CNS Tumor

Differential considerations, including epithelioid sarcoma, poorly differentiated chordoma, CRINET, choroid plexus carcinoma, and rare composite tumors, further complicate the diagnostic landscape. A comprehensive, multimodal diagnostic approach combining histologic, immunophenotypic, and molecular data is essential to accurately identify AT/RT and guide clinical management, particularly in diagnostically ambiguous or atypical cases.

Finally, we outline a translational roadmap that pairs patient-derived iPSC/organoid and organ-on-a-chip platforms to stratify EndMT states and prioritize targets. We also explore combination regimens that integrate multi-pathway modulation with epigenetic and immune approaches, aiming to deliver clinically meaningful anti-fibrotic benefits while better preserving physiological signaling.

Overall, the R273C mutation, although mechanistically unclear, is more prevalent than other TP53 variants and defines a distinct biological subset of LGIMAs, marked by increased Ki-67 and female predominance. Incorporating TP53 and broader genetic profiling via NGS could improve our understanding of LGIMAs and support a refined classification system, enhancing diagnostic and prognostic accuracy.

Finally, we propose future directions focused on decoding tissue-specific immunodynamics and developing spatiotemporally controlled, multiorgan immunoregulatory frameworks. Together, this review underscores cGAS-STING as a promising therapeutic axis in the evolving landscape of neuroimmunology.

Dabrafenib plus trametinib has shown superiority over chemotherapy in pediatric low-grade gliomas and activity against high-grade diseases. Larotrectinib and entrectinib provide tumor-agnostic options for NTRK-fusion-positive tumors with central nervous system penetration. Selumetinib offers clinical benefits in NF1-associated plexiform neurofibromas and shows promise for treating NF1-related low-grade gliomas. Tovorafenib, a type II RAF inhibitor active in BRAF-altered tumors (including BRAFKIAA1549 fusion), achieved robust responses, thereby leading to FDA approval. ONC201 (dordaviprone) has received accelerated approval for the treatment of H3 K27M-mutant diffuse midline gliomas, with Japanese trials and patient-initiated programs expanding access. Abemaciclib, a CDK4/6 inhibitor, is under phase II evaluation for pediatric high-grade glioma and diffuse midline glioma, including sites in Japan. Neurosurgeons play a pivotal role in securing high-quality biopsies, thus enabling comprehensive molecular diagnostics and facilitating enrollment in international trials. This review summarizes current targeted therapies and ongoing studies and outlines practical considerations for integrating precision oncology into pediatric neuro-oncology in Japan.

In here we report a case of a female patient who developed LMD from a Pleomorphic Xanthoastrocytoma (PXA), BRAFV600-mutated, who has shown successful response to treatment with BRAF/MEKi (Encorafinib/Binimetinib) for over 3 years since initial LMD diagnosis. The effectiveness of therapy in this patient was initially observed as stable disease, with radiographic progression when BRAF/MEKi were withheld, and immediate tumor control achieved when reinstated. Despite being just one case, this hopefully could serve as proof-of-concept for use of targeted therapy for BRAF V600E-mutated tumors with LMD progression, sparing patients from alternative tumor control options such as radiation therapy.

The patient subsequently underwent chemotherapy with temozolomide and external beam radiation therapy with 60 Gy over 30 fractions...The patient was subsequently placed on bevacizumab...Additionally, there is difficulty in differentiating these tumors from meningiomas, with resultant misdiagnosis and management. It is critical to inform readers of its presence and emphasize the importance of its consideration in the differential diagnosis of dural-based tumors.

We analyze the correlation between CXCL13/CXCR5 and the infiltration of immune cells (T cells, macrophages), the expression of immune checkpoints (PD-L1, CD39). The CXCL13/ CXCR5 axis may exert a bidirectional regulatory effect of anti-tumor immunity and tumor immune evasion through multiple mechanisms, such as influencing the infiltration of immune cells, the expression of immune checkpoints, and the immune function of the peripheral blood, which ultimately affects the therapeutic efficacy and prognosis of PCNS-DLBCL.

This review aims to comprehensively examine the association between IDH1/2 mutations and BBB disruption, elucidating how IDH1/2-mutant gliomas alter tumor-associated metabolic and epigenetic pathways, which subsequently influence microglial activation and polarization, contributing to BBB impairment. Furthermore, we propose that microglia-mediated BBB disruption may be one of the underlying mechanisms contributing to complications in IDH1/2-mutant gliomas, such as vasogenic edema and immune-mediated encephalopathy, both of which are closely associated with BBB breakdown.

P1/2, N=14, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2025 --> Oct 2026

Despite initial histopathologic features of benignity and absence of BRAF mutation, the lesion showed aggressive behavior. This case underscores the diagnostic pitfalls associated with primary CNS melanocytic tumors and highlights the importance of long-term vigilance, even for histologically benign lesions.

P1, N=12, Not yet recruiting, Neonc Technologies, Inc. | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2025 --> Oct 2026