α-Mannosylated HLA-II glycopeptide antigens dominate the immunopeptidome of immortalised cells and tumour tissues.

Immunopeptides are cell surface-located protein fragments that aid our immune system to recognise and respond to pathogenic insult and malignant transformation. In this two-part communication, we firstly summarise and reflect on our recent discovery documenting that MHC-II-bound immunopeptides from immortalised cell lines prevalently carry N-glycans that differ from the cellular glycoproteome (Goodson, Front Immunol, 2023), data discussed at the 2023 SfG Annual Meeting. These findings are important as immunopeptide glycosylation remains poorly understood in immunosurveillance. The study also opened up new technical and biological questions that we address in the second part of this communication. Our study highlighted that the performance of the search engines used to detect glycosylated immunopeptides from LC-MS/MS data remains untested and, importantly, that little biochemical in vivo evidence is available to document the nature of glycopeptide antigens in tumour tissues. To this end, we compared the N-glycosylated MHC-II-bound immunopeptides that were reported from tumour tissues of 14 meningioma patients in the MSFragger-HLA-Glyco database (Bedran, Nat Commun, 2023) to those we identified with the commercial Byonic software. Encouragingly, the search engines produced similar outputs supporting that N-glycosylated MHC-II-bound immunopeptides are prevalent in meningioma tumour tissues. Consistent also with in vitro findings, the tissue MHC-II-bound immunopeptides were found to predominantly carry hyper-processed (paucimannosidic- and chitobiose core-type) and hypo-processed (oligomannosidic-type) N-glycans that varied in prevalence and distribution between patients. Taken together, evidence is emerging suggesting that α-mannosidic glycoepitopes abundantly decorate MHC-II-bound immunopeptides in both immortalised cells and tumour tissues warranting further research into their functional roles in immunosurveillance.

Case Report: Atypical visual presentation caused by a large convexity meningioma-a nerve stretching and stalk indentation effect.

Visual field defects are commonly present in patients with brain tumors, particularly due to direct compression on the optic apparatus. However, there are instances where brain tumors, despite not directly compressing the optic pathway, can still cause visual symptoms, albeit rarely reported but not uncommonly observed. These mechanisms are thought to be associated with increased intracranial pressure (IICP). We report a case of a 32-year-old man who presented with right blurred vision and was diagnosed with a right convexity meningioma. Upon reviewing his magnetic resonance images, we hypothesized that the indentation of the pituitary stalk on the optic chiasm and the stretching of the optic nerve, combined with a focal effect of IICP, could be responsible for his atypical visual field defect.

RNA splicing as a biomarker and phenotypic driver of meningioma DNA methylation groups.

BACKGROUND: Advances in our understanding of the molecular biology of meningiomas have led to significant gains in the ability to predict patient prognosis and tumor recurrence and to identify novel targets for therapeutic design. Specifically, classification of meningiomas based on DNA methylation has greatly improved our ability to risk stratify patients, however new questions have arisen in terms of the underlying impact these DNA methylation signatures have on meningioma biology. METHODS: This study utilizes RNA-seq data from 486 meningioma samples corresponding to three meningioma DNA methylation groups (Merlin-intact, Immune-enriched, and Hypermitotic), followed by in vitro experiments utilizing human meningioma cell lines. RESULTS: We identify alterations in RNA splicing between meningioma DNA methylation groups including individual splicing events that correlate with Hypermitotic meningiomas and predict tumor recurrence and overall patient prognosis and compile a set of splicing events that can accurately predict DNA methylation classification based on RNA-seq data. Furthermore, we validate these events using RT-PCR in patient samples and meningioma cell lines. Additionally, we identify alterations in RNA binding proteins and splicing factors that lie upstream of RNA splicing events, including upregulation of SRSF1 in Hypermitotic meningiomas which we show drives alternative RNA splicing changes. Finally, we design splice switching antisense oligonucleotides to target RNA splicing changes in NASP and MFF observed in Hypermitotic meningiomas, providing a rationale for RNA-based therapeutic design. CONCLUSIONS: RNA splicing is an important driver of meningioma phenotypes that can be useful in prognosticating patients and as a potential exploit for therapeutic vulnerabilities.

Treatment of tumor-induced cerebral venous sinus stenosis: Technical note and review of the literature.

INTRODUCTION: Tumors that invade or compress the venous sinuses have the potential to impair venous drainage. Rarely, this may be so severe as to induce intracranial hypertension. Other studies have previously described venous sinus stenting (VSS) for the treatment of these symptomatic lesions. In this report, we present our series of eight cases of VSS for symptomatic tumor-induced venous sinus stenosis and review the existing literature. CASES: Eight patients with mostly intracranial tumors were found to have symptomatic venous sinus stenosis with the most common presenting symptom being elevated intracranial pressure. Six of the eight (75%) patients presented with papilledema on neuro-ophthalmological exam. The most affected locations were the transverse and sigmoid sinuses in four patients, followed by the superior sagittal sinus in three patients. All eight patients underwent VSS with no adverse events. In total, 6 out of 8 (75%) of patients had complete resolution of their symptoms, while the remaining patients experienced at least partial improvement. CONCLUSION: Tumors that cause symptomatic venous sinus stenosis may be successfully managed with VSS to improve venous drainage. This may facilitate continued conservative management of meningiomas or allow for treatment with noninvasive means, such as stereotactic radiosurgery. Depending on the size of the target stenosis, balloon-mounted coronary stents may be a suitable option to treat these lesions.

Primary pulmonary meningioma presenting as a pulmonary ground glass nodule: a case report and review of the literature.

BACKGROUND: A primary pulmonary meningioma is an extremely rare entity. Primary pulmonary meningiomas manifested with a ground glass nodule are a very rare occurrence in clinical practice. CASE PRESENTATION: In this study, we report a case of a primary pulmonary meningioma with atypical computed tomography features. A 59-year-old Han Chinese female came to our hospital for treatment and reported that her physical examination revealed a ground glass nodule in the right lung for over 3 months. The histologic result revealed a primary pulmonary meningioma. The patient underwent a thoracoscopic lung wedge resection of the right upper lobe for a ground glass nodule. After 1 year of follow-up, the patient is still alive without evidence of metastasis or recurrence. CONCLUSIONS: Primary pulmonary meningiomas could have a variety of radiological findings. As there are no specific radiologic features for the diagnosis of primary pulmonary meningiomas, complete resection of the lesion is required for both diagnosis and treatment. It is necessary to note the imaging features of primary pulmonary meningiomas, presenting as a ground glass nodule; this rare tumor should be considered in differential diagnoses.

Challenging Resection of Bilateral Parasagittal and Falcine Meningioma Involving Both Anterior Third and Middle Third of the Superior Sagittal Sinus: A Case Report and Literature Review.

Meningiomas typically manifest as benign, slow-growing, and well-defined tumors on a macroscopic level and are usually asymptomatic. However, the mass effect caused by large meningiomas may lead to various neurological symptoms, commonly headaches and visual problems. Radiological imaging can establish the diagnosis, and a biopsy can provide a definitive diagnosis. Our case report describes the surgical intervention for bilateral parasagittal-falcine meningioma in a 57-year-old male who presented to the emergency department with a tonic-clonic seizure. On examination, he had a bifrontal longitudinal mass. Magnetic resonance imaging (MRI) revealed a large anterior superior falcine extra-axial mass, measuring about 5.7 x 5.3 x 3.1 cm, with surrounding vasogenic edema and superior sagittal sinus invasion. He underwent surgery for tumor resection involving the anterior third and middle third of the superior sagittal sinus without radiotherapy. He did not develop any intraoperative complications, and during the post-operative evaluation, he was symptom-free. A follow-up MRI with contrast performed three months later showed no neurological complications or recurrent tumor. To achieve better outcomes, surgical intervention for parasagittal and falcine meningiomas involving the superior sagittal sinus should aim to eliminate clinical signs, control tumor growth, and prevent neurological deterioration post-operatively.

Intracranial meningioma: A review of recent and emerging data on the utility of preoperative imaging for management.

Meningiomas are the most common neoplasms of the central nervous system, accounting for approximately 40% of all brain tumors. Surgical resection represents the mainstay of management for symptomatic lesions. Preoperative planning is largely informed by neuroimaging, which allows for evaluation of anatomy, degree of parenchymal invasion, and extent of peritumoral edema. Recent advances in imaging technology have expanded the purview of neuroradiologists, who play an increasingly important role in meningioma diagnosis and management. Tumor vascularity can now be determined using arterial spin labeling and dynamic susceptibility contrast-enhanced sequences, allowing the neurosurgeon or neurointerventionalist to assess patient candidacy for preoperative embolization. Meningioma consistency can be inferred based on signal intensity; emerging machine learning technologies may soon allow radiologists to predict consistency long before the patient enters the operating room. Perfusion imaging coupled with magnetic resonance spectroscopy can be used to distinguish meningiomas from malignant meningioma mimics. In this comprehensive review, we describe key features of meningiomas that can be established through neuroimaging, including size, location, vascularity, consistency, and, in some cases, histologic grade. We also summarize the role of advanced imaging techniques, including magnetic resonance perfusion and spectroscopy, for the preoperative evaluation of meningiomas. In addition, we describe the potential impact of emerging technologies, such as artificial intelligence and machine learning, on meningioma diagnosis and management. A strong foundation of knowledge in the latest meningioma imaging techniques will allow the neuroradiologist to help optimize preoperative planning and improve patient outcomes.

Primary Typical Meningioma of the Sphenoid Sinus: A Case Report and Literature Review.

Primary cranial meningioma is extremely rare and only rarely described in clinical practice, as is primary sinus ectopic meningioma. We detailed the surgical management of a female patient, aged 83, who had a primary meningioma of the sphenoid sinus. This uncommon clinical entity was the subject of a study of the literature, and its prognosis was summarized. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04722-8.

Recovery of cranial nerve neuropathies after LINAC-based stereotactic radiosurgery for benign cavernous sinus meningioma.

PURPOSE: Cranial Nerve Neuropathies (CNNs) often accompany Cavernous Sinus Meningioma (CSM), for which Stereotactic Radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSR) are established treatments. This study assesses CNNs recovery in CSM patients treated with LINAC, offering insight into treatment effectiveness. METHODS: This study was conducted on 128 patients with CSM treated with LINAC-based SRS/FSR between 2005 and 2020 at a single institution. 46 patients presented with CNNs. The study analyzed patients' demographics, clinical parameters, SRS/FSR treatment characteristics, post-treatment CNNs recovery duration, status, and radiological control on their last follow-up. RESULTS: The median follow-up duration was 53.4 months. Patients were treated with SRS (n = 25) or FSR (n = 21). The mean pretreatment tumor volume was 9.5 cc decreasing to a mean end-of-follow-up tumor volume was 5.1 cc. Radiological tumor control was achieved in all cases. CNN recovery was observed in 80.4% of patients, with specific nerve recoveries documented as follows: extra-ocular nerves (43.2%), trigeminal nerve (32.4%), and optic nerve (10.8%). A higher CNNs recovery rate was associated with a smaller pre-treatment tumor volume (p < 0.001), and the median time-to-improvement was 3.7 months. Patients with tumor volumes exceeding 6.8 cc and those treated with FSR exhibited prolonged time-to-improvement (P < 0.03 and P < 0.04 respectively). CONCLUSIONS: This study suggests that SRS/FSR for CSM provides good and sustainable CNNs recovery outcomes with excellent long-term radiological control. A higher CNNs recovery rate was associated with a smaller pre-treatment tumor volume. while shorter time-to-improvement was identified in patients treated with SRS compared to FSR, particularly in those with small pre-treatment tumor volume.

Endoscope-assisted supraorbital approach for excision of tuberculum sella meningioma: Technical nuances.

Background: Tuberculum sellae meningiomas (TSMs) are benign dural-based lesions of the anterior cranial fossa, which mainly present with impaired visual acuity/field deficits secondary to compression of the optic apparatus. Surgical management is recommended as the optimal strategy for large compressive TSMs, with goals of safe maximal resection, optic nerve decompression, and potential vision restoration. The philosophy of adapting keyhole approaches for such resections is commonly highlighted; however, it comes with notable criticism of encountering major blind spots during surgical resection and limited anatomical exposure. Adding angled endoscopes enhances the expanded panoramic view of the skull base and provides a synergistic modality to microsurgery for maximizing total resection and navigating the blind spots. Case Description: This video case presentation aims to highlight the technical nuances of endoscope-assisted microscopic supraorbital craniotomy for TSM resection invading bilateral optic canals in a 66-year-old female presenting with progressive right eye vision loss (OD Hand motion). The video emphasizes traditional skull-base surgical principles of TSM resection through the optics of a keyhole approach augmented by endoscopic tumor removal. Gross total resection was achieved, the patient's vision improved to 20/25, and she was discharged home on postoperative day 2. Conclusion: The endoscope-assisted supraorbital craniotomy offers a safe surgical corridor for TSM, using a limited craniotomy with minimal brain retraction in appropriately selected individuals, particularly with larger tumors with greater lateral extension and above the planum.

A Single Hepatic Metastasis of Cranial Meningioma on [18F]FDG PET/CT 16 Years After Initial Surgery.

Hepatic metastases of cranial meningiomas are rare, particularly when they present as a delayed, solitary metastasis, which poses a challenge for imaging-based diagnosis. [18F]FDG PET/CT facilitates diagnosis and posttreatment restaging, whereas somatostatin receptor-targeted PET demonstrates high sensitivity and specificity in the diagnosis of meningiomas and may potentially evaluate the viability of theranostics approaches, particularly for treatment-resistant meningiomas.

Velocity and pattern of growth of intracranial meningiomas.

OBJECTIVE: The authors' aim was to assess the velocity and pattern of growth of meningiomas and to correlate the kinetics of tumor growth with their previously reported two-item radiological risk stratification and CNS WHO grade (5th edition, 2021). METHODS: The authors performed a serial volumetric analysis of meningiomas diagnosed radiologically at their institution between 2003 and 2015. The primary endpoint was velocity of diametric expansion (VDE), which represents the slope of the linear regression of the mean tumor diameter against time. For the secondary analysis, they categorized the growth patterns as linear or exponential by fitting time-volume curves to a linear and exponential function. Three radiological risk categories based on T2-weighted iso/hyperintensity and absence of calcifications were compared: low risk (T2-weighted hypointense), intermediate-risk (T2-weighted iso/hyperintense with calcifications), and high-risk (T2-weighted iso/hyperintense without calcifications) tumors. RESULTS: For the entire cohort of 240 meningiomas, the median (IQR) VDE was 0.33 (0.00-0.71) mm/year. Distribution of VDE differed significantly among radiological risk categories (0.49 vs 0.35 vs 0.05 mm/year, p < 0.001). High-risk and intermediate-risk tumors more frequently tended to grow exponentially compared to low-risk tumors (43.8% vs 37.0% vs 8.3%, p = 0.067). The authors found no correlation of growth velocity with CNS WHO grade in their cohort (1.30 mm/year for CNS WHO grade 1 vs 4.01 mm/year for CNS WHO grade 2, p = 0.185). CONCLUSIONS: A radiological risk assessment using two parameters-T2-weighted signal iso/hyperintensity and absence of calcifications-allows estimation of growth velocity and characteristics of untreated intracranial meningiomas. Only high-risk tumors exhibit the potential for rapid growth. However, rapid tumor growth does not indicate a higher CNS WHO grade per se.

The Prognostic Utility of Frailty on the Outcomes of Primary Brain Tumor Surgery Patients: A Meta-analysis.

BACKGROUND: Frailty refers to a state of weakness that can arise due to age or illnesses, and frailty predisposes individuals to several adverse health outcomes. This has been postulated to prognosticate the outcome of various surgeries, including surgeries for primary brain tumors; however, no meta-analysis has validated this finding. METHODS: We conducted a systematic review and meta-analysis to investigate the prognostic utility of frailty for the outcome of primary brain tumor surgery. We performed a systematic search of the PubMed, EMBASE, and SCOPUS databases for studies investigating the ability of frailty to predict the outcome of primary brain tumor surgery. RESULTS: Meta-analysis of the information provided in the thirteen studies that made up our sample. Hospital length of stay (LOS) (effect size 0.94; 95% confidence interval [CI]: 0.37, 1.51; p: 0.00), postoperative complications (effect size 10.31; 95% CI: -5.88, 26.86; p: 0.21), readmission (effect size 0.82; 95% CI: 0.23, 1.41; p: 0.01), nonroutine discharge (effect size 1.07; 95% CI: 0.48, 1.65; 0.00), postoperative mortality (effect size 1.48; 95% CI: 0.81, 2.02; p: 0.00), and overall survival (effect size 1.53; 95% CI: 0.29, 2.76; p: 0.02). CONCLUSION: This study showed little correlation with postoperative mortality, readmission, nonroutine discharge, length of hospital stay, or overall survival, and fragility had less significance in these areas but showed no statistical significance in predicting postoperative complications following surgery for primary brain tumors.

Perioperative blood transfusion management in surgical resection of intracranial meningiomas: A meta-analysis.

Background: Gross total resection (GTR) of intracranial meningiomas is curative in most cases. However, perioperative blood transfusions may be necessary for complex skull bases and/or high-grade meningiomas. Guidelines for blood transfusions during intracranial meningioma surgery remain unclear. This scoping review aims to delineate the main characteristics of patients who underwent intracranial meningioma surgery, the prevalence of the selected patients who required blood transfusions, and common causes for transfusion. Methods: A scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Extension for Scoping Reviews guidelines to include studies reporting eligibility, protocols, and potential complications related to blood transfusion within the perioperative management of intracranial meningiomas. Results: A total of 33 articles encompassing 3009 meningioma patients were included in the study. The most common symptom was headache (18%), and the most frequent type of meningioma was World Health Organization grade-1 meningothelial (50.4%). The lateral supraorbital approach was the most common surgical corridor (59.1%) in skull base meningiomas, and most patients underwent GTR (69%). Blood transfusion was required for 20% of patients, with a mean estimated intraoperative blood loss of 703 mL (ranging from 200 mL to 2000 mL). The main indications for blood transfusion in meningioma surgery were intraoperative blood loss (86%) and preoperative anemia (7.3%). Conclusion: This scoping found that 20% of the included patients required blood transfusion. It also points out that several factors could influence the necessity for a transfusion, encompassing surgical blood loss, pre-existing anemia, and the surgery's length. This scoping review may provide surgeons with a potential guide to inform their decision-making process regarding blood transfusions during meningioma surgeries.

Communicating hydrocephalus after resection of a meningioma ventral to the foramen magnum.

Background: Tumors in or near the foramen magnum may cause communicating or non-communicating hydrocephalus (HC), depending on their size and location. Here, an 81-year-old female developed communicating HC following the resection of a meningioma ventral to the foramen magnum. Case Description: An 81-year-old female presented with numbness in the left neck and left hemiparesis. The magnetic resonance revealed an 18-mm tumor ventral to the foramen magnum that significantly enlarged over the past 6 months. She underwent total tumor resection but then presented with progressive HC both clinically (i.e., instability of gait with confusion) and radiographically (computed tomography). Following placement of a lumboperitoneal (LP) shunt, symptoms markedly improved. Further, the cerebrospinal fluid (CSF) analysis showed elevated cell counts and protein concentrations, indicating likely "leakage" of intratumoral contents postoperatively contributing to the progressive HC. Conclusion: Patients presenting with acute meningiomas ventral to the foramen magnum may develop postoperative communicating HC attributed to tumor-related CSF leakage of necrotic intratumoral components that can be successfully treated with a LP shunt.

Review of metastasis to meningiomas with case examples.

Introduction: A tumor-to-tumor metastasis (TTM) is a rare metastatic process where a primary malignant tumor metastasizes to another tumor, most commonly a benign tumor such as a meningioma. Here, we present two recent cases of tumor-to-meningioma metastases (TMM) from our clinical practice and review of recent literature. The primary cancers were prostate and breast cancer, respectively. Material and methods: We reviewed the electronic medical records of the two patients and conducted a literature review of TTM, focusing on biological mechanisms related to TMM. Results: Our first patient, a man with a history of stable prostate cancer, underwent resection of two WHO grade 1 meningiomas, and the largest tumor was found to have TMM. Our second patient, a woman with progressive breast cancer, was operated for a WHO grade II meningioma, and the meningioma harbored breast cancer metastases. TMM is a rare occurrence, but breast cancer is a much more frequent cause than prostate cancer and we reviewed 50 cases. Only 15 of cases of TMM from prostate cancer have been described. Discussion and conclusion: TMM is a rare phenomenon, but it is important to be aware of this as more and more patients live with cancer and meningiomas have a high prevalence, The possibility of TMM may impact not only both the surgical and oncological treatment but also surveillance of incidental meningiomas.

Impact of Perioperative Acetylsalicylic Acid (ASA) Administration on Postoperative Intracranial Hemorrhage (pICH) and Thromboembolic Events in Patients with Intracranial Meningiomas.

Background: In routine medical practice, patients are increasingly using ASA for primary and secondary prevention. Although many of these patients discontinue ASA prior to elective intracranial surgery, there are limited data to support whether perioperative ASA use raises the risk of postoperative hemorrhage. This study aimed to investigate the implications of continuing or stopping ASA around the time of surgery in patients with intracranial meningiomas, focusing on postoperative hemorrhage and thromboembolic events. Methods: For this purpose, medical records and radiological images of 1862 patients who underwent cranial neurosurgical procedures for brain tumors over a decade at our neurosurgical institute were retrospectively analyzed. The risk of postoperative hemorrhage was evaluated by comparing meningioma patients who received ASA treatment with those who did not. Furthermore, we investigated other factors that influence postoperative hemorrhage and thromboembolic events, particularly in patients receiving ASA treatment. Results: A total of 422 patients diagnosed with meningiomas underwent surgical intervention. Among the patients who received ASA preoperatively, 4 out of 46 (8.69%) experienced postoperative hemorrhage requiring surgical intervention, whereas the same complication occurred in only 4 out of 376 patients (1.06%) in the non-ASA group (p = 0.007). There was no significant difference in the incidence of thromboembolic events between the two groups. Conclusions: Our analysis revealed an increased risk of postoperative hemorrhage in patients using ASA.

Malignant Transformation of Meningioma With TERT Promoter Mutation: A Case Report.

High-grade meningiomas make up a relatively minor proportion of meningiomas, which are one of the most common types of primary intracranial tumors in adults. Though rare, a considerable portion of high-grade meningiomas arise from malignant transformation of benign meningiomas. The 2021 World Health Organization (WHO) classification criteria introduced molecular markers in the diagnosis and grading of central nervous system (CNS) tumors and assigned certain genomic mutations to grade 3 meningiomas. We report a case of a 54-year-old male patient who underwent stepwise malignant transformation of meningioma from WHO grade 1 to grade 3 within 10 years, during the course of five surgeries followed by adjuvant stereotactic radiosurgery and radiotherapy. We performed next-generation sequencing (NGS) on the most recent grade 3 meningioma specimen and found that it carried a telomerase reverse transcriptase promoter (TERTp) mutation (c.-124C>T) in accordance with the 2021 WHO criteria for grade 3 meningiomas. We then retrospectively examined the previous grade 1 and 2 specimens and found them to have the same mutation. We reviewed the significance of molecular markers in the diagnosis of meningiomas, possible genetic alterations associated with their malignant transformation, and what measures could be taken to effectively manage meningiomas considering NGS findings.