RESUMEN

This article discusses a rare case of coexistent meningiomas and Primary familial brain calcification (PFBC). PFBC is a neurodegenerative disease characterized by brain calcifications and a variety of neuropsychiatric symptoms and signs, with pathogenic variants in specific genes. The study explores the potential link between PFBC and meningiomas, highlighting shared features like intralesional calcifications and common genes such as MEA6. The article also revisits PFBC patients developing other brain tumors, particularly gliomas, emphasizing the intersection of oncogenes like PDGFB and PDGFRB in both calcifications and tumor progression. In recent investigations, attention has extended beyond brain tumors to breast cancer metastasis, unveiling a noteworthy connection. These findings suggest a broader connection between brain calcifications and tumors, encouraging a reevaluation of therapeutic approaches for PFBC.

Asunto(s)

Neoplasias Encefálicas , Calcinosis , Meningioma , Humanos , Calcinosis/genética , Calcinosis/patología , Meningioma/genética , Meningioma/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Femenino , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patología , Encefalopatías/genética , Encefalopatías/patología , Encefalopatías/metabolismo

RESUMEN

INTRODUCTION: Meningiomas are the most common primary brain and central nervous system tumors, accounting for approximately 40% of these tumors. The most important exams for the radiological study of meningiomas are computed tomography (CT) and magnetic resonance imaging (MRI). We aimed to analyze the radiological features of patients with meningioma related to the simultaneous presence of bilateral macronodular adrenocortical disease (BMAD), with or without pathogenic variants of ARMC5. METHODS: This study included 10 patients who were diagnosed with BMAD. All of them had a radiological diagnosis of expansive brain lesions suggestive of meningioma. All patients underwent brain MRI and a neuroradiolgist analyzed the following parameters: number, site and size of lesions; presence of calcification, edema and bone involvement. RESULTS AND DISCUSSION: Eight patients presented with germline variants of ARMC5; the other 2, did not. The most significant result was the incidence of multiple meningiomas, which was 50% in BMAD patients, whereas the average incidence described thus far is lower than 10%. Considering location, the 22 tumors in the BMAD patients were 5 convexity tumors (22.7%), and 17 skull base tumors (77.2%), the opposite proportion of patients without BMAD. A total of 40.9% of the tumors had calcification, 9% had cerebral edema and 40.9% had bone invasion due to hyperostosis. The literature describes meningioma calcification in 25% of patients, bone invasion by tumor hyperostosis in 20%, and cerebral edema in approximately 60%. CONCLUSION: Relevant results were found considering the rate of multiple meningiomas and tumor location. This finding reinforces the need for further research into the neurological effects caused by genetic variants of ARMC5 in patients with BMAD.

Asunto(s)

Imagen por Resonancia Magnética , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/genética , Meningioma/diagnóstico por imagen , Meningioma/patología , Femenino , Masculino , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/patología , Persona de Mediana Edad , Adulto , Anciano , Tomografía Computarizada por Rayos X , Proteínas del Dominio Armadillo

RESUMEN

Historically, the classification of tumors of the central nervous system (CNS) relies on the histologic appearance of cells under a microscope; however, the molecular era of medicine has resulted in new diagnostic paradigms anchored in the intrinsic biology of disease. The 2021 World Health Organization (WHO) reformulated the classification of CNS tumors to incorporate molecular parameters, in addition to histology, to define many tumor types. A contemporary classification system with integrated molecular features aims to provide an unbiased tool to define tumor subtype, the risk of tumor progression, and even the response to certain therapeutic agents. Meningiomas are heterogeneous tumors as depicted by the current 15 distinct variants defined by histology in the 2021 WHO classification, which also incorporated the first moelcular critiera for meningioma grading: homozygous loss of CDKN2A/B and TERT promoter mutation as criteria for a WHO grade 3 meningioma. The proper classification and clinical management of meningioma patients requires a multidisciplinary approach, which in addition to the information on microscopic (histology) and macroscopic (Simpson grade and imaging), should also include molecular alterations. In this chapter, we present the most up-to-date knowledge in CNS tumor classification, particularly in meningioma, in the molecular era and how it could affect their future classification and clinical management of patients with these diseases.

Asunto(s)

Neoplasias del Sistema Nervioso Central , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/diagnóstico , Meningioma/genética , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/genética , Sistema Nervioso Central , Técnicas Histológicas , Neoplasias Meníngeas/genética

RESUMEN

Introduction: Mutations in the promoter region of telomerase reverse transcriptase occur frequently in meningiomas. Objective: To estimate the prognostic importance of telomerase reverse transcriptase mutations in Colombian patients with grades II and III meningioma. Materials and methods: This was a multicenter retrospective cohort study of patients diagnosed with refractory or recurrent WHO grades II and III meningiomas, recruited between 2011 and 2018, and treated with systemic therapy (sunitinib, everolimus ± octreotide, and bevacizumab). Mutation status of the telomerase reverse transcriptase promoter was established by PCR. Results: Forty patients were included, of which telomerase reverse transcriptase mutations were found in 21 (52.5%), being C228T and C250T the most frequent variants with 87.5 % and 14.3 %, respectively. These were more frequent among patients with anaplastic meningiomas (p=0.18), with more than 2 recurrences (p=0.04); and in patients with parasagittal region and anterior fossa lesions (p=0.05). Subjects characterized as having punctual mutations were more frequently administered with everolimus, sunitinib and bevacizumab drug series (p=0.06). Overall survival was 23.7 months (CI95% 13.1-34.2) and 43.4 months (CI95% 37.5-49.3; p=0.0001) between subjects with and without mutations, respectively. Multivariate analysis showed that the number of recurrences and the presence of telomerase reverse transcriptase mutations were tthe only variables that negatively affected overall survival. Conclusions: Mutations in telomerase reverse transcriptase allows the identification of high-risk patients and could be useful in the selection of the best medical treatment.

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Introducción. En los meningiomas, ocurren con frecuencia mutaciones en la región promotora de la transcriptasa inversa de la telomerasa. Objetivo. Estimar la importancia pronóstica de las mutaciones de la transcriptasa inversa de la telomerasa en pacientes colombianos con meningiomas de grados II y III. Materiales y métodos. Es un estudio de cohorte, retrospectivo y multicéntrico, que incluyó pacientes con diagnóstico de meningioma persistente o recidivante, de grados II y III, según la clasificación de la OMS, reclutados entre el 2011 y el 2018, con tratamiento sistémico (sunitinib, everolimus con octreótido o sin él, y bevacizumab). El estado de la mutación del promotor de la transcriptasa inversa de la telomerasa se determinó por medio de la PCR. Resultados. Se incluyeron 40 pacientes, en 21 (52,5 %) de los cuales se encontraron mutaciones en la transcriptasa inversa de la telomerasa, siendo las variantes más frecuentes la C228T (87,5 %) y la C250T (14,3 %). Estas fueron más frecuentes entre los pacientes con meningiomas anaplásicos (p=0,18), en aquellos con más de dos recurrencias (p=0,04), y en los que presentaron lesiones en la región parasagital y la fosa anterior (p=0,05). Los sujetos caracterizados por tener alteraciones puntuales fueron tratados con mayor frecuencia con la serie de medicamentos everolimus, sunitinib y bevacizumab (p=0,06). Tras el inicio del tratamiento médico, la supervivencia global fue de 23,7 meses (IC95% 13,1-34,2) en los pacientes con mutaciones y, de 43,4 meses (IC95% 37,5-49,3), entre aquellos sin mutaciones (p=0,0001). Los resultados del análisis multivariado demostraron que, únicamente, el número de recurrencias y la presencia de mutaciones en el gen de la transcriptasa inversa de la telomerasa, fueron factores que afectaron negativamente la supervivencia global. Conclusiones. Las mutaciones en el gen promotor de la transcriptasa inversa de la telomerasa permiten identificar los pacientes con alto riesgo, cuya detección podría ser de utilidad para seleccionar el mejor esquema terapéutico.

Asunto(s)

Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/genética , Bevacizumab , Sunitinib , Everolimus , Estudios Retrospectivos , Neoplasias Meníngeas/genética

RESUMEN

BACKGROUND/AIM: Breast cancer 1, early onset (BRCA1) gene is expressed in the cells of the breast and other tissues, where it plays a role in cell-cycle regulation, transcription, repair of DNA double-stranded breaks, ubiquitination, transcriptional regulation as well as other functions, such as cell response regulation to mitogenic signals triggered by estrogens. Considering that meningioma shows greater tumor growth during pregnancy, can express estrogen receptors and proliferate in response to estrogenic stimulation, the hypothesis that this type of tumor may share molecular mechanisms that involve exposure to estrogen should be investigated. Therefore, the aim of the present study was to investigate the BRCA1 gene methylation profile in meningioma. MATERIALS AND METHODS: Methylation-specific polymerase chain reaction (PCR) assay was performed on 50 meningioma samples from male and female patients. Statistical analysis was carried out using Fisher's exact test. RESULTS: The most important finding of this study was that 100% of the male patients over 55 years with meningioma showed BRCA1 methylated in their tumor cells. CONCLUSION: The silencing of BRCA1 through hypermethylation seems to play an important role in meningioma.

Asunto(s)

Proteína BRCA1/genética , Neoplasias Meníngeas/genética , Meningioma/genética , Adulto , Anciano , Anciano de 80 o más Años , Metilación de ADN , Femenino , Genes BRCA1 , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

We investigated a possible role of hMLH1 hypermethylation and microsatellite instability in meningioma progression. Fifty meningomas were examined for methylation of hMLH1 using a methylation-specific PCR; 43 of them were analyzed for microsatellite instability using nine microsatellite markers. Loss of heterozygosity on chromosome 22q was detected using two markers. Two atypical meningiomas showed microsatellite instability at four loci; one was methylated on hMLH1 and the other was unmethylated. Nine meningiomas were found to have methylated hMLH1; the frequencies in the different grades of meningioma were one of 20, two of 16, and six of 14, respectively. We concluded that the methylation status of hMLH1 is associated with the meningioma grade but not with microsatellite instability. Loss of heterozygosity was detected in 22 cases in at least one marker. The frequency of loss of heterozygosity increased with meningioma grade, but the tendency was not significant. The correlation between loss of heterozygosity and methylation of the hMLH1 gene was also not significant. We conclude that hypermethylation of the promoter of hMLH1 is an epigenetic change in meningiomas and is associated with the tumor grade, while microsatellite instability is an uncommon event in meningiomas.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales/genética , Metilación de ADN/genética , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patología , Meningioma/genética , Meningioma/patología , Inestabilidad de Microsatélites , Proteínas Nucleares/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cromosomas Humanos Par 22/genética , Progresión de la Enfermedad , Femenino , Sitios Genéticos/genética , Humanos , Pérdida de Heterocigocidad/genética , Masculino , Persona de Mediana Edad , Homólogo 1 de la Proteína MutL , Proteínas Nucleares/metabolismo , Reacción en Cadena de la Polimerasa , Adulto Joven

RESUMEN

OBJECTIVE: The goal of this study was to determine the epidemiology, clinical presentation, associated factors, pathological features, and treatment outcome of pediatric meningiomas in a single-center institution. METHODS: Clinical data of 15 patients under 18 years of age operated on for meningiomas from January 1994 to December 2010 were reviewed. RESULTS: The study group included nine males and six females (mean age of 13 years at surgery). The most common symptoms at presentation were headaches in 6 out of 15 (40 %), raised intracranial pressure in 3 out of 15 (20 %), and seizures in 3 out of 15 (20 %). Sole operated tumors were found in 12 out of 15 (80 %), whose location is as follows: parasagittal in 4 out of 12 (33.3 %), 2 in the convexity (16.6 %), 2 at the skull base (16.6 %), and 4 in other sites (33.3 %). Six children presented with radiation-induced (RT) meningiomas and five had evidence of neurofibromatosis type 2 (NF2). Three patients had multiple meningiomas (all of them had NF2). Simpson's grade I excision was achieved in 12 out of 15 (80 %). On histopathology, 11 out of 15 (73.3 %) were grade I and 4 out of 15 (26.6 %) were grade II (all of them atypical). Five tumors (33.3 %) recurred, four of which had RT or NF2. During the mean follow-up period of 5 years, 12 out of 15 (80 %) had a good outcome (GOS=5). CONCLUSIONS: Childhood meningiomas are uncommon lesions with a slight male predominance. Absence of large series with long follow-up precludes any definite conclusions on the clinical course and outcome of these tumors. Associated factors (such as RT and NF2), location, and extent of excision appear to be more important than histopathological grade in predicting outcome.

Asunto(s)

Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/terapia , Meningioma/terapia , Pediatría , Adolescente , Encéfalo/patología , Niño , Análisis Citogenético , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Neoplasias Meníngeas/genética , Meningioma/diagnóstico , Meningioma/genética , Estudios Retrospectivos , Médula Espinal/patología

RESUMEN

INTRODUCTION: The cannabinoid receptor gene 1 (CNR1) encodes the human cannabinoid receptor CB1. This receptor has a widespread distribution in the central nervous system (CNS), the main ligands being anandamide, 2-araquidonoil glycerol and marijuana constituents. There is evidence to suggest an anti-neoplastic effect of these ligands in glial tissues mediated through stimulation of the receptor. MATERIAL AND METHODS: We have studied the G1359A polymorphism of the gene CNR1 with a TaqMan allelic discrimination assay in 200 patients diagnosed with glioma, 109 patients diagnosed with meningioma and 403 healthy subjects. Results Genotypic distribution of the G1359A CNR1 polymorphism in glioma patients showed significant differences when compared to the control group. DISCUSSION: Our results suggest that allele G of the CNR1 gene could be associated with a lower susceptibility to glioma.

Asunto(s)

Neoplasias del Sistema Nervioso Central/genética , Glioma/genética , Polimorfismo Genético , Receptor Cannabinoide CB1/genética , Adulto , Alelos , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Neoplasias Meníngeas/genética , Meningioma/genética , Persona de Mediana Edad , España

RESUMEN

Neurofibromatosis 2 is a familial syndrome characterized by the development of schwannomas, meningiomas and ependymomas. Most of them are benign however, their location in the nervous system has harmful effects on important cranial and spinal structures. These tumors are developed as the outcome of NF2 gene (22q12) inactivation. The NF2 protein, merlin or schwannomin belongs to the Ezrin, Radixin, Moesin (ERM) family involved in the cytoskeletal network and has a tumor suppressor function. Inactivating mutations occur as "de novo" (more frequently) or as inherited, and most of them are frameshift or nonsense. Our aim is to study NF2 gene alterations in Argentine patients and relate them to clinical features. 10 families and 29 single patients were analyzed for: 1) at-risk haplotype by STR-segregation analysis and 2) NF2 gene mutations by SSCP/heteroduplex/sequencing. The at-risk haplotype was uncovered in 8 families and mutations were identified in 5 patients. The molecular data are in full agreement with the clinical features supporting previous reports. The obtained results were important for the detection of mutation-carrying relatives and exclusion of other individuals from risk.

Asunto(s)

Neurofibromatosis 2/genética , Neurofibromina 2/genética , Adolescente , Adulto , Anciano , Argentina , Niño , Ependimoma/genética , Ependimoma/fisiopatología , Femenino , Haplotipos , Humanos , Masculino , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/fisiopatología , Meningioma/genética , Meningioma/fisiopatología , Persona de Mediana Edad , Técnicas de Diagnóstico Molecular , Mutación , Neurofibromatosis 2/fisiopatología , Linaje , Adulto Joven

RESUMEN

Hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, the cMET tyrosine kinase participate in cancer invasion, angiogenesis and metastasis in a wide variety of neoplastic cells. Meningioma is a bening tumour, however, it has a high rate of recurrence after surgery; the most important factor to predict relapse is the extent of surgical resection, several other potentially predictive factors have been studied with poor results. We examined by immunohistochemistry the expression of HGF/SF and its cMET receptor in a group of patients with benign meningioma with or without recurrence (n = 17 and n = 25, respectively), after a minimal follow-up of least 6 years. Expression and coexpression of HGF/SF and cMET were compared with cell proliferation index, vascular density and clinical outcome. Coexpression of HGF/SF and cMET in meningiomas had a significant association with cell proliferation index and with recurrence (P < 0.037). Determination of HGF and cMET coexpression in meningiomas could be used as a predictor of recurrence.

Asunto(s)

Biomarcadores de Tumor/análisis , Perfilación de la Expresión Génica , Factor de Crecimiento de Hepatocito/biosíntesis , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patología , Meningioma/genética , Meningioma/patología , Recurrencia Local de Neoplasia , Proteínas Proto-Oncogénicas c-met/biosíntesis , Adulto , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pronóstico , Resultado del Tratamiento

RESUMEN

Cytogenetic analysis of an untreated sarcomatous meningioma from a patient submitted to two surgeries separated by 1 year are reported. The material from the first surgery was mostly hypodiploid, with a modal chromosome number of 42. Alterations of chromosome 22 were found in 80.6% of the cells. Four chromosome markers were found involving chromosomes 1, 2, 6, and 22, and numerical alterations involving chromosomes 8, 9, 10, 13, 14, 15, 18, 19, 20, 21, and Y. Although the modal chromosome number of the material from the second surgery was 45 (17.9% of the cells), 43.1% of its cells were hyperdiploid, 73% of these being in the triploid-tetraploid range. Dicentric and ring chromosomes were very frequent. Alterations involving chromosome 22 were still present. There was a recurrent trisomy of chromosome 3. To our knowledge, this is the first cytogenetic description, with banding techniques, of a malignant meningioma.

Asunto(s)

Aberraciones Cromosómicas , Neoplasias Meníngeas/genética , Meningioma/genética , Bandeo Cromosómico , Humanos , Cariotipificación , Masculino , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/cirugía , Meningioma/patología , Meningioma/cirugía , Persona de Mediana Edad , Ploidias , Factores de Tiempo

RESUMEN

Quatro meningiomas primários humanos foram colocados em cultura e tiveram suas células analisadas citogenéticamente: 1 me meningioma transicional com número modal de 46 cromossomos (I), 2 meningiomas fibroblásticos ambos com número modal de 45 cromossomos (II e III) e 1 meningioma meningoendoteliomatoso com uma classe modal correspondente a 78 - 82 cromossomos (IV). A alteraçäo mais consistente encontrada em todos os tumores foi a monossomia total ou parcial do cromossomo 22 (I - 30%; II - 25%; III - 69% e IV - 30%). O tumor I apresentou também perda do cromossomo Y (80% das célulkas), além de outros marcadores nao identificados. O tumor II apresentou a deleçäo 12p12 - 12pter (65% das células) e del (19) (qter - p13:) (50% das células). O tumor III apresentou 3 marcadores recorrentes, näo identificados. O tumor IV apresentou um marcador acrocêntrico grande, näo identificado. Monossomias, trissomias e tetrassomias esporádicas também foram encontradas nesses tumores. Os pontos de quebra recorrentes foram comparados com os locais de sítios frágeis, pontos específicos de quebras neoplásicas, genes muito ativos de células diferenciadas e oncogenes, já descritos na literatura

Asunto(s)

Humanos , Células Neoplásicas Circulantes/análisis , Citogenética , Meningioma/genética , Neoplasias Meníngeas/genética , Recuento de Células , Bandeo Cromosómico