Atypical Meningioma Research Articles

Meningioma sampling: how much is enough for the accurate grading of atypical meningiomas?

Meningioma grading relies on several pathological criteria (brain invasion, mitotic count, sheeting, small cell foci, necrosis, macronucleoli and hypercellularity) and histopathological subtypes. Regardless of histopathological subtype, the presence of these pathological parameters can be focally present and not present on each slide of a meningioma. We performed (1) a retrospective work comparing the frequency of parameters used for meningioma grading between two periods with different sampling techniques, and (2) we calculated the probability of presence of each criterion on resected meningiomas entirely processed included and examined. First, we compared two time periods: between 2002-2008 where meningiomas were not all entirely sampled, and between 2012-2018 where all meningiomas were entirely sampled. The frequency of tumour grades was not significantly different between the two periods (p=0.17). Mitosis ≥4/1.6mm2, small cell foci, macronucleoli and hypercellularity were more frequently found when meningiomas were entirely sampled (p<0.05). Second, we focused on 59 grade 2 meningiomas entirely sampled to highlight the distribution of histopathological parameters used for meningioma grading. We have shown that a correct grading of more than 95% of meningiomas can be achieved when at least six slides are examined. Our work suggests that meningioma sampling might be an issue and the sampling system must be specified in research works on grading.

Treatment of WHO Grade 2 Meningiomas With Stereotactic Radiosurgery: Identification of an Optimal Group for SRS Using RPA

This study assesses a large multi-institutional database to present the outcomes of World Health Organization grade 2 meningiomas treated with stereotactic radiosurgery (SRS). We also compare the 3-year progression-free survival (PFS) to that reported in the Radiation Therapy Oncology Group 0539 phase 2 cooperative group meningioma trial. From an international, multicenter group, data were collected for grade 2 meningioma patients treated with SRS for demonstrable tumor from 1994 to 2019. Statistical methods used included the Kaplan-Meier method, Cox proportional hazards analysis, and recursive partitioning analysis. Two hundred thirty-three patients treated at 12 institutions were included. Patients presented at a median age of 60 years (range, 13-90), and many had at least 2 prior resections (30%) or radiation therapy (22%). Forty-eight percent of patients had prior gross total resection. At SRS, the median treatment volume was 6.1 cm3 (0.1-97.6). A median 15 Gy (10-30) was delivered to a median percent isodose of 50 (30-80), most commonly in 1 fraction (95%). A model was developed using recursive partitioning analysis, with one point attributed to age >50 years, treatment volume >11.5 cm3, and prior radiation therapy or multiple surgeries. The good-prognostic group (score, 0-1) had improved PFS (P < .005) and time to local failure (P < .005) relative to the poor-prognostic group (score, 2-3). Age >50 years (hazard ratio = 1.85 [95% confidence interval, 1.09-3.14]) and multiple prior surgeries (hazard ratio = 1.80 [1.09-2.99]) also portended reduced PFS in patients without prior radiation therapy. Two hundred eighteen of 233 patients in this study qualified for the high-risk group of Radiation Therapy Oncology Group 0539, and they demonstrated similar outcomes (3-year PFS: 53.9% vs 58.8%). The good-prognostic group of SRS patients demonstrated slightly improved outcomes (3-year PFS: 63.1% vs 58.8%). SRS should be considered in carefully selected patients with atypical meningiomas. We suggest the use of our good-prognostic group to optimize patient selection, and we strongly encourage the initiation of a clinical trial to prospectively validate these outcomes.

Surgery on giant meningiomas in very old patients entails frequent postoperative intracranial hemorrhages and atypical histopathology

PurposeSurgical resection of intracranial meningiomas in patients that are 80 years old and older, i.e. very old patients, is increasingly considered. Meningiomas with a largest diameter of at least 5 cm—‘giant meningiomas’—form a distinct entity, and their surgical resection is considered more difficult and prone to complications. Here, we evaluated functional outcome, morbidity and mortality, and the prognostic value of tumor size in very old patients who underwent resection of giant supratentorial meningiomas.MethodsWe retrospectively reviewed clinical and radiological data, functional performance (Karnofsky Performance Score), histopathological diagnosis and complications of very old patients who underwent surgery of a supratentorial meningioma at the Helsinki University Hospital between 2010 and 2018.ResultsWe identified 76 very old patients, including 28 with a giant meningioma. Patients with a giant meningioma suffered from major complications more commonly than those with a non-giant meningioma (36% vs. 17%, p = 0.06), particularly from postoperative intracranial hemorrhages (ICH). At the 1-year follow-up, functional performance and mortality rate were comparable between patients with giant meningiomas and those with non-giant meningiomas. An exceptionally high rate of giant meningiomas were diagnosed as atypical meningiomas (WHO II) at an (11 out of 28 cases).ConclusionsGiant meningioma surgery entails a high complication rate in frail, very old patients. The prevention of postoperative ICH in this specific patient group is of utmost importance. An atypical histopathology was notably frequent among very old patients with a giant meningioma, which should be taken into account when planning the surgical strategy.

Malignant Progression Contributes to the Failure of Combination Therapy for Atypical Meningiomas.

ObjectiveTo investigate the independent risk factors for recurrence in intracranial atypical meningiomas (AMs) treated with gross total resection (GTR) and early external beam radiotherapy (EBRT).MethodsClinical, radiological, and pathological data of intracranial AMs treated with GTR-plus-early-EBRT between January 2008 and July 2016 were reviewed. Immunohistochemical staining for Ki-67 was performed. Kaplan–Meier curves and univariate and multivariate Cox proportional hazards regression analyses were used to explore independent predictors of tumor recurrence. Chi square test was performed to compare variables between subgroups.ResultsForty-six patients with intracranial AMs underwent GTR and early EBRT. Ten (21.7%) recurred and three (6.5%) died during a median follow-up of 76.00 months. Univariate and multivariate Cox analyses revealed that malignant progression (MP) (P = 0.009) was the only independent predictor for recurrence, while Ki-67 was of minor value in this aspect (P = 0.362). MP-AMs had a significantly higher recurrence rate (P = 0.008), a higher proportion of irregularly shaped tumors (P = 0.013) and significantly lower preoperative Karnofsky Performance Scale (KPS) scores (P = 0.040) than primary (Pri) AMs. No significant difference in Ki-67 expression was detected between these subgroups (P = 0.713).ConclusionsMP was significantly correlated with an increased incidence of recurrence in GTR-plus-early-EBRT-treated intracranial AMs. Significantly higher frequencies of tumor relapse and irregularly shaped tumors and lower preoperative KPS scores were observed in MP-AMs compared with Pri-AMs. Ki-67 expression is of minor value in predicting tumor recurrence or distinguishing tumor origins in AMs.

Necrosis and Brain Invasion Predict Radio-Resistance and Tumor Recurrence in Atypical Meningioma: A Retrospective Cohort Study.

Meningiomas are the most common tumors occurring in the central nervous system, with variable recurrence rates depending on World Health Organization grading. Atypical (Grade II) meningioma has a higher rate of recurrence than benign (Grade I) meningioma. The efficacy of adjuvant radiotherapy (RT) to improve tumor control has been questioned. To investigate clinical and histopathological predictors of tumor recurrence and radio-resistance in atypical meningiomas. This cohort study retrospectively reviewed all patients in St. Michael's Hospital CNS tumor patient database who underwent surgical resection of a Grade II meningioma from 1995 to 2015. Cases with neurofibromatosis type II, multiple satellite tumors, spinal cord meningioma, radiation-induced meningioma, and perioperative death were excluded. Patient demographics, neuropathological diagnosis, tumor location, extent of resection, radiation therapy, and time to recurrence or progression were recorded. Cox univariate regression and Kaplan-Meier survival analysis were employed to identify risk factors for recurrence and radio-resistance. Among 181 patients, the combination of necrosis and brain invasion was associated with an increased recurrence risk (hazard ratio [HR]=4.560, P=.001) and the lowest progression-free survival (PFS) relative to other pathological predictors. This trend was maintained after gross total resection (GTR, P=.001). RT was associated with decreased PFS (P=.001), even in patients who received GTR (P=.001). The combination of necrosis and brain invasion is a strong predictor of tumor recurrence and radio-resistance in meningioma, regardless of EOR or adjuvant RT. Our findings question the sensibility of brain invasion as an absolute criterion for Grade II status.

Differentiation of Typical and Atypical Meningiomas Using Magnetic Resonance Imaging

Background: Meningiomas are the most common intracranial neoplasms. They are usually homogeneously enhancing extraaxial masses. However, 10% of meningiomas are atypical with different imaging appearance. Distinguishing typical from atypical meningiomas on imaging is highly important in surgical and treatment planning. Materials and Methods: Our study was a retrospective one comprising twenty cases each of pathologically proven typical and atypical meningiomas excluding enplaque lesions. Magnetic resonance images were reviewed with each of the lesions showed as dural-based enhancing mass. Individual features analyzed were age, gender, maximum size, location, signal characteristics on T1, T2 weighted, susceptibility weighted imaging, diffusion-weighted, apparent diffusion coefficient, contrast-enhanced T1, interface with adjacent brain tissue, signal changes in adjacent brain tissue, and changes in overlying bone. Aim: The aim of the study is to retrospectively assess the magnetic resonance imaging (MRI) features of pathologically proven typical and atypical meningiomas. Results: Magnetic resonance features such as diffusion restriction, bony changes in form of destruction, indistinct interface with brain parenchyma, heterogeneous postcontrast enhancement, and edematous changes &gt;6 mm thick in adjacent brain parenchyma were in favor of atypical meningioma. Conclusion: MRI has the ability to differentiate typical and atypical meningiomas based on imaging appearance which is important in surgical and treatment planning.

Bioinformatic Analyses Determine the Importance of CXCL2 and CXCL8 in Atypical Meningioma Development and Reoccurrence.

To compare gene expression profiles between atypical meningiomas and normal meninges from the National Center of Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database to identify key genes and pathways. The microarray datasets GSE43290 and GSE16581 were downloaded from Gene Expression Omnibus (GEO) database to explore the key genes involved in meningioma formation and reocurrence. Additionally, the relationship between the key genes identified and clinical factors, including age, survival, and recurrence, was assessed. To investigate the the biological functions of the key genes, the gene ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) pathways enrichment analyses were performed. Finally, the differences in immune infiltration between atypical meningiomas and healthy tissues were assessed. A total of 286 hub genes were identified, which were enriched in leukocyte migration, collagen-containing extracellular matrix, signaling receptor activator activity, and receptor-ligand activity. The differentially expressed genes(DEGs) were mainly enriched in the IL-17 signaling pathway and focal adhesion. Among these hub genes, two overlapping genes, including CXCL8 and CXCL2, were selected as key genes which were correlated with tumor survival and recurrence. These two genes were enriched in mediating chemokine and cytokine responses, especially neutrophil and granulocyte responses, and influenced the immune cells infiltrated in the tumor tissue, thereby, influencing prognosis. The implications of this study excavated the key genes in atypical meningiomas which could help us understand the molecular mechanisms and provide the candidate therapeutic targets.

Outcomes following upfront radiation versus monitoring in atypical meningiomas: 16-year experience at a tertiary medical center.

BackgroundThe role of postoperative upfront radiotherapy (RT) in the management of gross totally resected atypical meningiomas remains unclear. This single-center retrospective review of newly diagnosed histologically confirmed cases of World Health Organization (WHO) Grade II atypical meningioma at Weill Cornell Medicine from 2004 to 2020 aims to compare overall survival (OS) and progression-free survival (PFS) of postoperative upfront RT versus observation, stratified by resection status (gross total resection [GTR] vs subtotal resection [STR]).MethodsNinety cases of atypical meningioma were reviewed (56% women; median age 61 years; median follow-up 41 months).ResultsIn patients with GTR, hazard ratio (HR) of PFS was 0.09 for postoperative upfront RT versus observation alone (95% confidence interval [CI] 0.01–0.68; P = .02), though HR for OS was not significant (HR 0.46; 95% CI 0.05–4.45; P = .5). With RT, PFS was 100% at 12 and 36 months (compared to 84% and 63%, respectively, with observation); OS at 36 months (OS36) was 100% (compared to 94% with observation). In patients with STR, though PFS at 36 months was higher for RT arm versus observation (84% vs 74%), OS36 was 100% in both arms. HR was not significant (HR 0.76; 95% CI 0.16–3.5; P = .73).ConclusionsThis retrospective study suggests postoperative upfront RT following GTR of atypical meningioma is associated with improved PFS compared to observation. Further studies are required to draw conclusions about OS.

Outcome After Protontherapy for Progression or Recurrence of Surgically Treated Meningioma.

BackgroundTo assess the outcome after meningioma surgery and protontherapy (PT).MethodsWe processed the French Système National des Données de Santé database to retrieve appropriate cases of meningiomas operated and irradiated between 2008 and 2017. Survival methods were implemented.ResultsOne hundred ninety-three patients who received PT after meningioma surgery over a 10-year period were identified. Of the 193 patients, 75.6% were female. Median age at surgery was 50 years (interquartile range [IQR] 41–62). The median number of PT fractions was 31 (IQR 30–39) given over a median duration of 52 days (IQR 44–69). Fourteen patients (7.3%) also received photon radiotherapy and six patients (3.1%) stereotactic radiosurgery. Median follow-up was 4.4 years (IQR 3.86–4.71). Five-year progression-free survival (PFS) rate was 69% (95% confidence interval [CI] 62.1–76.6). For benign, atypical, and malignant meningioma, 5-year PFS rates were 71.5% (95% CI 64.4–79.4), 55.6% (95% CI 32.5–95), and 35.6% (95% CI 12.8–98.9), respectively (p<0.01). In the adjusted regression, tumour location (hazard ratio [HR]=0.1, 95% CI 0.05–0.22, p<0.001), aggressive meningioma (HR=2.26, 95% CI 1.1–4.66, p=0.027), and the need of cerebrospinal fluid (CSF) insertion for hydrocephalus (HR=3.51, 95% CI 1.32–9.31, p=0.012) remained significantly associated to the PFS. All grades considered, 5-year overall survival (OS) rates was 89.7% (95% CI 84.6–95.1). For benign, atypical, and malignant meningioma, 5-year OS rates were 93% (95% CI 88.7–97.4), 76.4% (95% CI 51.4–100), and 44.4% (95% CI 16.7–100), respectively (p<0.01). In the multivariable regression, an older age above 70 years (HR=5.95, 95% CI 2.09–16.89, p<0.001) associated to a high level of comorbidities (HR=5.31, 95% CI 1.43–19.78, p=0.013) and a malignant meningioma (HR=5.68, 95% CI 1.54–20.94, p=0.009) remained significantly associated to a reduced OS.ConclusionFive-year PFS and OS after meningioma surgery and PT is favourable but impaired for older patients with high level of morbidities, tumour of the convexity, malignant histopathology and for those requiring CSF shunting. Further inclusion and prolonged follow-up is required to assess other predictors such as sex, tumour volume, or given dose.

Predictors of survival in atypical meningiomas

Predictors of survival in atypical meningiomas

The Importance of surgical resection in the treatment of intracranial atypical meningiomas

The Importance of surgical resection in the treatment of intracranial atypical meningiomas

Pure Agraphia Associated with a Frontal Meningioma on Left Superior Frontal Gyrus

<i>Background</i>: The existence of cerebral area specifically involved in coding for writing movements in the left middle frontal gyrus is a matter of debate. We present a rare case of pure agraphia associated with a left frontal meningioma. The location of the lesion associated with this disorder could help to feed this debate. <i>Method</i>: We report a case of pure agraphia in a 69-year-old man. The patient had a writing disorder evolving over several months with a dominant, left frontal lesion. On neuropsychological evaluation, the writing difficulties were present whatever the nature of the writing (spontaneous, dictation, coping). The writing disorder was isolated, with no features of aphasia, alexia or limb apraxia. Phonological and lexical processing was preserved. The imaging showed a probable frontal meningioma restricted to the foot of the first and second left frontal circumvolutions (MNI coordinates /barycenter of the lesion: x=-19.8, y=1.5, z=52.2). <i>Results</i>: The patient was operated and the whole lesion was removed. After surgical resection, the patient’s writing disorder improved. Other components of language assessed were the same as before the surgery and showed no disturbances. The pathological study concluded on an OMS grade II atypical meningioma. <i>Conclusion</i>: We think that the disorder presented by our patient was related to the disturbance of the frontal graphemic center located in the Exner area. Here, we describe and analyze his condition through a neuro-anatomical and a cognitive approach.

Pathologic Characteristics Associated With Local Recurrence of Atypical Meningiomas Following Surgical Resection.

BackgroundOptimal management of grade II meningiomas following resection remains controversial, owing mostly to the heterogeneity of post-operative (post-op) recurrence patterns across studies. Improved risk stratification of these patients would ensure that only those most at risk of recurrence would undergo appropriate post-op radiation therapy (RT).MethodsMedical records from patients who underwent resection for grade II meningiomas were retrospectively reviewed. Demographic, disease characteristics, treatment, and clinical course data were retrospectively collected. Logistic regression, Cox proportional hazards modeling, and Kaplan-Meier curves with log rank testing were conducted to describe any potential relationships with time of recurrence.ResultsOf the 49 patients identified, 18 (36.7%) suffered a local recurrence following resection with a median follow-up of 3.1 years (range: 0.23 - 17.1 years). Past recurrence of the meningioma (P = 0.002) and extent of resection (P = 0.02) were significantly associated with local recurrence. On multivariable analysis, only prior meningioma recurrence was associated with time to local failure (P = 0.021). No histopathologic factors were found to be associated with the initial local failure. Of those who suffered a local recurrence, the presence of bone invasion (hazard ratio: 0.069, P = 0.008) and lack of salvage RT (P = 0.02) were associated with subsequent local failure.ConclusionsCurrently considered histopathologic factors appear not to be helpful in guiding initial treatment course. History of prior local failure and bone invasion appear to be associated with multiple recurrences. Optimal surgical resection is critical to improving outcomes, and salvage RT may reduce subsequent local failure.

Brain radionecrosis after radiation therapy for atypical meningioma

Introduction. Atypical Meningioma (AM) is at high risk of local failure. The role of radiation therapy (XRT) as an adjuvant to surgical resection is incompletely defined. The most deleterious consequence of brain-directed XRT is radiation necrosis. Brain radionecrosis (BRN) after AM has been rarely reported. The relevant literature is reviewed, highlighting its diagnostic challenges. Case Presentation. We report a 25-year-old male with a BRN after adjuvant XRT for AM, which has been misdiagnosed as a recurrent neoplastic lesion upon magnetic resonance spectroscopy (MRS) examination. Surgery and histopathological description were made and yielded a definitive diagnosis of BRN. The patient was treated by dexamethasone with concomitant hyperbaric oxygen therapy (HBO2). The patient showed a further progression of the disease. Therefore, he was elected to receive bevacizumab. However, the patient finally died for refractory brain edema. Conclusion. BRN is a relatively rare instance after XRT for AM. There is no single modality that can reliably distinguish BRN from tumour recurrence. Therefore, reaching an early prompt treatment decision is challenging.

Morphological spectrum of intracranial meningiomas on computed tomography (CT) and magnetic resonance imaging (MRI)

Meningiomas are the most common extra axial and non-glial primary neoplasms of the central nervous system. They account for nearly 15% of all intracranial neoplasms. The present study was planned to identify and describe the morphological and imaging characteristics of both typical and atypical meningiomas on CT and MRI, including Diffusion Weighted Imaging (DWI) and MR Spectroscopy (MRS). CT and MRI images of 43 patients histologically proven to have meningioma were retrospectively evaluated. The images were evaluated for- tumor location, imaging characteristics, atypical patterns of presentation and as well as advanced imaging features. Statistical analysis used included percentage and frequency. Institutional ethical committee clearance was obtained prior to commencement of the study. Our study population comprised of 23 females and 20 males. The bulk of our population belonged to 5th decade group (44%). The most common tumor site was the frontal lobe (40%). Features seen on imaging included- well defined margins (100%), broad dural base (67%), calcification-84% (n=36/43) and peritumoral edema (51%). On MRI, 84% and 67% of the lesions were T1 isointense and T2 mildly hyperintense respectively, when compared to the brain parenchyma, diffusion restriction was variable (benign meningiomas- 46% and atypical meningiomas-100%). Choline (100%) and Alanine peaks (28%) were observed on MRS. On post contrast imaging, homogeneous enhancement was seen in 95%, while a dural tail was seen in only 51% of the cases. Benign meningiomas present with typical extra-axial features (broad dural base, white matter buckling, CSF cleft, dural tail etc.), while atypical meningiomas have varied presentations which include-cystic/necrotic areas, significant vasogenic edema with mass effect and diffusion restriction on DWI. Keywords: Meningioma, Extra-axial lesion, Dural tail.

The histopathological diagnosis of atypical meningioma: glass slide versus whole slide imaging for grading assessment

Limited studies on whole slide imaging (WSI) in surgical neuropathology reported a perceived limitation in the recognition of mitoses. This study analyzed and compared the inter- and intra-observer concordance for atypical meningioma, using glass slides and WSI. Two neuropathologists and two residents assessed the histopathological features of 35 meningiomas—originally diagnosed as atypical—in a representative glass slide and corresponding WSI. For each histological parameter and final diagnosis, we calculated the inter- and intra-observer concordance in the two viewing modes and the predictive accuracy on recurrence. The concordance rates for atypical meningioma on glass slides and on WSI were 54% and 60% among four observers and 63% and 74% between two neuropathologists. The inter-observer agreement was higher using WSI than with glass slides for all parameters, with the exception of high mitotic index. For all histological features, we found median intra-observer concordance of ≥ 79% and similar predictive accuracy for recurrence between the two viewing modes. The higher concordance for atypical meningioma using WSI than with glass slides and the similar predictive accuracy for recurrence in the two modalities suggest that atypical meningioma may be safely diagnosed using WSI.

CNS Invasion in Meningioma—How the Intraoperative Assessment Can Improve the Prognostic Evaluation of Tumor Recurrence

Simple SummaryBrain invasion has been integrated into the new WHO classification of meningiomas to improve the prognostic assessment regarding tumor recurrence. However, its role has been questioned. One of the reasons is that for complete histopathological assessment, tissue sampling of the complete brain–tumor interface is necessary, but not always surgically and technically feasible. Therefore, the additional intraoperative assessment of CNS invasion may be of value for a more precise assessment of this tumor characteristic. We therefore studied the prognostic impact of the histopathological and intraoperative assessment of CNS invasion regarding radiographic tumor recurrence and found that both factors by themselves do not reach a prognostic significance. However, if both factors are combined, CNS invasion is an independent negative prognostic factor. Our findings show the prognostic potential of a thorough assessment and underline the need for a standardization and documentation of meningioma tissue sampling for the optimal recurrence risk assessment.The detection of the infiltrative growth of meningiomas into CNS tissue has been integrated into the WHO classification as a stand-alone marker for atypical meningioma. However, its prognostic impact has been questioned. Infiltrative growth can also be detected intraoperatively. The prognostic impact of the intraoperative detection of the central nervous system tissue invasion of meningiomas was analyzed and compared to the histopathological assessment. The clinical data of 1517 cases with follow-up data regarding radiographic recurrence was collected. Histopathology and operative reports were reviewed and invasive growth was seen during resection in 23.7% (n = 345) while histopathology detected it in 4.8% (n = 73). The histopathological and intraoperative assessments were compatible in 63%. The prognostic impact of histopathological and intraoperative assessment was significant in the univariate but not in the multivariate analysis. Both methods of assessment combined reached statistical significance in the multivariate analysis (p = 0.0409). A score including all independent prognostic factors divided the cohort into three prognostic subgroups with a risk of recurrence of 33.8, 64.7 and 88.5%, respectively. The intraoperative detection of the infiltrative growth of primary meningiomas into the central nervous system tissue can complement the histopathological assessment of CNS invasion. The combined assessment is an independent prognostic factor regarding tumor recurrence and allows a risk-adapted tumor stratification.

Brachytherapy as an Adjuvant for Recurrent Atypical and Malignant Meningiomas

Brachytherapy as an Adjuvant for Recurrent Atypical and Malignant Meningiomas

Rapid growth of an atypical meningioma in association with cyproterone acetate use: Case report

Meningiomas are extremely common intracranial tumours. When classified based on their histological appearance, the majority (approximately 80%) are World Health Organisation (WHO) Grade 1 benign tumours. A small percentage of meningiomas are atypical (WHO Grade 2) or anaplastic (WHO Grade 3), with higher-grade tumours demonstrating aggressive clinical and pathological characteristics. There is a well-recognised relationship between meningioma growth during periods of elevated circulating female sex hormones; this has been demonstrated in pregnancy or with the administration of exogenous synthetic hormones.

Review of Atypical and Anaplastic Meningiomas: Classification, Molecular Biology, and Management.

Although the majority of meningiomas are slow-growing and benign, atypical and anaplastic meningiomas behave aggressively with a penchant for recurrence. Standard of care includes surgical resection followed by adjuvant radiation in anaplastic and partially resected atypical meningiomas; however, the role of adjuvant radiation for incompletely resected atypical meningiomas remains debated. Despite maximum treatment, atypical, and anaplastic meningiomas have a strong proclivity for recurrence. Accumulating mutations over time, recurrent tumors behave more aggressively and often become refractory or no longer amenable to further surgical resection or radiation. Chemotherapy and other medical therapies are available as salvage treatment once standard options are exhausted; however, efficacy of these agents remains limited. This review discusses the risk factors, classification, and molecular biology of meningiomas as well as the current management strategies, novel therapeutic approaches, and future directions for managing atypical and anaplastic meningiomas.