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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 -
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 -
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 -
Frontiers in Immunology 2020Glioblastoma (GBM) is the most malignant form of astrocytoma with short survival and a high recurrence rate and remains a global problem. Currently, surgery,... (Review)
Review
Glioblastoma (GBM) is the most malignant form of astrocytoma with short survival and a high recurrence rate and remains a global problem. Currently, surgery, chemotherapy, radiotherapy, and other comprehensive treatments are the main treatment modalities, but patients still have a poor prognosis mainly due to the infiltrative growth of GBM and the protective effect of the blood-brain barrier on tumor cells. Therefore, immunotherapy is expected to be a good option for GBM. In the immune system, different cells play varying roles in the treatment of GBM, so understanding the roles played by various immune cells in treating GBM and considering how to combine these effects to maximize the efficacy of these cells is important for the selection of comprehensive and optimal treatment plans and improving GBM prognosis. Therefore, this study reviews the latest research progress on the role of various types of immune cells in the treatment of GBM.
Topics: Blood-Brain Barrier; Brain Neoplasms; Glioblastoma; Humans; Immunotherapy, Adoptive
PubMed: 33193310
DOI: 10.3389/fimmu.2020.544563 -
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 -
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 -
Biomaterials Aug 2021Cells tend to soften during cancer progression, suggesting that mechanical phenotyping could be used as a diagnostic or prognostic method. Here we investigate the cell...
Cells tend to soften during cancer progression, suggesting that mechanical phenotyping could be used as a diagnostic or prognostic method. Here we investigate the cell mechanics of gliomas, brain tumors that originate from glial cells or glial progenitors. Using two microrheology techniques, a single-cell parallel plates rheometer to probe whole-cell mechanics and optical tweezers to probe intracellular rheology, we show that cell mechanics discriminates human glioma cells of different grades. When probed globally, grade IV glioblastoma cells are softer than grade III astrocytoma cells, while they are surprisingly stiffer at the intracellular level. We explain this difference between global and local intracellular behaviours by changes in the composition and spatial organization of the cytoskeleton, and by changes in nuclear mechanics. Our study highlights the need to combine rheology techniques for potential diagnostic or prognostic methods based on cancer cell mechanophenotyping.
Topics: Brain Neoplasms; Cytoskeleton; Glioblastoma; Glioma; Humans; Optical Tweezers; Rheology
PubMed: 34102526
DOI: 10.1016/j.biomaterials.2021.120903 -
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