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OBJECTIVE: We aim to report the epidemiology, surgical outcomes, and survival rates of pediatric patients with posterior fossa tumors in a large single-center case series. METHODS: A retrospective analysis was conducted on pediatric patients who underwent surgical treatment for posterior fossa tumors between January 2011 and January 2019. RESULTS: A total of 135 pediatric patients, with an average age of 7.5 years at diagnosis and a mean follow-up of 35.7 months, were included in the study. Most tumors were located within the midline, with ventriculomegaly observed in 71.4% of the patients. Pilocytic astrocytomas encompassed the majority of tumors (34.1%), followed by medulloblastomas (27.4%) and ependymomas (11.8%). Gross total resection (GTR) was achieved in 71.8% of the patients, with a recurrence rate of 20%. Surgical complications were observed in 25.9% of the patients. GTR significantly impacted 5-year overall survival (OS) and 4-year progression-free survival (PFS) in patients with posterior fossa tumors. Patients who underwent GTR had a 5-year OS of 89.7%, compared to 72.7% for near-total resection and 70.8% for subtotal resection. The 4-year PFS for patients who underwent GTR was 82.5%, whereas it was 63.6% for patients who underwent near-total resection and 54.2% for patients who underwent subtotal resection. CONCLUSION: Surgical resection remains the main treatment for pediatric posterior fossa tumors, and higher resection rates are linked to better survival outcomes. Despite limited resources for molecular diagnosis, our institution has demonstrated that a specialized neurooncological center with a high surgical volume can still achieve favorable survival outcomes for these patients.
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Neoplasias Infratentoriais , Procedimentos Neurocirúrgicos , Humanos , Neoplasias Infratentoriais/cirurgia , Criança , Masculino , Feminino , Estudos Retrospectivos , Pré-Escolar , Procedimentos Neurocirúrgicos/métodos , Adolescente , Lactente , Resultado do Tratamento , América Latina/epidemiologia , Taxa de SobrevidaRESUMO
Pilocytic astrocytoma is the most common primary CNS neoplasm in children and adolescents, rare after the first two decades of life. While some authors report a favorable prognosis in the adult age group with the tumor, others have associated it with higher mortality. The molecular alteration most observed in cases of pilocytic astrocytoma in the pediatric group is the BRAF-KIAA1549 gene fusion, and there are still few studies confirming the presence of this fusion in the adult population. This work investigated genetic alterations involving the 7q34 region in BRAF gene in 21 adult individuals with pilocytic astrocytoma, by FISH. In addition, was identified the immunohistochemical expression of BRAFV600E, correlating these findings with histopathological and clinical ones. BRAF-KIAA1549 fusion appeared in only one case, while in two other cases were found deletions related to the FAM131B-BRAF fusion, suggesting that maybe the latter is more frequently in this population. Through the evaluation of immunoreactivity, 71% of the cases were considered positive and 29% negative. Cases considered positive for BRAFV600E immunoreactivity can potentially be treated through drug therapy with BRAF inhibitors; however, it is always recommended to carry out a molecular study for diagnostic confirmation. This is the first Brazilian study that aimed to investigate possible genetic alterations in the BRAF gene in pilocytic astrocytomas, specifically in adults. Only 1 patient died, but due to operative complications and not the disease itself, suggesting a good evolution of these individuals.
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Astrocitoma , Neoplasias Encefálicas , Adolescente , Criança , Humanos , Adulto , Neoplasias Encefálicas/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas de Fusão Oncogênica/genética , Astrocitoma/genética , Astrocitoma/patologia , MutaçãoRESUMO
While in adults most intracranial tumors develop around the cerebral hemispheres, 45 to 60% of pediatric lesions are found in the posterior fossa, although this anatomical region represents only 10% of the intracranial volume. The latest edition of the WHO classification for CNS tumors presented some fundamental paradigm shifts that particularly affected the classification of pediatric tumors, also influencing those that affect posterior fossa. Molecular biomarkers play an important role in the diagnosis, prognosis, and treatment of childhood posterior fossa tumors and can be used to predict patient outcomes and response to treatment and monitor its effectiveness. Although genetic studies have identified several posterior fossa tumor types, differing in terms of their location, cell of origin, genetic mechanisms, and clinical behavior, recent management strategies still depend on uniform approaches, mainly based on the extent of resection. However, significant progress has been made in guiding therapy decisions with biological or molecular stratification criteria and utilizing molecularly targeted treatments that address specific tumor biological characteristics. The primary focus of this review is on the latest advances in the diagnosis and treatment of common subtypes of posterior fossa tumors in children, as well as potential therapeutic approaches in the future. Conclusion: Molecular biomarkers play a central role, not only in the diagnosis and prognosis of posterior fossa tumors in children but also in customizing treatment plans. They anticipate patient outcomes, measure treatment responses, and assess therapeutic effectiveness. Advances in neuroimaging and treatment have significantly enhanced outcomes for children with these tumors. What is Known: ⢠Central nervous system tumors are the most common solid neoplasms in children and adolescents, with approximately 45 to 60% of them located in the posterior fossa. ⢠Multimodal approaches that include neurosurgery, radiation therapy, and chemotherapy are typically used to manage childhood posterior fossa tumors What is New: ⢠Notable progress has been achieved in the diagnosis, categorization and management of posterior fossa tumors in children, leading to improvement in survival and quality of life.
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Neoplasias Encefálicas , Neoplasias Infratentoriais , Adulto , Adolescente , Criança , Humanos , Qualidade de Vida , Neoplasias Infratentoriais/diagnóstico , Neoplasias Infratentoriais/terapia , Neoplasias Infratentoriais/patologia , Prognóstico , BiomarcadoresRESUMO
Pilocytic astrocytoma is a central nervous system tumor of slow growth, which represents 5 % of all gliomas and most often develops in the cerebellum (42-60 %), but can also arise in other neural areas, such as the optic pathway or hypothalamus (9-30 %); brainstem (9 %); spinal cord (2 %). In the pediatric population, this tumor is the second most common cause of neoplasms and, on the other hand, in adults, it is often rare, probably due to its aggressiveness in these individuals. Studies reveal that the origin of pilocytic astrocytoma is characterized by a fusion between the BRAF gene and the KIAA1549 locus, and the application of the immunohistochemistry technique for the analysis of BRAF protein expression can be a valuable tool for diagnostic purposes. Due to the relative rarity of this disease in adults, there are few publications on the most effective diagnostic and treatment strategies for this tumor. The general objective of this study was to analyze the histopathological and immunohistochemical characteristics of pilocytic astrocytoma in these patients. For this, a retrospective study of patients aged over 17 years with a diagnosis of pilocytic astrocytoma was carried out at the Department of Pathology of UNIFESP/EPM, from 1991 to 2015. In order to define BRAF positivity in the immunohistochemical analysis, at least three consecutive fields with more than 50 % immunostaining were used as criteria and, thus, it was inferred that the 7 cases analyzed were considered positive for the cytoplasmic marker BRAF V600E. Histopathological analysis associated with BRAF immunostaining is of paramount importance as a diagnostic method in these cases. However, future molecular studies will be necessary both for a better understanding of the aggressiveness and prognostic of this tumor and for research involving specific therapies for pilocytic astrocytoma in adults.
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Astrocitoma , Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Humanos , Criança , Adulto , Idoso , Neoplasias Encefálicas/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Estudos Retrospectivos , Astrocitoma/genética , Neoplasias do Sistema Nervoso Central/genéticaRESUMO
Objective: Analyze a series of pediatric patients with cPAs evaluating factors that may modify or determine the final outcome in terms of neurological status, CMS and hydrocephalus. Materials and methods: Single Center, retrospective cohort study of surgical patients with cPA and at least 12 months of follow-up. Clinical, imaging and surgical features, histopathology and adjuvancy were assessed. Clinical outcome was categorized using the FSS and modified Bloom-Scale in the short and long term. Recurrency, PFS and mortality were also analyzed. Results: A total of 100 patients with a mean follow-up of 53.9 months, with no gender predilection, and a mean age of 7.6 years were included. The most frequent location was central and 24% of the tumors presented brainstem invasion. 79 patients had hydrocephalus at diagnosis and 48% required preoperative treatment. RT was achieved in 67% of cases. CMS was observed in 15 patients, statistically associated with location, pontine invasion, preoperative Bloom-score, and postoperative meningitis/ventriculitis. The functional "outcome" was correlated with complications such as meningitis/ventriculitis and cerebellar hematoma, mutism and recurrence. Recurrence was observed in 26% of cases and surgical reintervention was the chosen therapy. Conclusion: The treatment of cPAs in pediatric patients is associated with relatively favorable results. Recurrence, CMS and surgical complications play a prognostic value in the outcome and therefore must be managed appropriately. Early treatment with the intention of GTR should be considered, opting, if this is not possible, to leave a tumor residue over neurological damage. The treatment of hydrocephalus in the preoperative instance requires individualized management.
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Type-1 neurofibromatosis (NF1) is a neurocutaneous syndrome classically known as peripheral NF to distinguish it from type-2 NF (central NF). Its main characteristic is the high predisposition to the growth of multiple tumors, which specially arouses the interest of spinal surgeons due to the presence of spinal cord compression and spinal deformities. Considering this, we have performed a comprehensive review, with illustrative cases of the main manifestations of NF1, focusing on the perspective of the spine surgeon. Articles were grouped according to the following subjects: diagnosis, skeletal complications, spinal deformity, and spinal tumors. For all of them, a detailed discussion on pearls for practice was presented. The diagnosis of NF1 is based on the presence of at least two out of seven criteria. Cutaneous findings are very common in NF1, and the most usual tumor is cutaneous neurofibroma (NFB). Plexiform neurofibromas are also found and present a high risk of becoming malignant peripheral nerve sheath tumors (MPNSTs), reducing life expectancy. Astrocytomas, especially pilocytic astrocytomas, are the most common central nervous system tumor, including in the spinal cord. Surgery is necessary to resect as much as possible without adding new neurological deficits. Spinal deformities are also commonly found (in 3070% of the cases), potentially associated with dystrophic changes, which may result in acute and rapid progression. In the present review, we discuss specific characteristics found in this group of patients which are of paramount importance to properly manage this challenging disease.
A neurofibromatose do tipo 1 (NF1) é uma síndrome neurocutânea classicamente conhecida como NF periférica para distingui-la da NF do tipo 2 (ou NF central). Sua principal característica é a alta predisposição ao crescimento de múltiplos tumores, o que desperta especialmente a interesse dos cirurgiões de coluna devido à presença de compressão medular e deformidades. Diante disso, realizamos uma revisão abrangente, com casos ilustrativos das principais manifestações da NF1, com foco na perspectiva do cirurgião de coluna. Os artigos foram agrupados de acordo com os seguintes assuntos: diagnóstico, compli cações esqueléticas, deformidade da coluna vertebral e tumores da coluna vertebral. Para todos esses assuntos, uma discussão detalhada sobre dicas para a prática foi apresentada. O diagnóstico de NF1 é baseado na presença de pelo menos dois dos sete critérios. Achados cutâneos são muito comuns na NF1, sendo o tumor mais comum o neurofibroma cutâneo (NFB). Neurofibromas plexiformes também são encontrados e apresentam alto risco de se tornarem tumores malignos da bainha do nervo periférico (MPNSTs), reduzindo a expectativa de vida. Astrocitomas, especialmente astrocitomas pilocíticos, são os tumores mais comuns no sistema nervoso central, inclusive na medula espinhal. A cirurgia é necessária para ressecar tanto quanto possível sem adicionar novos déficits neurológicos. As deformidades da coluna também são comumente encontrada (em até 3070% dos casos), potencialmente associada a deformidades distróficas que podem resultar em progressão aguda e rápida. No presente artigo, discutimos características específicas encontradas neste grupo de pacientes que são de suma importância para manejar adequadamente pacientes com esta doença desafiadora.
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BACKGROUND: Pilocytic astrocytoma is the most frequent pediatric glioma. Despite its overall good prognosis, complete surgical resection is sometimes unfeasible, especially for patients with deep-seated tumors. For these patients, the identification of targetable genetic alterations such as NTRK fusions, raised as a new hope for therapy. The presence of gene fusions involving NTRK2 has been rarely reported in pilocytic astrocytoma. The aim of the present study was to investigate the frequency of NTRK2 alterations in a series of Brazilian pilocytic astrocytomas. METHODS: Sixty-nine pilocytic astrocytomas, previously characterized for BRAF and FGFR1 alterations were evaluated. The analysis of NTRK2 alterations was performed using a dual color break apart fluorescence in situ hybridization (FISH) assay. RESULTS: NTRK2 fusions were successfully evaluated by FISH in 62 of the 69 cases. Neither evidence of NTRK2 gene rearrangements nor NTRK2 copy number alterations were found. CONCLUSIONS: NTRK2 alterations are uncommon genetic events in pilocytic astrocytomas, regardless of patients' clinicopathological and molecular features.
Assuntos
Astrocitoma , Neoplasias Encefálicas , Glioma , Astrocitoma/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Fusão Gênica , Glioma/genética , Humanos , Hibridização in Situ Fluorescente , Proteínas Proto-Oncogênicas B-raf/genéticaRESUMO
Introduction Pilocytic astrocytoma of the cerebellopontine angle (CPA) is uncommon, and its spread to the cerebrospinal fluid (CSF) at the time of diagnosis has not been reported in the literature. Case Presentation We report the case of a 33-year-old man with multifocal pilocytic astrocytoma diagnosed by magnetic resonance imaging (MRI) and confirmed by histopathological examination, and present the radiological and histopathological findings. Conclusion In the case herein reported, we observed spread of the pilocytic astrocytoma of the CPA to the CSF at the initial diagnosis, and early detection by MRI is very important regarding the treatment modality and prognosis.
Introdução O astrocitoma pilocítico no ângulo pontocerebelar (APC) é incomum, e sua disseminação liquórica no momento do diagnóstico não foi relatada na literatura. Apresentação do Caso Relatamos o caso de um homem de 33 anos com astrocitoma pilocítico multifocal diagnosticado por ressonância magnética (RM) e confirmado por exame histopatológico, e apresentamos os achados radiológicos e histopatológicos. Conclusão No caso relatado, observou-se disseminação liquórica de astrocitoma pilocítico no APC no diagnóstico inicial, e a detecção precoce por RM é muito importante para a modalidade de tratamento e o prognóstico.
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Pilocytic astrocytoma (PA) is the most frequent solid neoplasm in childhood. It has a good 5-year overall survival (90% in childhood and 52% in adults). However, up to 20% of patients experience residual tumor growth, recurrence, and death. Although the main genetic alteration of PAs, including KIAA1549:BRAF fusion, involves chromosome 7q34, we previously found frequent loss in chr9q34.3 locus in a small subset of these tumors. Among the genes present in this locus, EGFL7 is related to poor prognosis in several tumor types. In this study, we aimed to assess EGFL7 expression through immunohistochemistry, and to evaluate its prognostic value in a series of 64 clinically and molecularly well-characterized pilocytic astrocytomas. We found high expression of EGFL7 in 71.9% of patients. Low EGFL7 expression was associated with older patients, the mean age mainly older than 11 years (P = 0.027). EGFL7 expression was not associated with presence of KIAA1549:BRAF fusion, BRAF mutation, FGFR1 mutation, nor FGFR1 duplication. Moreover, high EGFL7 expression was associated with high FGFR1 (P = 0.037) and 5'-deoxy-5'-methyltioadenosine phosphorylase (MTAP) (P = 0.005) expression, and with unfavorable outcome of patients (P = 0.047). Multivariate analysis revealed low EGFL7 expression related to older patients and high EGFL7 expression related to retained expression of MTAP. In addition, we found a borderline significance of unfavorable outcome and high EGFL7 expression. Finally, EGFL7 expression was not associated with overall or event-free survival of PA patients. Our findings point to EGFL7 expression as a novel candidate prognostic marker in PA, which should be further investigated.
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Astrocitoma/diagnóstico , Astrocitoma/metabolismo , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/metabolismo , Proteínas de Ligação ao Cálcio/biossíntese , Família de Proteínas EGF/biossíntese , Adolescente , Adulto , Astrocitoma/genética , Neoplasias Encefálicas/genética , Proteínas de Ligação ao Cálcio/genética , Criança , Pré-Escolar , Família de Proteínas EGF/genética , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mutação/genética , Prognóstico , Adulto JovemRESUMO
Pilocytic astrocytomas are the primary tumors most frequently found in children and adolescents, accounting for approximately 15.6% of all brain tumors and 5.4% of all gliomas. They are mostly found in infratentorial structures such as the cerebellum and in midline cerebral structures such as the optic nerve, hypothalamus, and brain stem. The present study aimed to list the main characteristics about this tumor, to better understand the diagnosis and treatment of these patients, and was conducted on search of the published studies available in NCBI, PubMed, MEDLINE, Scielo, and Google Scholar. It was possible to define the main histologic findings observed in these cases, such as mitoses, necrosis, and Rosenthal fibers. We described the locations usually most affected by tumor development, and this was associated with the most frequent clinical features. The comparison between the molecular diagnostic methods showed great use of fluorescent in situ hybridization, polymerase chain reaction (PCR), and reverse transcriptase-PCR, important techniques for the detection of BRAF V600E mutation and BRAF-KIAA1549 fusion, characteristic molecular alterations in pilocytic astrocytomas.
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Astrocitoma/diagnóstico , Neoplasias Encefálicas/diagnóstico , Hibridização in Situ Fluorescente/métodos , Reação em Cadeia da Polimerase/métodos , Astrocitoma/fisiopatologia , Astrocitoma/terapia , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/terapia , HumanosRESUMO
OBJECTIVE: Pilocytic astrocytoma (PA) is rare in adults comprising 5.1% of the primary central nervous system tumors. The aim is to describe the first Brazilian series of adult patients with PA and compare its features with the available literature. METHODS: We retrospectively review all patients 18 years or older with PA from our institution's database from 1991 to 2018. We analyzed information regarding clinical presentation, location, imaging features, extent of resection, adjuvant treatments, and follow-up. RESULTS: Twenty-three patients with PA were analyzed: 60.9% male; median age 26 years. The most frequent symptoms were headache (34.8%) and seizure (26.1%). Temporal and parietal lobes were the most common locations, 21.7% each. All patients underwent a surgical procedure, gross total resection in 40.9%, subtotal resection in 22.7%, and biopsy in 27.3%. Adjuvant treatment with radiotherapy was performed in 2 patients. Only 4 patients had disease progression, 2 after gross total resection and 2 after subtotal resection. They were all alive and without evidence of new progression at the last follow-up (October 2018). Median overall survival was not reached after a median follow-up time of 88.9 months. CONCLUSIONS: This is the first Brazilian series regarding adults with PA, and our patients had a favorable outcome as reported in recent literature reviews. The tumor's prevalence reduces within older patients and supratentorial lesions are more frequent, especially on the temporal lobe. There was no significant relationship between location and progression, although according to the literature the extent of resection remains the most important prognostic factor.
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Astrocitoma/cirurgia , Neoplasias Encefálicas/cirurgia , Adolescente , Adulto , Astrocitoma/complicações , Astrocitoma/epidemiologia , Astrocitoma/radioterapia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/radioterapia , Brasil/epidemiologia , Terapia Combinada , Irradiação Craniana , Progressão da Doença , Feminino , Seguimentos , Cefaleia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia Adjuvante , Estudos Retrospectivos , Convulsões/etiologia , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSES: Pilocytic astrocytoma (PA) is a low-grade neoplasm frequently found in childhood. PA is characterized by slow growth and a relatively good prognosis. Genetic mechanisms such as activation of MAPK, BRAF gene deregulation and neurofibromatosis type 1 (NF1) syndrome have been associated with PA development. Epigenetic signature and miRNA expression profile are providing new insights about different types of tumor, including PAs. METHODS: In the present study we evaluated global miRNA expression in 16 microdissected pediatric PA specimens, three NF1-associated PAs and 11 cerebral white matter (WM) samples by the microarray method. An additional cohort of 20 PAs was used to validate by qRT-PCR the expression of six miRNAs differentially expressed in the microarray data. RESULTS: Unsupervised hierarchical clustering analysis distinguished one cluster with nine PAs, including all NF1 cases and a second group consisting of the WM samples and seven PAs. Among 88 differentially expressed miRNAs between PAs and WM samples, the most underexpressed ones regulate classical pathways of tumorigenesis, while the most overexpressed miRNAs are related to pathways such as focal adhesion, P53 signaling pathway and gliomagenesis. The PAs/NF1 presented a subset of underexpressed miRNAs, which was also associated with known deregulated pathways in cancer such as cell cycle and hippo pathway. CONCLUSIONS: In summary, our data demonstrate that PA harbors at least two distinct miRNA signatures, including a subgroup of patients with NF1/PA lesions.
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Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Substância Branca/metabolismo , Adolescente , Astrocitoma/genética , Neoplasias Encefálicas/genética , Criança , Pré-Escolar , Análise por Conglomerados , Feminino , Perfilação da Expressão Gênica , Humanos , Lactente , Masculino , Neurofibromatose 1/genéticaRESUMO
El síndrome diencefálico es una causa infrecuente de desnutrición. Se produce por la disfunción del hipotálamo y está asociado a tumores del encéfalo. Los pacientes presentan una grave y progresiva pérdida de peso, aunque el apetito y la ingesta calórica son, por lo general, adecuados. Característicamente, los síntomas neurológicos son tardíos, lo que retrasa la sospecha diagnóstica. Se presenta a un paciente de 2 años y 6 meses de edad con desnutrición crónica grado II, derivado con diagnóstico presuntivo de enfermedad celíaca con mala adherencia y fracaso del tratamiento. Durante la internación, se arribó al diagnóstico de síndrome diencefálico secundario a un astrocitoma pilocítico grado I.
Diencephalic syndrome is an infrequent cause of malnutrition. It is produced by a malfunctioning hypothalamus, and it is related to encephalic tumors. Patients present a serious and progressive weight loss although the appetite and calorie intake are, usually, adequate. Neurological symptoms typically have a late appearance, delaying diagnostic suspicion. We present a patient aged 2 years and a half with grade II chronic malnutrition, referred with presumptive diagnosis of celiac disease, with poor adherence and treatment failure. During hospitalization, diagnosis of diencephalic syndrome secondary to grade I pilocytic astrocytoma was reached.
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Humanos , Masculino , Pré-Escolar , Astrocitoma/diagnóstico , Transtornos da Nutrição Infantil/diagnóstico , Doença Celíaca/diagnóstico , Doenças Hipotalâmicas/diagnóstico , Astrocitoma/complicações , Doença Crônica , Doenças Hipotalâmicas/etiologiaRESUMO
Diencephalic syndrome is an infrequent cause of malnutrition. It is produced by a malfunctioning hypothalamus, and it is related to encephalic tumors. Patients present a serious and progressive weight loss although the appetite and calorie intake are, usually, adequate. Neurological symptoms typically have a late appearance, delaying diagnostic suspicion. We present a patient aged 2 years and a half with grade II chronic malnutrition, referred with presumptive diagnosis of celiac disease, with poor adherence and treatment failure. During hospitalization, diagnosis of diencephalic syndrome secondary to grade I pilocytic astrocytoma was reached.
El síndrome diencefálico es una causa infrecuente de desnutrición. Se produce por la disfunción del hipotálamo y está asociado a tumores del encéfalo. Los pacientes presentan una grave y progresiva pérdida de peso, aunque el apetito y la ingesta calórica son, por lo general, adecuados. Característicamente, los síntomas neurológicos son tardíos, lo que retrasa la sospecha diagnóstica. Se presenta a un paciente de 2 años y 6 meses de edad con desnutrición crónica grado II, derivado con diagnóstico presuntivo de enfermedad celíaca con mala adherencia y fracaso del tratamiento. Durante la internación, se arribó al diagnóstico de síndrome diencefálico secundario a un astrocitoma pilocítico grado I.
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Astrocitoma/diagnóstico , Transtornos da Nutrição Infantil/diagnóstico , Doenças Hipotalâmicas/diagnóstico , Astrocitoma/complicações , Doença Celíaca/diagnóstico , Pré-Escolar , Doença Crônica , Humanos , Doenças Hipotalâmicas/etiologia , MasculinoRESUMO
OBJECTIVE: To compare cerebral perfusion and diffusion in survivors of childhood posterior fossa brain tumor with neurologically normal controls and correlate differences with cognitive dysfunction. STUDY DESIGN: We analyzed retrospectively arterial spin-labeled cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) in 21 patients with medulloblastoma (MB), 18 patients with pilocytic astrocytoma (PA), and 64 neurologically normal children. We generated ANCOVA models to evaluate treatment effects on the cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, and cerebral white matter at time points an average of 5.7 years after original diagnosis. A retrospective review of patient charts identified 12 patients with neurocognitive data and in whom the relationship between IQ and magnetic resonance imaging variables was assessed for each brain structure. RESULTS: Patients with MB (all treated with surgery, chemotherapy, and radiation) had significantly lower global CBF relative to controls (10%-23% lower, varying by anatomic region, all adjusted P?
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Encéfalo/patologia , Circulação Cerebrovascular/fisiologia , Neoplasias Infratentoriais/fisiopatologia , Adolescente , Astrocitoma/fisiopatologia , Astrocitoma/terapia , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Neoplasias Infratentoriais/terapia , Imageamento por Ressonância Magnética , Masculino , Meduloblastoma/fisiopatologia , Meduloblastoma/terapia , Testes Neuropsicológicos , Fluxo Sanguíneo Regional/fisiologia , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Pilocytic astrocytoma is a rare tumour, usually occurring in paediatric ages, and mainly located in the posterior fossa. It can cause hydrocephalus and intracranial hypertension and, less frequently, seizures, or a focal neurological deficit. The main imaging study by magnetic resonance imaging, which shows a tumour with solid and cystic components without peri-lesional swelling. The election treatment is surgical, and the patient is considered cured if a total resection is accomplished. CLINICAL CASE: The case is presented of 22-year-old female patient with a supratentorial pilocytic astrocytoma and epilepsy. Histopathology reported a low grade glial proliferation, with an extensive fibrillar matrix, small cells without atypia, extensive calcifications and piloid areas consisting of bipolar fusiform cells, and some Rosenthal fibres. There were also spongiotic areas consisting of multipolar cells and associated microcysts. The final report was a pilocytic astrocytoma. CONCLUSIONS: Pilocytic astrocytoma is more frequent in paediatric patients and in the posterior fossa. The case presented is of a young female adult with supratentorial location, making it a special case. The surgery achieved a total resection. The long-term prognosis is good, but it is necessary to perform a follow-up, particularly in adult patients because of a higher risk of recurrence.
Assuntos
Astrocitoma/complicações , Craniotomia/métodos , Convulsões/etiologia , Neoplasias Supratentoriais/complicações , Anticonvulsivantes/uso terapêutico , Astrocitoma/diagnóstico por imagem , Astrocitoma/patologia , Astrocitoma/cirurgia , Colecistite Aguda/complicações , Feminino , Humanos , Levetiracetam , Imageamento por Ressonância Magnética , Neuroimagem , Piracetam/análogos & derivados , Piracetam/uso terapêutico , Indução de Remissão , Convulsões/tratamento farmacológico , Neoplasias Supratentoriais/diagnóstico por imagem , Neoplasias Supratentoriais/patologia , Neoplasias Supratentoriais/cirurgia , Adulto JovemRESUMO
Nuestro objetivo fue mostrar y describir casos de astrocitomas pilocíticos (AP) supra e infratentoriales en sus formas típicas y atípicas de presentación en resonancia magnética y tomografía computada. Para ello, fueron seleccionados de nuestra casuística 32 pacientes: 24 tuvieron diagnóstico confirmado de AP por anatomía patológica y los 8 restantes mostraban gliomas de la vía óptica, por lo que el AP era el diagnóstico presuntivo más relevante. Veinte pacientes eran de sexo masculino y 12 de sexo femenino, con un rango etario entre los 10 meses y los 65 años. A todos se les pidió una resonancia magnética de cerebro con gadolinio, solo a 6 se les realizó difusión y espectroscopia, y en 6 también se llevó a cabo una tomografía computada. Las localizaciones de los AP seleccionados (n = 32) fueron: vía óptica y región hipotálamoquiasmática (n = 17), cerebelo (n = 7), tálamo (n = 6) y parénquima (n = 2). En la resonancia magnética, la mayoría de los AP se presentaron como lesiones sólido-quísticas, iso-hipointensas en ponderación T1 e hiperintensas en ponderación T2 y mesencéfalo talámico, con realce poscontraste. Cuatro pacientes presentaron características atípicas: 1 AP cerebeloso sólido con calcificaciones, 1 AP hipotalámico en un niño sin neurofibromatosis tipo 1 ni realce poscontraste, y 1 AP parenquimatoso en una mujer de 65 años. Los AP son gliomas de grado I, según la clasificación de la Organización Mundial de la Salud. Sus localizaciones más frecuentes son la vía óptica, la región hipotálamo-quiasmática y la fosa posterior. Son tumores circunscriptos, sólido-quísticos, de baja celularidad y, en general, de lento crecimiento.(AU)
Our purpose is to illustrate and describe the typical and atypical imaging findings of supra and infratentorial pilocytic astrocytoma (PA) with computed tomography (CT) and magnetic resonance imaging (MRI). For this, 32 patients with PA from our case series were selected. Twenty-four patients had confirmed PA from histologic analysis. The remaining 8 patients presented optic pathway gliomas and PA was the most accurate presumptive diagnosis. All patients, 20 male and 12 female (age range 10 months-65 years), underwent unenhanced and enhanced MRI. Diffusion-weighted images and MR spectroscopy (MRS) were performed in 6 patients, and 6 patients underwent CT. The locations of the PA selected (n = 32) were: optic pathway and hipotalamous-quiasmatic region (n = 17), cerebellum (n = 7), talamous (n = 6) and cerebral hemisphere (n = 2). At MRI most PA appeared as solid-cystic masses, iso to hypointense in T1-weighted images and hyperintense in T2-weighted images and FLAIR, with post-contrast enhancement. Four patients presented atypical characteristics: 1 solid cerebellum PA with calcifications, 1 hypothalamus PA in a child without NF1 with no contrast enhancement and 1 cerebral hemisphere PA in a 65 year old woman. The PA are regarded as grade I tumors in the WHO classification. The optic pathway and the hypothalamic-quiasmatic region, as well as the posterior fossa are the most frequent locations. PA are typically well-circumscribed and solid-cystic lesions with low cellularity and slow growth.(AU)
RESUMO
Brainstem gangliogliomas (GGs), often cannot be resected, have a much poorer prognosis than those located in more common supratentorial sites and may benefit from novel therapeutic approaches. Therapeutically targetable BRAF c.1799T>A (p.V600E) (BRAF(V600E) ) mutations are harbored in roughly 50% of collective GGs taken from all anatomical sites. Large numbers of pediatric brainstem GGs, however, have not been specifically assessed and anatomic-and age-restricted assessment of genetic and biological factors are becoming increasingly important. Pediatric brainstem GGs (n = 13), non-brainstem GGs (n = 11) and brainstem pilocytic astrocytomas (PAs) (n = 8) were screened by standard Sanger DNA sequencing of BRAF exon 15. Five of 13 (38%) pediatric GG harbored a definitive BRAF(V600E) mutation, with two others exhibiting an equivocal result by this method. BRAF(V600E) was also seen in five of 11 (45%) non-brainstem GGs and one of eight (13%) brainstem PAs. VE1 immunostaining for BRAF(V600E) showed concordance with sequencing in nine of nine brainstem GGs including the two cases equivocal by Sanger. The equivocal brainstem GGs were subsequently shown to harbor BRAF(V600E) using a novel, more sensitive, RNA-sequencing approach, yielding a final BRAF(V600E) mutation frequency of 54% (seven of 13) in brainstem GGs. BRAF(V600E) -targeted therapeutics should be a consideration for the high percentage of pediatric brainstem GGs refractory to conventional therapies.
Assuntos
Neoplasias do Tronco Encefálico/genética , Ganglioglioma/genética , Proteínas Proto-Oncogênicas B-raf/genética , Adolescente , Neoplasias do Tronco Encefálico/patologia , Criança , Pré-Escolar , Éxons , Feminino , Ganglioglioma/patologia , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Estudos Retrospectivos , Adulto JovemRESUMO
INTRODUCTION: Glial and neuroglial cell neoplasms comprise pilocytic astrocytoma (PA), pleomorphic xanthoastrocytoma (PXA) and ganglioglioma (GG), which share various similarities, though PA has better prognosis. As ganglion cells (GC) may be scarce in GG and these gangliogliomas may recur or progress to grade III, an accurate diagnosis is essential. OBJECTIVES: The aim was to identify GC and eosinophilic granular bodies (EGB) in PA and PXA, to evaluate its effect on patients outcome and compare them with GG. METHODS: A retrospective analysis of radiological, morphological and follow-up aspects (disease free-survival, recurrence and death) of 30 cases (14 PA, 8 PXA, 8 GG). Hematoxylin and eosin (HE) stained sections were reviewed to identify the presence of neoplastic GC and EGB. They were immunostained for synaptophysin (SYN) and neurofilament (NF). Glial fibrillary acidic protein (GFAP) immunostaining was performed in selected cases. RESULTS: Six PA were reclassified as GG due to the presence of GC by HE or immunohistochemistry. Some EGB resembling degenerate GC were also immunostained for SYN/NF and most of them were negative for GFAP. The mean disease-free survival was 62.16 months. Four tumors recurred and one patient died. All PXA had GC, suggesting that they were variants of GG, 4 of which recurred and one patient died. Mean disease-free survival was 69 months. The radiological aspect was predominantly cystic. CONCLUSION: We propose that PA and PXA with GC or with EGB immunopositive for neuronal markers could be variants of GG, and some EGB may represent degenerate GC. However, the presence of GC does not seem to modify the biological behavior of these neoplasms.
INTRODUÇÃO: As neoplasias circunscritas incluem astrocitoma pilocítico (AP), xantoastrocitoma pleomórfico (XP) e ganglioglioma (GG), que compartilham diversas semelhanças, sendo o AP o de melhor prognóstico. Como as células ganglionares (CG) no GG podem ser escassas e os GGs podem recidivar ou evoluir (grau III), é fundamental o diagnóstico preciso. OBJETIVOS: Identificar CG e corpos granulares eosinofílicos (CGE) em AP e XP, avaliar sua implicação na evolução e comparar com o GG. MÉTODOS: Análise retrospectiva dos aspectos radiológicos, morfológicos e evolutivos (tempo livre de doença, recidiva e óbito) de 30 casos (14 AP, oito XP, oito GG). Cortes corados com hematoxilina e eosina (HE) foram revistos para a identificação da presença de CG neoplásicas e CGE. Estes foram imunomarcados para sinaptofisina (SIN) e neurofilamento (NF) e, em casos selecionados, para glial fibrillary acidic protein (GFAP). RESULTADOS: Seis AP foram reclassificados para GG pela presença de CG (HE ou imunomarcação). Alguns CGE, semelhantes às CG degeneradas, também imunomarcaram para SIN/NF, a maioria sendo negativa para GFAP. O tempo médio livre de doença foi de 62,16 meses. Quatro tumores recidivaram; um deles evoluiu para óbito. Todos os XP possuíam CG, sugerindo que são variantes de GG, dos quais quatro recidivaram (um óbito). O tempo médio livre de doença foi de 69 meses. O aspecto radiológico foi predominantemente cístico. CONCLUSÃO: Sugerimos que AP e XP com CG ou CGE imunopositivos para marcadores neuronais possam ser variantes de GG e alguns CGE representem CG degeneradas; entretanto, a presença de CG ganglionares parece não modificar o comportamento biológico dessas neoplasias.
Assuntos
Astrocitoma/classificação , Ganglioglioma/classificaçãoRESUMO
Pilocytic astrocytoma (PA) is a grade I glial neoplasm arising mainly in the cerebellum of children. Herein, the authors report a case of PA in a 21 year-old male patient, who presented headache, vomiting and delayed pubertal development. Serum level of cortisol and testosterone corresponded to 32.8 ug/dl and 0.19 ng/ml, respectively. The computed tomography/magnetic resonance (CT/RM) imaging showed an expansive process compromising suprasellar/hypothalamic region and determining hydrocephalus. The patient underwent resection of the process. Histological evaluation revealed a glial neoplasm constituted by loose glial tissue, small microcysts, areas of dense piloid tissue and Rosenthal fibers. The neoplastic cells were immunoreactive for glial fibrillary acidic protein (GFAP) and negative for chromogranin and synaptophysin. The diagnosis of PA was then established.
O astrocitoma pilocítico (AP) é uma neoplasia glial grau I encontrada principalmente no cerebelo de crianças. Os autores relatam um caso de AP em paciente masculino, 21 anos de idade, que apresenta cefaleia, vômitos e retardo do desenvolvimento puberal. Os níveis séricos de cortisol e testesterona corresponderam a 32,8 ug/dl e 0,19 ng/ml. A tomografia computadorizada/ressonância magnética (TC/RM) identificaram um processo expansivo que comprometia a região suprasselar/hipotalâmica e determinava hidrocefalia.O paciente foi submetido à ressecção do processo. À microscopia, foi identificada uma neoplasia glial constituída por tecido glial frouxo, pequenos microcistos, áreas de tecido piloide denso e fibras de Rosenthal. As células neoplásicas foram imunopositivas para glial fibrillary acidic protein (GFAP) e negativas para cromogranina e sinaptofisina. O diagnóstico de AP foi, então, estabelecido.