RESUMO
PURPOSE: We conducted a National Cancer Database (NCDB) study to investigate the epidemiological characteristics and identify predictors of outcomes associated with geriatric meningiomas. METHODS: The NCDB was queried for adults aged 60-89 years diagnosed between 2010 and 2017 with grade 2 and 3 meningiomas. The patients were classified into three age groups based on their age: 60-69 (hexagenarians), 70-79 (septuagenarians), and 80-89 (octogenarians). The log-rank test was utilized to compare the differences in overall survival (OS). Univariate and multivariate Cox proportional hazards regressions were used to evaluate the mortality risk associated with various patient and disease parameters. RESULTS: A total of 6585 patients were identified. Hexagenerians were the most common age group (49.8%), with the majority of meningiomas being classified as grade 2 (89.5%). The incidence of high-grade meningiomas increased in all age groups during the study period. Advanced age, male sex, black race, lower socioeconomic status, Charlson-Deyo score ≥ 2, and higher tumor grade were independent factors of poor survival. Among the modes of treatment, the extent of surgical resection, adjuvant radiotherapy, and treatment at a noncommunity cancer program were linked with better outcomes. CONCLUSION: In geriatric patients with high-grade meningiomas, the greater extent of surgical resection and radiotherapy are associated with improved survival. However, the management and outcome of geriatric patients with higher-grade meningiomas are also associated with several socioeconomic factors.
Assuntos
Bases de Dados Factuais , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/epidemiologia , Meningioma/mortalidade , Meningioma/patologia , Idoso , Masculino , Pessoa de Meia-Idade , Feminino , Idoso de 80 Anos ou mais , Neoplasias Meníngeas/epidemiologia , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/patologia , Estados Unidos/epidemiologia , Fatores Etários , Gradação de TumoresRESUMO
The role of radiotherapy (RT) and stereotactic radiosurgery (SRS) as adjuvant or salvage treatment in high-grade meningiomas (HGM) is still debated. Despite advances in modern neuro-oncology, HGM (WHO grade II and III) remains refractory to multimodal therapies. Published reports present aggregated data and are extremely varied in population size, exclusion criteria, selection bias, and inclusion of mixed histologic grades, making it extremely difficult to draw conclusions when taken individually. This current work aims to gather the existing evidence on RT and SRS as adjuvants following surgery or salvage treatment at recurrence after multimodality therapy failure and to conduct a systematic comparison between these two modalities. An extensive systematic literature review and meta-analysis were performed. A total of 42 papers were eligible for final analysis (RT n = 27; SRS n = 15) after searching MEDLINE via PubMed, Web-of-science, Cochrane Wiley, and Embase databases. Adjuvant regimens were addressed in 37 papers (RT n = 26; SRS n = 11); salvage regimens were described in 5 articles (RT n = 1; SRS n = 4). The primary outcomes of the study were the overall recurrence rate and mortality. Other actuarial rates (local and distant control, OS, PFS, and complications) were retrieved and analyzed as secondary outcomes. A total of 2853 patients harboring 3077 HGM were included. The majority were grade II (87%) with a mean pre-radiation volume of 8.7 cc. Adjuvant regimen: 2742 patients (76.4% RT; 23.6% SRS) with an overall grade II/III rate of 6.6/1. Lesions treated adjSRS were more frequently grade III (17 vs 12%, p < 0.001), and received subtotal resection (57 vs 27%, p = 0.001) compared to the RT cohort. AdjSRS cohort had a significantly shorter mean follow-up than adjRT (36.7 vs 50.3 months, p = 0.01). The overall recurrence rate was 38% in adjRT vs 25% in adjSRS (p = 0.01), while mortality did not differ between the groups (20% vs 23%, respectively; p = 0.80). The median time to recurrence was 1.5 times longer in the RT group (p = 0.30). Five-year local control was 55% in adjRT and 26% in adjSRS (p = 0.01), while 5-year OS was 73% and 78% (p = 0.62), and 5-year PFS was 62% and 40% in adjRT and adjSRS (p = 0.008). No difference in the incidence of complications (24% vs 14%, p = 0.53). Salvage regimen: 110 patients (37.3% RT; 62.7% SRS) with a grade II/III rate of 8.6/1. The recurrence rate was 46% in salRT vs 24% in salSRS (p = 0.39), time to recurrence was 1.8 times longer in the salRT group (35 vs 18.5 months, p = 0.74). Mortality was slightly yet not significantly higher in salRT (34% vs 12%, p = 0.54). Data on local and distant control were only available for salSRS. The 5-year OS was 49% and 83% (p = 0.90), and the 5-year PFS was 39% and 50% in salRT and salSRS (p = 0.66), respectively. High-grade meningiomas (WHO grade II and III) receiving adjuvant RT showed a higher overall recurrence rate than meningiomas receiving adjuvant SRS. The adjRT cohort, however, achieved higher 5-year LC and PFS rates, thus suggesting a potentially longer time to recurrence compared to adjSRS patients, who, meanwhile, experienced a significantly shorter follow-up. This result must also consider the higher number of grade III lesions and the smaller extent of resection achieved in the adjSRS group. Overall mortality did not differ between the two groups. No differences in outcome measures were observed in salvage regimens.
Assuntos
Neoplasias Meníngeas , Meningioma , Radiocirurgia , Humanos , Meningioma/radioterapia , Meningioma/cirurgia , Meningioma/patologia , Resultado do Tratamento , Terapia de Salvação , Estudos Retrospectivos , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/patologia , Organização Mundial da Saúde , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/patologia , SeguimentosRESUMO
Meningiomas are the most common intracranial tumors. Most meningiomas are WHO grade 1 tumors whereas less than one-quarter of all meningiomas are classified as atypical (WHO grade 2) and anaplastic (WHO grade 3) tumors, based on local invasiveness and cellular features of atypia. Surgical resection remains the cornerstone of meningioma therapy and represents the definitive treatment for the majority of patients; however, grade 2 and grade 3 meningiomas display more aggressive behavior and are difficult to treat. Several retrospective series have shown the efficacy and safety of postoperative adjuvant external beam radiation therapy (RT) for patients with atypical and anaplastic meningiomas. More recently, two phase II prospective trials by the Radiation Therapy Oncology Group (RTOG 0539) and the European Organisation for Research and Treatment of Cancer (EORTC 2042) have confirmed the potential benefits of fractionated RT for patients with intermediate and high-risk meningiomas; however, several issues remain a matter of debate. Controversial topics include the timing of radiation treatment in patients with totally resected atypical meningiomas, the optimal radiation technique, dose and fractionation, and treatment planning/target delineation. Ongoing randomized trials are evaluating the efficacy of early adjuvant RT over observation in patients undergoing gross total resection.
Assuntos
Neoplasias Encefálicas , Neoplasias Meníngeas , Meningioma , Criança , Humanos , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/cirurgia , Meningioma/patologia , Meningioma/radioterapia , Meningioma/cirurgia , Estudos Prospectivos , Estudos RetrospectivosRESUMO
INTRODUCTION: Atypical (WHO grade II) and malignant meningiomas (WHO Grade III) are a rare subset of primary intracranial tumors. Given their relatively high recurrence rate after surgical resection and radiotherapy, there has been a recent push to explore other adjuvant treatment options for these treatment-refractory tumors. Recent advances in molecular sequencing of tumors have elucidated new pathways and drug targets which are currently being studied. This article provides a thorough overview of novel investigational therapeutics including targeted therapy, immunotherapy, and new technological modalities for atypical and malignant meningiomas. METHODS: We performed a comprehensive review of the available literature regarding preclinical and clinical evidence for emerging treatments for high grade meningiomas from 1980 to 2020 including contemporaneous clinical trials. RESULTS: There is encouraging preclinical evidence regarding the efficacy of the emerging treatments discussed in this article. Several clinical trials are currently recruiting patients to translate targeted molecular therapy for meningiomas. Several clinical studies have suggested a clinical benefit of combinatorial treatment for these treatment-refractory tumors. CONCLUSION: With numerous active clinical trials for high grade meningiomas, a meaningful improvement in the outcomes for these tumors may be on the horizon.
Assuntos
Neoplasias Meníngeas , Meningioma , Humanos , Neoplasias Meníngeas/terapia , Meningioma/terapia , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Terapias em EstudoRESUMO
Background: Meningiomas represent â¼30% of primary central nervous system (CNS) tumors. Although advances in surgery and radiotherapy have significantly improved survival, there remains an important subset of patients whose tumors have more aggressive behavior and are refractory to conventional therapy. Recent advances in molecular genetics and epigenetics suggest that this aggressive behavior may be due to the deletion of the DNA repair and tumor suppressor gene, CHEK2, neurofibromatosis Type 2 (NF2) mutation on chromosome 22q12, and genetic abnormalities in multiple RTKs including FGFRs. Management of higher-grade meningiomas, such as anaplastic meningiomas (AM: WHO grade III), is truly challenging and there isn't an established chemotherapy option. We investigate the effect of active multi tyrosine receptor kinase inhibitor Dovitinib at stopping AM cell growth in in vitro with either frequent codeletion or mutated CHEK2 and NF2 gene.Methods: Treatment effects were assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, western blot analysis, caspases assay, and DNA fragmentation assay.Results: Treatment of CH157MN and IOMM-Lee cells with Dovitinib suppressed multiple angiokinases-mainly FGFRs, leading to suppression of downstream signaling by RAS-RAF-MAPK molecules and PI3K-AKT molecules which are involved in cell proliferation, cell survival, and tumor invasion. Furthermore, Dovitinib induced apoptosis via downregulation of survival proteins (Bcl-XL), and over-expression of apoptotic factors (Bax and caspase-3) regardless of CHEK2 and NF2 mutation status.Conclusions: This study establishes the groundwork for the development of Dovitinib as a therapeutic agent for high-grade AM with either frequent codeletion or mutated CHEK2 and NF2, an avenue with high translational potential.
Assuntos
Benzimidazóis/farmacologia , Quinase do Ponto de Checagem 2/genética , Meningioma/tratamento farmacológico , Neurofibromina 2/genética , Quinolonas/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Meningioma/genética , Meningioma/patologia , Mutação/genética , Estadiamento de Neoplasias , Fosfatidilinositol 3-Quinases/genética , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/genética , Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Receptores de Fatores de Crescimento de Fibroblastos/genética , Transdução de Sinais/efeitos dos fármacos , Proteína X Associada a bcl-2/genética , Proteína bcl-X/genéticaRESUMO
PURPOSE: Microcystic meningioma (MCM) appears similar to atypical meningioma(AM) as per conventional diagnostic imaging. However, considering their different recurrence rate and prognosis, accurate differential diagnosis is essential for determine the appropriate treatment strategy. The aim of the study was to differentiate MCM from AM by diffusion-weighted imaging (DWI), in order to provide the basis for accurate preoperative diagnosis. METHODS: The preoperative clinical data, conventional MRI and DWI data of 15 MCM and 30 AM cases were retrospectively analyzed. The average apparent diffusion coefficient (ADCmean), minimum ADC (ADCmin) and normalized ADC (nADC) between MCM and AM were compared using two sample t-tests. The value of ADCmean, ADCmin and nADC in the differential diagnosis of MCM and AM were calculated by the receiver operating curve (ROC) analysis. RESULTS: The ADCmean (1.06 ± 0.10 vs 0.80 ± 0.11 × 10-3 mm2/s; P < 0.001), ADCmin (0.99 ± 0.10 vs 0.74 ± 0.12 × 10-3 mm2/s; P < 0.001) and nADC (1.45 ± 0.17 vs 1.07 ± 0.17; P < .0001) were significantly higher in MCM compared to AM. ADCmean of 0.91 × 10-3 mm2/s showed an optimum area under the ROC curve of 0.967 ± 0.022, and distinguished between MCM and AM with 86.67% sensitivity, 100% specificity and 88.89% accuracy. In addition, its positive and negative predictive values were 96.29% and 77.78% respectively. CONCLUSIONS: DWI can differentially diagnose MCM and AM, and ADCmean is a potential quantitative tool that can improve preoperative diagnosis of both tumors.
Assuntos
Cistos/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Neoplasias Meníngeas/diagnóstico por imagem , Meningioma/diagnóstico por imagem , Adulto , Idoso , Cistos/patologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Neoplasias Meníngeas/patologia , Meningioma/patologia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVEThe purpose of this study was to describe effects of adjuvant radiotherapy (RT) for anaplastic meningiomas (AMs) on long-term survival, and to analyze patient and RT characteristics associated with long-term survival.METHODSThe authors queried a retrospective cohort of patients with AM from the National Cancer Database (NCDB) diagnosed between 2004 and 2015 to describe treatment trends. For outcome analysis, patients with at least 10 years of follow-up were included, and they were stratified based on adjuvant RT status and propensity matched to controls for covariates. Survival curves were compared. A data-driven approach was used to find a biologically effective dose (BED) of RT with the largest difference between survival curves. Factors associated with long-term survival were quantified.RESULTSThe authors identified 2170 cases of AM in the NCDB between 2004 and 2015. They observed increased use of adjuvant RT in patients treated with higher doses. A total of 178 cases met the inclusion criteria for outcome analysis. Forty-five percent (n = 80) received adjuvant RT. Patients received a BED of 80.23 ± 16.6 Gy (mean ± IQR). The median survival time was not significantly different (32.8 months for adjuvant RT vs 38.5 months for no RT; p = 0.57, log-rank test). Dichotomizing the patients at a BED of 81 Gy showed maximal difference in survival distribution with a decrease in median survival in favor of no adjuvant RT (31.2 months for adjuvant RT vs 49.7 months for no RT; p = 0.03, log-rank test), but this difference was not significant after false discovery rate correction. Age was a significant predictor for long-term survival.CONCLUSIONSAMs are aggressive tumors that carry a poor prognosis. Conventional adjuvant RT improves local control. However, the effect of adjuvant radiation on overall survival is unclear. Further investigation into this area is warranted.
Assuntos
Irradiação Craniana , Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Radioterapia Adjuvante , Fatores Etários , Idoso , Terapia Combinada , Craniotomia , Gerenciamento Clínico , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/cirurgia , Meningioma/mortalidade , Meningioma/cirurgia , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Radiocirurgia , Dosagem Radioterapêutica , Estudos Retrospectivos , Fatores Socioeconômicos , Resultado do TratamentoRESUMO
The epochal developments in the treatment of meningioma-microsurgery, skull base techniques, and radiation therapy-will be appended to include the rational application of targeted and immune therapeutics, previously ill-fitting concepts for a tumor that has traditionally been a regarded as a surgical disease. The genomic and immunological architecture of these tumors continues to be defined in ever-greater detail. Grade I meningiomas are driven by NF2 alterations or mutations in AKT1, SMO, TRAF7, PIK3CA, KLF4, POLR2A, SUFU, and SMARCB1. Higher-grade tumors, however, are driven nearly exclusively by NF2/chr22 loss and are marked by infrequent targetable mutations, although they may harbor a greater mutation burden overall. TERT mutations may be more common in tumors that progress in histological grade; SMARCE1 alteration has become a signature of the clear cell subtype; and BAP1 in rhabdoid variants may confer sensitivity to pharmacological inhibition. Compared with grade I meningiomas, the most prominent alteration in grade II and III meningiomas is a significant increase in chromosomal gains and losses, or copy number alterations, which may have behavioral implications. Furthermore, integrated genomic analyses suggest phenotypic subgrouping by methylation profile and a specific role for PRC2 complex activation. Lastly, there exists a complex phylogenetic relationship among recurrent high-grade tumors, which continues to underscore a role for the most traditional therapy in our arsenal: surgery.
Assuntos
Neoplasias Encefálicas/cirurgia , Neoplasias Meníngeas/cirurgia , Meningioma/genética , Meningioma/cirurgia , Neoplasias Encefálicas/genética , Proteínas Cromossômicas não Histona/genética , Proteínas de Ligação a DNA/genética , Genômica , Humanos , Fator 4 Semelhante a Kruppel , Neoplasias Meníngeas/genética , Mutação/genética , Gradação de Tumores , Base do Crânio/cirurgia , Proteínas Supressoras de Tumor/genéticaRESUMO
To retrospectively analyze and assess the outcomes and prognostic factors in patients with anaplastic meningioma (AM) (WHO Grade III). Clinical data and outcome [overall (OS) and progression-free (PFS) survival] from 18 patients with Grade III meningioma (AM, based on World Health Organization 2016 definition) initially treated between March 2000 and June 2015 were analyzed. Eleven patients (61%) were male, median age at diagnosis was 63 (range 48-86), and 55% (10/18 patients) had good performance status (KPS ≥ 80). Eight patients (45%) had lower grade disease (Grade I-n = 2; Grade II-n = 6) prior to being upgraded to AM. Ten patients had fractionated radiation after primary surgery, eight patients had salvage fractionated RT, stereotactic radiosurgery (SRS) boost along with primary RT in 1 patient, and salvage SRS to 18 separate areas in 14 patients. Salvage chemotherapy was mainly considered in third or fourth recurrences. 13 (72%) patients recurred and 10 (56%) have died. Median PFS was 14.5 months (95% CI 6.9-22.2). The 5-year survival rate was 40 ± 15% and median OS was 55.8 months (95% CI 27.7-80.3). Of all factors examined, only Karnofsky performance status (KPS) affected outcome (PFS p = 0.0003; OS p = 0.0003). With median OS of 55 months (4.6 years) our results are consistent with existing reports of the poor outcomes for AM patients. From the available data, surgical resection followed by RT and salvage radiosurgery and/or chemotherapy can lead to extended survival; however the benefit may decrease with successive treatments.
Assuntos
Neoplasias Meníngeas/epidemiologia , Meningioma/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais , Masculino , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/terapia , Meningioma/patologia , Meningioma/terapia , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Organização Mundial da SaúdeRESUMO
A 49-year-old female underwent multiple craniotomies for resection of recurrent malignant meningiomata (WHO grade III). She re-presented with sepsis due to a ventricular empyema. The craniotomy wound was urgently debrided, and isolates of the gram-negative rod, Weeksella virosa, were identified on 16S PCR. This species is most commonly found as a genitourinary commensal. We present the first documented intracranial infection by Weeksella virosa and its successful treatment with oral ß-lactam antibiotics.
Assuntos
Infecções do Sistema Nervoso Central/microbiologia , Craniotomia , Empiema/microbiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Sepse/microbiologia , Infecção da Ferida Cirúrgica/microbiologia , Feminino , Humanos , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Complicações Pós-OperatóriasRESUMO
BACKGROUND: It is extremely rare to see cerebrospinal fluid dissemination of intraventricular meningioma, particularly with the development of acute, progressive brainstem/cerebellar dysfunction with an absence of mass formation in the corresponding anatomical sites. CASE PRESENTATION: An 81-year-old man was admitted because of double vision, right facial nerve palsy and truncal ataxia. Brain magnetic resonance imaging showed normal findings except for a tumor mass in the left lateral ventricle, which had been noted over 6 months previously. The patient developed hiccups, hyperventilation, and drowsiness, which worsened progressively, and did not respond to corticosteroid or intraventricular immunoglobulin therapy. Cerebrospinal fluid study revealed a mild elevation of protein, and cytology was negative. The patient died and an autopsy was performed. Postmortem investigation disclosed a malignant transformation of benign fibroid meningioma with cerebrospinal fluid dissemination of the malignant cells, diversely involving the surface of brainstem, cerebellum, and spinal cords, secondarily resulting in extensive ischemia in the brain parenchyma by vessel occlusion. CONCLUSION: If a patient with an intraventricular tumor develops acute, progressive neurological symptoms, the possibility that it is be caused by cerebrospinal fluid dissemination of tumor cells, after malignant transformation, should be considered.
Assuntos
Encefalopatias/patologia , Doenças dos Nervos Cranianos/patologia , Neoplasias Meníngeas/patologia , Meningioma/patologia , Idoso de 80 Anos ou mais , Tronco Encefálico/patologia , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
The patient was a 74-year-old man, who developed progressive cognitive impairment and gait instability. Neuroradiological examination demonstrated a large and predominantly extra-axial tumor spreading over the bilateral frontal base, indicative of olfactory groove meningioma. The greater part of the resected tumor consisted of a dense, patternless proliferation of large, round or polygonal cells, and compactly fascicular growth of spindle cells. Tumor cells showed markedly anaplastic cytological features. In small areas of the tumor, a typical meningothelial meningioma showing no cellular atypism was found. Both tumor components were closely juxtaposed and no pathological features of an intermediate grade (atypical meningioma) were noted. Shortly after the operation, the patient developed a local recurrence of the tumor and multiple metastases to the cerebrum, bone and skin. Anaplastic meningioma is a rare, highly malignant neoplasm which arises de novo or as a result of the progressive transformation of a low-grade meningioma. The coexistence of anaplastic and low-grade components in a single meningeal tumor has been rarely reported. This dimorphic appearance is reminiscent of "dedifferentiation", a phenomenon infrequently seen in various mesenchymal and salivary gland neoplasms. We think that the term "dedifferentiated meningioma" can be appropriately applied to tumors such as that reported herein.
Assuntos
Desdiferenciação Celular , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , Meningioma/diagnóstico por imagem , Meningioma/patologia , Idoso , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/patologia , Humanos , Masculino , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologiaRESUMO
Meningiomas (MGs) are the most frequent primary tumours of the central nervous system (CNS) and exhibit a large spectrum of histological types and clinical phenotypes. The WHO classification of CNS tumours established strict diagnostic criteria of the benign (Grade 1), atypical (Grade 2) and anaplastic (Grade 3) subtypes. Combined with the resection rate, WHO grading has the most crucial role as the prognostic factor. Additionally, such biomarkers as Ki-67/MIB-1, progesterone receptors and phosphor-histone H3 were correlated with MG progression. Recently, it was suggested that the aggressive behaviour of some MGs is attributed to molecular alterations, regardless of their histopathology. The analysis of loss of heterozygosity (LOH) at chromosomes 1, 9, 10, 14 and 22 was performed. The presented case of WHO Grade 2 MG initially exhibited LOH at chromosomes 10, 14 and 22. In the first recurrence, the tumour genetic profiling revealed additional LOH at chromosome 1p and atypical histopathology. During the second recurrence, an aggressive phenotype was observed and tumour progressed to an anaplastic form. Considering the appearance of the tumour relapses, the set of molecular changes overtook the histopathological progression. The genetic and histopathological imbalance in the tumour progression in secondary anaplastic MGs has not been previously described. The evolution of genetic and histopathological changes was presented in the same patient. In the future, the individualised therapy of potentially more aggressive forms of MGs could be based on certain chromosome aberrations.
Assuntos
Encéfalo/patologia , Neoplasias Meníngeas/patologia , Meningioma/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Progressão da Doença , Humanos , Perda de Heterozigosidade , Masculino , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/genética , Meningioma/diagnóstico por imagem , Meningioma/genética , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
Meningioma is a common adult intracranial tumor, and while several cases are considered benign, a subset is malignant with biologically aggressive behavior and is refractory to current treatment strategies of combined surgery and radiotherapy. Anaplastic meningiomas are quite aggressive and correspond to a World Health Organization (WHO) Grade III tumor. This highly aggressive phenotype mandates the need for more efficacious therapies. Designing rational therapies for treatment will have its foundation in the biologic understanding of involved genes and molecular pathways in these types of tumors. Anaplastic meningiomas (WHO Grade III) can arise from malignant transformation of lower grade (WHO Grade I/II) tumors, however there is an incomplete understanding of specific genetic drivers of malignant transformation in these tumors. Here, the current understanding of anaplastic meningiomas is reviewed in the context of human neuropathologic specimens and small animal models.
Assuntos
Neoplasias Meníngeas/patologia , Meningioma/patologia , Modelos Teóricos , Neuropatologia , Patologia Molecular , Adulto , Animais , Progressão da Doença , Humanos , Neoplasias Meníngeas/genética , Meningioma/genéticaRESUMO
The management of WHO Grade II "atypical" meningiomas (AMs) and Grade III "malignant" meningiomas (MMs) remains controversial and under-investigated in prospective studies. The roles of surgery, radiation therapy, radiosurgery, and chemotherapy have been incompletely delineated. This has left physicians to decipher how they should treat patients on a case-by-case basis. In this study, the authors review the English-language literature on the management and clinical outcomes associated with AMs and MMs diagnosed using the WHO 2000/2007 grading criteria. Twenty-two studies for AMs and 7 studies for MMs were examined in detail. The authors examined clinical decision points using the literature and concepts from evidence-based medicine. Acknowledging the retrospective nature of the studies concerning AM and MM, the authors did find evidence for the following clinical strategies: 1) maximal safe resection of AM and MM; 2) active surveillance after gross-total resection of AM; 3) adjuvant radiation therapy after subtotal resection of AM, especially in the absence of putative radioresistant features; and 4) adjuvant radiation therapy after resection of MM.
Assuntos
Algoritmos , Gerenciamento Clínico , Medicina Baseada em Evidências , Neoplasias Meníngeas , Meningioma , Bases de Dados Bibliográficas/estatística & dados numéricos , Humanos , Neoplasias Meníngeas/classificação , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/terapia , Meningioma/classificação , Meningioma/genética , Meningioma/terapia , Estudos RetrospectivosRESUMO
We report on a 51-year-old woman who presented with a cervical spinal cord tumor clinically suspected to be a metastasis. Histological examination revealed an anaplastic meningioma containing epithelial nests arranged in a gland-like pattern suggestive of adenocarcinoma. This component strongly expressed cytokeratins whereas the meningothelial component was vimentin--epithelial membrane antigen--and progesterone receptor-immunoreactive, suggesting either anaplastic meningioma with adenocarcinoma-like metaplasia, or adenocarcinoma metastasis in a meningioma, but the search for a primitive neoplasia including thoracic-abdominal-pelvic computed tomography and mammography was negative. Anaplastic meningiomas with adenocarcinoma-like metaplasia are uncommon lesions, 4 cases having been reported in the literature so far. Their immunohistochemical and chromosomal characteristics are similar to those observed in secretory meningiomas. When available, fluorescence in situ hybridization detects the same chromosomal alterations in the two components, confirming a common clonal origin. This observation demonstrates the necessity to perform the correct diagnosis of malignant meningioma with adenocarcinomatous metaplasia, whose prognosis and treatment radically differ from those of metastatic adenocarcinoma located in a meningioma.
Assuntos
Neoplasias Meníngeas/patologia , Meningioma/patologia , Adenocarcinoma/diagnóstico , Antiporters/análise , Biomarcadores Tumorais/análise , Neoplasias da Mama , Carcinoma/diagnóstico , Carcinoma/secundário , Células Clonais/patologia , Diagnóstico Diferencial , Feminino , Humanos , Hibridização in Situ Fluorescente , Queratina-7/análise , Imageamento por Ressonância Magnética , Neoplasias Meníngeas/química , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/diagnóstico , Meningioma/química , Meningioma/complicações , Meningioma/diagnóstico , Metaplasia , Pessoa de Meia-Idade , Mucina-1/análise , Receptores de Progesterona/análise , Compressão da Medula Espinal/etiologia , Vimentina/análiseRESUMO
This case report highlights the diagnostic and therapeutic journey of a 16-year-old female presenting with chronic headaches, ultimately diagnosed with anaplastic meningioma. Despite its rarity in pediatric patients, anaplastic meningioma necessitates swift recognition and management due to its aggressive nature. Imaging findings, including CT and MRI, initially suggested a provisional diagnosis of hemangiopericytoma, emphasizing the diagnostic challenge posed by this condition. Surgical intervention revealed unexpected histopathological findings, highlighting the importance of thorough evaluation. Treatment involved frontal craniectomy and excision followed by adjuvant radiotherapy. While the patient's postoperative course was uneventful, histopathology confirmed the presence of anaplastic meningioma, leading to the adjustment of her clinical management. This case shows the need for heightened suspicion and comprehensive evaluation in similar presentations to facilitate timely intervention and improve patient outcomes.
RESUMO
Background: The World Health Organization (WHO) grade 2 meningiomas behave aggressively with a high proclivity toward recurrence despite maximal surgical resection. Our institution, a pioneer of proton therapy, uses exclusively proton beam radiation, and thus, we present a retrospective cohort analysis of patients with WHO grade 2 meningiomas treated with adjuvant proton beam therapy (PBT) at our institution between 2007 and 2019. The effects of adjuvant PBT were evaluated. Methods: Data collected include diagnosis, gender, histological subtype, WHO grade, the extent of surgical resection, adjuvant PBT radiation, details of the PBT radiation, recurrence, any additional PBT radiation, systemic medical therapy, and disease-specific survival. Results: Among the WHO grade 2 meningiomas (n = 50) recommended PBT, 80% and 78% of patients with gross-total resection (GTR) and subtotal resection (STR), respectively, followed through with PBT. The median radiation dose of PBT was 59.5 Gy and 59.92 Gy for patients with GTR and STR, respectively, with a median of 33 fractions delivered in 1.8 Gy doses for both groups. Combined 3-year progression-free survival (PFS) was 96%, and 5-year PFS was 92%. Combined overall survival was 95% at five years. Minimal radiation side effects were reported with no grade 3 or higher toxicities. Conclusion: Our results suggest that adjuvant PBT is well tolerated with minimal radiation toxicity. Alternative to photon radiation, PBT may be considered at least as safe and effective for adjuvant treatment of WHO grade 2 meningiomas when it is available.
RESUMO
Primary tumors in the central nervous system, known as meningiomas, are frequently found and constitute a substantial proportion of tumor cases. Although generally benign, there are occasional cases where they might exhibit malignant characteristics. Anaplastic meningioma is a rare subtype of malignant meningiomas, representing only a small proportion of cases. We present the case of a 70-year-old female patient who presented to the Neurosurgery Clinic of University Hospital "Saint George" with clinical manifestations of monocular vision and blurry vision in the right eye for three months. On physical examination, unilateral ptosis and mydriasis were noted in the left eye. MRI revealed an extra-axial mass located supratentorial in the left temporopolar region affecting the wing of the left sphenoidal bone, invading the cavernous sinus, suppressing the left and right optic nerves, and involving the left orbit. Operative treatment was performed through a left pterional craniotomy and resection of the tumor mass by microsurgical technique. The subdural, epidural, and intraorbital mass were resected. Total removal of the tumor was not achievable and subtotal resection was performed. Pathology results showed that the tumor mass was anaplastic meningioma. Surgery-related complications were not observed. Postoperatively, the patient was mobilized on the day after intervention and the control CT scan showed no ischemic or hemorrhagic events. The patient experienced relief in her symptoms and was discharged on the fifth day. The patient underwent radiation therapy, resulting in the complete removal of the left tumor in the cavernous sinus. After six months, no tumor recurrence was found, and a long-term follow-up is planned to monitor for possible recurrence.
RESUMO
Orbital meningioma is a rare type of orbital tumor with high invasiveness and recurrence rates, making it extremely challenging to treat. Due to the special location of the disease, surgery often cannot completely remove the tumor, requiring postoperative radiation therapy. Here, we report a case of an elderly male patient with right-sided proptosis, visual impairment, and diplopia. Imaging diagnosis revealed a space-occupying lesion in the extraconal space of the right orbit. Pathological and immunohistochemical examination of the resected tumor confirmed it as a grade 3 anaplastic meningioma. Two months after surgery, the patient complained of right eye swelling and a magnetic resonance imaging (MRI) scan showed a recurrence of the tumor. The patient received helical tomotherapy (TOMO) in the postoperative tumor bed and high-risk areas within the orbit with a total dose of 48Gy. However, there was no significant improvement in the patient's right eye swelling, and the size of the recurrent lesion showed no significant change on imaging. Gamma knife multifractionated stereotactic radiosurgery (MF-SRS) was then given to the recurrent lesion with 50% prescription dose 13.5Gy/3f, once every other day. An imaging diagnosis performed 45 days later showed that the tumor had disappeared completely. The patient's vision remained unchanged, but diplopia was significantly relieved after MF-SRS. We propose a new hybrid treatment model for recurrent orbital meningioma, where conventional radiation therapy ensures local control of high-risk areas around the postoperative cavity, and MF-SRS maximizes the radiation dose to recurrent lesion areas while protecting surrounding tissues and organs.