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Journal of Neuro-oncology May 2023Astrocytomas and oligodendrogliomas are mainly diffuse primary brain tumors harboring a diagnostic and prognostically favorable isocitrate dehydrogenase mutation. They... (Review)
Review
PURPOSE
Astrocytomas and oligodendrogliomas are mainly diffuse primary brain tumors harboring a diagnostic and prognostically favorable isocitrate dehydrogenase mutation. They are still incurable besides growing molecular knowledge and therapy options. Circumscribed astrocytomas are also discussed here, although they represent a separate entity despite similarities in the nomenclature.
METHODS
We reviewed clinical trials, preclinical approaches as well as guideline recommendations form the major scientific Neuro-Oncology organizations for astrocytomas and oligodendrogliomas according to PRISMA guidelines.
RESULTS
After histopathological diagnosis and eventually a maximal safe resection, patients with good prognostic factors may be followed by magnetic resonance imaging (MRI). If further treatment is necessary, either after diagnosis or at progression, diffuse astrocytomas and oligodendrogliomas are mainly treated with combined radiochemotherapy or maximal safe resection followed by combined radiochemotherapy according to current guidelines based on randomized trials. Circumscribed gliomas like pilocytic astrocytomas, CNS WHO grade 1, or pleomorphic xanthoastrocytomas, CNS WHO grade 2, are often treated with surgery alone. Current approaches for therapy optimization include decision of the best chemotherapy regimen. The IDH mutation presents a rational target for small molecule inhibition and immune therapy in diffuse astrocytomas and oligodendrogliomas, while the BRAF pathway is frequently mutated and treatable in circumscribed gliomas.
CONCLUSION
Despite establishment of standard treatment approaches for gliomas that include resection, radio- and chemotherapy, there is a lack of effective treatments for progressive disease. Immune- and targeted therapies are currently investigated.
Topics: Humans; Oligodendroglioma; Astrocytoma; Glioma; Magnetic Resonance Imaging; Mutation
PubMed: 36566461
DOI: 10.1007/s11060-022-04216-z -
Graefe's Archive For Clinical and... Dec 2023Acute acquired comitant esotropia (AACE) is an uncommon subtype of esotropia characterized by sudden and usually late onset of a relatively large angle of comitant... (Review)
Review
BACKGROUND
Acute acquired comitant esotropia (AACE) is an uncommon subtype of esotropia characterized by sudden and usually late onset of a relatively large angle of comitant esotropia with diplopia in older children and adults.
METHODS
A literature survey regarding neurological pathologies in AACE was conducted using databases (PubMed, MEDLINE, EMBASE, BioMed Central, the Cochrane Library, and Web of Science) in order to collect data for a narrative review of published reports and available literature.
RESULTS
The results of the literature survey were analyzed to provide an overview of the current knowledge of neurological pathologies in AACE. The results revealed that AACE with unclear etiologies can occur in many cases in both children and adults. Functional etiological factors for AACE were found to be due to many reasons, such as functional accommodative spasm, the excessive near work use of mobile phones/smartphones, and other digital screens. In addition, AACE was found to be associated with neurological disorders, such as astrocytoma of the corpus callosum, medulloblastoma, tumors of the brain stem or cerebellum, Arnold-Chiari malformation, cerebellar astrocytoma, Chiari 1 malformation, idiopathic intracranial hypertension, pontine glioma, cerebellar ataxia, thalamic lesions, myasthenia gravis, certain types of seizures, and hydrocephalus.
CONCLUSIONS
Previously reported cases of AACE with unknown etiologies have been reported in both children and adults. However, AACE can be associated with neurological disorders that require neuroimaging probes. The author recommends that clinicians should perform comprehensive neurological assessments to rule out neurological pathologies in AACE, especially in the presence of nystagmus or abnormal ocular and neurological indications (e.g., headache, cerebellar imbalance, weakness, nystagmus, papilloedema, clumsiness, and poor motor coordination).
Topics: Child; Adult; Humans; Esotropia; Arnold-Chiari Malformation; Astrocytoma; Headache; Eye; Acute Disease; Retrospective Studies
PubMed: 37145335
DOI: 10.1007/s00417-023-06092-3 -
Proceedings of the National Academy of... May 2023In 2021, the World Health Organization reclassified glioblastoma, the most common form of adult brain cancer, into isocitrate dehydrogenase (IDH)-wild-type glioblastomas...
In 2021, the World Health Organization reclassified glioblastoma, the most common form of adult brain cancer, into isocitrate dehydrogenase (IDH)-wild-type glioblastomas and grade IV IDH mutant (G4 IDHm) astrocytomas. For both tumor types, intratumoral heterogeneity is a key contributor to therapeutic failure. To better define this heterogeneity, genome-wide chromatin accessibility and transcription profiles of clinical samples of glioblastomas and G4 IDHm astrocytomas were analyzed at single-cell resolution. These profiles afforded resolution of intratumoral genetic heterogeneity, including delineation of cell-to-cell variations in distinct cell states, focal gene amplifications, as well as extrachromosomal circular DNAs. Despite differences in IDH mutation status and significant intratumoral heterogeneity, the profiled tumor cells shared a common chromatin structure defined by open regions enriched for nuclear factor 1 transcription factors (NFIA and NFIB). Silencing of or suppressed in vitro and in vivo growths of patient-derived glioblastomas and G4 IDHm astrocytoma models. These findings suggest that despite distinct genotypes and cell states, glioblastoma/G4 astrocytoma cells share dependency on core transcriptional programs, yielding an attractive platform for addressing therapeutic challenges associated with intratumoral heterogeneity.
Topics: Adult; Humans; Glioblastoma; Chromatin; Transcriptome; Astrocytoma; Brain Neoplasms; Mutation; Isocitrate Dehydrogenase
PubMed: 37155843
DOI: 10.1073/pnas.2210991120 -
CNS Oncology Nov 2019Pleomorphic xanthoastrocytoma (PXA) is a rare primary CNS tumor. Recent advances in the molecular characterization are helping to define subtypes of tumor. The discovery... (Review)
Review
Pleomorphic xanthoastrocytoma (PXA) is a rare primary CNS tumor. Recent advances in the molecular characterization are helping to define subtypes of tumor. The discovery of mutations within a substantial percentage of PXA fosters a clearer understanding of the pathophysiology of these tumors with clear prognostic and therapeutic implications. These findings are expected to provide insight into the spectrum of clinical behavior observed in PXA, ranging from cure with surgery to diffuse dissemination throughout the neuraxis. This review details the clinical presentation including radiographic appearance of PXA. Pathology, including molecular pathology is discussed. Therapeutic management including surgical resection, radiotherapy and systemic therapies are reviewed.
Topics: Astrocytoma; Brain Neoplasms; Combined Modality Therapy; Humans; Prognosis
PubMed: 31535562
DOI: 10.2217/cns-2019-0009 -
Neuro-oncology Oct 2022The brain tumor microenvironment contains numerous distinct types of nonneoplastic cells, which each serve a diverse set of roles relevant to the formation, maintenance,... (Review)
Review
The brain tumor microenvironment contains numerous distinct types of nonneoplastic cells, which each serve a diverse set of roles relevant to the formation, maintenance, and progression of these central nervous system cancers. While varying in frequencies, monocytes (macrophages, microglia, and myeloid-derived suppressor cells), dendritic cells, natural killer cells, and T lymphocytes represent the most common nonneoplastic cellular constituents in low- and high-grade gliomas (astrocytomas). Although T cells are conventionally thought to target and eliminate neoplastic cells, T cells also exist in other states, characterized by tolerance, ignorance, anergy, and exhaustion. In addition, T cells can function as drivers of brain cancer growth, especially in low-grade gliomas. Since T cells originate in the blood and bone marrow sinuses, their capacity to function as both positive and negative regulators of glioma growth has ignited renewed interest in their deployment as immunotherapeutic agents. In this review, we discuss the roles of T cells in low- and high-grade glioma formation and progression, as well as the potential uses of modified T lymphocytes for brain cancer therapeutics.
Topics: Astrocytoma; Brain Neoplasms; Glioma; Humans; Microglia; T-Lymphocytes; Tumor Microenvironment
PubMed: 35325210
DOI: 10.1093/neuonc/noac055 -
Pathologica Dec 2022The WHO 2021 classification of central nervous system cancers distinguishes diffuse gliomas that arise in adults (referred to as the "adult type") and those that arise... (Review)
Review
The WHO 2021 classification of central nervous system cancers distinguishes diffuse gliomas that arise in adults (referred to as the "adult type") and those that arise in children (defined as "paediatric") based on clinical and molecular characteristics."). However, paediatric-type gliomas may occasionally be present in younger adults and occasionally adult-type gliomas may occur in children. Diffuse low-grade paediatric glioma includes diffuse astrocytoma altered by MYB or MYBL1, low-grade polymorphic juvenile neuroepithelial tumour, angiocentric glioma, and diffuse low-grade glioma with an altered MAPK pathway. Here, we examine these newly recognised entities according to WHO diagnostic criteria and propose an integrated diagnostic approach that can be used to separate these clinically and biologically distinct tumor groups.
Topics: Adult; Child; Humans; Brain Neoplasms; Glioma
PubMed: 36534420
DOI: 10.32074/1591-951X-828 -
International Journal of Molecular... Oct 2022Central nervous system tumors are the most common solid neoplasia during childhood and represent one of the leading causes of cancer-related mortality. Tumors arising...
Central nervous system tumors are the most common solid neoplasia during childhood and represent one of the leading causes of cancer-related mortality. Tumors arising from astrocytic cells (astrocytomas) are the most frequently diagnosed, and according to their histological and pathological characteristics, they are classified into four categories. However, an additional layer of molecular classification considering the DNA sequence of the tumorigenesis-associated genes and has recently been incorporated into the classification guidelines. Although mutations in are found exclusively in a subtype of grade IV pediatric astrocytoma, mutations in genes are very rare in children under 14 years of age. The transcriptomic profiles of astrocytoma in adults and children have been extensively studied. However, there is scarce information on these profiles in pediatric populations considering the status of tumorigenesis-associated genes. Therefore, here we report the transcriptomic landscape of the four grades of pediatric astrocytoma by RNA sequencing. We found several well-documented biological functions associated with the misregulated genes in the four grades of astrocytoma, as well as additional biological pathways. Among the four grades of astrocytoma, we found shared misregulated genes that could have implications in tumorigenesis. Finally, we identified a transcriptional signature for almost all grades of astrocytoma that could be used as a transcription-based identification method.
Topics: Adult; Child; Humans; Transcriptome; Brain Neoplasms; Astrocytoma; Mutation; Carcinogenesis
PubMed: 36293551
DOI: 10.3390/ijms232012696 -
Acta Neuropathologica Dec 2023Diffuse midline gliomas (DMG) H3 K27-altered are incurable grade 4 gliomas and represent a major challenge in neuro-oncology. This tumour type is now classified in four...
Diffuse midline gliomas (DMG) H3 K27-altered are incurable grade 4 gliomas and represent a major challenge in neuro-oncology. This tumour type is now classified in four subtypes by the 2021 edition of the WHO Classification of the Central Nervous System (CNS) tumours. However, the H3.3-K27M subgroup still appears clinically and molecularly heterogeneous. Recent publications reported that rare patients presenting a co-occurrence of H3.3K27M with BRAF or FGFR1 alterations tended to have a better prognosis. To better study the role of these co-driver alterations, we assembled a large paediatric and adult cohort of 29 tumours H3K27-altered with co-occurring activating mutation in BRAF or FGFR1 as well as 31 previous cases from the literature. We performed a comprehensive histological, radiological, genomic, transcriptomic and DNA methylation analysis. Interestingly, unsupervised t-distributed Stochastic Neighbour Embedding (tSNE) analysis of DNA methylation profiles regrouped BRAF and all but one FGFR1 DMG in a unique methylation cluster, distinct from the other DMG subgroups and also from ganglioglioma (GG) or high-grade astrocytoma with piloid features (HGAP). This new DMG subtype harbours atypical radiological and histopathological profiles with calcification and/or a solid tumour component both for BRAF and FGFR1 cases. The analyses of a H3.3-K27M BRAF tumour at diagnosis and corresponding in vitro cellular model showed that mutation in H3-3A was the first event in the oncogenesis. Contrary to other DMG, these tumours occur more frequently in the thalamus (70% for BRAF and 58% for FGFR1) and patients have a longer overall survival with a median above three years. In conclusion, DMG, H3 K27 and BRAF/FGFR1 co-altered represent a new subtype of DMG with distinct genotype/phenotype characteristics, which deserve further attention with respect to trial interpretation and patient management.
Topics: Adult; Humans; Child; Histones; Brain Neoplasms; Proto-Oncogene Proteins B-raf; Glioma; Astrocytoma; Central Nervous System Neoplasms; Mutation; Receptor, Fibroblast Growth Factor, Type 1
PubMed: 38066305
DOI: 10.1007/s00401-023-02651-4 -
Pathology Oncology Research : POR 2022CXCL13 may act as a mediator of tumor-associated macrophage immunity during malignant progression. The present study clarifies the clinicopathological significances of...
CXCL13 may act as a mediator of tumor-associated macrophage immunity during malignant progression. The present study clarifies the clinicopathological significances of CXCL13 and its corresponding trend with M2 macrophage in human astrocytoma. The predictive potential of CXCL13 was performed using 695 glioma samples derived from TCGA lower-grade glioma and glioblastoma (GBMLGG) dataset. CXCL13 and M2 biomarker CD163 were observed by immunohistochemistry in 112 astrocytoma tissues. An in-depth analysis showed that expression was related to the poor prognosis of glioma patients ( = 0.0002) derive from TCGA analysis. High level of CXCL13 was detected in 43 (38.39%) astrocytoma and CXCL13/CD163 coexpression was expressed in 33 (29.46%) cases. The immunoreactivities of CXCL13 and CXCL13/CD163 were found in the malignant lesions, which were both significantly associated with grade, patient survival, and IDH1 mutation. Single CXCL13 and CXCL13/CD163 coexpression predicted poor overall survival in astrocytoma ( = 0.0039 and = 0.0002, respectively). Multivariate Cox regression analyses manifested CXCL13/CD163 phenotype was a significant independent prognostic indicator of patient outcome in astrocytoma (CXCL13, = 0.0642; CXCL13/CD163, = 0.0368). CXCL13 overexpression is strongly linked to CD163+ M2 infiltration in malignant astrocytoma. CXCL13/CD163 coexpression would imply M2c-related aggressive characteristics existing in astrocytoma progression could also provide predictive trends of patient outcomes.
Topics: Astrocytoma; Chemokine CXCL13; Glioblastoma; Glioma; Humans; Prognosis; Tumor Microenvironment
PubMed: 35570844
DOI: 10.3389/pore.2022.1610230 -
Neuro-oncology Oct 2021Pediatric low-grade gliomas (pLGGs) are the most common brain tumor in children and are associated with lifelong clinical morbidity. Relative to their high-grade adult... (Review)
Review
Pediatric low-grade gliomas (pLGGs) are the most common brain tumor in children and are associated with lifelong clinical morbidity. Relative to their high-grade adult counterparts or other malignant childhood brain tumors, there is a paucity of authenticated preclinical models for these pLGGs and an incomplete understanding of their molecular and cellular pathogenesis. While large-scale genomic profiling efforts have identified the majority of pathogenic driver mutations, which converge on the MAPK/ERK signaling pathway, it is now appreciated that these events may not be sufficient by themselves for gliomagenesis and clinical progression. In light of the recent World Health Organization reclassification of pLGGs, and pilocytic astrocytoma (PA), in particular, we review our current understanding of these pediatric brain tumors, provide a conceptual framework for future mechanistic studies, and outline the challenges and pressing needs for the pLGG clinical and research communities.
Topics: Astrocytoma; Brain Neoplasms; Child; Glioma; Humans; MAP Kinase Signaling System; Signal Transduction
PubMed: 34131743
DOI: 10.1093/neuonc/noab138