pediatric neuro-oncology.

Background/Objectives: Oligodendroglioma-like morphology may generate diagnostic uncertainty in central nervous system tumors, although oligodendroglioma is defined by the integrated presence of IDH mutation and whole-arm 1p/19q codeletion. This study aimed to evaluate the diagnostic pitfalls of oligodendroglioma-like morphology by comparing initial microscopic impressions with final integrated diagnoses. Methods: We retrospectively reviewed 23 non-oligodendroglial central nervous system tumors showing focal or predominant oligodendroglioma-like morphology but not fulfilling the integrated diagnostic criteria for oligodendroglioma. Clinical, radiological, histopathological, immunohistochemical, molecular/cytogenetic, initial microscopic impression, final integrated diagnosis, and follow-up data were analyzed descriptively. Results: Initial microscopic impressions included low-grade glial tumor, high-grade glial tumor, dysembryoplastic neuroepithelial tumor, ependymoma, astroblastoma, oligodendroglioma, dysplasia, central neurocytoma, metastatic epithelial tumor, and pilocytic astrocytoma/low-grade glial tumor. Final integrated diagnoses were astrocytoma, IDH-mutant, CNS WHO grade 2-4 (n = 9); dysembryoplastic neuroepithelial tumor (n = 3); central neurocytoma (n = 3); metastatic renal cell carcinoma (n = 2); low-grade glioneuronal tumor (n = 2); and PLNTY, glioblastoma IDH-wildtype, supratentorial ependymoma, and pilocytic astrocytoma (n = 1 each). Conclusions: Oligodendroglioma-like morphology should be interpreted as a diagnostic pitfall pattern rather than a specific diagnosis. Structured integrated reappraisal using targeted immunohistochemical and molecular/cytogenetic testing helps refine differential diagnosis in routine neuropathology practice.

Adolescents and young adults (AYA) with central nervous system (CNS) tumors represent a distinct and historically underrecognized population that spans the traditional pediatric-adult oncology divide, with unique biological, clinical, and survivorship considerations. The central nervous system (CNS) tumor spectrum in this age band is thus broad: pediatric-type entities driven by MAPK-pathway alterations, adult-type IDH- and H3-mutant gliomas, embryonal tumors, ependymomas, and intracranial germ cell tumors all appear, and prognosis and treatment are increasingly determined by molecular subtype rather than chronologic age. Integrated workflows combining neuroimaging, histopathology, and molecular profiling now anchor diagnosis and risk stratification. Treatment strategy - surgery, radiotherapy, systemic and targeted agents, and emerging immunotherapies - must balance efficacy against the cumulative late effects that come with it: neurocognitive change, endocrinopathy, vasculopathy, fertility loss, psychosocial disruption, and gaps in transition of care. Germline predisposition syndromes contribute meaningfully to disease biology and have implications for treatment, surveillance, and family screening. This review synthesizes the current evidence across diagnosis, treatment, survivorship, and predisposition, and argues for the consolidation of AYA neuro-oncology as a distinct discipline supported by dedicated trial access and survivorship infrastructure.