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Neuro-oncology Dec 2022In the new WHO 2021 Classification of CNS Tumors the chapter "Circumscribed astrocytic gliomas, glioneuronal and neuronal tumors" encompasses several different rare...
In the new WHO 2021 Classification of CNS Tumors the chapter "Circumscribed astrocytic gliomas, glioneuronal and neuronal tumors" encompasses several different rare tumor entities, which occur more frequently in children, adolescents, and young adults. The Task Force has reviewed the evidence of diagnostic and therapeutic interventions, which is low particularly for adult patients, and draw recommendations accordingly. Tumor diagnosis, based on WHO 2021, is primarily performed using conventional histological techniques; however, a molecular workup is important for differential diagnosis, in particular, DNA methylation profiling for the definitive classification of histologically unresolved cases. Molecular factors are increasing of prognostic and predictive importance. MRI finding are non-specific, but for some tumors are characteristic and suggestive. Gross total resection, when feasible, is the most important treatment in terms of prolonging survival and achieving long-term seizure control. Conformal radiotherapy should be considered in grade 3 and incompletely resected grade 2 tumors. In recurrent tumors reoperation and radiotherapy, including stereotactic radiotherapy, can be useful. Targeted therapies may be used in selected patients: BRAF and MEK inhibitors in pilocytic astrocytomas, pleomorphic xanthoastrocytomas, and gangliogliomas when BRAF altered, and mTOR inhibitor everolimus in subependymal giant cells astrocytomas. Sequencing to identify molecular targets is advocated for diagnostic clarification and to direct potential targeted therapies.
Topics: Child; Adolescent; Young Adult; Humans; Glioma; Brain Neoplasms; Proto-Oncogene Proteins B-raf; Astrocytoma; Ganglioglioma
PubMed: 35908833
DOI: 10.1093/neuonc/noac188 -
The Lancet. Oncology Jun 2017The European Association for Neuro-Oncology guideline provides recommendations for the clinical care of adult patients with astrocytic and oligodendroglial gliomas,... (Review)
Review
The European Association for Neuro-Oncology guideline provides recommendations for the clinical care of adult patients with astrocytic and oligodendroglial gliomas, including glioblastomas. The guideline is based on the 2016 WHO classification of tumours of the central nervous system and on scientific developments since the 2014 guideline. The recommendations focus on pathological and radiological diagnostics, and the main treatment modalities of surgery, radiotherapy, and pharmacotherapy. In this guideline we have also integrated the results from contemporary clinical trials that have changed clinical practice. The guideline aims to provide guidance for diagnostic and management decisions, while limiting unnecessary treatments and costs. The recommendations are a resource for professionals involved in the management of patients with glioma, for patients and caregivers, and for health-care providers in Europe. The implementation of this guideline requires multidisciplinary structures of care, and defined processes of diagnosis and treatment.
Topics: Adult; Antineoplastic Agents; Astrocytoma; Brain Neoplasms; Combined Modality Therapy; Humans; Magnetic Resonance Imaging; Molecular Diagnostic Techniques; Neuroimaging; Oligodendroglioma; Positron-Emission Tomography; Radiotherapy
PubMed: 28483413
DOI: 10.1016/S1470-2045(17)30194-8 -
CNS Oncology Jul 2016Anaplastic astrocytoma (AA) is a diffusely infiltrating, malignant, astrocytic, primary brain tumor. AA is currently defined by histology although future classification... (Review)
Review
Anaplastic astrocytoma (AA) is a diffusely infiltrating, malignant, astrocytic, primary brain tumor. AA is currently defined by histology although future classification schemes will include molecular alterations. AA can be separated into subgroups, which share similar molecular profiles, age at diagnosis and median survival, based on 1p/19q co-deletion status and IDH mutation status. AA with co-deletion of chromosomes 1p and 19q and IDH mutation have the best prognosis. AA with IDH mutation and no 1p/19q co-deletion have intermediate prognosis and AA with wild-type IDH have the worst prognosis and share many molecular alterations with glioblastoma. Treatment of noncodeleted AA based on preliminary results from the CATNON clinical trial consists of maximal safe resection followed by radiotherapy with post-radiotherapy temozolomide (TMZ) chemotherapy. The role of concurrent TMZ and whether IDH1 subgroups benefit from TMZ is currently being evaluated in the recently completed randomized, prospective Phase III clinical trial, CATNON.
Topics: Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Chromosome Deletion; Chromosomes, Human, Pair 1; Humans; Isocitrate Dehydrogenase; Mutation
PubMed: 27230974
DOI: 10.2217/cns-2016-0002 -
Acta Neuropathologica Mar 2020
Topics: Astrocytoma; Brain Neoplasms; Humans; Isocitrate Dehydrogenase; Mutation; Neoplasm Grading; Terminology as Topic; World Health Organization
PubMed: 31996992
DOI: 10.1007/s00401-020-02127-9 -
Cells Jun 2022Glioblastoma (GBM, grade IV astrocytoma), the most frequently occurring primary brain tumor, presents unique challenges to therapy due to its location, aggressive...
Glioblastoma (GBM, grade IV astrocytoma), the most frequently occurring primary brain tumor, presents unique challenges to therapy due to its location, aggressive biological behavior, and diffuse infiltrative growth, thus contributing to having disproportionately high morbidity and mortality [...].
Topics: Astrocytoma; Brain Neoplasms; Glioblastoma; Humans; Molecular Biology
PubMed: 35681545
DOI: 10.3390/cells11111850 -
Journal of Ayub Medical College,... 2023Granular cell astrocytoma (GCA) is a rare glial neoplasm composed of abundant granular cytoplasm gives immunoreactivity for GFAP and S100 stains. We report a case of GCA...
Granular cell astrocytoma (GCA) is a rare glial neoplasm composed of abundant granular cytoplasm gives immunoreactivity for GFAP and S100 stains. We report a case of GCA in a 64 years old male presented with history of fits, right sided weakness and loss of consciousness. The microscopy showed sheets of large cells with abundant eosinophilic granular cytoplasm. No high-grade features were seen. Its differential diagnosis includes most of the benign histiocytic conditions. Granular cell astrocytoma has an aggressive clinical course and its survival rate is less than 1 year. That's why early correct diagnosis is very essential.
Topics: Humans; Male; Middle Aged; Coloring Agents; Diagnosis, Differential; Microscopy; Staining and Labeling; Astrocytoma
PubMed: 36849399
DOI: 10.55519/JAMC-01-10493 -
International Journal of Molecular... Nov 2020Astrocytomas and, in particular, their most severe form, glioblastoma, are the most aggressive primary brain tumors and those with the poorest vital prognosis. Standard... (Review)
Review
Astrocytomas and, in particular, their most severe form, glioblastoma, are the most aggressive primary brain tumors and those with the poorest vital prognosis. Standard treatment only slightly improves patient survival. Therefore, new therapies are needed. Very few risk factors have been clearly identified but many epidemiological studies have reported a higher incidence in men than women with a sex ratio of 1:4. Based on these observations, it has been proposed that the neurosteroids and especially the estrogens found in higher concentrations in women's brains could, in part, explain this difference. Estrogens can bind to nuclear or membrane receptors and potentially stimulate many different interconnected signaling pathways. The study of these receptors is even more complex since many isoforms are produced from each estrogen receptor encoding gene through alternative promoter usage or splicing, with each of them potentially having a specific role in the cell. The purpose of this review is to discuss recent data supporting the involvement of steroids during gliomagenesis and to focus on the potential neuroprotective role as well as the mechanisms of action of estrogens in gliomas.
Topics: Animals; Astrocytoma; Disease Progression; Female; Hormones; Humans; Male; Models, Biological; Receptors, Steroid; Sex Characteristics
PubMed: 33266110
DOI: 10.3390/ijms21239114 -
BMJ Case Reports Aug 2016Psychotic symptoms are rarely documented in association with cortex-sparing central nervous system (CNS) lesions limited to the midbrain. We present the case of a... (Review)
Review
Psychotic symptoms are rarely documented in association with cortex-sparing central nervous system (CNS) lesions limited to the midbrain. We present the case of a 15-year-old boy with hereditary and environmental risk factors for psychiatric illness, as well as a history of midbrain pilocytic astrocytoma treated with chemotherapy and focused radiation, who presented with non-epileptic seizures, hyper-religiosity and frank psychosis. The space-occupying midbrain lesion has been radiographically stable while the patient has decompensated psychiatrically. Differential aetiology for the patient's psychiatric decompensation is discussed, including psychosis secondary to a lesion of the midbrain. Literature linking midbrain lesions to psychotic features, such as in peduncular hallucinosis, is briefly reviewed. This case suggests that a midbrain lesion in a susceptible patient may contribute to psychosis.
Topics: Adolescent; Astrocytoma; Brain Stem Neoplasms; Humans; Male; Psychotic Disorders
PubMed: 27511753
DOI: 10.1136/bcr-2016-216165 -
Child's Nervous System : ChNS :... Nov 2016The purpose of this review is to document the various types of astrocytoma that occur in the fetus and neonate, their locations, initial findings, pathology, and... (Review)
Review
INTRODUCTION
The purpose of this review is to document the various types of astrocytoma that occur in the fetus and neonate, their locations, initial findings, pathology, and outcome. Data are presented that show which patients are likely to survive or benefit from treatment compared with those who are unlikely to respond.
MATERIALS AND METHODS
One hundred one fetal and neonatal tumors were collected from the literature for study.
RESULTS
Macrocephaly and an intracranial mass were the most common initial findings. Overall, hydrocephalus and intracranial hemorrhage were next. Glioblastoma (GBM) was the most common neoplasm followed in order by subependymal giant cell astrocytoma (SEGA), low-grade astrocytoma, anaplastic astrocytoma, and desmoplastic infantile astrocytoma (DIA). Tumors were detected most often toward the end of the third trimester of pregnancy.
CONCLUSION
A number of patients were considered inoperable since their tumor occupied much of the intracranial cavity involving large areas of the brain. High-grade astrocytomas were more common than low-grade ones in this review. Fetuses and neonates with astrocytoma have a mixed prognosis ranging from as low as 20 % (GBM) to a high of 90 %. The overall survival was 47/101 or 46 %.
Topics: Astrocytoma; Brain Neoplasms; Female; Fetus; Humans; Infant, Newborn; Pregnancy
PubMed: 27568373
DOI: 10.1007/s00381-016-3215-y -
Neuro-oncology Jun 2022ATRX inactivation occurs with IDH1R132H and p53 mutations in over 80% of Grades II/III astrocytomas. It is believed that ATRX loss contributes to oncogenesis by...
BACKGROUND
ATRX inactivation occurs with IDH1R132H and p53 mutations in over 80% of Grades II/III astrocytomas. It is believed that ATRX loss contributes to oncogenesis by dysregulating epigenetic and telomere mechanisms but effects on anti-glioma immunity have not been explored. This paper examines how ATRX loss contributes to the malignant and immunosuppressive phenotypes of IDH1R132H/p53mut glioma cells and xenografts.
METHODS
Isogenic astrocytoma cells (+/-IDH1R132H/+/-ATRXloss) were established in p53mut astrocytoma cell lines using lentivirus encoding doxycycline-inducible IDH1R132H, ATRX shRNA, or Lenti-CRISPR/Cas9 ATRX. Effects of IDH1R132H+/-ATRXloss on cell migration, growth, DNA repair, and tumorigenicity were evaluated by clonal growth, transwell and scratch assays, MTT, immunofluorence and immunoblotting assays, and xenograft growth. Effects on the expression and function of modulators of the immune microenvironment were quantified by qRT-PCR, immunoblot, T-cell function, macrophage polarization, and flow cytometry assays. Pharmacologic inhibitors were used to examine epigenetic drivers of the immunosuppressive transcriptome of IDH1R132H/p53mut/ATRXloss cells.
RESULTS
Adding ATRX loss to the IDH1R132H/p53mut background promoted astrocytoma cell aggressiveness, induced expression of BET proteins BRD3/4 and an immune-suppressive transcriptome consisting of up-regulated immune checkpoints (e.g., PD-L1, PD-L2) and altered cytokine/chemokine profiles (e.g., IL33, CXCL8, CSF2, IL6, CXCL9). ATRX loss enhanced the capacity of IDH1R132H/p53mut cells to induce T-cell apoptosis, tumorigenic/anti-inflammatory macrophage polarization and Treg infiltration. The transcriptional and biological immune-suppressive responses to ATRX loss were enhanced by temozolomide and radiation and abrogated by pharmacologic BET inhibition.
CONCLUSIONS
ATRX loss activates a BRD-dependent immune-suppressive transcriptome and immune escape mechanism in IDH1R132H/p53mut astrocytoma cells.
Topics: Astrocytoma; Brain Neoplasms; Carcinogenesis; Glioma; Humans; Isocitrate Dehydrogenase; Mutation; Tumor Microenvironment; X-linked Nuclear Protein
PubMed: 34951647
DOI: 10.1093/neuonc/noab292