Intracranial Tumors Research Articles

Expanding the clinicopathologic spectrum and genomic landscape of tumors with SMARCA2/4::CREM fusions.

CREB gene family (ATF1, CREB1, CREM) fusions with either EWSR1 or FUS gene partners drive the pathogenesis of a wide range of neoplasms, including various soft tissue tumors, intracranial myxoid mesenchymal tumors (IMMTs), hyalinizing clear cell carcinoma (HCCC), and rare mesotheliomas. Recently, a SMARCA2::CREM fusion was reported in one case each of IMMT and HCCC. In this study, we expand the clinicopathologic and molecular spectrum of these neoplasms by describing three additional cases with SMARCA2::CREM and one with a novel SMARCA4::CREM fusion, highlighting the recurrent potential of additional CREB gene fusion partners beyond FET family members. To evaluate if these fusions define a new pathologic entity, we performed a comprehensive genomic and methylation analysis and compared the results to other related tumors. Tumors occurred in children and young adults (median age 20 years) and spanned a broad anatomic distribution, including soft tissue, intracranial, head and neck, and prostatic urethra. Microscopically, the tumors shared an undifferentiated round to epithelioid cell phenotype and a hyalinized fibrous stroma. Immunohistochemically, a polyphenotypic profile was observed, with variable expression of SOX10, desmin, and/or epithelial markers. No targetable genomic alterations were found using panel-based DNA sequencing. By DNA methylation and transcriptomic analyses, tumors grouped closely to FET::CREB entities, but not with SMARCA4/SMARCB1-deficient tumors. High expression of CREM by immunohistochemistry was also documented in these tumors. Patients experienced local recurrence (n = 2), locoregional lymph node metastases (n = 2), and an isolated visceral metastasis (n = 1). Overall, our study suggests that SMARCA2/4::CREM fusions define a distinct group of neoplasms with round cell to epithelioid histology, a variable immunoprofile, and a definite risk of malignancy. Larger studies are needed to further explore the pathogenetic relationship with the FET::CREB family of tumors. © 2024 The Pathological Society of Great Britain and Ireland.

Indications and scientific support for supratentorial unilateral decompressive craniectomy for different subgroups of patients: A scoping review.

Even though supratentorial unilateral decompressive craniectomy (DC) has become the gold standard neurosurgical procedure aiming to provide long term relief of intractable intracranial hypertension, its indication has only been validated by high-quality evidence for traumatic brain injury and malignant middle cerebral artery infarction. This scoping review aims to summarize the available evidence regarding DC for these two recognized indications, but also for less validated indications that we may encounter in our daily clinical practice. A scoping review was conducted on Medline / Pubmed database from inception to present time looking for articles focused on 7 possible indications for DC indications. Studies' level of evidence was assessed using Oxford University level of evidence scale. Studies' quality was assessed using Newcastle-Ottawa scale for systematic reviews of cohort studies and Cochrane Risk of Bias Tool for randomized controlled trials. Two randomized trials (level 1b) reported the possible efficacy of unilateral DC and the mitigated efficiency of bifrontal DC in the trauma setting. Five systematic reviews meta-analyses (level 2a) supported DC for severely injured young patients with acute subdural hematoma probably responsible for intraoperative brain swelling, while one randomized controlled trial (level 1b) showed comparable efficacy of DC and craniotomy for ASH with intraoperative neutral brain swelling. Three randomized controlled trials (level 1b) and two meta-analyses (level 1a and 3a) supported DC efficacy for malignant ischemic stroke. One systematic review (level 3a) supported DC efficacy for malignant meningoencephalitis. One systematic review meta-analysis (level 3a) supported DC efficacy for malignant cerebral venous thrombosis. The mitigated results of one randomized trial (level 1b) did not allow to conclude for DC efficacy for intracerebral hemorrhage. One systematic review (level 3a) reported the possible efficacy of primary DC and the mitigated efficacy of secondary DC for aneurysmal subarachnoid hemorrhage. Too weak evidence (level 4) precluded from drawing any conclusion for DC efficacy for intracranial tumors. To date, there is some scientific background to support clinicians in the decision making for DC for selected cases of severe traumatic brain injury, acute subdural hematoma, malignant ischemic stroke, malignant meningoencephalitis, malignant cerebral venous thrombosis, and highly selected cases of aneurysmal subarachnoid hemorrhage.

Multiple Meningiomas with Different Histological Patterns in the Same Patient: Do They Exist? A Case Report and Literature Review

AbstractMeningiomas are the most common form of primary intracranial tumors, accounting for 13 to 26% of total neoplasms arising from arachnoid cap cells of the meningeal layer covering the central nervous system. Multiple intracranial meningiomas, which often have a syndromic association, account for less than 10% of total meningiomas. Multiple meningiomas with different histological patterns or grades in the same patient are very rare. Here we report such a rare case of meningioma with different histological patterns in the same patient. A 56-year-old lady presented to us with complaints of progressive right-sided weakness and speech disturbances, and her magnetic resonance imaging (MRI) showed two distinct extra-axial lesions over left frontal convexity and left fronto-temporo-parietal convexity. She underwent left fronto-temporo-parietal craniectomy and Simpson grade 1 excision of the lesions. Her histopathological examination revealed two different histological patterns: lesion 1 (left fronto-temporo-parietal convexity) was reported as a transitional World Health Organization (WHO) grade 1 meningioma and lesion 2 (left frontal convexity) was reported as angiomatous WHO grade 1 meningioma. She recovered well and was discharged in a stable condition after 3 weeks. Multiple meningiomas are defined as at least two spatially separated meningiomas occurring at the same time or more than two meningiomas arising sequentially from two clearly distinct regions. The exact mechanism of multicentricity is unknown. The treatment protocol for different histological types in the same patient is not clear. The extent of surgical resection remains the mainstay of the treatment and these patients should be followed up closely to watch for recurrence or malignant transformation. The role of radiotherapy in multiple meningiomas is yet to be established.

Deep learning-based detection and classification of intracranial tumors on magnetic resonance imaging

AbstractBackgroundWe evaluated the capability of an AI application to independently detect, segment and classify intracranial tumors in MRI.MethodsIn this retrospective single-centre study, 138 patients (65 female and 73 male) with a mean age of 35 ± 26y were included. 97 were diagnosed with an intracranial neoplasm, while 41 exhibited no intracranial pathology. Inclusion criteria were a 1.5 or 3.0T MRI dataset with the following sequences: T2 axial, T1 axial pre- and post-contrast with a slice thickness between 3 and 6 mm and no previous brain surgery. Image analysis was performed by two human readers (R1 = 5 years and R2 = 10 years of experience in brain MRI) and a deep learning (DL)-based AI model. Sensitivity, specificity and accuracy of the AI model and the human readers to detect and correctly classify brain tumors were measured. Histological results served as the gold standard.ResultsThe AI model reached a sensitivity of 93.81% [87.02–97.70] and a specificity of 63.41% [46.94–77.88], while human readers reached 100% [96.27–100.00] and 100% [91.40–100.00], respectively. Human readers provided a significantly higher accuracy rate with R1 0.93 (95% CI: 0.88–0.97) and R2 0.98 (95% CI: 0.94, 0.99) vs. 0.74 (95% CI: 0.66–0.81) for the AI model (P-value <0.001).ConclusionThe underlying DL-based AI algorithm can independently identify and segment intracranial tumors while providing satisfactory results for establishing the correct diagnosis. Despite its current inferiority compared to experienced radiologists, it still experiences ongoing development and it is a step towards developing an artificial intelligence-augmented radiology workflow.

Hemorrhagic versus non-hemorrhagic presentation of presumed reversible cerebral vasoconstriction syndrome (RCVS): Presentations and outcomes

Introduction Reversible cerebral vasoconstriction syndrome (RCVS) can present with hemorrhage, ischemia, or both. We aim to compare the differences in presentation and outcomes between patients with RCVS. Methods The hemorrhagic presentation group had 58 patients, and the non-hemorrhagic presentations had 30 patients. Subgroup analysis compared patients with evidence of one or more types of hemorrhage ( n = 53), no evidence of hemorrhage or infarction ( n = 23), evidence of infarction only ( n = 7), and combination of hemorrhage and infarction ( n = 5). Clinical and radiographic data were analyzed. Results Migraine ( p = 0.030) and intracranial tumors ( p = 0.004) were more frequent in non-hemorrhagic presentation. Seizures on admission ( p = 0.047) and higher than average C-reactive protein (CRP) ( p = 0.037) were seen at a higher rate in patients with hemorrhagic presentation. RCVS2 scores were not unexpectedly higher in patients with hemorrhage than non-hemorrhagic presentations ( p = 0.010). Outcomes between the hemorrhagic and non-hemorrhagic groups were comparable. Subgroup analysis found a higher subset of patients with opiate use ( p = 0.046) in the hemorrhage-only group. Patients with hemorrhage presented with a thunderclap headache ( p < 0.001) more often when compared to the other three groups. RCVS2 score was not unexpectedly higher in the hemorrhage-only group compared with the other groups ( p = 0.004). Conclusion A history of migraines was associated with ischemia, while intracranial tumor was significantly associated with evidence of either an infarct, or no changes on imaging. Exposure to opiates, and seizures or thunderclap headache on presentation were associated with hemorrhage. If our data are reproducible, the RCVS2 score may benefit from inclusion of other, small hemorrhages as criterion for diagnosis for RCVS.

Lipomatous Meningioma: A Rare Variant of a Commun Tumor

Meningiomas are the most common primary intracranial tumors, accounting for approximately 20% of all intracranial tumors. Lipomatous meningiomas are a rare variant of meningiomas, constituting less than 1% of all meningiomas. We report a case of an 83-year-old woman who presented with decreased visual acuity. CT and MRI revealed an extra-axial mass in the left cerebellopontine angle with lipomatous features.

Intracranial Solitary Fibrous Tumor in a 25-Year-Old Woman

<p><strong>Introduction:</strong> Intracranial solitary fibrous tumors (ISFTs) are extremely rare spindle cell tumors originating from dendritic mesenchymal cells expressing CD34 antigens that are usually benign, although malignant transformation had been reported. The knowledge of natural course and prognostic factors of ISFTs is still limited and the tumor is easily misdiagnosed.</p><p><strong>Case Presentation:</strong> An intra-cranial extra-axial tumor tissue resection from a 25-year-old woman was evaluated in the Surgical Pathology Laboratory. Histologic findings (cellular spindle cell tumor with ‘patternless’ pattern, staghorn blood vessels and <5 mitoses per 10 hpf) and immunophenotype (positive for CD34, weakly and focally positive for STAT6) suggested a diagnosis of intracranial solitary fibrous tumor WHO Grade II.</p><p><strong>Discussion:</strong> ISFTs have very low incidence in the CNS and are difficult to distinguish radiologically from meningiomas, thus post operative pathological examination and immunohistochemistry markers evaluations are the mainstay for diagnosis. ISFT is associated with NAB2-STAT6 gene fusion and may exhibits a wide spectrum of histological features. STAT6 immunohistochemistry is considered as one of the most sensitive diagnostic methods, while the evaluation of CD34 expression can be used as alternative diagnostic method despite having lower sensitivity.</p>

Synchronous intracranial arteriovenous malformation and papillary glioneuronal tumour: hypothesis or reality?

Brain arteriovenous malformations (AVM) rarely occur with spatial and/or temporal co-localisation to intracranial neoplasms. Most prior reports describe this association with high-grade gliomas; however, reports of a co-occurrence with low grade gliomas are very rare. It is unclear whether such cases represent a true co-occurrence of separate pathologies or simply an unusually vascular phenotype of the neoplasm. Most such reports pre-date the era of molecularly defined gliomas. We present the first report of the spatial and temporal co-occurrence of an intracranial arteriovenous malformation traversing and within a papillary glioneuronal tumour, molecularly defined by the presence of SLC44A1::PRKCA fusion. This case was successfully managed by resection of both lesions adhering to the principles of AVM surgery. It is possible these exceptionally rare co-occurrences may have common underlying molecular drivers relating to the mitogen activated protein kinase (MAPK) pathway.

Quantitative tissue analysis reveals AK2, COL1A1, & PLG protein signatures: Targeted therapeutics for meningioma.

Meningioma is the most prevalent primary intracranial brain tumor and accounts for one-third of all CNS tumors. Meningioma is known to be the most common yet life-threatening brain tumor with a higher recurrence rate. Globally, there is an increase in the healthcare burden due to meningioma and hence in its research. The present clinical approach includes surgical resection, chemotherapy, and radiation therapies to which the malignancy does not seem to respond efficiently. Targeted therapies and molecular markers provide elite patient treatment and care for individuals suffering from meningiomas as compared to conventional measures. Although there is proteomic data on meningioma the knowledge of potential biomarkers differentiating the grades is scarce. To identify the best set of biomarkers, validation of reported markers in large and independent sample cohorts in the future is necessary. A total of 12 samples, 3 each of control (which made pool 1) Meningioma grade I (which made 2 sets: pool 2 and pool 3), and Meningioma grade II (which made pool 4) were taken for LC-MS/MS. After this, the expression of three proteins was checked by immunocytochemistry, flow cytometry, and western blotting. Protein expression was analyzed using various techniques like mass spectrometry, immunocytochemistry, flow cytometry, and western blotting. Mass spectrometry is the most commonly used standard and reliable technique for identifying and quantifying protein expression. We got three highly upregulated proteins namely AK2, COL1A1, and PLG using this technique. The biomarker potential of these proteins was further checked by ICC, western blotting, and flow cytometry. Three important proteins were found to be upregulated namely AK2 (Adenylate Kinase 2), COL1A1 (Collagen 1A1), and PLG (Plasminogen). The order of increased protein expression was control < MG grade I < MG grade II according to mass spectrometry and western blotting. In immunocytochemistry, we found that COL1A1 expression increases significantly with grades in comparison to control. Similarly, AK2 and PLG also showed little increase but not as much as COL1A1. In flow cytometry, PLG showed higher upregulation in grades than control. While AK2 and COL1A1 showed little increase in expression in grades than control. All techniques, especially mass spectrometry and western blotting presented higher expression of these proteins in grades as compared to control. In the quest to find a suitable therapeutic marker, this study incorporates quantitative labeling and detection followed by flow cytometry, Immunocytochemistry, and western blotting for early diagnosis and treatment of meningioma. The article further explores the efficacy of some proteins namely AK2, COL1A1 & PLG to be the targeted molecules.

GABA(A) Receptor Activation Drives GABARAP-Nix Mediated Autophagy to Radiation-Sensitize Primary and Brain-Metastatic Lung Adenocarcinoma Tumors.

In non-small cell lung cancer (NSCLC) treatment, radiotherapy responses are not durable and toxicity limits therapy. We find that AM-101, a synthetic benzodiazepine activator of GABA(A) receptor, impairs the viability and clonogenicity of both primary and brain-metastatic NSCLC cells. Employing a human-relevant ex vivo 'chip', AM-101 is as efficacious as docetaxel, a chemotherapeutic used with radiotherapy for advanced-stage NSCLC. In vivo, AM-101 potentiates radiation, including conferring a significant survival benefit to mice bearing NSCLC intracranial tumors generated using a patient-derived metastatic line. GABA(A) receptor activation stimulates a selective-autophagic response via the multimerization of GABA(A) receptor-associated protein, GABARAP, the stabilization of mitochondrial receptor Nix, and the utilization of ubiquitin-binding protein p62. A high-affinity peptide disrupting Nix binding to GABARAP inhibits AM-101 cytotoxicity. This supports a model of GABA(A) receptor activation driving a GABARAP-Nix multimerization axis that triggers autophagy. In patients receiving radiotherapy, GABA(A) receptor activation may improve tumor control while allowing radiation dose de-intensification to reduce toxicity.

Meningiomas in Elderly Subjects: Retrospective Studies of 8 Cases and a Literature Review

Aim. Intracranial meningiomas in adults are mainly benign tumors that develop from the meninges. They are common, accounting for about 18 to 20% of primary intracranial tumors, and they are slow-growing, with a predominance in women. They can occur at any age but are most common after the age of 56. Symptoms vary depending on the location of the tumor, its size, and the anatomical structures it comes into contact with. Surgery is the main treatment modality for meningiomas. The objective of this study is to evaluate the cases of meningiomas in our series and to compare their different aspects, such as epidemiological, clinical, radiological, therapeutic, histological, evolutionary, and prognostic characteristics, with those reported in other series of the literature. We seek to highlight the similarities and differences between our series and previous studies, considering recent advances in this field. Materials and measures. In our series, the retrospective study of 8 cases of intracranial meningioma in elderly subjects diagnosed and operated on at the Neurosurgery Department of a hospital over a period of 4 years. Brain CT and MRI were the primary preoperative diagnostic means. The use of these imaging techniques was essential to establish the diagnosis and plan the surgical procedure. The histopathological study was performed to confirm the post-operative diagnosis and determine the histological type, as well as the grade of the meningiomas, referring to the WHO classification to plan an appropriate follow-up of the management. Results. Meningiomas accounted for 2.33% of intracranial meningiomas in elderly subjects, and 22.22% were in subjects under 65 years of age out of 342 tumors operated on in the Department during the same period. The female predominance was clear, at 62%, compared to 38% for men. The average age of our patients was 69.9 years, with extremes of 65 and 74 years. The main clinical symptoms observed in our patients were headache, motor deficit (hemiparesis, hemiplegia), sensory deficit, convulsions, and cranial pair involvement (optic nerve and facial nerve).On CT, the tumor mass was spontaneously hyperdense in 100% of cases. After the injection of iodine product, there was a homogeneous intense contrast intake in all cases. Only 2 patients in our series performed CT scans, of which we found perilesional edema and mass effect in 100% of cases. No calcifications or bone abnormalities were detected. MRI was performed on all our patients, allowing us to better specify the topographical diagnosis of meningiomas. Overall, surgical excision was complete (Simpson’s grade I and grade II) in 62.5% of cases. The most common histological types were meningotheliomatous meningioma (4 cases), transitional meningioma (1 case), mucoid fibrous meningioma (1 case), and atypical meningioma (2 cases). The post-operative course was favorable in most patients, and the post-operative complications consisted mainly of wound infection (1 case), CSF leakage (1 case), and hemorrhage (1 case).

Probing the glioma micro-environment: Analysis using biopsy in combination with ultra-fast cyclic immunolabeling

The interaction between gliomas and the immune system is poorly understood and thus hindering development of effective immunotherapies for glioma patients. The immune response is highly variable during tumor development, and affected by therapies such as surgery, radiation, and chemotherapy. Currently, analysis of these local changes is difficult due to poor accessibility of the tumor and high-morbidity of sampling. In this study, we developed a model for repeat-biopsy in mice to study these local immunological changes over time. Using fine needle biopsy we were able to safely and repeatedly collect cells from intracranial tumors in mice. Ultra-fast cycling technology (FAST) was used for multi-cycle immunofluorescence of retrieved cells, and provided insights in the changing immune response over time. The combination of these techniques can be utilized to study changes in the immune response in glioma or other intracranial diseases over time, and in response to treatment within the same animal.

Andrographolide sensitizes glioma to temozolomide by inhibiting DKK1 expression.

Temozolomide (TMZ) is the first-line chemotherapeutic drug for gliomas treatment. However, the clinical efficacy of TMZ in glioma patients was very limited. Therefore, it is urgently needed to discover a novel approach to increase the sensitivity of glioma cells to TMZ. Western blot, immunohistochemical staining, and qRT-PCR assays were used to explore the mechanisms underlying TMZ promoting DKK1 expression and andrographolide (AND) inhibiting DKK1 expression. HPLC was used to detect the ability of andrographolide (AND) to penetrate the blood-brain barrier. MTT assay, bioluminescence images, magnetic resonance imaging (MRI) and H&E staining were employed to measure the proliferative activity of glioma cells and the growth of intracranial tumors. TMZ can promote DKK1 expression in glioma cells and brain tumors of an orthotopic model of glioma. DKK1 could promote glioma cell proliferation and tumor growth in an orthotopic model of glioma. Mechanistically, TMZ increased EGFR expression and subsequently induced the activation of its downstream MEK-ERK and PI3K-Akt pathways, thereby promoting DKK1 expression in glioma cells. Andrographolide inhibited TMZ-induced DKK1 expression through inactivating MEK-ERK and PI3K-Akt pathways. Andrographolide can cross the blood-brain barrier, the combination of TMZ and andrographolide not only improved the anti-tumor effects of TMZ but also showed a survival benefit in an orthotopic model of glioma. Andrographolide can enhance anti-tumor activity of TMZ against glioma by inhibiting DKK1 expression.

A deep learning model for differentiating paediatric intracranial germ cell tumour subtypes and predicting survival with MRI: a multicentre prospective study

BackgroundThe pretherapeutic differentiation of subtypes of primary intracranial germ cell tumours (iGCTs), including germinomas (GEs) and nongerminomatous germ cell tumours (NGGCTs), is essential for clinical practice because of distinct treatment strategies and prognostic profiles of these diseases. This study aimed to develop a deep learning model, iGNet, to assist in the differentiation and prognostication of iGCT subtypes by employing pretherapeutic MR T2-weighted imaging.MethodsThe iGNet model, which is based on the nnUNet architecture, was developed using a retrospective dataset of 280 pathologically confirmed iGCT patients. The training dataset included 83 GEs and 117 NGGCTs, while the retrospective internal test dataset included 31 GEs and 49 NGGCTs. The model’s diagnostic performance was then assessed with the area under the receiver operating characteristic curve (AUC) in a prospective internal dataset (n = 22) and two external datasets (n = 22 and 20). Next, we compared the diagnostic performance of six neuroradiologists with or without the assistance of iGNet. Finally, the predictive ability of the output of iGNet for progression-free and overall survival was assessed and compared to that of the pathological diagnosis.ResultsiGNet achieved high diagnostic performance, with AUCs between 0.869 and 0.950 across the four test datasets. With the assistance of iGNet, the six neuroradiologists’ diagnostic AUCs (averages of the four test datasets) increased by 9.22% to 17.90%. There was no significant difference between the output of iGNet and the results of pathological diagnosis in predicting progression-free and overall survival (P = .889).ConclusionsBy leveraging pretherapeutic MR imaging data, iGNet accurately differentiates iGCT subtypes, facilitating prognostic evaluation and increasing the potential for tailored treatment.Graphical

Evaluating the atherosclerosis cardiovascular disease risk score in patients with brain metastases: Associations with overall survival and high-value care outcomes

ObjectiveBrain metastases (BM) constitute the most common intracranial tumor in adults. Prior literature indicates the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score is associated with increased risk of cancer, potentially attributable to shared risk factors. Understanding the role of ASCVD risk scores in BM may help optimize their care and inform clinical decision-making. Our aim was to explore associations between ASCVD risk score in BM patients and their overall survival, hospital charges, and non-routine discharge disposition. MethodsElectronic medical records were reviewed to collect clinical data for BM patients undergoing surgery at a single institution (2017–2021). Regression analyses were performed accordingly and maximally selected rank statistics were employed to identify an optimal cutoff for ASCVD risk scores. The random survival forest (RSF) machine learning technique identified the most important variable associated with survival outcomes in BM patients. ResultsA total of 139 patients were included with average age 62.93±9.29 years, 48.2 % male, 25.2 % with high hospital charges, and 23.7 % experiencing non-routine discharge. Among these patients, 32.3 % had prior history of an ASCVD event, while 67.7 % did not. Overall, this cohort had an average 10-year ASCVD risk score of 12.51±12.98, indicating intermediate risk of ASCVD among all BM patients. On multivariate logistic regression, prior history of ASCVD was associated with higher odds of high hospital charges (OR=3.670, p=0.018), and higher ASCVD risk scores were associated with greater odds of non-routine discharge (OR=1.059, p=0.012). On the multivariate Cox regression model, higher ASCVD risk scores correlated with worse overall survival (HR=1.031, p=0.014). A threshold of 25.1 was identified for high-risk ASCVD scores. Patients with ASCVD scores >25.1 exhibited reduced overall survival in Kaplan-Meier analysis (p=0.015) and multivariate Cox regression (HR: 2.811, p=0.016). Notably, ASCVD risk scores were found to be the most important variable in predicting worse survival outcomes in BM patients compared to other established frailty indices. ConclusionThis study indicates higher ASCVD risk scores in BM patients are associated with worse overall survival. Integrating ASCVD assessment into clinical workflow may facilitate more informed risk-based decision-making.

Third ventricle teratoma with malignant transformation

Intracranial germ cell tumors(GCTs) are rare and heterogeneous group of primary brain tumors, mainly affecting pediatric population and young adults. The current understanding of the etiology of intracranial GCTs and their optimal management strategies remain controversial. Treatment plans differ depending on the subtype GCT and may vary among physicians and institutions. Central nervous system non-germinomatous germ cell tumor (NGGCT) usually requires surgical resection with histological verification, chemotherapy, and radiation. The extent of surgical resection is an important prognostic factor alongside the etiology and genetics of NGGCT. This article presents a rare clinical case of a rapidly growing teratoma located in the posterior part of third ventricle of a 17-year-old male presenting with symptoms of intracranial hypertension. Surgical total resection was preceded by endoscopic third ventriculostomy. Immunohistochemistry revealed the presence of embryonal carcinoma and immature teratoma cells turning the tumor into mixed type NGGCT with unfavorable prognosis. Despite the complete resection of the tumor and the timely initiation of adjuvant therapy, a rapid progression of the disease with subsequent unfavorable outcome was observed 3.6 months after the surgical treatment.

The Molecular and Immunological Landscape of Meningiomas.

Meningiomas are the most common primary intracranial tumors in adults and typically have a slow-growing and benign nature. However, there is also a substantial subset of meningiomas that shows aggressive clinical behavior and is refractory to standard treatment modalities, which are still limited to surgery and/or radiotherapy. Despite intensive research, no systemic treatment options are yet available in the clinic for these challenging tumors, resulting in poor patient outcome. Intensive research on the molecular pathogenesis of meningiomas has led to improved diagnostic tools, but so far there is no standardized implementation for the molecular profiling of these tumors for clinical practice. Recent research advances have also focused on the immunophenotyping of meningiomas, leading to several clinical trials examining the use of immune checkpoint blockade therapy in patients with clinically aggressive subtypes. In this review, we aim to summarize the current knowledge on the molecular and immunological landscape of meningiomas in detail and provide current and progressive ideas for future directions.

Single-Center Experience and Literature Review of Radiotherapy Outcomes for Adult Ependymomas

Objective: To retrospectively determine the long-term outcome of adult intracranial and spinal ependymoma patients treated with postoperative radiation therapy after surgery. Methods: Fourteen adult patients who underwent radiotherapy after surgery at a single center between 1999 and 2022 were included. The endpoints analyzed were overall survival and progression-free survival, together with prognostic factors. Results: The median (range) age was 29.5 (23–58) years. The majority (71.4%) of the tumors were located in the spinal canal and gross total resection was performed in nine (64.3%) patients. Six patients were irradiated after recurrence (spinal n=4, intracranial n=2) of whom three had myxopapillary and two had anaplastic histology. Patients were followed up for a median duration of 106.5 (13-172) months. Overall, 4 patients (intracranial n=3, spinal n=1) had recurrences and died after radiotherapy as a direct result of disease progression during the follow-up period. All of these intracranial tumors exhibited anaplastic histology and the spinal tumor was myxopapillary type. Patients with intracranial lesions had a 5-year survival of 50% and no patient was alive on the 10th year, compared with 5- and 10-year overall survival of 87.5 % for patients with spinal tumors. Patients with spinal tumors had a 5- and 10-year progression-free survival rate of 52.5%, while those with intracranial lesions had a rate of 25%. Conclusion: In low-grade spinal ependymomas radiotherapy appears to control disease, even after recurrence. For myxopapillary ependymoma patients, in subtotally resected intracranial and all high-grade tumors, regardless of the extent of resection, adjuvant radiotherapy should be administered.

Eslicarbazepine induces apoptosis and cell cycle arrest in C6 glioma cells in vitro and suppresses tumor growth in an intracranial rat model

BackgroundGlioblastoma multiforme (GBM) is the most malignant brain tumor, with a poor prognosis and life expectancy of 14–16 months after diagnosis. The standard treatment for GBM consists of surgery, radiotherapy, and chemotherapy with temozolomide. Most patients become resistant to treatment after some time, and the tumor recurs. Therefore, there is a need for new drugs to manage GBM. Eslicarbazepine (ESL) is a well-known antiepileptic drug belonging to the dibenzazepine group with anticancer potentials. In this study, for the first time, we evaluated the potential effects of ESL on C6 cell growth, both in vitro and in vivo, and examined its molecular effects.MethodsTo determine the effect of ESL on the c6 cell line, cell viability, proliferation, and migration were evaluated by MTT assay, colony formation, and wound healing assay. Also, apoptosis and cell cycle were examined by flow cytometry, qRT-PCR, and western blotting. In addition, an intracranial model in Wistar rats was used to investigate the effect of ESL in vivo, and the tumor size was measured using both Caliper and MRI.ResultsThe obtained results are extremely consistent and highly encouraging. C6 cell viability, proliferation, and migration were significantly suppressed in ESL-treated C6 cells (p < 0.001), as determined by cell-based assays. ESL treatment led to significant enhancement of apoptosis (p < 0.01), as determined by flow cytometry, and upregulation of genes involved in cell apoptosis, such as the Bax/Bcl2 ratio at RNA (p < 0.05) and protein levels (5.37-fold). Flow cytometric analysis of ESL-treated cells revealed G2/M phase cell cycle arrest. ESL-treated cells demonstrated 2.49-fold upregulation of p21 alongside, 0.22-fold downregulation of cyclin B1, and 0.34-fold downregulation of cyclin-dependent kinase-1 at the protein level. Administration of ESL (30 mg/kg) to male rats bearing C6 intracranial tumors also suppressed the tumor volume and weight (p < 0.01).ConclusionsBased on these novel findings, ESL has the potential for further experimental and clinical studies in glioblastoma.Graphical abstract

Integrated Microbiome and Metabolome Analysis Reveals Hypothalamic-Comorbidities Related Signatures in Craniopharyngioma.

Craniopharyngioma (CP) is an intracranial tumor with high mortality and morbidity. Though biologically benign, CP will damage the hypothalamus, inducing comorbidities such as obesity, metabolic syndrome, and cognitive impairments. The roles of gut microbiome and serum metabolome in CP-associated hypothalamic comorbidities are aimed to be explored. Patients with CP are characterized by increased Shannon diversity, Eubacterium, Clostridium, and Roseburia, alongside decreased Alistipes and Bacteroides. CP-enriched taxa are positively correlated with dyslipidemia and cognitive decline, while CP-depleted taxa are negatively associated with fatty liver. Subsequent serum metabolomics identified notably up-regulated purine metabolism, and integrative analysis indicated an association between altered microbiota and elevated hypoxanthine. Phenotypic study and multi-omics analysis in the Rax-CreERT2::BrafV600E/+::PtenFlox/+ mouse model validated potential involvement of increased Clostridium and dysregulated purine metabolism in hypothalamic comorbidities. To further consolidate this, intervention experiments are performed and it is found that hypoxanthine co-variated with the severity of hypothalamic comorbidities and abundance of Clostridium, and induced dysregulated purine metabolism along with redox imbalance in target organs (liver and brain cortex). Overall, the study demonstrated the potential of increased Clostridium and up-regulated purine metabolism as signatures of CP-associated hypothalamic-comorbidities, and unveiled that elevated Clostridium, dysregulated purine metabolism, and redox imbalance may mediate the development and progression of CP-associated hypothalamic-comorbidities.