Primary Intracranial Tumors Research Articles

Factors Influencing Long-Term Outcomes of Single-Session Gamma Knife Radiosurgery in Large-Volume Meningiomas >10 cc

Introduction: Meningiomas are the most common primary intracranial tumour. Gamma knife radiosurgery (GKRS) is a frequently employed non-invasive method of treatment, with good remission rates and low morbidity in literature. However, the role of GKRS in the management of “large” meningiomas is unclear, with reported outcomes that vary by centre. We aimed to assess the factors that influence long-term outcomes following GKRS in meningiomas >10 cc in volume. Methods: A retrospectively analysed all patients with meningiomas exceeding 10 cc in volume who underwent GKRS between January 2006 and December 2021 at the National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru. Demographic, clinical, radiological, and follow-up data were acquired, and factors associated with progression following GKRS were assessed. Results: The cohort comprised 76 patients 29 males (38.2%) and 47 females (61.8%) with a mean age of 46.3 ± 11.02 years. Thirty-nine patients had been previously operated (51.3%). Meningiomas were most frequently located in the parasagittal region (26 tumours, 34.2%) and sphenopetroclival region (23 tumours, 30.3%), with mean lesion volume of 12.55 ± 5.22 cc, ranging 10.3 cc–25 cc. The mean dose administered to the tumour margin was 12.5 Gy ± 1.2 Gy (range 6–15 Gy). The median duration of clinical follow-up was 48 months, over which period radiological progression occurred in 14 cases (20%), with unchanged tumour volume in 20 cases (28.6%) and reduction in size of the tumour in 36 cases (51.4%). Progression-free survival after GKRS was 72% at 5 years, was significantly poorer among meningiomas with tumour volume >14 cc (log-rank test p = 0.045), tumours presenting with limb motor deficits (log-rank test p = 0.012), and tumours that underwent prior Simpson grade 3 or 4 excision (log-rank test p = 0.032). Conclusions: Meningiomas >10 cc in volume appear to display a high rate of progression and subsequent need for surgery following GKRS. Primary surgical resection, when not contraindicated, may be considered with GKRS serving an adjuvant role, especially in tumours exceeding 14 cc in volume, and presenting with limb motor deficits. Long-term clinical and radiological follow-up is essential following GKRS as the response of large meningiomas may be unpredictable.

Secreted clusterin inhibits tumorigenesis by modulating tumor cells and macrophages in human meningioma.

Meningioma is the most common primary intracranial tumor with a high frequency of postoperative recurrence, yet the biology of the meningioma malignancy process is still obscure. To identify potential therapeutic targets and tumor suppressors, we performed single-cell transcriptome analysis through meningioma malignancy, which included 18 samples spanning normal meninges, benign and high-grade in situ tumors, and lung metastases, for extensive transcriptome characterization. Tumor suppressor candidate gene and molecular mechanism were functionally validated at the animal model and cellular levels. Comprehensive analysis and validation in mice and clinical cohorts indicated clusterin (CLU) had suppressive function for meningioma tumorigenesis and malignancy by inducing mitochondria damage and triggering type 1 interferon pathway dependent on its secreted isoform, and the inhibition effect was enhanced by TNFα as TNFα also induced type 1 interferon pathway. Meanwhile, both intra- and extracellular CLU overexpression enhanced macrophage polarization towards M1 phenotype and TNFα production, thus promoting tumor killing and phagocytosis. CLU might be a key brake of meningioma malignance by synchronously modulating tumor cells and their microenvironment. Our work provides comprehensive insights into meningioma malignancy and a potential therapeutic strategy.

Lethal Complications of Meningiomas: A Case Series.

Meningiomas are the most prevalent type of primary intracranial tumor in adults, comprising nearly one-third of all intracranial tumors. They are typically benign, slow-growing, and asymptomatic but may cause neurological symptoms as they expand due to mass effect. Classification is determined by World Health Organization (WHO) grades 1 to 3 following pathological examination corresponding to benign, atypical, and anaplastic (malignant), respectively, reflecting their rate of growth and risk of recurrence. The vast majority are WHO grade 1 and their slow growth permits timely presentation for elective resection; however, meningiomas in vulnerable locations and coexisting morbidities can result in sudden death. We present a series of four adult patients with meningiomas which resulted in death, including a case of fatal seizure, midline hemorrhagic meningioma, postresection meningitis, and compression of the cerebellum. Retrospective review of the authors' cases was conducted. Available pathology, medical, and autopsy records including gross images were reviewed in each case. The inclusion criteria were adult patients (>18 years old) and that the cause of death had to include meningioma. The four patients included a 61-year-old male, an 84-year-old female, a 62-year-old male, and a 37-year-old female. Qualitative; autopsy reports describing cause of death and pathology report findings including gross and microscopic analysis. Meningiomas are often benign in nature but can rarely result in death. Size and location of the tumor and risk factors are contributory. Autopsy examination can be instrumental in identifying the cause and mechanism of deaths associated with meningiomas.

The Clinicopathological Profile and Recurrence of Meningioma at Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital

Background Meningioma represents the most frequent primary intracranial tumor, and some subtypes may demonstrate aggressive characteristics with a correspondingly elevated risk of recurrence. To predict the likelihood of recurrence, clinical and pathological parameters are essential. More aggressive treatment strategies and strict follow-up can be implemented using these parameters. Therefore, this study aims to determine clinicopathological characteristics of meningioma and its relationship with recurrence. Method This study adopted a retrospective cross-sectional approach using secondary data of meningioma cases from the archives of the Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital in 2019-2021. The clinical data were obtained through electronic medical records, and histopathological data assessment, including grade, mitosis, brain invasion, bone invasion, and dural invasion, was conducted through microscopic examination. Result The data indicate that a total of 219 cases of meningioma were reassessed. The mean age of patients was 45±11 years, and the majority (88.1%) were female. The mean tumor size was 5±1.8 cm, with the most common tumor location being the skull base (71%) and 38.6% of cases showed radiological evidence of bone invasion. Subtotal resection was the treatment of choice for most patients (67.8%). CNS WHO grade 1 was found in 91.8% of cases, while Mitotic index ≥4/10 HPF, microscopic evidence of bone invasion, brain invasion, and dural invasion were found in 5%, 33.6%, 3.2%, and 16.8%, respectively. A minimum follow-up of 6 months was fulfilled by 71 cases, and 28% experienced recurrence/progression. These findings showed a significant association between the extent of resection (p=0.007) and tumor size (p=0.02) with the incidence of recurrence. Conclusion Clinical parameters such as the extent of resection and tumor size play a role in predicting the likelihood of meningioma recurrence. The predictive factors knowledge for meningioma recurrence is important in determining treatment strategies and follow-up

Intracranial meningioma: an unusual silent killer—about two cases report and a literature review

BackgroundMeningiomas are common benign intracranial tumors, accounting for 1/3 of all primary intracranial neoplasms, and hence, are not considered the chief cause of death when encountered incidentally during autopsy. These tumors are usually slow-growing, and the clinical course may be asymptomatic to the point of acute complications. Sudden unexpected deaths due to meningiomas are exceptional and rarely reported in the literature.In the present report, we describe two autopsy cases of sudden unexpected death due to meningiomas and we discuss the mechanism of death.Case presentationTwo apparently healthy men were discovered dead in their home. A judicial autopsy was ordered. At dissection, a pedunculated firm mass, attached to the dura was found in both cases. Tumors were located in the anterior and middle fossa. The remaining organs were congestive without any abnormality. A microscopic examination confirmed the diagnosis of meningiomas. Postmortem toxicology analysis was negative. Forensic pathologists concluded to sudden unexpected death due to intracranial meningioma.ConclusionsThese cases illustrate the possibility of meningioma remaining silent till acute complication and fatal outcome. Therefore, clinicians must bear in mind the possibility, albeit extremely rare, of sudden unexpected death in cases of undiagnosed intracranial meningiomas, as documented in the present report. Thus, we emphasize the value of promptly and thoroughly investigating even seemingly minor neurological symptoms, such as headaches or acute epileptic seizures, in adults. We also stress the importance of the early detection and appropriate management of brain tumors in fatal outcome prevention, and we highlight the role of the post-mortem examination to detect such a fatal complication.

Epidemiology, Genetics, and DNA Methylation Grouping of Hyperostotic Meningiomas.

Meningiomas are the most common primary intracranial tumors and are among the only tumors that can form lamellar, hyperostotic bone in the tumor microenvironment. Little is known about the epidemiology or molecular features of hyperostotic meningiomas. Using a retrospective database of 342 meningiomas treated with surgery at a single institution, we correlated clinical, tumor-related, targeted next-generation DNA sequencing (n = 39 total, 16 meningioma-induced hyperostosis [MIH]), and surgical variables with the presence of MIH using generalized linear models. Meningioma DNA methylation grouping was analyzed on a separate population of patients from the same institution with preoperative imaging studies sufficient for identification of MIH (n = 200). MIH was significantly correlated with anterior fossa (44.3% of MIH vs 17.5% of non-MIH were in the anterior fossa P < .001, c2) or skull base location (62.5% vs 38.3%, P < .001, c2) and lower MIB-1 labeling index. Gross total resection was accomplished in 27.3% of tumors with MIH and 45.5% of nonhyperostotic meningiomas (P < .05, t test). There was no association between MIH and histological World Health Organization grade (P = .32, c2). MIH was significantly more frequent in meningiomas from the Merlin-intact DNA methylation group (P < .05). Somatic missense mutations in the WD-repeat-containing domain of the TRAF7 gene were the most common genetic alteration associated with MIH (n = 12 of 15, 80%, P < .01, c2). In this article, we show that MIH has a predilection for the anterior skull base and affected tumors are less amenable to gross total resection. We find no association between MIH and histological World Health Organization grade, but show that MIH is more common in the Merlin-intact DNA methylation group and is significantly associated with TRAF7 somatic missense mutations. These data provide a framework for future investigation of biological mechanisms underlying MIH.

Tumor microenvironment targeting for glioblastoma multiforme treatment via hybrid cell membrane coating supramolecular micelles

Glioblastoma multiforme (GBM) is one of the most common primary intracranial tumors in the central nervous system with poor prognosis, high invasiveness, risk of recurrence and low survival rate. Thus, it is urgent and vital to develop drug effective delivery systems that efficiently to traverse the blood–brain barrier and targeted transport therapeutic agents into the GBM tumor site for the treatment of brain tumors. Recently, amphiphilic cucurbit[7]uril-polyethylene glycol-hydrophobic Chlorin e6 (CB[7]-PEG-Ce6) polymer was designed, prepared, and self-assembled into micells (CPC) in an aqueous solution, and chemo drug methyl-triazeno-imidazole-carboxamide (MTIC), loaded into the cavity of CB[7] was subsequently coated with hybrid membrane mUMH (HMC3 membrane: macrophage membrane: U87MG membrane = 1:1:2) to afford mUMH@CPC@MTIC. The surface hybrid membrane mUMH potentially enhance the targeted delivery of CPC@MTIC to GBM tissue. Bioactive MTIC was released from the cavity of CB[7] in response to the high spermine level in GBM tumor microenvironments for effective tumor chemotherapy. The biomimetic mUMH@CPC@MTIC exhibited superior antitumor efficacy against GBM in mice. These findings provide new strategies for the design of biomimetic nanoparticle-based drug delivery systems and promising therapy of GBM.

High expression of SIGLEC7 may promote M2-type macrophage polarization leading to adverse prognosis in glioma patients.

Gliomas are the most common primary intracranial tumors, known for their high invasiveness and destructiveness. Sialic acid-binding immunoglobulin-like lectin 7 (SIGLEC7) is present in various immune cells, especially macrophages, and significantly affects immune homeostasis and cancer cell response. However, research on the role and prognostic impact of SIGLEC7 in glioma patients is currently limited. We utilized transcriptomic data from 702 glioma patients in The Cancer Genome Atlas (TCGA) and 693 glioma patients in the Chinese Glioma Genome Atlas (CGGA), along with clinical samples we collected, to comprehensively investigate the impact of SIGLEC7 on glioma expression patterns, biological functions, and prognostic value. We focused on its role in glioma-related immune responses and immune cell infiltration and analyzed its expression at the single-cell level. Finally, we validated the role of SIGLEC7 in gliomas through tissue and cell experiments. SIGLEC7 expression was significantly increased in glioma patients with malignant characteristics. Survival analysis indicated that glioma patients with high SIGLEC7 expression had significantly lower survival rates. Gene function analysis revealed that SIGLEC7 is primarily involved in immune and inflammatory responses and is strongly negatively correlated with tumor-associated immune regulation. Additionally, the expression of most immune checkpoints was positively correlated with SIGLEC7, and immune cell infiltration analysis clearly demonstrated a significant positive correlation between SIGLEC7 expression and M2 macrophage infiltration levels. Single-cell analysis, along with tissue and cell experiments, confirmed that SIGLEC7 enhances macrophage polarization towards the M2 phenotype, thereby promoting glioma invasiveness through the immunosuppressive effects of M2 macrophages. Cox regression analysis and the establishment of survival prediction models indicated that high SIGLEC7 expression is an unfavorable prognostic factor for glioma patients. High SIGLEC7 expression predicts poor prognosis in glioma patients and is closely associated with M2 macrophages in the tumor environment. In the future, SIGLEC7 may become a promising target for glioma immunotherapy.

Clinical and Histopathological Aspects of Primary Intracranial Tumours: Case Series of 178 Patients in Yaounde

Clinical and Histopathological Aspects of Primary Intracranial Tumours: Case Series of 178 Patients in Yaounde

Neurosurgical treatment and outcome patterns in patients with meningioma in South Moravian region-a population-based study.

Meningiomas are usually slow-growing tumours, constituting about one third of all primary intracranial tumours. They occur more frequently in women. Clinical manifestation of meningiomas depends on their location, tumour size and growth rate. In most cases, surgical treatment is the procedure of choice. The success of this treatment is, however, associated with the radicality of the resection. Radiotherapy represents an additional or alternative treatment modality. Gamma knife surgery is another notable treatment method, especially in small and/or slow-growing tumours in eloquent areas or in elderly patients. Authors describe their experience with the diagnosis, treatment and outcome of the patients with meningioma (n = 857). Furthermore, they also assess the postoperative morbidity/mortality and recurrence rate. In view of the benign histology of meningiomas, the success of the treatment largely depends (besides the tumour grading) on the radicality of the resection. The emphasis is also put on appropriate follow-up of the patients. In certain patients, the watch and wait strategy should be also considered as a suitable treatment method.

Ginsenoside CK Induces the Mitochondrial Apoptosis in Glioma Cells through the Activation of the p53-Bax-Caspase Pathway

Background Gliomas are harmful to human health; they are the most common primary intracranial tumor. Ginsenoside CK (GS-CK) is converted from the diol ginsenoside. This study aimed to explore the effects of GS-CK on glioma cells SHG-44 and U251MG in order to provide clinical value for the treatment of gliomas. Materials and Methods Cell proliferation was detected using the CCK-8 and CFU detection experiments. Cell apoptosis was detected by DAPI and acridine orange/ethidium bromide (AO/EB) fluorescence staining. Cell scratch and transwell assay were used to detect the effect of GS-CK on cell migration and invasion ability. Apoptosis-related protein expression was detected in the two cell lines after treatment with GS-CK. Results Cell proliferation is obviously inhibited, and cell migration and invasion were also significantly inhibited by GS-CK. It also induced cell apoptosis in a time- and dose-dependent manner. GS-CK induced significant changes in mitochondrial apoptosis pathway-related protein expression of cytochrome C, p53, Bax, Bcl-2, Caspase-3/8/9, Cleaved Caspase-3, and MMP-9 in glioma cells. Conclusion GS-CK can inhibit glioma cells by regulating mitochondria-related apoptosis p53-bax-caspases pathway.

Analysis of the clinical display effect of imaging techniques on the staging of gliomas

Glioma is a primary intracranial malignant tumor, which is difficult to be cured and has the characteristics of easy recurrence and high mortality rate, therefore, it is of great clinical significance to accurately grade glioma before operation. Since biopsy of gliomas is relatively difficult and its accuracy cannot be guaranteed, imaging examination has become an important means of clinical grading of gliomas. This paper, through the literature analysis method, reviews the previous studies of applying imaging methods to grade gliomas in China and abroad and summarizes the main techniques of MRI and CT and their grading effects. Finally, this paper finds that MRI and CT can be used to grade gliomas alone, but both have limitations, while the combined application of MRI and CT has high sensitivity and specificity for the diagnosis and grading of gliomas, which makes up for their respective shortcomings, and is worthy of wide application.

Abstract A089: NST-628 is a potent, fully brain-penetrant, RAS/MAPK pathway molecular glue inhibitor with efficacy in CNS tumor models

Abstract Alterations in the RAS/RAF/MEK/ERK signaling cascade are common across multiple solid tumor types and aberrant signaling of the pathway is a driver for RAS- and RAF-driven cancers. Apart from approved mutation selective inhibitors for BRAF Class I and KRAS G12C mutations, other mutations of RAS and RAF are not directly addressable by currently approved inhibitors and there is a need for inhibitors with superior efficacy, durability and tolerability for the MAPK pathway in RAS- and RAF-driven cancers. Currently approved inhibitors of the RAS-MAPK pathway also have limited central nervous system (CNS) exposure and an area of significant unmet patient need exists for patients with primary and metastatic tumors harboring RAS-MAPK pathway alterations. NST-628 has CNS permeability, with a Kpu,u &amp;gt;1, that is far higher than trametinib or VS-6766 (Kpu,u of 0.11 and 0.18 respectively). The predicted effective human half-life of NST-628 (~9h) is amenable to daily dosing in the clinic. In vivo, NST-628 leads to a dose-dependent inhibition of the MAPK pathway in murine brain tissue[KS1] as measured by phospho-ERK. In an intracranial luciferase-tagged SK-MEL-2 xenograft model (NRAS Q61R), NST-628 leads to tumor regressions with a daily dosing regimen (3 mg/kg QD). Tumor regressions as measured by bioluminescent imaging (BLI) were only seen with NST-628 (50%) in the SK-MEL-2 model, whereas trametinib and VS-6766 showed minimal efficacy due to low exposure in the CNS. In the NF-1 mutant MeWo (NF1 Q1336*) melanoma intracranial xenograft model (luciferase tagged), NST-628 led to tumor regressions at two dosing regimens (1, 3 mg/kg QD) and tumor stasis at lower doses (0.3 mg/kg) as measured by BLI. In contrast, the brain penetrant type II RAF inhibitor DAY101 (formerly TAK580) showed no efficacy in the MeWo model and resulted in paradoxical pathway hyper-activation, as determined by enhanced PD response and tumor growth. Only NST-628 effectively inhibited MAPK signaling as measured by DUSP6 transcript in a time- and dose-dependent manner. Overall, survival of mice harboring MeWo intracranial tumors was also significantly increased versus vehicle control and DAY101 treatment groups. These data collectively support best-in-class potential of NST-628 and initiation of clinical trials in patients with solid tumors harboring RAS- and RAF-mutations, including those presenting clinically with brain metastases and primary intracranial tumors. Citation Format: Meagan B Ryan, Chun Li, Yongxin Han, Klaus P Hoeflich, Michael R Hale, Margit Hagel. NST-628 is a potent, fully brain-penetrant, RAS/MAPK pathway molecular glue inhibitor with efficacy in CNS tumor models [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A089.

Domestic Animal Models of Central Nervous System Tumors: Focus on Meningiomas.

Intracranial primary tumors (IPTs) are aggressive forms of malignancies that cause high mortality in both humans and domestic animals. Meningiomas are frequent adult IPTs in humans, dogs, and cats, and both benign and malignant forms cause a decrease in life quality and survival. Surgery is the primary therapeutic approach to treat meningiomas, but, in many cases, it is not resolutive. The chemotherapy and targeted therapy used to treat meningiomas also display low efficacy and many side effects. Therefore, it is essential to find novel pharmacological approaches to increase the spectrum of therapeutic options for meningiomas. This review analyzes the similarities between human and domestic animal (dogs and cats) meningiomas by evaluating the molecular and histological characteristics, diagnosis criteria, and treatment options and highlighting possible research areas to identify novel targets and pharmacological approaches, which are useful for the diagnosis and therapy of this neoplasia to be used in human and veterinary medicine.

Case of Metastatic Atypical Meningioma to Lung: Utility of Cytological Preparations for Intraoperative Diagnosis

Abstract Introduction/Objective Meningiomas are the most common primary intracranial and intraspinal tumors. They are typically benign with an indolent behavior but can metastasize extracranially to the skin, bone, lymph node and liver. Lung metastasis is exceptionally rare, and the diagnosis can be challenging, especially during intraoperative diagnosis without ancillary studies. We describe a metastatic atypical meningioma to the lung for which intraoperative cytology facilitated the diagnosis and guided management. Methods/Case Report A 53-year-old woman with a history of left frontal atypical meningioma and multiple surgical resections for recurrences at outside hospitals, presented with an incidental left lung nodule. A lung wedge resection was performed and submitted for intraoperative diagnosis. Gross examination revealed a well-circumscribed, tan- white, and rubbery subpleural nodule. Cytological preparations— Diff-Quik and H&amp;E stains—and frozen section were prepared. Cytologically, the nodule displayed cohesive distinctive papillary whorls of uniform eosinophilic cells with indistinct cell membranes, round to oval nuclei with central nucleoli and intranuclear pseudoinclusions. The frozen section exhibited similar cytological features, few identifiable whorls and predominantly solid sheets of tumor cells typical of non-small cell carcinoma. Based primarily on the cytological findings, the intraoperative diagnosis was a neoplasm with papillary growth pattern, and a metastasis was favored based on the whorled pattern and clinical history; no further resection was performed. Permanent sections displayed mitoses and no necrosis. Immunohistochemical analysis revealed positivity for somatostatin receptor 2a, progesterone receptor, and EMA (focal); no staining was seen with pancytokeratin, TTF-1, or p40. A diagnosis of atypical meningioma, WHO grade 2, was rendered. Subsequently, an atypical cranial and temporalis muscle meningioma at the site of the prior craniotomy bone flap was resected and had an identical molecular profile (1p36 deletion) to that in the lung, further supporting metastasis to the lung. Results (if a Case Study enter NA) NA Conclusion This case illustrates a rare presentation of metastatic atypical meningioma and highlights the distinctive intraoperative utility of cytology preparations—architectural and cytological details—for diagnosis and appropriate management. Cytology preparations can be a valuable tool and complement frozen sections, in which certain morphological features may be less obvious or confounded by freezing artifact.

Photodynamic therapy in brain cancer: mechanisms, clinical and preclinical studies and therapeutic challenges

Cancer is a main cause of death and preferred methods of therapy depend on the type of tumor and its location. Gliomas are the most common primary intracranial tumor, accounting for 81% of malignant brain tumors. Although relatively rare, they cause significant mortality. Traditional methods include surgery, radiotherapy and chemotherapy; they also have significant associated side effects that cause difficulties related to tumor excision and recurrence. Photodynamic therapy has potentially fewer side effects, less toxicity, and is a more selective treatment, and is thus attracting increasing interest as an advanced therapeutic strategy. Photodynamic treatment of malignant glioma is considered to be a promising additional therapeutic option that is currently being extensively investigated in vitro and in vivo. This review describes the application of photodynamic therapy for treatment of brain cancer. The mechanism of photodynamic action is also described in this work as it applies to treatment of brain cancers such as glioblastoma multiforme. The pros and cons of photodynamic therapy for brain cancer are also discussed.

A SURPRISE DIAGNOSIS FROM A UNILATERAL HEARING LOSS AND VERTIGO CASE FROM CEREBELLOPONTINE ANGLE TUMOR

Meningiomas are generally benign intracranial tumors that arise from the dural coverings of the brain. They represent approximately one-third of all primary intracranial tumors and about 10-15% of cerebellopontine angle (CPA) tumors. Meningiomas develop from arachnoid cells and have been previously observed to be slow-growing. Despite their benign classification, these tumors can impact cranial nerves leading to a myriad of symptoms including hearing loss, imbalance or vertigo, tinnitus, and diminished facial sensation. Technology such as computerized tomography (CT) and magnetic resonance imaging (MRI) are vital tools in the definitive diagnosis of CPA meningiomas.

Translocator protein (TSPO) expression in neoplastic cells and tumor-associated macrophages in meningiomas.

Meningiomas are the most common primary intracranial tumors and show extensive infiltration of macrophages. The mitochondrial membrane protein translocator protein (TSPO) has been used as an in vivo marker of microglia and macrophage activation to visualize neuroinflammation. However, it is unknown which cell types express TSPO in meningiomas. Immunohistochemistry of 38 WHO grade 1-3 meningiomas was subjected to segmentation and deep learning classification of TSPO expression to either Iba1-positive tumor-associated macrophages (TAMs) or all other (mainly neoplastic) cells. A possible association between clinical data and TSPO expression intensities was also investigated. TAMs accounted for 15.9%-26% of all cells in the meningioma tissue. Mean fluorescence intensity of TSPO was significantly higher in TAMs (p < 0.0001), but the mass of neoplastic cells in the tumors exceeded that of TAMs. Thus, the summed fluorescence intensity of TSPO in meningioma cells was 64.1% higher than in TAMs (p = 0.0003). We observed no correlation between TSPO expression intensity and WHO grade. These results indicate that both macrophage-lineage and neoplastic cells in meningiomas express TSPO and that the SPECT-TSPO signal in meningiomas mainly reflects the latter; TSPO is expressed equally in parenchymal activated and resting macrophage/microglia lineage cells.

PATH-48. KI-67 INDEX AS A PREDICTIVE MARKER OF MENINGIOMA CLINICO-PATHOLOGIC COURSE AND RECURRENCE FOLLOWING SURGICAL RESECTION: A RETROSPECTIVE STUDY

Abstract BACKGROUND/OBJECTIVE Meningiomas are the most common primary intracranial tumor in adults. Although usually benign, they have a variable clinical course. Ki-67, a nuclear protein involved in cell cycle regulation, has been widely studied as a marker of cellular proliferation in various cancers. However, the prognostic significance of Ki-67 in meningiomas remains controversial. Here, we investigate the Ki-67 index, as a predictive marker of meningioma recurrence following surgical resection and compare it to established prognostic markers such as WHO grade and degree of resection. METHODS The medical records of 451 consecutive patients with previously untreated cranial meningiomas who underwent resections from January 2011 to January 2021 at North Shore University Hospital (NSUH) were reviewed. Collected data included WHO grade, Ki-67 proliferative index, degree of resection, and meningioma recurrence. RESULTS There were 290 patients with grade I, 154 with grade II, and 7 with grade III meningiomas. The average post-resection follow-up period was 4 years, and 82 tumors (18%) recurred. Recurrence occurred significantly more frequently in tumors with a Ki67 index of 5 or more (31%) compared to those with a Ki67 index less than 5 (10.4%). Likewise, higher WHO grades were associated with a higher rates of recurrence, with rates of 11.3%, 27.9%, and 71.4% for grades 1, 2, and 3, respectively. Higher WHO grades also correlated with higher Ki67 scores (2.59, 10.01, and 20.71) for grades 1, 2, and 3, respectively. Additionally, a multivariate logistic regression model identified ki67, WHO grade and degree of resection as independent predictive variables for meningioma recurrence. CONCLUSION Our 10-year retrospective study suggests that the Ki67 index is a promising predictive marker for recurrence of intracranial meningioma following surgical resection. Our findings add to a growing body of data which supports inclusion of ki67 index in the WHO grading criteria.

Unveiling a Biomarker Signature of Meningioma: The Need for a Panel of Genomic, Epigenetic, Proteomic, and RNA Biomarkers to Advance Diagnosis and Prognosis.

Meningiomas are the most prevalent primary intracranial tumors. The majority are benign but can undergo dedifferentiation into advanced grades classified by World Health Organization (WHO) into Grades 1 to 3. Meningiomas' tremendous variability in tumor behavior and slow growth rates complicate their diagnosis and treatment. A deeper comprehension of the molecular pathways and cellular microenvironment factors implicated in meningioma survival and pathology is needed. This review summarizes the known genetic and epigenetic aberrations involved in meningiomas, with a focus on neurofibromatosis type 2 (NF2) and non-NF2 mutations. Novel potential biomarkers for meningioma diagnosis and prognosis are also discussed, including epigenetic-, RNA-, metabolomics-, and protein-based markers. Finally, the landscape of available meningioma-specific animal models is overviewed. Use of these animal models can enable planning of adjuvant treatment, potentially assisting in pre-operative and post-operative decision making. Discovery of novel biomarkers will allow, in combination with WHO grading, more precise meningioma grading, including meningioma identification, subtype determination, and prediction of metastasis, recurrence, and response to therapy. Moreover, these biomarkers may be exploited in the development of personalized targeted therapies that can distinguish between the 15 diverse meningioma subtypes.