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Immune checkpoint inhibitors (ICIs) are effective against many advanced malignancies. However, many patients are nonresponders to immunotherapy, and overcoming this resistance to treatment is important. Boron neutron capture therapy (BNCT) is a local chemoradiation therapy with the combination of boron drugs that accumulate selectively in cancer and the neutron irradiation of the cancer site. Here, we report the first boron neutron immunotherapy (B-NIT), combining BNCT and ICI immunotherapy, which was performed on a radioresistant and immunotherapy-resistant advanced-stage B16F10 melanoma mouse model. The BNCT group showed localized tumor suppression, but the anti-PD-1 antibody immunotherapy group did not show tumor suppression. Only the B-NIT group showed strong tumor growth inhibition at both BNCT-treated and shielded distant sites. Intratumoral CD8+ T-cell infiltration and serum high mobility group box 1 (HMGB1) levels were higher in the B-NIT group. Analysis of CD8+ T cells in tumor-infiltrating lymphocytes (TILs) showed that CD62L- CD44+ effector memory T cells and CD69+ early-activated T cells were predominantly increased in the B-NIT group. Administration of CD8-depleting mAb to the B-NIT group completely suppressed the augmented therapeutic effects. This indicated that B-NIT has a potent immune-induced abscopal effect, directly destroying tumors with BNCT, inducing antigen-spreading effects, and protecting normal tissue. B-NIT, immunotherapy combined with BNCT, is the first treatment to overcome immunotherapy resistance in malignant melanoma. In the future, as its therapeutic efficacy is demonstrated not only in melanoma but also in other immunotherapy-resistant malignancies, B-NIT can become a new treatment candidate for advanced-stage cancers.
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PURPOSE: Glioblastoma is a malignant brain tumor with a poor prognosis. Genetic mutations associated with this disease are complex are not fully understood and require further elucidation for the development of new treatments. The purpose of this study was to comprehensively analyze genetic mutations in glioblastomas and evaluate the usefulness of RNA sequencing. PATIENTS AND METHODS: We analyzed 42 glioblastoma specimens that were resected in routine clinical practice and found wild-type variants of the IDH1 and IDH2 genes. RNA was extracted from frozen specimens and sequenced, and genetic analyses were performed using the CLC Genomics Workbench. RESULTS: The most common genetic alterations in the 42 glioblastoma specimens were TP53 mutation (28.6%), EGFR splicing variant (16.7%), EGFR mutation (9.5%), and FGFR3 fusion (9.5%). Novel genetic mutations were detected in 8 patients (19%). In 12 cases (28.6%), driver gene mutations were not detected, suggesting an association with PPP1R14A overexpression. Our findings suggest the transcription factors SOX10 and NKX6-2 are potential markers in glioblastoma. CONCLUSION: RNA sequencing is a promising approach for genotyping glioblastomas because it provides comprehensive information on gene expression and is relatively cost-effective.
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Neoplasias Encefálicas , Glioblastoma , Isocitrato Desidrogenase , Mutação , Humanos , Glioblastoma/genética , Isocitrato Desidrogenase/genética , Masculino , Feminino , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Pessoa de Meia-Idade , Idoso , Adulto , Análise de Sequência de RNA/métodos , Biomarcadores Tumorais/genética , Genômica/métodos , Adulto Jovem , Idoso de 80 Anos ou mais , PrognósticoRESUMO
INTRODUCTION: Diffuse hemispheric glioma, H3 G34-mutant (DHGs), is a newly categorized tumor in pediatric-type diffuse high-grade gliomas, World Health Organization grade 4, with a poor prognosis. Although prognostic factors associated with genetic abnormalities have been reported, few reports have examined the clinical presentation of DHGs, especially from the viewpoint of imaging findings. In this study, we investigated the relationship between clinical factors, including imaging findings, and prognosis in patients with DHGs. METHODS: We searched Medline through the PubMed database using two search terms: "G34" and "glioma", between 1 April 2012 and 1 July 2023. We retrieved articles that described imaging findings and overall survival (OS), and added one DHG case from our institution. We defined midline invasion (MI) as invasion to the contralateral cerebrum, brainstem, corpus callosum, thalamus, and basal ganglia on magnetic resonance imaging. The primary outcome was 12-month survival, estimated using Kaplan-Meier curves and logistic regression. RESULTS: A total of 96 patients were included in this study. The median age was 22 years, and the proportion of male patients was 48.4%. Lesions were most frequently located in the frontal lobe (52.6%). MI was positive in 39.6% of all patients. The median OS was 14.4 months. Univariate logistic regression analysis revealed that OS was significantly worse in the MI-positive group compared with the MI-negative group. Multivariate logistic regression analysis revealed that MI was an independent prognostic factor in DHGs. CONCLUSIONS: In this study, MI-positive cases had a worse prognosis compared with MI-negative cases. PREVIOUS PRESENTATIONS: No portion of this study has been presented or published previously.
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Neoplasias Encefálicas , Glioma , Humanos , Masculino , Criança , Adulto Jovem , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Histonas/genética , Mutação , Glioma/diagnóstico por imagem , Glioma/genética , PrognósticoRESUMO
Organized chronic subdural hematoma (OCSDH) is a relatively rare condition that forms over a longer period of time compared to chronic subdural hematoma and is sometimes difficult to diagnose with preoperative imaging. We resected an intracranial lesion in a 37-year-old Japanese man; the lesion had been increasing in size for >17 years. The preoperative diagnosis based on imaging findings was meningioma; however, pathological findings revealed OCSDH. Clinicians should be aware that OCSDH mimics other tumors and consider surgical strategies for this disease.
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Hematoma Subdural Crônico , Neoplasias Meníngeas , Meningioma , Humanos , Masculino , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Hematoma Subdural Crônico/diagnóstico por imagem , Hematoma Subdural Crônico/cirurgia , Hematoma Subdural Crônico/diagnóstico , Adulto , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/cirurgia , Diagnóstico Diferencial , Tomografia Computadorizada por Raios X , Imageamento por Ressonância MagnéticaRESUMO
Hydrogen peroxide (H2 O2 ) induces oxidative stress and cytotoxicity, and can be used for treating cancers in combination with radiotherapy. A product comprising H2 O2 and sodium hyaluronate has been developed as a radiosensitizer. However, the effects of H2 O2 on antitumor immunity remain unclear. To investigate the effects of H2 O2 , especially the abscopal effect when combined with radiotherapy (RT), we implanted murine tumor cells simultaneously in two locations in mouse models: the hind limb and back. H2 O2 mixed with sodium hyaluronate was injected intratumorally, followed by irradiation only at the hind limb lesion. No treatment was administered to the back lesion. The H2 O2 /RT combination significantly reduced tumor growth at the noninjected/nonirradiated site in the back lesion, whereas H2 O2 or RT individually did not reduce tumor growth. Flow cytometric analyses of the tumor-draining lymph nodes in the injected/irradiated areas showed that the number of dendritic cells increased significantly with maturation in the H2 O2 /RT combination group. In addition, analyses of tumor-infiltrating lymphocytes showed that the number of CD8+ (cluster of differentiation 8) T cells and the frequency of IFN-γ+ (interferon gamma) CD8+ T cells were higher in the noninjected/nonirradiated tumors in the H2 O2 /RT group compared to those in the other groups. PD-1 (programmed death receptor 1) blockade further increased the antitumor effect against noninjected/nonirradiated tumors in the H2 O2 /RT group. Intratumoral injection of H2 O2 combined with RT therefore induces an abscopal effect by activating antitumor immunity, which can be further enhanced by PD-1 blockade. These findings promote the development of H2 O2 /RT therapy combined with cancer immunotherapies, even for advanced cancers.
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A 35-year-old female presented with headache, photophobia and developed sudden loss of vision after having undergone right-side ophthalmectomy and radiochemotherapy for retinoblastoma in infancy. A neoplastic lesion was found in the left middle cranial fossa and was surgically removed. The diagnosis was radiation-induced osteosarcoma with RB1 gene alteration. Although she received chemotherapy for the residual tumor, it progressed 17 months later. Maximal surgical resection with craniofacial reconstruction was required. We utilized two three-dimensional models for surgical planning. She was discharged without neurological deficits other than loss of light perception subsequent to left ophthalmectomy. In cases where retinoblastoma is treated with radiotherapy, long-term follow-up is necessary to monitor for radiation-induced tumor development.
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Neoplasias Ósseas , Osteossarcoma , Neoplasias da Retina , Retinoblastoma , Adulto , Feminino , Humanos , Osteossarcoma/cirurgia , Proteínas de Ligação a Retinoblastoma , Base do Crânio , Ubiquitina-Proteína Ligases , Lesões por Radiação/cirurgiaRESUMO
In the current World Health Organization classification of central nervous system tumors, comprehensive genetic and epigenetic analyses are considered essential for precise diagnosis. A 14-year-old male patient who presented with a cerebellar tumor was initially diagnosed with glioblastoma and treated with radiation and concomitant temozolomide chemotherapy after resection. During maintenance temozolomide therapy, a new contrast-enhanced lesion developed in the bottom of the cavity formed by the resection. A second surgery was performed, but the histological findings in specimens from the second surgery were different from those of the first surgery. Although genome-wide DNA methylation profiling was conducted using frozen tissue for a precise diagnosis, the proportion of tumor cells was insufficient and only normal cerebellum was observed. We then performed comprehensive genetic analysis using formalin-fixed paraffin-embedded sections, which revealed MYCN amplification without alteration of IDH1, IDH2, or Histone H3. Finally, the patient was diagnosed with pediatric-type diffuse high-grade glioma, H3-wildtype and IDH-wildtype. In conclusion, comprehensive genetic and epigenetic analysis should be considered in pediatric brain tumor cases.
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Neoplasias Encefálicas , Glioma , Masculino , Humanos , Criança , Adolescente , Temozolomida , Mutação , Glioma/diagnóstico , Glioma/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , GenômicaRESUMO
BACKGROUND: Glioblastoma multiforme (GBM) is the most common high-grade malignant brain tumour in adults and arises from the glial cells in the brain. The prognosis of treated GBM remains very poor with 5-year survival rates of 5%, a figure which has not improved over the last few decades. Currently, there is a modest 14-month overall median survival in patients undergoing maximum safe resection plus adjuvant chemoradiotherapy. HOX gene dysregulation is now a widely recognised feature of many malignancies. METHODS: In this study we have focused on HOX gene dysregulation in GBM as a potential therapeutic target in a disease with high unmet need. RESULTS: We show significant dysregulation of these developmentally crucial genes and specifically that HOX genes A9, A10, C4 and D9 are strong candidates for biomarkers and treatment targets for GBM and GBM cancer stem cells. We evaluated a next generation therapeutic peptide, HTL-001, capable of targeting HOX gene over-expression in GBM by disrupting the interaction between HOX proteins and their co-factor, PBX. HTL-001 induced both caspase-dependent and -independent apoptosis in GBM cell lines. CONCLUSION: In vivo biodistribution studies confirmed that the peptide was able to cross the blood brain barrier. Systemic delivery of HTL-001 resulted in improved control of subcutaneous murine and human xenograft tumours and improved survival in a murine orthotopic model.
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Neoplasias Encefálicas , Glioblastoma , Adulto , Animais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Genes Homeobox , Glioblastoma/tratamento farmacológico , Glioblastoma/terapia , Humanos , Camundongos , Peptídeos/genética , Distribuição TecidualRESUMO
PURPOSE: Pilocytic astrocytoma (PA) is a circumscribed low-grade astrocytic glioma, generally considered to be associated with a good prognosis. However, a subset of PA patients shows unfavorable outcomes. In this study, we retrospectively reviewed PA patients and performed further molecular analysis, such as DNA methylation profiling, to identify prognostic factors. METHODS: We analyzed 29 histologically-confirmed PA patients from a single center from 2002 to 2021 and conducted integrated molecular analyses among elderly PA patients since age was an independent prognostic factor for poor outcomes. RESULTS: The median age at diagnosis was 14 years (range 3-82 years) and 4 patients (14%) were elderly (patients ≥ 60 years old). Age over 60 was associated with poor progression-free survival and overall survival. We performed DNA methylation analysis on 2 of the 4 elderly patients. Both cases were histologically diagnosed as PA, but DNA methylation profiling revealed one as high-grade astrocytoma with piloid features (all methylation class scores were below 0.3 in both v11b4 and v12.5) and the other as glioblastoma, IDH-wildtype (score was over 0.5 in both v11b4 and v12.5), using the German Cancer Research Center methylation profiling classifiers and t-SNE analysis. CONCLUSIONS: Elderly patients with PA morphology showed unfavorable outcomes in this cohort. In those patients, further molecular analysis and DNA methylation profiling revealed the possibility of high-grade astrocytic tumors, including newly defined entities.
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Astrocitoma , Neoplasias Encefálicas , Humanos , Idoso , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Metilação de DNA , Estudos Retrospectivos , Neoplasias Encefálicas/patologia , Mutação , Astrocitoma/patologia , Isocitrato Desidrogenase/genéticaRESUMO
Glioneuronal tumor with neuropil-like islands (GNTNI) is a very rare subtype of glioneuronal tumor. We present a case of a 62-year-old man with GNTNI. Two adjacent lesions in the left parietal lobe were removed by left parietal craniotomy. The histological findings were glial cell proliferation and scattered rosettes consisting of synaptophysin-positive and NeuN-positive cells, leading to the diagnosis of GNTNI. Target sequencing revealed a genetic alteration similar to glioblastoma, IDH-wild type, which suggested adjuvant therapies. There are few previous reports on the treatment of this disease, and the patient should be followed carefully.
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Neoplasias Encefálicas , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Genômica , Humanos , Ilhas , Masculino , Pessoa de Meia-Idade , Neurópilo/metabolismo , Neurópilo/patologia , SinaptofisinaRESUMO
Malignant gliomas have a poor prognosis despite advances in surgical procedures, radiotherapy, and the emergence of new treatments have improved outcomes. One of these new treatments is gene therapy, which has been developed as a new therapeutic strategy. Recently, new methods and approaches have been developed. Gene therapy involves the introduction of genes or cells into a glioma, or the human body, to treat gliomas; various genes such as cancer-suppressing genes, immunomodulation cytokine-related genes, and suicide genes are used in this treatment. Viral therapy is a treatment that oncolytic viral replicates in tumor cells to destroy tumors. Various viral genes can also be used as therapeutic genes. Currently, the most well-studied and accumulated viruses are adenoviruses and HSV-1. Various clinical trials have been conducted using gene therapy and viral therapy, some of which are scheduled to be approved in the near future. Gene therapy and viral therapy have dramatically improved and have developed progressively since their first clinical use.
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Neoplasias Encefálicas , Glioma , Terapia Viral Oncolítica , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Terapia Genética , Glioma/genética , Glioma/terapia , HumanosRESUMO
Gliomas are characterized as highly diffuse infiltrating tumors, and currently available treatments such as surgery, radiation and chemotherapy are unfeasible or show limited efficacy against these tumors. Recent genetic and epigenetic analyses of glioma have revealed increasing evidence of the role of driver genetic alterations in glioma development and led to the identification of prognostic factors. Despite these findings, the survival rates of glioma patients remain low, and alternative treatments and novel targets are needed. Recent studies identified neural stem cells as the possible origin of gliomas, and some evidence has revealed shared functions and mechanisms between glioma cells and neurons, also supporting their similarity. The cytoskeleton plays important roles in the migration of normal cells as well as cancer cells. Recent reports have described a role for microtubules, a component of the cytoskeleton, in glioma invasion. Notably, several factors that regulate microtubule functions, such as microtubule-associated proteins, plus-end tracking proteins, or motor proteins, are upregulated in glioma tissues compared with normal tissue, and upregulation of these factors is associated with high invasiveness of glioma cells. In this review, we describe the mechanism of microtubules in glioma invasion and discuss the possibility of microtubule-targeted therapy to inhibit glioma invasion.
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Glioma/patologia , Microtúbulos , Invasividade Neoplásica/patologia , HumanosRESUMO
Atypical teratoid/rhabdoid tumor(AT/RT)is a rare and lethal childhood cancer. Although radiation therapy in children less than three years of age is generally deferred because of its neural toxicity, recent studies have shown that multimodal therapies, including radiation therapy, are effective in pediatric patients with AT/RT less than three years of age. We treated four infant AT/RT patients and investigated the impact of radiation therapy and genetic classification on the prognosis. The mean age at the time of the operation was 9.3 months and all patients were female. All patients underwent surgical resection. Of the four patients, two received combined irradiation and chemotherapy. Specifically, one patient received conformal craniospinal radiation therapy and the other received craniospinal irradiation with proton beams. Immunohistochemical analyses of tumor specimens revealed that the two patients were positive for ASCL1, a regulator of Notch signaling. Patients who received radiation therapy and exhibited ASCL1-positive tumors had a better prognosis. We conclude that radiation therapy may prolong survival in AT/RT patients who are less than 3 years of age. However, further study is required to evaluate long-term functional outcomes.
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Neoplasias Encefálicas/radioterapia , Tumor Rabdoide/radioterapia , Neoplasias da Coluna Vertebral/radioterapia , Teratoma/radioterapia , Neoplasias Encefálicas/diagnóstico , Criança , Terapia Combinada/métodos , Feminino , Humanos , Masculino , Prognóstico , Radioterapia Conformacional/métodos , Tumor Rabdoide/diagnóstico , Neoplasias da Coluna Vertebral/diagnóstico , Teratoma/diagnósticoRESUMO
A 62-year-old man with high fever and in a state of disorientation was transferred to our hospital. One year before this transfer, he had undergone total arch replacement surgery for thoracic aortic dissection. On admission to our hospital, head MRI revealed multiple brain abscesses in the territory of the vertebral-basilar artery, and chest CT showed gas around the aortic graft, in particular, at the origin of the left subclavian artery. We diagnosed him with brain abscesses in the left vertebral-basilar artery resulting from an infected aortic graft. We immediately began administration of intravenous antibiotics. Although his blood, urine, and cerebrospinal fluid cultures were negative, fortunately, the brain abscesses and ectopic gas disappeared. Since reports of only antibiotic use for treating brain abscesses due to aortic graft infection are rare, the appropriate duration of antibiotic administration has not been established yet. Therefore, careful observation is required in this case.
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Aorta Torácica/cirurgia , Artéria Basilar/cirurgia , Abscesso Encefálico/cirurgia , Complicações Pós-Operatórias/microbiologia , Artéria Vertebral/cirurgia , Prótese Vascular , Abscesso Encefálico/microbiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Artéria Subclávia/cirurgia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Advanced surgical interventions are required to treat malignancies in the anterior skull base (ASB). This study investigates the utility of endoscopic endonasal and transcranial surgery (EETS) using a high-definition three-dimensional exoscope as an alternative to traditional microscopy. METHODS: Six patients with carcinomas of varying histopathologies underwent surgery employing the EETS maneuver, which synchronized three distinct surgical modalities: harvesting of the anterolateral thigh flap, initiation of the transnasal technique, and initiation of the transcranial procedure. RESULTS: The innovative strategy enabled successful tumor resection and skull base reconstruction without postoperative local neoplastic recurrence, cerebrospinal fluid leakage, or neurological deficits. CONCLUSION: The integration of the exoscope and EETS is a novel therapeutic approach for ASB malignancies. This strategy demonstrates the potential of the exoscope in augmenting surgical visualization, enhancing ergonomics, and achieving seamless alignment of multiple surgical interventions. This technique represents a progressive shift in the management of these complex oncological challenges.
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Procedimentos de Cirurgia Plástica , Neoplasias da Base do Crânio , Humanos , Neoplasias da Base do Crânio/cirurgia , Neoplasias da Base do Crânio/patologia , Recidiva Local de Neoplasia/patologia , Retalhos Cirúrgicos/patologia , Endoscopia/métodos , Base do Crânio/cirurgia , Base do Crânio/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: The FDA approval of oncolytic herpes simplex-1 virus (oHSV) therapy underscores its therapeutic promise and safety as a cancer immunotherapy. Despite this promise, the current efficacy of oHSV is significantly limited to a small subset of patients largely due to the resistance in tumor and tumor microenvironment (TME). METHODS: RNA sequencing (RNA-Seq) was used to identify molecular targets of oHSV resistance. Intracranial human and murine glioma or breast cancer brain metastasis (BCBM) tumor-bearing mouse models were employed to elucidate the mechanism underlying oHSV therapy-induced resistance. RESULTS: Transcriptome analysis identified IGF2 as one of the top secreted proteins following oHSV treatment. Moreover, IGF2 expression was significantly upregulated in 10 out of 14 recurrent GBM patients after treatment with oHSV, rQNestin34.5v.2 (71.4%) (p=0.0020) (ClinicalTrials.gov, NCT03152318). Depletion of IGF2 substantially enhanced oHSV-mediated tumor cell killing in vitro and improved survival of mice bearing BCBM tumors in vivo. To mitigate the oHSV-induced IGF2 in the TME, we constructed a novel oHSV, oHSV-D11mt, secreting a modified IGF2R domain 11 (IGF2RD11mt) that acts as IGF2 decoy receptor. Selective blocking of IGF2 by IGF2RD11mt significantly increased cytotoxicity, reduced oHSV-induced neutrophils/PMN-MDSCs infiltration, and reduced secretion of immune suppressive/proangiogenic cytokines, while increased CD8+cytotoxic T lymphocytes (CTLs) infiltration, leading to enhanced survival in GBM or BCBM tumor-bearing mice. CONCLUSION: This is the first study reporting that oHSV-induced secreted IGF2 exerts a critical role in resistance to oHSV therapy, which can be overcome by oHSV-D11mt as a promising therapeutic advance for enhanced viro-immunotherapy.
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Synovial sarcomas compromise between 5 to 10% of all soft tissue sarcomas in adults. Synovial sarcoma commonly occurs in the vicinity of the large joints and cranial metastasis is rare. Here, we describe a case with intracranial metastases of a synovial sarcoma. A 41-year-old woman was admitted to our department with sensory aphasia. She had a history of a left inguinal synovial sarcoma and underwent surgery and chemotherapy for primary and metastatic lesions. Head MRI revealed three gadolinium-enhancing lesions in the left frontal, parietal and parietotemporal lobe. Gross total resection was achieved in the left parietotemporal lesion and pathological diagnosis was synovial sarcoma. Two weeks after surgery, she received cyber-knife radiosurgery and her neurological deficit was almost completely resolved. Intracranial metastatic synovial sarcoma is rare. Surgical resection and stereotaxic radiosurgery was very effective in the present case.
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Neoplasias Encefálicas/cirurgia , Radiocirurgia/métodos , Sarcoma Sinovial/cirurgia , Adulto , Neoplasias Encefálicas/secundário , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Sarcoma Sinovial/diagnóstico , Sarcoma Sinovial/patologia , Resultado do TratamentoRESUMO
Despite the current progress of treatment, pediatric-type diffuse glioma is one of the most lethal primary malignant tumors in the central nervous system (CNS). Since pediatric-type CNS tumors are rare disease entities and highly heterogeneous, the diagnosis is challenging. An accurate diagnosis is essential for the choice of optimal treatment, which leads to precision oncology and improvement of the patient's outcome. Genome-wide DNA methylation profiling recently emerged as one of the most important tools for the diagnosis of CNS tumors, and the utility of this novel assay has been reported in both pediatric and adult patients. In the current World Health Organization classification published in 2021, several new entities are recognized in pediatric-type diffuse gliomas, some of which require methylation profiling. In this review, we investigated the utility of genome-wide DNA methylation profiling in pediatric-type diffuse glioma, as well as issues in the clinical application of this assay. Furthermore, the combination of genome-wide DNA methylation profiling and other comprehensive genomic assays, which may improve diagnostic accuracy and detection of the actionable target, will be discussed.
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Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Glioma , Adulto , Humanos , Criança , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Metilação de DNA/genética , Medicina de Precisão , Glioma/diagnóstico , Glioma/genética , Glioma/patologia , Neoplasias do Sistema Nervoso Central/genéticaRESUMO
Background Pilocytic astrocytomas (PAs) are central nervous system tumors with variable prognosis and poorly understood risk factors. Little evidence exists regarding the effect of age on mortality in PA. Therefore, we conducted a thorough characterization of PA in the US. Methods We queried the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2018 to extract age-adjusted incidence rate (AAIR), age-adjusted mortality rate (AAMR), and survival data on PA. The age group comparisons for each measure varied depending on available SEER data. We compared trends in AAIR and AAMR by two age groups (children, 0-19 years; adults, 20 + years) and by sex. The cumulative incidence function and the Fine-Gray competing risk model were applied by 0-19, 20-39, 40-59, and 60 + years of age groups. Results This study included 5211 incident PA and 462 PA-specific deaths between 2000 and 2018. Trends in AAIRs and AAMRs were almost constant between 2000 and 2018. Average AAIRs had a sharp peak in 1-4 years of age groups, whereas AAMRs had a gradual peak in 80-84 years of age groups. Age groups, tumor location, and race/ethnicity were significantly associated with PA-specific death, whereas only age was associated with other cause of deaths. Conclusions Trends in AAIRs and AAMRs were constant regardless of age. PAs in older populations, especially over 60 years old, have higher incidence of death than those in younger populations.
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Astrocitoma , Neoplasias do Sistema Nervoso Central , Criança , Adulto , Humanos , Idoso , Recém-Nascido , Lactente , Pré-Escolar , Adolescente , Adulto Jovem , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Programa de SEER , Astrocitoma/epidemiologia , Incidência , PrognósticoRESUMO
Diffusely infiltrative midline gliomas are known to have a poor prognosis. The standard treatment for typical diffuse midline glioma in the pons is local radiotherapy as surgical resection is inappropriate. This case reports a brainstem glioma in which stereotactic biopsy and foramen magnum decompression were concomitantly performed to confirm the diagnosis and improve symptoms. A 23-year-old woman was referred to our department with a chief complaint of headache for six months. Magnetic resonance imaging (MRI) showed diffuse T2 hyperintense swelling of the brainstem with the pons as the main locus. Enlargement of the lateral ventricles was observed because of cerebrospinal fluid obstruction out of the posterior fossa. This was atypical for a diffuse midline glioma in terms of the longstanding slow progression of symptoms and patient age. Stereotactic biopsy was performed for diagnosis, and foramen magnum decompression (FMD) was concomitantly performed to treat the obstructive hydrocephalus. The histological diagnosis was astrocytoma, IDH-mutant. Post-surgery, the patient's symptoms were relieved, and she was discharged on the fifth day after surgery. The hydrocephalus was resolved, and the patient returned to normal life without any symptoms. The tumor size follow-up with MRI demonstrated no marked change for 12 months. Even though diffuse midline glioma is considered to have a poor prognosis, clinicians should contemplate if it is atypical. In atypical cases like the one described herein, surgical treatment may contribute to pathological diagnosis and symptom improvement.