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Two children without neurofibromatosis type 1 presented with unilateral decreased vision and MRI revealing optic nerve tumors. In the first case, chemotherapy was initiated empirically for presumed optic pathway glioma, but the lesion increased in size with associated clinical worsening, raising concern for a possible alternate diagnosis. Biopsy of the involved optic nerve resulted in worsening of vision due to a branch retinal artery occlusion and showed a grade I pilocytic astrocytoma. In the second case, sudden symptom onset and rapid tumor growth prompted an optic nerve biopsy, resulting in vision loss due to a central retinal artery occlusion and revealing grade I pilocytic astrocytoma. In both cases, tissue diagnosis did not alter the course of management. Instead, biopsy was associated with additional vision loss, highlighting the risk of biopsy in children with isolated optic nerve tumors and imaging that is most consistent with an optic pathway glioma.
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Biópsia/efeitos adversos , Cegueira/etiologia , Glioma do Nervo Óptico/patologia , Nervo Óptico/patologia , Adolescente , Cegueira/diagnóstico , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
Accurate identification of spinal cord segments in relation to vertebral landmarks is essential to surgery aimed at experimental spinal cord injury. We have analyzed a complete series of high-resolution magnetic resonance (MR) images from the mouse spine in order to delineate the boundaries of spinal cord segments in relation to vertebral landmarks. The resulting atlas can be used to plan experimental approaches that require the accurate identification of a target spinal cord segment.
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Medula Espinal/anatomia & histologia , Coluna Vertebral/anatomia & histologia , Animais , Imageamento por Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BLRESUMO
This is the life story of Dr. Lucy B. Rorke-Adams, who was raised in the rural Midwest of the United States by Armenian immigrant parents during the Depression. The youngest in a family of five girls, she was lovingly nurtured by her parents and sisters. She was encouraged to become educated in order to lead a worthwhile life and contribute to society. She chose medicine, specifically the specialty of pediatric neuropathology, and over her long career succeeded in advancing the field. In particular, she made major contributions to understanding childhood brain tumors, central nervous system (CNS) malformations, and pathophysiology of abusive CNS injury in infants and children.
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LAY ABSTRACT: Recently, therapy has been delivered at a distance (i.e. remotely) to help control the spread of coronavirus. Clinicians have voiced concerns that remote delivery is unsuitable for certain individuals, including those who are autistic, but they have also highlighted potential benefits for autistic individuals. Benefits include some individuals feeling more comfortable receiving therapy at home. This is the first study to interview autistic individuals about their experience of remote therapy. Participants were six young people aged 15-18 years and eight clinicians. Participants described their experience of remote delivery, including challenges, benefits, and suggestions. Most of these supported previous research findings, but some were new or provided further insight into those already identified. A newly identified challenge was knowing online social etiquette. All participants found aspects of the experience challenging, but all identified benefits and most voiced that remote sessions should be offered to young people. Participants further identified individual characteristics that may make someone less suited to remote delivery (e.g. shyness). They also identified ways of making the experience of remote delivery easier (e.g. sitting with a pet). Young people's and clinicians' views were similar overall, with only subtle differences. For example, young people uniquely voiced that remote delivery was similar to in-person, that benefits were hard to identify, and provided distinct reasons for the social interaction feeling less intense remotely. Findings may be used to improve remote delivery, for guiding future research, and as a case for continuing to offer it to those who may most benefit.
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Transtorno do Espectro Autista , Transtorno Autístico , COVID-19 , Humanos , Adolescente , Intervenção Psicossocial , EmoçõesRESUMO
PURPOSE: Standard therapy for childhood intracranial ependymoma is maximal tumor resection followed by involved-field irradiation. Although not used routinely, chemotherapy has produced objective responses in ependymoma, both at recurrence and in infants. Because the presence of residual tumor following surgery is consistently associated with inferior outcome, the potential impact of pre-irradiation chemotherapy was investigated. METHODS: Between 1995 and 1999, the Children's Cancer Group undertook a Phase II trial of pre-irradiation chemotherapy in children 3-21 years of age with intracranial ependymoma and radiological evidence of post-operative residual tumor. RESULTS: Of 84 patients, 41 had residual tumor, and were given four cycles of cisplatin-based chemotherapy prior to irradiation. Of 35 patients fully evaluable for response to chemotherapy, 14 (40%) demonstrated complete response, 6 (17%) partial response, 10 (29%) minor response or stable disease, and 5 (14%) demonstrated progressive tumor growth. For the entire group, 5-year overall survival (OS) and event-free survival (EFS) was 71 ± 6%, and 57 ± 6%, respectively. The pre-irradiation chemotherapy group demonstrated EFS comparable to that of patients with no residual tumor who received irradiation alone (55 ± 8% vs. 58 ± 9%, P = 0.45). Any benefit of chemotherapy was restricted to patients with greater than 90% tumor resection. CONCLUSIONS: Children with near total resection of ependymoma may benefit from pre-irradiation chemotherapy. Patients with subtotal resection have inferior outcome despite responses to chemotherapy, and should be considered for second-look surgery prior to irradiation. Pediatr Blood Cancer 2012; 59: 1183-1189. © 2012 Wiley Periodicals, Inc.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/radioterapia , Ependimoma/radioterapia , Terapia Neoadjuvante , Adolescente , Adulto , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Criança , Pré-Escolar , Intervalo Livre de Doença , Ependimoma/tratamento farmacológico , Ependimoma/mortalidade , Feminino , Humanos , Masculino , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: The epidemiological, prognostic, and therapeutic features of child and adolescent meningioma are poorly defined. Clinical knowledge has been drawn from small case series and extrapolation from adult studies. This study was done to pool and analyse the clinical evidence on child and adolescent meningioma. METHODS: Searches of PubMed, Medline, and Embase identified 35 case series of child and adolescent meningioma completed over the past 21 years. Individual patient data were obtained from 30 studies via direct communication with investigators. Primary outcomes were relapse-free survival (RFS) and overall survival. Prognostic variables were extent of initial surgery, use of upfront radiotherapy, age, sex, presence of neurofibromatosis, tumour location, and tumour grade. RFS and overall survival were analysed using Kaplan-Meier survival curves and multivariable Cox regression models. FINDINGS: From a total of 677 children and adolescents with meningioma, 518 were eligible for RFS analysis and 547 for overall survival analysis. Multivariable analysis showed that patients who underwent initial gross-total resection had better RFS (hazard ratio 0·16, 95% CI 0·10-0·25; p<0·0001) and overall survival (0·21, 0·11-0·39; p<0·0001) than those who had subtotal resection. No significant benefit was seen for upfront radiotherapy in terms of RFS (0·59, 0·30-1·16; p=0·128) or overall survival (1·10, 0·53-2·28; p=0·791). Patients with neurofibromatosis type 2 (NF2) had worse RFS than those without neurofibromatosis (2·36, 1·23-4·51; p=0·010). There was a significant change in overall survival with time between patients with NF2 compared with those without neurofibromatosis (1·45, 1·09-1·92; p=0·011); although overall survival was initially better for patients with NF2 than for those without neurofibromatosis, overall survival at 10 years was worse for patients with NF2. Patients with WHO grade III tumours had worse RFS than those with WHO grade I (3·90, 2·10-7·26; p<0·0001) and grade II tumours (2·49, 1·11-5·56; p=0·027). INTERPRETATION: Extent of initial surgical resection is the strongest independent prognostic factor for child and adolescent meningioma. No benefit for upfront radiotherapy was noted. Hence, aggressive surgical management, to achieve gross-total resection, is the initial treatment of choice. In the event of a subtotal resection, repeat resection is recommended to achieve maximum extirpation. Close observation is warranted for patients who have a subtotal resection or who have WHO grade III tumours. Patients without neurofibromatosis should have a minimum 10-year follow-up, whereas patients with NF2 should be considered a special risk category, necessitating life-long follow-up. FUNDING: None.
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Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Procedimentos Neurocirúrgicos , Adolescente , Fatores Etários , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/patologia , Meningioma/mortalidade , Meningioma/patologia , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/mortalidade , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Reoperação , Medição de Risco , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
Background: The COVID-19 pandemic necessitated the adoption of telemental health (TMH). Pre-pandemic, clinicians had voiced many TMH concerns, but these had not been investigated with respect to autism spectrum disorder (ASD) even with it being known that there are distinct ASD-associated challenges for in-person mental health interventions. Method: A convenience sample of (n = 55) clinicians completed an online survey regarding their perspectives of adopting TMH interventions in ASD, with closed- and open-answered questions. Quantitative and qualitative data were analysed descriptively/inferentially and via Content Analysis, respectively. Results: Multiple clinicians endorsed each TMH challenges/barrier previously identified as concerns in the non-ASD literature. However, overall levels of concern over challenges/barriers were low, and challenges were more likely to be predicted than experienced and considered to be case/presentation specific. Challenges that were considered ASD-specific included the exacerbation of those associated with in-person delivery in ASD, alongside difficulties with trust and appropriate remote social behaviour. On average, clinicians indicated a preference for 50% TMH interventions post-pandemic. Clinicians' perceived technological competence and extent of professional experience with ASD were not significantly associated with levels of concern, nor number of experienced challenges, with TMH interventions in ASD. Conclusion: In support of the existing TMH literature, challenges/barriers were more likely to be predicted than experienced and were considered to be case/presentation-specific, though this may be more variable in ASD owing to the well-established marked heterogeneity in this population. Remote provision of interventions exacerbated in-person ASD-associated challenges, as predicted, but clinician-level factors appeared not to impact TMH perceptions.
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We report the case of a child who presented at 3 months of age with complex partial seizures, a linear facial nevus, and magnetic resonance imaging (MRI) showing delayed myelination and thickened cortex in the left temporal, parietal, and occipital regions. A repeat 3Tesla MRI scan with and without contrast at 6 months again showed cortical dysplasia of the left hemisphere. No other abnormalities were seen. A third scan at 3 years 6 months showed a 2.5 cm, round, hyperintense lesion on both T(2) and T(1) sequences. The lesion and surrounding dysplastic cortex were resected. Palmini grade IIA dysplasia and a ganglioglioma were diagnosed. These findings suggest that cellular components of cortical dysplasias have oncogenic potential.
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Neoplasias Encefálicas/etiologia , Ganglioglioma/etiologia , Malformações do Desenvolvimento Cortical/complicações , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Lactente , Imageamento por Ressonância Magnética , Malformações do Desenvolvimento Cortical/metabolismo , Fosfopiruvato Hidratase/metabolismoRESUMO
BACKGROUND: X-linked lymphoproliferative disorder typically presents as an Epstein-Barr virus-specific immune defect with a poor prognosis. Herein we present the clinical and pathologic findings for the first known case of X-linked lymphoproliferative disorder with visual symptoms at initial presentation. METHODS: Retrospective chart review, clinicopathologic correlation (brain biopsy and postmortem brain and eye tissue), and literature review. RESULTS: An 18-year-old boy had a unique presentation of X-linked lymphoproliferative disorder with visual symptoms and retinal findings. He subsequently developed central nervous system vasculitis. He never had evidence of Epstein-Barr virus infection during his clinical course, but in situ hybridization was positive in scattered cells in the brain postmortem. Eye pathologic examination at autopsy showed ischemic changes, but no inflammation. CONCLUSION: When a young patient presents with cotton wool spots, a thorough workup must be done, and immunologic disorders should be considered in the differential diagnosis. X-linked lymphoproliferative disorder-associated eye findings may not always be associated with Epstein-Barr virus infection and, as demonstrated by this case, can be indicative of an underlying vasculitic process.
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Isquemia/diagnóstico , Transtornos Linfoproliferativos/diagnóstico , Doenças Retinianas/diagnóstico , Vasos Retinianos/patologia , Aciclovir/uso terapêutico , Adolescente , Antivirais/uso terapêutico , Diagnóstico Diferencial , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/virologia , Evolução Fatal , Herpesvirus Humano 4 , Humanos , Hibridização In Situ , Isquemia/tratamento farmacológico , Isquemia/virologia , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/virologia , Masculino , Vacinas Meningocócicas/administração & dosagem , Reação em Cadeia da Polimerase em Tempo Real , Doenças Retinianas/tratamento farmacológico , Doenças Retinianas/virologia , Estudos Retrospectivos , Dermatopatias Virais/diagnóstico , Dermatopatias Virais/tratamento farmacológico , Dermatopatias Virais/virologia , Vasculite do Sistema Nervoso Central/diagnóstico , Vasculite do Sistema Nervoso Central/tratamento farmacológico , Vasculite do Sistema Nervoso Central/virologiaRESUMO
Although mutations in the human doublecortin gene (DCX) cause profound defects in cortical neuronal migration, a genetic deletion of Dcx in mice produces a milder defect. A second locus, doublecortin-like kinase (Dclk), encodes a protein with similar "doublecortin domains" and microtubule stabilization properties that may compensate for Dcx. Here, we generate a mouse with a Dclk mutation that causes no obvious migrational abnormalities but show that mice mutant for both Dcx and Dclk demonstrate perinatal lethality, disorganized neocortical layering, and profound hippocampal cytoarchitectural disorganization. Surprisingly, Dcx(-/y);Dclk(-/-) mutants have widespread axonal defects, affecting the corpus callosum, anterior commissure, subcortical fiber tracts, and internal capsule. Dcx/Dclk-deficient dissociated neurons show abnormal axon outgrowth and dendritic structure, with defects in axonal transport of synaptic vesicle proteins. Dcx and Dclk may directly or indirectly regulate microtubule-based vesicle transport, a process critical to both neuronal migration and axon outgrowth.
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Axônios/fisiologia , Movimento Celular/fisiologia , Proteínas Associadas aos Microtúbulos/genética , Neurônios/fisiologia , Neuropeptídeos/genética , Proteínas Serina-Treonina Quinases/genética , Animais , Animais Recém-Nascidos , Axônios/ultraestrutura , Encéfalo/anormalidades , Encéfalo/embriologia , Anormalidades Congênitas/genética , Anormalidades Congênitas/mortalidade , Anormalidades Congênitas/patologia , Dendritos/ultraestrutura , Proteínas do Domínio Duplacortina , Proteína Duplacortina , Quinases Semelhantes a Duplacortina , Embrião de Mamíferos/metabolismo , Embrião de Mamíferos/patologia , Camundongos , Camundongos Knockout , Camundongos Mutantes , Proteínas Associadas aos Microtúbulos/fisiologia , Neocórtex/embriologia , Proteínas do Tecido Nervoso/deficiência , Neuropeptídeos/fisiologia , Proteínas Serina-Treonina Quinases/fisiologia , RNA Mensageiro/metabolismo , Vesículas Sinápticas/metabolismo , Sobrevivência de TecidosRESUMO
OBJECTIVE: A comprehensive case-control study was conducted to determine potential risk factors for medulloblastoma/primitive neuroectodermal tumor (PNET), a common brain tumor in children. This analysis evaluated possible associations between previous head injury and ionizing radiation exposure through diagnostic X-rays and medulloblastoma/PNET. METHODS: Mothers of 318 cases <6 years of age at diagnosis between 1991 and 1997 and registered with the Children's Oncology Group were interviewed. Mothers of 318 matching controls were selected through random digit dialing and interviewed. RESULTS: An association was not detected between previous head injury (OR: 0.78, 95% CI: 0.40-1.5) or head X-ray for any reason including head injury with medulloblastoma/PNET. A statistically non-significant excess of cases reported having an X-ray for reason other than head injury (OR 2.3, 95% CI 0.91-5.7). When cases that received an X-ray for a common symptom of medulloblastoma/PNET were considered unexposed this association weakened (OR: 1.3, 95% CI: 0.49-3.7). No dose-response relationship was observed. CONCLUSIONS: Head injury and exposure to diagnostic head X-rays were not associated with medulloblastoma/PNET in this study. Future studies should investigate all imaging procedures with ionizing radiation exposure including computed tomography scans and utilize radiation dose estimations.
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Neoplasias Encefálicas/etiologia , Neoplasias Cerebelares/etiologia , Traumatismos Craniocerebrais/complicações , Meduloblastoma/etiologia , Tumores Neuroectodérmicos Primitivos/etiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Humanos , Lactente , Radiografia/efeitos adversos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Faculty mentoring of undergraduate students is an essential and necessary component in helping students achieve exposure and success in cocurricular activities that they may not get in the classroom. It is through these cocurricular activities that faculty can expose students to the realms of various clinical activities, nursing research and education, and various service-related opportunities, such as tutoring and committee work. The intrinsic and extrinsic awards of watching your students succeed and grow into nursing leaders make mentoring worth it. This article outlines the benefits and difficulties experienced by 1 faculty member in his crusade to mentor undergraduate nursing students.
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Bacharelado em Enfermagem/normas , Docentes de Enfermagem/psicologia , Docentes de Enfermagem/normas , Tutoria/normas , Mentores/psicologia , Estudantes de Enfermagem/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa em Enfermagem , Estados Unidos , Adulto JovemRESUMO
OBJECTIVE: A comprehensive case-control study was conducted to evaluate parental risk factors for medulloblastoma (MB) and primitive neuroectodermal tumor (PNET). This analysis was conducted to evaluate associations between fathers' hobbies and risk of their children developing MB/PNET. The hobbies chosen for study were those with similar exposures as occupations associated with childhood cancers. METHODS: Cases were 318 subjects under six years of age at diagnosis between 1991 and 1997 and registered with the Children's Cancer Group. An equal number of controls were selected through random digit dialing and individually matched to cases. RESULTS: In multivariate analyses, a significant association was seen for lawn care with pesticides [during pregnancy: odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.0, 2.5; after birth: OR = 1.8, 95% CI: 1.2, 2.8] and a weak association was seen for stripping paint [during pregnancy: OR = 1.4, 95% CI: 0.8, 2.6; after birth: OR = 1.4, 95% CI: 0.7, 2.6]. CONCLUSIONS: This study suggests that household exposures from hobbies, particularly pesticides, may increase risk of MB/PNET in children; previous research has been mostly limited to occupational exposures.
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Neoplasias Encefálicas/induzido quimicamente , Pai , Passatempos , Meduloblastoma/induzido quimicamente , Tumores Neuroectodérmicos Primitivos/induzido quimicamente , Estudos de Casos e Controles , Pré-Escolar , Intervalos de Confiança , Feminino , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Praguicidas/efeitos adversosRESUMO
Postmortem examination is a cornerstone in identifying the cause of unexplained sudden death in children. Even in cases of suspected or known abuse, an autopsy may help characterize the nature of the abuse, which is particularly important in the forensic autopsy of children in the first 3 to 4 years of life when inflicted neurotrauma is most common. Forensic examinations are vital in cases that might otherwise be diagnosed as sudden infant death syndrome. The ocular autopsy in particular may demonstrate findings that were not appreciated on antemortem clinical examination. This protocol for postmortem examination of the eyes and orbits was developed to promote more consistent documentation of findings, improved clinical and forensic decision making, and more replicable and coherent research outcomes.
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Autopsia/normas , Maus-Tratos Infantis , Traumatismos Oculares/patologia , Morte Súbita do Lactente/patologia , Pré-Escolar , Feminino , Medicina Legal/métodos , Humanos , Lactente , Recém-Nascido , Masculino , Estados UnidosRESUMO
We conducted a case-control study of medulloblastoma/primitive neuroectodermal tumors of brain (PNET) to pursue findings related to vitamin and mineral supplements, micronutrients, and cured meat consumption during gestation. Mothers of 315 cases ages <6 years at diagnosis in 1991 to 1997 identified from the United States and Canada through the Children's Oncology Group and mothers of 315 controls selected by random-digit dialing were interviewed. In the periconception period of the index pregnancy, case mothers were less likely than control mothers to report use of multivitamins [adjusted odds ratio (OR), 0.7; 95% confidence interval (95% CI), 0.4-1.0; P = 0.08] and to be in the highest quartile of iron and folate intake from food and supplements combined (adjusted OR for iron, 0.5; 95% CI, 0.3-0.9; P(trend) = 0.008; adjusted OR for folate, 0.5; 95% CI, 0.3-0.9; P(trend) = 0.007). Case and control mothers had similar intakes of cured meats, although case mothers were more likely to have the combination of high cured meat and low vitamin C intake (OR, 1.5; 95% CI, 1.0-2.3; P = 0.08). The results of the study add to the evidence of a protective role for multivitamins, suggest a possible role for micronutrients early in pregnancy, and generally do not support an association between cured meats and medulloblastoma/PNET.
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Neoplasias Cerebelares/etiologia , Suplementos Nutricionais , Produtos da Carne/efeitos adversos , Meduloblastoma/etiologia , Micronutrientes/administração & dosagem , Estudos de Casos e Controles , Neoplasias Cerebelares/prevenção & controle , Criança , Feminino , Ácido Fólico/administração & dosagem , Humanos , Ferro/administração & dosagem , Meduloblastoma/prevenção & controle , Razão de Chances , Gravidez , Vitaminas/administração & dosagemRESUMO
Idiopathic granulomatous encephalitis is a rare disorder of unknown etiology, undetermined treatment, and often grave prognosis. This article describes a 4-year-old female who presented with a single focal febrile convulsion followed a few weeks later by right-sided hemiparesis. A huge infiltrative cerebral mass tumor was found which proved to be a granuloma on histologic study. Despite a thorough evaluation, including tissue studies and search for an infectious agent, no etiology could be identified, and the final diagnosis was idiopathic granulomatous encephalitis. Recurrent resections and high-dose steroid treatment failed to control the process, and the patient died of disease 6 months after presentation. Evaluation and treatment of idiopathic granulomatous encephalitis should be aggressive, and the possibility of chemotherapy and perhaps even radiotherapy should be considered if there is no response to steroids.
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Neoplasias Encefálicas/diagnóstico , Granuloma/diagnóstico , Imageamento por Ressonância Magnética , Meningoencefalite/diagnóstico , Antibacterianos/uso terapêutico , Encéfalo/patologia , Encéfalo/cirurgia , Edema Encefálico/diagnóstico , Edema Encefálico/patologia , Edema Encefálico/cirurgia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Pré-Escolar , Terapia Combinada , Dexametasona/uso terapêutico , Diagnóstico Diferencial , Progressão da Doença , Dominância Cerebral/fisiologia , Encefalocele/diagnóstico , Encefalocele/patologia , Encefalocele/cirurgia , Epilepsias Parciais/etiologia , Evolução Fatal , Feminino , Seguimentos , Granuloma/patologia , Granuloma/cirurgia , Humanos , Meningoencefalite/patologia , Meningoencefalite/cirurgia , Prednisolona/uso terapêutico , Convulsões Febris/etiologiaAssuntos
Neoplasias do Ventrículo Cerebral/cirurgia , Ependimoma/cirurgia , Quarto Ventrículo/cirurgia , Insuficiência Cardíaca/etiologia , Edema Pulmonar/etiologia , Neoplasias do Ventrículo Cerebral/complicações , Neoplasias do Ventrículo Cerebral/patologia , Pré-Escolar , Ependimoma/complicações , Ependimoma/patologia , Feminino , Quarto Ventrículo/patologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Recidiva Local de Neoplasia/complicações , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Edema Pulmonar/fisiopatologiaRESUMO
The majority of pediatric low-grade gliomas (LGGs) are characterized by constitutive activation of the mitogen-activated protein kinase (MAPK) pathway through various mechanisms including BRAF mutations, inactivation of NF1, and KIAA1549-BRAF and FAM131B-BRAF fusions. The KIAA1549-BRAF fusion typically results from a 2.0 Mb tandem duplication in chromosome band 7q34. In the present study, single nucleotide polymorphism (SNP)-based array analysis of three LGGs demonstrated deletions in 7q34 that resulted in a BRAF fusion. Case 1 was likely a pilocytic astrocytoma (PA) with three deletions in 7q33q34 and an exon 15-9 KIAA1549-BRAF fusion. SNP array analysis of case 2, a possible dysembryoplastic neuroepithelial tumor (DNT), revealed a 2.6 Mb deletion, which included the 5' end of BRAF and extended to the 3' end of FAM131B. In case 3, deletions involving BRAF and FAM131B were observed in both a primary and a recurrent PA. RNA-based sequence analysis of cases 2 and 3 confirmed a fusion between FAM131B exon 2 and BRAF exon 9. The presence of fusion transcripts in these three LGGs highlights the utility of SNP array analysis to identify deletions that are suggestive of fusion proteins. BRAF fusions can result from multiple non-overlapping deletions, suggesting various complex mechanisms of formation.
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Neoplasias Encefálicas/genética , Deleção Cromossômica , Cromossomos Humanos Par 7/genética , Glioma/genética , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas B-raf/genética , Adolescente , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Criança , Feminino , Glioma/patologia , Humanos , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Single nucleotide polymorphism (SNP) array analysis is currently used as a first tier test for pediatric brain tumors at The Children's Hospital of Philadelphia. The results from 100 consecutive patients are summarized in the present report. Eighty-seven percent of the tumors had at least one pathogenic copy number alteration. Nineteen of 56 low grade gliomas (LGGs) demonstrated a duplication in 7q34, which resulted in a KIAA1549-BRAF fusion. Chromosome band 7q34 deletions, which resulted in a FAM131B-BRAF fusion, were identified in one pilocytic astrocytoma (PA) and one dysembryoplastic neuroepithelial tumor (DNT). One ganglioglioma (GG) demonstrated a 6q23.3q26 deletion that was predicted to result in a MYB-QKI fusion. Gains of chromosomes 5, 6, 7, 11, and 20 were seen in a subset of LGGs. Monosomy 6, deletion of 9q and 10q, and an i(17)(q10) were each detected in the medulloblastomas (MBs). Deletions and regions of loss of heterozygosity that encompassed TP53, RB1, CDKN2A/B, CHEK2, NF1, and NF2 were identified in a variety of tumors, which led to a recommendation for germline testing. A BRAF p.Thr599dup or p.V600E mutation was identified by Sanger sequencing in one and five gliomas, respectively, and a somatic TP53 mutation was identified in a fibrillary astrocytoma. No TP53 hot-spot mutations were detected in the MBs. SNP array analysis of pediatric brain tumors can be combined with pathologic examination and molecular analyses to further refine diagnoses, offer more accurate prognostic assessments, and identify patients who should be referred for cancer risk assessment.