Meningiomas are common intracranial tumors, but their slowly progressive and atypical presentations are frequently mistaken for peripheral neurologic, musculoskeletal, or ocular conditions. We describe a 60-year-old left-handed man who developed several months of progressive right-sided gait imbalance, proprioceptive deficits, intermittent binocular visual blurring, and late cognitive changes. Evaluations by podiatry, chiropractic care, physical therapy, and optometry initially failed to uncover the cause. Brain MRI eventually revealed a large left posterior parietal dural-based mass with classic meningioma features, marked vasogenic edema, mass effect, and midline shift. Gross-total resection confirmed a WHO grade 1 meningioma (Ki-67 index 15 %). This case emphasizes an atypical presentation with progressive unilateral gait dysfunction accompanied by proprioceptive loss, pyramidal signs, visual symptoms, or cognitive decline. Refractory treatments should prompt early neuroimaging, even after negative peripheral workups. It also highlights how specialty-specific anchoring bias can delay recognition of central nervous system lesions.

Primary cardiac angiosarcoma is a rare and aggressive malignancy that mainly affects the right atrium of the heart. In this report, we present a rare variant known as cardiac epithelioid angiosarcoma. Due to its rarity, the epidemiology and pathogenesis of this disease are not well understood. We present the case of a 44-year-old woman who presented with palpitations, chest pain, and symptomatic bradycardia. Multimodal imaging identified a large, sessile right atrial mass. The location of the mass near the sinoatrial node region likely contributed to the patient's bradycardia. The patient underwent surgical resection with bovine pericardial patch reconstruction. Histopathology favored epithelioid angiosarcoma, and the margins were unclear due to specimen fragmentation. The postoperative course was complicated by junctional rhythm bradyarrhythmia requiring pacing. Comprehensive staging, including brain MRI and CT of the chest, abdomen, and pelvis, ruled out distant metastasis. The patient was deemed not to be a candidate for radiation therapy due to the tumor's location in the heart. Although adjuvant AIM chemotherapy (doxorubicin, ifosfamide, mesna) was recommended by oncology, the patient opted for observation, given the limited expected benefit of chemotherapy. This case highlights the complexity of managing primary cardiac angiosarcoma, particularly when standard therapeutic options are limited, and underscores the need for individualized, multidisciplinary care.

Primary intracranial Ewing sarcoma / Ewing-like sarcoma is an exceptionally rare malignant small round cell tumor. Its radiological appearance is often non-specific and may mimic other aggressive intracranial neoplasms, leading to diagnostic delay. We report the case of a young adult presenting with progressive headaches and recurrent generalized tonic-clonic seizures for six months, followed by rapid bilateral visual loss. Neurological examination revealed papilledema and decreased visual acuity, prompting brain imaging. MRI demonstrated a large aggressive frontal mass with heterogeneous enhancement, marked diffusion restriction, meningeal involvement, and significant mass effect with midline crossing. Initial staging showed no extracranial disease. Histopathology revealed a small round cell tumor with strong membranous CD99 expression consistent with an intracranial Ewing-like sarcoma. The patient received multimodal treatment including radiotherapy and VDC/IE chemotherapy. Follow-up imaging demonstrated partial tumor response. However, no visual recovery occurred, and the patient remained limited to light and shadow perception. This case highlights the diagnostic challenges of primary intracranial Ewing-like sarcoma and its potential to present with severe and irreversible visual impairment. Early neuroimaging in patients with persistent seizures is essential to avoid diagnostic delay, and molecular confirmation remains crucial for future cases.

We present a rare case of pulmonary large-cell neuroendocrine carcinoma (LCNEC) manifesting as a solitary, calcified brain metastasis (CBM) in a 69-year-old woman with no known malignancy or respiratory symptoms. Computed tomography (CT) of the brain revealed a large, heterogeneous left frontal lobe mass with coarse intratumoral calcification and central necrosis. Magnetic resonance imaging (MRI) demonstrated ring-like peripheral enhancement, peritumoral edema, and signal voids on gradient-echo (GRE) sequences, suggesting calcification and/or hemorrhage. A solitary pulmonary nodule was identified in the right upper lobe on preoperative chest CT, and the serum progastrin-releasing peptide (proGRP) level was markedly elevated, suggesting a neuroendocrine tumor. Differential diagnoses included high-grade glioma, particularly oligodendroglioma, based on the lesion's location and calcification. Intraoperatively, the tumor was partially calcified and infiltrated the eloquent cortex, necessitating subtotal resection near the pyramidal tract. Frozen sections revealed a proliferation of atypical large cells with rosette-like structures and nuclear palisading, which are inconsistent with glioma and suggestive of a metastatic neuroendocrine neoplasm. Final pathological examination confirmed metastatic LCNEC. Although CBMs are not exceedingly rare, their imaging features can mimic those of primary brain tumors, potentially delaying diagnosis. This case underscores the importance of considering metastatic LCNEC in the differential diagnosis of solitary calcified brain lesions and highlights the practical impact of intraoperative pathology on surgical decision-making.

Pituitary carcinoma is an exceptionally rare and aggressive tumor, often diagnosed late due to nonspecific symptoms. Its presentation as postpartum cerebral venous thrombosis is extremely uncommon, and the coexistence of antiphospholipid syndrome further complicates diagnosis and management. We report the case of a 30-year-old woman with a history of recurrent miscarriages who presented 45 days postpartum with severe intracranial hypertension syndrome. Brain magnetic resonance imaging (MRI) with venous MR angiography demonstrated thrombosis of the right lateral sinus extending into the internal jugular vein, along with an invasive intra-sellar mass compressing the optic chiasm and filling the sphenoid sinus. Endoscopic endonasal transsphenoidal surgery allowed partial tumor resection with optic pathway decompression, and histopathology confirmed pituitary carcinoma. The etiologic workup identified positive antiphospholipid antibodies. Management included full-dose anticoagulation and close neurological, endocrinological, and hematological monitoring. This report illustrates a rare and diagnostically challenging coexistence of antiphospholipid syndrome and invasive pituitary carcinoma. It highlights the diagnostic complexity and the need for rapid, multidisciplinary management in atypical presentations.

Meningiomas are the most common primary intracranial tumors and the only brain tumors that are more common in females compared with males1. Progestin hormonal therapies increase the risk of meningioma, and progestin-induced or pregnancy-associated meningiomas can regress as serum progestogen levels normalize2. The mechanisms that underlie sex differences and progestogen signaling in meningioma are unknown. Here we show that sex hormone interaction with PGRMC1, a transmembrane progesterone binding protein, regulates the activity of RNA processing proteins FXR1 and RBM39 to drive meningioma sex differences. The genomic architecture and stem cells underlying meningiomas are conserved across vertebrate species3-5 and, using mass spectrometry-based proteomics to analyze 703 meningioma and meningeal samples, we demonstrate that meningiomas are enriched in RNA processing proteins in humans and dogs. Interactions between PGRMC1, FXR1, and RBM39 are inhibited by progestogens and stabilized by testosterone. After release from PGRMC1, FXR1 and RBM39 bind and stabilize progesterone receptor (PR) transcript to enable expression of PR protein, which induces cell cycle, membrane, and cytoskeleton remodeling genes that drive tumor growth. These findings reveal therapeutic strategies and a PR target gene biomarker that may improve outcomes for patients. More broadly, we elucidate an estrogen receptor-independent mechanism of PR expression that underlies sex differences in cancer.

Immune checkpoint modulation has emerged as a promising strategy in cancer therapy, including the treatment of aggressive tumors such as glioblastoma. Among these targets, programmed death-ligand 1 (PD-L1) plays a key role in tumor immune evasion and represents an attractive target for small-molecule inhibitor development. In this study, a virtual screening approach was applied to identify potential PD-L1 modulators within a library of nucleoside-related compounds and structurally similar molecules. A dataset of 400 compounds was evaluated using molecular docking to predict their binding affinity (free energy values and binding pose) toward PD-L1. The resulting complexes were analyzed to identify nonbond interactions within the hydrophobic pocket formed at the PD-L1 dimer interface. In addition to docking results, physicochemical descriptors associated with drug-likeness and blood-brain barrier penetration were calculated, including lipophilicity, molecular weight, hydrogen bond donors and acceptors, as well as topological polar surface area. To integrate these parameters, a multiparameter optimization (MPO) score was implemented. Finally, molecular dynamics simulations of protein-ligand interactions were performed to explore the structural stability for 100 ns using the most promising ligands. The analysis revealed that several top-ranked compounds exhibited favorable docking scores and physicochemical properties compatible with drug-like behavior. Interestingly, BMS-1, a known PD-L1 inhibitor, was identified among the highest-scoring compounds, supporting the reliability of the MPO protocol. Furthermore, multiple candidates displaying nucleoside-like scaffolds combined with reduced polarity and moderate lipophilicity emerged as promising molecules according to the MPO ranking. Overall, the results suggest that nucleoside-derived scaffolds may represent a viable starting point for the development of small-molecule PD-L1 modulators with potential applicability in glioblastoma therapy.

Oncogenic BRAF alterations occur in a subset of diffuse gliomas across WHO grades and are increasingly identified through modern molecular diagnostics. In addition to standard glioma therapies, targeted treatments are available for patients with BRAF-altered glioma supported by variable evidence spanning randomized trials, single-arm studies, and real-world evidence. This joint consensus review from the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO) synthesizes current knowledge on the diagnosis and management of BRAF-altered gliomas across age groups, tumor grades, and lines of therapy. Particular emphasis is placed on expert consensus in clinical scenarios where high-quality trial evidence remains limited. The review addresses rationale testing for BRAF alterations, selection, and monitoring of targeted therapies, management of treatment-related toxicities, approaches to resistance, and priorities for future research. It aims to provide practical, evidence-based guidance for clinicians while highlighting gaps to inform prospective studies.

Synovial sarcoma is a high-grade soft-tissue sarcoma that commonly affects adolescents and young adults. Involvement of the head and neck region is rare, and tumors arising from the sinonasal tract are particularly uncommon and diagnostically challenging. We report the case of a 38-year-old male who presented with head trauma and decreased consciousness following a transient neurological episode while driving. Brain computed tomography revealed a lesion involving the left anterior ethmoidal air cells with associated old cerebral infarctions. Further magnetic resonance imaging demonstrated an aggressive enhancing sinonasal mass with limited intracranial extension, associated with radiologic findings suggestive of vasculitis and acute-on-chronic ischemic insults. Histopathological evaluation showed a spindle-cell neoplasm considered most consistent with synovial sarcoma based on morphology and available immunohistochemical findings. The patient was started on neoadjuvant chemotherapy, after which the vasculitic findings showed regression, suggesting a probable paraneoplastic vasculitic association. Due to the complex anatomical location and local extension of the tumor, complete surgical resection was not initially feasible. Planned management included combined chemoradiotherapy with consideration of future surgical intervention. This case highlights the diagnostic and therapeutic challenges of sinonasal synovial sarcoma and emphasizes the importance of multidisciplinary evaluation, particularly in cases associated with unusual vasculitic and ischemic manifestations.

Concurrent thyrotropin (TSH) secreting and growth hormone (GH) secreting pituitary adenomas are rare entities. Although tumors of the PIT-1 lineage may coexpress TSH and GH, concurrent biologically active secretion resulting in central hyperthyroidism and acromegaly is uncommon. We report the case of a 42-year-old woman presenting with weight loss, palpitations, amenorrhea, and progressive acromegalic features. Biochemical evaluation revealed central hyperthyroidism with elevated free T4 and inappropriately normal TSH, markedly elevated insulin-like growth factor 1 (IGF-1) and GH, hyperprolactinemia, and elevated α-subunit. Pituitary magnetic resonance imaging demonstrated a 2.7-cm macroadenoma with cavernous sinus extension. She underwent transsphenoidal resection without complications. Pathology confirmed a mature plurihormonal PIT-1 lineage adenoma immunopositive for TSH, GH, and prolactin with a Ki-67 of 3%. Immediately postoperatively, thyrotoxicosis and hyperprolactinemia resolved, IGF-1 levels declined, acromegalic features improved, and menses resumed. Over the ensuing months, thyroid and prolactin tests remained within normal range, but the IGF-1 level remained elevated. This case illustrates the rare presentation of a PIT-1 lineage adenoma secreting biologically active TSH, GH, and prolactin. Comprehensive hormonal evaluation and long-term biochemical and radiologic surveillance are essential, given the risk of incomplete remission despite apparent surgical cure.

Conventional imaging techniques lack the ability to quantify localized brain tissue displacements and strains associated with Glioblastoma (GBM) growth and treatment response. In this proof-of-concept study, a non-invasive approach is presented to map displacement and strain fields using Digital Volume Correlation (DVC) on serial T1-Gadolinium MRI scans of a GBM patient over 63 days. A comprehensive MRI pre-processing pipeline was applied, followed by the generation of meshes segmenting healthy brain tissue, tumor, and ventricles. Three distinct regularization scenarios were implemented to capture localized tissue deformations. DVC results were qualitatively compared to MRI anatomical changes and quantitatively validated against symmetric normalization (SyN) registration. DVC outperforms conventional SyN registration in capturing heterogeneous tissue deformations. These preliminary findings suggest greater sensitivity to biomechanical alterations induced by tumor progression and demonstrate the potential of DVC-augmented imaging to serve as a quantitative biomarker for assessing GBM-induced brain mechanics. By generating maps of ventricle deformation, the method provides new opportunities for early detection and monitoring of elevated intracranial pressure (ICP) in GBM patients.

Immune checkpoint inhibitors (ICIs), a widely adopted therapeutic option for metastatic renal cell carcinoma, are also associated with a range of immune-related adverse events, some of which can be severe and life-threatening. Here, we describe the case of a 70-year-old man with renal cell carcinoma and brain, lung, and bone metastases who developed ICI-associated encephalitis, which was fatal. Initial computed tomography imaging revealed a 9.8 cm mass in the right kidney, multiple pulmonary nodules, and an osteolytic lesion in the left fifth rib. Brain magnetic resonance imaging revealed metastatic lesions in the right parietal lobe and left lateral ventricle. The patient underwent therapy with pembrolizumab and lenvatinib in combination with stereotactic radiotherapy targeting the brain metastases. On day 20 of treatment, the patient developed a generalized seizure, followed by a rapid deterioration in consciousness. He died the following day. Post-mortem examination revealed widespread lymphocytic infiltration of the brain parenchyma, which was consistent with the diagnosis of ICI-associated encephalitis.

Glioblastoma (GBM) response to Temozolomide (TMZ) critically depends on O[6]-methylguanine-DNA methyltransferase (MGMT) promoter methylation. Clinically, the unmethylated MGMT subtype─representing the predominant GBM population─universally develops TMZ resistance, driving an urgent need for novel therapeutics. While metabolic reprogramming represents a potential therapeutic target, current methylation detection methods cannot provide targetable metabolic information. To elucidate methylation-associated metabolic signatures while mitigating complex biological background noise, we established a stepwise validation framework using CRISPR-engineered cell models. Raman spectroscopy (RS) analyzed CRISPR-dCas9-edited GBM cell lines to extract pure metabolic fingerprints. In MGMT hypermethylated (MGMT-HYPER) GBMs, the saturated fatty acid (SFA) Raman peak was elevated. Conversely, MGMT hypomethylated (MGMT-HYPO) GBMs exhibited enhanced peaks for deoxyribonucleic acid (DNA), amino acids, and unsaturated fatty acids (UFAs). RS-identified metabolites were validated by liquid chromatography-mass spectrometry. Subsequently, uniform manifold approximation and projection (UMAP) effectively clustered HYPER/HYPO Raman spectra. A Raman classification model utilizing a core 13-feature signature from in vitro findings achieved a 94.5% area under the curve (AUC) in distinguishing methylation status across 62 clinical specimens. Correlation analysis demonstrated: (1) a positive correlation of SFA content (1444 cm[-1]) with methylation levels in MGMT-HYPER tumors; (2) an inverse association of DNA levels (1093 cm[-1]) with methylation in intermediate-methylation GBMs; and (3) a negative correlation between UFA content (1266 cm[-1]) and methylation in unmethylated GBMs. This study confirms RS potential for assessing MGMT methylation status in tumors and elucidates metabolic signatures associated with differential methylation in GBMs, providing targets for metabolic intervention against TMZ resistance.