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Neuropathology and Applied Neurobiology Dec 2022Anaplastic ganglioglioma is a rare tumour, and diagnosis has been based on histological criteria. The 5th edition of the World Health Organization Classification of...
AIMS
Anaplastic ganglioglioma is a rare tumour, and diagnosis has been based on histological criteria. The 5th edition of the World Health Organization Classification of Tumours of the Central Nervous System (CNS WHO) does not list anaplastic ganglioglioma as a distinct diagnosis due to lack of molecular data in previous publications. We retrospectively compiled a cohort of 54 histologically diagnosed anaplastic gangliogliomas to explore whether the molecular profiles of these tumours represent a separate type or resolve into other entities.
METHODS
Samples were subjected to histological review, desoxyribonucleic acid (DNA) methylation profiling and next-generation sequencing. Morphological and molecular data were summarised to an integrated diagnosis.
RESULTS
The majority of tumours designated as anaplastic gangliogliomas resolved into other CNS WHO diagnoses, most commonly pleomorphic xanthoastrocytoma (16/54), glioblastoma, isocitrate dehydrogenase protein (IDH) wild type and diffuse paediatric-type high-grade glioma, H3 wild type and IDH wild type (11 and 2/54), followed by low-grade glial or glioneuronal tumours including pilocytic astrocytoma, dysembryoplastic neuroepithelial tumour and diffuse leptomeningeal glioneuronal tumour (5/54), IDH mutant astrocytoma (4/54) and others (6/54). A subset of tumours (10/54) was not assignable to a CNS WHO diagnosis, and common molecular profiles pointing to a separate entity were not evident.
CONCLUSIONS
In summary, we show that tumours histologically diagnosed as anaplastic ganglioglioma comprise a wide spectrum of CNS WHO tumour types with different prognostic and therapeutic implications. We therefore suggest assigning this designation with caution and recommend comprehensive molecular workup.
Topics: Child; Humans; Ganglioglioma; Retrospective Studies; Glioma; Astrocytoma; Brain Neoplasms; Central Nervous System Neoplasms; Isocitrate Dehydrogenase
PubMed: 35977725
DOI: 10.1111/nan.12847 -
Journal of Neurochemistry Jan 2019Astrocytic gliomas are the most common and lethal form of intracranial tumors. These tumors are characterized by a significant heterogeneity in terms of... (Review)
Review
Astrocytic gliomas are the most common and lethal form of intracranial tumors. These tumors are characterized by a significant heterogeneity in terms of cytopathological, transcriptional, and (epi)genomic features. This heterogeneity has made these cancers one of the most challenging types of cancers to study and treat. To uncover these complexities and to have better understanding of the disease initiation and progression, identification, and characterization of underlying cellular and molecular pathways related to (epi)genetics of astrocytic gliomas is crucial. Here, we discuss and summarize molecular and (epi)genetic mechanisms that provide clues as to the pathogenesis of astrocytic gliomas.
Topics: Animals; Astrocytoma; Brain Neoplasms; Epigenesis, Genetic; Humans
PubMed: 30347482
DOI: 10.1111/jnc.14616 -
Radiology Case Reports Sep 2021Anaplastic astrocytoma, a diffusely infiltrating, malignant, astrocytic, primary brain tumor, is most commonly observed between 30 and 50 years of age. Anaplastic...
Anaplastic astrocytoma, a diffusely infiltrating, malignant, astrocytic, primary brain tumor, is most commonly observed between 30 and 50 years of age. Anaplastic astrocytomas are now classified as WHO grade III lesions, with imaging characteristics and prognosis between diffuse low-grade astrocytomas (WHO grade II) and glioblastomas (WHO IV). Anaplastic astrocytoma can appear mostly in the cerebrum followed by cerebellum. However, it is rarely observed in the fourth ventricle. In this article, we aimed to describe an uncommon case of a pediatric, fourth-ventricular, anaplastic astrocytoma. A 9-year-old male who underwent MRI brain then adopted gross-total tumor eradication. The final histopathology findings were consistent with an anaplastic astrocytoma.
PubMed: 34345330
DOI: 10.1016/j.radcr.2021.06.050 -
Neuro-oncology Apr 2023
Topics: Humans; Senotherapeutics; Astrocytoma; Brain
PubMed: 36702510
DOI: 10.1093/neuonc/noad016 -
Cancer Medicine Sep 2023The latest fifth edition of the World Health Organization (WHO) classification of the central nervous system (CNS) tumors (WHO CNS 5 classification) released in 2021...
BACKGROUND
The latest fifth edition of the World Health Organization (WHO) classification of the central nervous system (CNS) tumors (WHO CNS 5 classification) released in 2021 defined astrocytoma, IDH-mutant, Grade 4. However, the understanding of this subtype is still limited. We conducted this study to describe the features of astrocytoma, IDH-mutant, Grade 4 and explored the similarities and differences between histological and molecular subtypes.
METHODS
Patients who underwent surgery from January 2011 to January 2022, classified as astrocytoma, IDH-mutant, Grade 4 were included in this study. Clinical, radiological, histopathological, molecular pathological, and survival data were collected for analysis.
RESULTS
Altogether 33 patients with astrocytoma, IDH-mutant, Grade 4 were selected, including 20 with histological and 13 with molecular WHO Grade 4 astrocytoma. Tumor enhancement, intratumoral-necrosis like presentation, larger peritumoral edema, and more explicit tumor margins were frequently observed in histological WHO Grade 4 astrocytoma. Additionally, molecular WHO Grade 4 astrocytoma showed a tendency for relatively longer overall survival, while a statistical significance was not reached (47 vs. 25 months, p = 0.22). TP53, CDK6, and PIK3CA alteration was commonly observed, while PIK3R1 (p = 0.033), Notch1 (p = 0.027), and Mycn (p = 0.027) alterations may affect the overall survival of molecular WHO Grade 4 astrocytomas.
CONCLUSIONS
Our study scrutinized IDH-mutant, Grade 4 astrocytoma. Therefore, further classification should be considered as the prognosis varied between histological and molecular WHO Grade 4 astrocytomas. Notably, therapies aiming at PIK3R1, Notch 1, and Mycn may be beneficial.
Topics: Humans; N-Myc Proto-Oncogene Protein; Brain Neoplasms; Isocitrate Dehydrogenase; Mutation; Astrocytoma; Central Nervous System Neoplasms; Glioblastoma; World Health Organization
PubMed: 37667984
DOI: 10.1002/cam4.6476 -
Veterinary Pathology Sep 2022This case series describes the clinical and pathological findings of intracranial neoplasms in cattle, a rare entity. Data and archived tissues from 24 intracranial...
This case series describes the clinical and pathological findings of intracranial neoplasms in cattle, a rare entity. Data and archived tissues from 24 intracranial tumors were reviewed and investigated by immunohistochemistry for S100, glial fibrillary acidic protein, synaptophysin, pancytokeratin, vimentin, neuron-specific enolase, oligodendrocyte transcription factor 2, and isocitrate dehydrogenase 1. Ages of affected cattle ranged from 6 months to 14 years (5.7 ± 3.6 years; mean ± SD). Predominant clinical signs were altered mental state, central vestibular dysfunction, and cerebellar incoordination. Twelve gliomas, all high grade, were the most common tumors observed: oligodendrogliomas (n = 6), astrocytomas (n = 4), and undefined gliomas (n = 2). The oligodendrogliomas were located in the brainstem and extended into the ventricles, whereas all astrocytomas were located in the forebrain. Isocitrate dehydrogenase 1 gene mutation as described in humans was not detected. The 5 meningiomas exhibited microcystic, chordoid, atypical, papillary, and anaplastic subtypes. Metastatic carcinomas (n = 4) were the only secondary tumor type present, and these were located at the level of the medulla with infiltration of cranial nerves and in one case leptomeningeal carcinomatosis. In addition, 2 medulloblastomas and 1 choroid plexus carcinoma were diagnosed. Immunohistochemistry for vimentin and pancytokeratin was particularly useful to distinguish meningiomas and choroid plexus carcinoma (positive for vimentin only) from mestastatic carcinomas (positive for cytokeratin only) as all showed a papillary growth pattern. Overall, the morphological features were comparable with other species and the human and canine classifications could be applied.
Topics: Animals; Astrocytoma; Brain Neoplasms; Carcinoma; Cattle; Cattle Diseases; Choroid Plexus Neoplasms; Glioma; Isocitrate Dehydrogenase; Meningeal Neoplasms; Meningioma; Oligodendroglioma; Retrospective Studies; Vimentin
PubMed: 35638647
DOI: 10.1177/03009858221100433 -
The Neuroradiology Journal Oct 2021To characterise peritumoral zones in glioblastoma and anaplastic astrocytoma evaluating T2 values using T2 mapping sequences.
PURPOSE
To characterise peritumoral zones in glioblastoma and anaplastic astrocytoma evaluating T2 values using T2 mapping sequences.
MATERIALS AND METHODS
In this study, 41 patients with histopathologically confirmed World Health Organization high grade gliomas and preoperative magnetic resonance imaging examinations were retrospectively identified and enrolled. High grade gliomas were differentiated: (a) by grade, glioblastoma versus anaplastic astrocytoma; and (b) by isocitrate dehydrogenase mutational state, mutated versus wildtype. T2 map relaxation times were assessed from the tumour centre to peritumoral zones by means of a region of interest and calculated pixelwise by using a fit model.
RESULTS
Significant differences between T2 values evaluated from the tumour centre to the peritumoral zone were found between glioblastoma and anaplastic astrocytoma, showing a higher decrease in signal intensity (T2 value) from tumour centre to periphery for glioblastoma (0.0049 - fit-model: glioblastoma -25.02± 19.89 (-54-10); anaplastic astrocytoma -5.57±22.94 (-51-47)). Similar results were found when the cohort was subdivided by their isocitrate dehydrogenase profile, showing an increased drawdown from tumour centre to periphery for wildtype in comparison to mutated isocitrate dehydrogenase ( = 0.0430 - fit model: isocitrate dehydrogenase wildtype -10.35±16.20 (-51) - 0; isocitrate dehydrogenase mutated 12.14±21.24 (-15-47)). A strong statistical proof for both subgroup analyses ( = 0.9987 - glioblastoma 0.93±0.08; anaplastic astrocytoma 0.94±0.15) was found.
CONCLUSION
Peritumoral T2 mapping relaxation time tissue behaviour of glioblastoma differs from anaplastic astrocytoma. Significant differences in T2 values, using T2 mapping relaxation time, were found between glioblastoma and anaplastic astrocytoma, capturing the tumour centre to the peritumoral zone. A similar curve progression from tumour centre to peritumoral zone was found for isocitrate dehydrogenase wildtype high grade gliomas in comparison to isocitrate dehydrogenase mutated high grade gliomas. This finding is in accordance with the biologically more aggressive behaviour of isocitrate dehydrogenase wildtype in comparison to isocitrate dehydrogenase mutated high grade gliomas. These results emphasize the potential of mapping techniques to reflect the tissue composition of high grade gliomas.
Topics: Astrocytoma; Brain Neoplasms; Glioblastoma; Humans; Isocitrate Dehydrogenase; Magnetic Resonance Imaging; Mutation; Retrospective Studies
PubMed: 33573473
DOI: 10.1177/1971400921989325 -
Neurobiology of Disease Jan 2016Glioblastoma (GBM, Grade IV astrocytoma) is the most common and most aggressive of the primary malignant brain tumors in adults. Hypoxia is a distinct feature in GBM and... (Review)
Review
Glioblastoma (GBM, Grade IV astrocytoma) is the most common and most aggressive of the primary malignant brain tumors in adults. Hypoxia is a distinct feature in GBM and plays a significant role in tumor progression, resistance to treatment and poor outcomes. This review considers the effects of hypoxia on astrocytic tumors and the mechanisms that contribute to tumor progression and therapeutic resistance, with a focus on the vascular changes, chemotaxic signaling pathways and metabolic alterations involved.
Topics: Animals; Astrocytoma; Brain Neoplasms; Humans; Hypoxia
PubMed: 26094595
DOI: 10.1016/j.nbd.2015.06.007 -
BMC Medical Imaging May 2022The accurate grading of IDH-mutant astrocytoma is essential to make therapeutic strategies and assess the prognosis of patients. The purpose of this study was to...
BACKGROUND
The accurate grading of IDH-mutant astrocytoma is essential to make therapeutic strategies and assess the prognosis of patients. The purpose of this study was to investigate the usefulness of DWI, SWI and DSC-PWI in grading IDH-mutant astrocytoma.
METHODS
One hundred and seven patients with IDH-mutant astrocytoma who underwent DWI, SWI and DSC-PWI were retrospectively reviewed. Minimum apparent diffusion coefficient (ADC), intratumoral susceptibility signal intensity(ITSS) and maximum relative cerebral blood volume (rCBV) values were assessed. ADC, ITSS and rCBV values were compared between grade 2 vs. grade 3, grade 3 vs. grade 4 and grade 2 + 3 vs. grade 4 tumors. Logistic regression, tenfold cross-validation,and receiver operating characteristic (ROC) curve analyses were used to assess their diagnostic performances.
RESULTS
Grade 4 IDH-mutant astrocytomas showed significantly lower ADC and higher rCBV as compared to grade 3 tumors (adjusted P < 0.001). IDH-mutant grade 3 astrocytomas showed significantly lower ITSS levels as compared with grade 4 tumors (adjusted P < 0.001). ITSS levels between IDH-mutant grade 2 and grade 3 astrocytomas were significantly different (adjusted P = 0.002). Combined the ADC, ITSS and rCBV resulted in the highest AUC for differentiation grade 2 and grade 3 tumors from grade 4 tumors.
CONCLUSION
ADC rCBV and ITSS can be used for grading the IDH-mutant astrocytomas. The combination of ADC ITSS and rCBV could improve the diagnostic performance in grading of IDH-mutant astrocytoma.
Topics: Astrocytoma; Brain Neoplasms; Glioblastoma; Humans; Magnetic Resonance Imaging; Perfusion; Retrospective Studies
PubMed: 35644621
DOI: 10.1186/s12880-022-00832-3 -
Clinical and Translational Medicine Feb 2024Paediatric and adult astrocytomas are notably different, where clinical treatments used for adults are not as effective on children with the same form of cancer and... (Review)
Review
Paediatric and adult astrocytomas are notably different, where clinical treatments used for adults are not as effective on children with the same form of cancer and these treatments lead to adverse long-term health concerns. Integrative omics-based studies have shown the pathology and fundamental molecular characteristics differ significantly and cannot be extrapolated from the more widely studied adult disease. Recent clinical advances in our understanding of paediatric astrocytomas, with the aid of next-generation sequencing and epigenome-wide profiling, have led to the identification of key canonical mutations that vary based on the tumour location and age of onset. These driver mutations, in particular the identification of the recurrent histone H3 mutations in high-grade tumours, have confirmed the important role epigenetic dysregulations play in cancer progression. This review summarises the current updates of the classification, epidemiology, pathogenesis and clinical management of paediatric astrocytoma based on their grades and the ongoing clinical trials. It also provides novel insights on genetic and epigenetic alterations as diagnostic biomarkers, highlighting the potential of targeting these pathways as therapeutics for this devastating childhood cancer.
Topics: Adult; Humans; Child; Brain Neoplasms; Astrocytoma; Histones; Epigenesis, Genetic; Epigenomics
PubMed: 38299304
DOI: 10.1002/ctm2.1560