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Neuropathology and Applied Neurobiology Aug 2022Astroblastomas are neuroepithelial tumours defined by the presence of MN1 rearrangement and are typically located in the cerebral hemispheres. Rare cases of...
Astroblastomas are neuroepithelial tumours defined by the presence of MN1 rearrangement and are typically located in the cerebral hemispheres. Rare cases of astroblastoma-like tumours carrying an EWSR1-BEND2 fusion have been recently described in the brain stem and spinal cord. We report a paediatric case of neuroepithelial astroblastoma-like tumour occurring in the spine and carrying a novel MAMLD1-BEND2 fusion. We believe that our case aligns with the rare astroblastoma-like tumours with EWSR1-BEND2 fusion, in terms of non-hemispheric location, pathology, methylation profile and activation of BEND2 transcription. Whether they may represent a distinct entity or a variant of MN1-altered astroblastoma is not clear.
Topics: Brain Neoplasms; Child; Chromosome Aberrations; DNA-Binding Proteins; Humans; Neoplasms, Neuroepithelial; Nuclear Proteins; Spinal Cord Neoplasms; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins
PubMed: 35301744
DOI: 10.1111/nan.12814 -
Surgical Neurology International 2016Astroblastoma is a rare neuroepithelial tumor that often originates in the cerebral hemisphere of children and young adults. Diagnosis of this obscure neoplasm can be...
BACKGROUND
Astroblastoma is a rare neuroepithelial tumor that often originates in the cerebral hemisphere of children and young adults. Diagnosis of this obscure neoplasm can be difficult because these tumors are so infrequently encountered and share common radiological and neuropathological features of other glial neoplasms. As such, it should be included in the differential diagnosis of astrocytoma and ependymoma if the clinical and radiographic features suggest it. Standardized treatment of astroblastomas remains under dispute because of the lack of knowledge regarding the tumor and a paucity of studies in the literature.
CASE DESCRIPTION
We present a case of a low-grade astroblastoma diagnosed in a 30-year-old female with seizures, headache, and vision changes. She underwent gross total resection and, without evidence of high-grade features, adjuvant therapy was not planned postoperatively. Post-operative surveillance suggested early recurrence, warranting referral to radiation therapy. Patient ended up expiring despite adjuvant therapy secondary to extensive recurrence and tumor metastasis.
CONCLUSIONS
Astroblastoma must be considered in the differential of supratentorial tumors in children and young adults. Treatment of such, as suggested by most recent literature, includes gross total resection and adjuvant radiotherapy for lesions exhibiting high-grade features.
PubMed: 28144474
DOI: 10.4103/2152-7806.195583 -
Brain Pathology (Zurich, Switzerland) Sep 2023Recent epigenomic analyses have revealed the existence of a new DNA methylation class (MC) of infant-type hemispheric glioma (IHG). Like desmoplastic infantile...
A comprehensive analysis of infantile central nervous system tumors to improve distinctive criteria for infant-type hemispheric glioma versus desmoplastic infantile ganglioglioma/astrocytoma.
Recent epigenomic analyses have revealed the existence of a new DNA methylation class (MC) of infant-type hemispheric glioma (IHG). Like desmoplastic infantile ganglioglioma/astrocytoma (DIG/DIA), these tumors mainly affect infants and are supratentorial. While DIG/DIA is characterized by BRAF or RAF1 alterations, IHG has been shown to have receptor tyrosine kinase (RTK) gene fusions (ALK, ROS1, NTRK1/2/3, and MET). However, in this rapidly evolving field, a more comprehensive analysis of infantile glial/glioneuronal tumors including clinical, radiological, histopathological, and molecular data is needed. Here, we retrospectively investigated data from 30 infantile glial/glioneuronal tumors, consecutively compiled from our center. They were analyzed by two experienced pediatric neuroradiologists in consensus, without former knowledge of the molecular data. We also performed a comprehensive clinical, and histopathological examination (including molecular evaluation by next-generation sequencing, RNA sequencing, and fluorescence in situ hybridization [FISH] analyses), as well as DNA methylation profiling for the samples having sufficient material available. The integrative histopathological, genetic, and epigenetic analyses, including t-distributed stochastic neighbor embedding (t-SNE) analyses segregated tumors into 10 DIG/DIA (33.3%), six IHG (20.0%), three gangliogliomas (10.0%), two pleomorphic xanthoastrocytomas (6.7%), two pilocytic astrocytomas (6.7%), two supratentorial ependymomas, ZFTA fusion-positive (6.7%), two supratentorial ependymomas, YAP1 fusion-positive (6.7%), two embryonal tumors with PLAGL2-family amplification (6.7%), and one diffuse low-grade glioma, MAPK-pathway altered. This study highlights the significant differential features, in terms of histopathology (leptomeningeal infiltration, intense desmoplasia and ganglion cells in DIG/DIA and necrosis, microvascular proliferation, and siderophages in IHG), and radiology between DIG/DIA and IHG. Moreover, these results are consistent with the literature data concerning the molecular dichotomy (BRAF/RAF1 alterations vs. RTK genes' fusions) between DIG/DIA and IHG. This study characterized histopathologically and radiologically two additional cases of the novel embryonal tumor characterized by PLAGL2 gene amplification.
Topics: Humans; Ganglioglioma; Brain Neoplasms; Proto-Oncogene Proteins B-raf; Retrospective Studies; In Situ Hybridization, Fluorescence; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Astrocytoma; Central Nervous System Neoplasms; Neoplasms, Neuroepithelial; Ependymoma; DNA-Binding Proteins; Transcription Factors; RNA-Binding Proteins
PubMed: 37349135
DOI: 10.1111/bpa.13182 -
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 -
European Journal of Radiology May 2020T2-FLAIR mismatch sign was reported as specific imaging marker in non-enhancing diffuse astrocytoma, IDH-mutant & 1p/19q non-codeleted. However, most of the previous...
PURPOSE
T2-FLAIR mismatch sign was reported as specific imaging marker in non-enhancing diffuse astrocytoma, IDH-mutant & 1p/19q non-codeleted. However, most of the previous studies for T2-FLAIR mismatch sign were confirmed only among lower grade glioma. The aim of this study is to assess the T2-FLAIR mismatch sign in dysembryoplastic neuroepithelial tumor (DNET) and unveil the exception rules of the sign.
METHOD
Eleven patients with histopathologically confirmed DNET were included in this study. The MR images were evaluated by 2 independent reviewers to assess (i) the presence or absence of T2-FLAIR mismatch sign and (ii) the presence or absence of gadolinium enhancement. CT was also performed to evaluate calcification and localized thinning of the skull bone. Inter-reviewer agreement with Cohen's kappa (κ) was calculated.
RESULTS
The T2-FLAIR mismatch sign was present in 8 cases (72.7 %) and absent in 3 cases (27.3 %). None of them showed contrast enhancement on initial MR images. The inter-reviewer agreement for T2-FLAIR mismatch and CT characteristics was excellent (κ = 1.00). All of the DNET without T2-FLAIR mismatch presented with calcification on CT. All of the DNET adjacent to skull vault (5 cases) presented with localized bone thinning overlying the tumor.
CONCLUSIONS
The T2-FLAIR mismatch sign was observed in more than half of the DNET and the sign is not specific for diffuse astrocytoma, IDH-mutant & 1p19q non-codeleted. The localized skull bone thinning overlying the tumor might help for diagnosis of DNET in some cases.
Topics: Adolescent; Adult; Biomarkers; Brain; Brain Neoplasms; Child; Child, Preschool; Diagnosis, Differential; Female; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Male; Neoplasms, Neuroepithelial; Retrospective Studies; Young Adult
PubMed: 32193035
DOI: 10.1016/j.ejrad.2020.108924 -
Neuro-oncology Jan 2017Astroblastomas (ABs) are rare glial tumors showing overlapping features with astrocytomas, ependymomas, and sometimes other glial neoplasms, and may be challenging to...
Morphological and molecular features of astroblastoma, including BRAFV600E mutations, suggest an ontological relationship to other cortical-based gliomas of children and young adults.
BACKGROUND
Astroblastomas (ABs) are rare glial tumors showing overlapping features with astrocytomas, ependymomas, and sometimes other glial neoplasms, and may be challenging to diagnose.
METHODS
We examined clinical, histopathological, and molecular features in 28 archival formalin-fixed, paraffin-embedded AB cases and performed survival analyses using Cox proportional hazards and Kaplan-Meier methods.
RESULTS
Unlike ependymomas and angiocentric gliomas, ABs demonstrate abundant distinctive astroblastic pseudorosettes and are usually Olig2 immunopositive. They also frequently exhibit rhabdoid cells, multinucleated cells, and eosinophilic granular material. They retain immunoreactivity to alpha thalassemia/mental retardation syndrome X-linked, are immunonegative to isocitrate dehydrogenase-1 R132H mutation, and only occasionally show MGMT promoter hypermethylation differentiating them from many diffuse gliomas. Like pleomorphic xanthoastrocytoma, ganglioglioma, supratentorial pilocytic astrocytoma, and other predominantly cortical-based glial tumors, ABs often harbor the BRAF mutation, present in 38% of cases tested (n = 21), further distinguishing those tumors from ependymomas and angiocentric gliomas. Factors correlating with longer patient survival included age less than 30 years, female gender, absent BRAF , and mitotic index less than 5 mitoses/10 high-power fields; however, only the latter was significant by Cox and Kaplan-Meier analyses (n = 24; P = .024 and .012, respectively). This mitotic cutoff is therefore currently the best criterion to stratify tumors into low-grade ABs and higher-grade anaplastic ABs.
CONCLUSIONS
In addition to their own characteristic histological features, ABs share some molecular and histological findings with other, possibly ontologically related, cortical-based gliomas of mostly children and young adults. Importantly, the presence of BRAF mutations in a subset of ABs suggests potential clinical utility of targeted anti-BRAF therapy.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Brain Neoplasms; Cerebral Cortex; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mutation; Neoplasm Grading; Neoplasms, Neuroepithelial; Prognosis; Proto-Oncogene Proteins B-raf; Survival Rate; Young Adult
PubMed: 27416954
DOI: 10.1093/neuonc/now118 -
Clinical Neuropathology 2024Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant tumor of the central nervous system characterized by biallelic inactivation of SWI/SNF chromatin... (Review)
Review
Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant tumor of the central nervous system characterized by biallelic inactivation of SWI/SNF chromatin remodeling complex members SMARCB1/INI1 or (rarely) SMARCA4/BRG1. Most high-grade central nervous system lesions showing loss of nuclear SMARCB1 or SMARCA4 protein expression can indeed be categorized as AT/RT. However, some high-grade lesions have been identified, whose clinical and/or molecular features justify separation from AT/RT. Furthermore, other recently described tumor types such as desmoplastic myxoid tumor, SMARCB1-mutant, and low-grade diffusely infiltrative tumor, SMARCB1-mutant, may even manifest as low-grade lesions. Here, we review recent developments in the definition of the molecular landscape of AT/RT and give an update on other rare high- and low-grade SWI/SNF-deficient central nervous system tumors.
Topics: Humans; SMARCB1 Protein; Rhabdoid Tumor; Neoplasms, Neuroepithelial; Central Nervous System; DNA Helicases; Nuclear Proteins; Transcription Factors
PubMed: 37969088
DOI: 10.5414/NP301594 -
Brain Pathology (Zurich, Switzerland) Sep 2018Astroblastoma is a rare, enigmatic tumor of the central nervous system (CNS) which shares some clinicopathologic aspects with other CNS tumors, especially ependymoma. To...
Astroblastoma is a rare, enigmatic tumor of the central nervous system (CNS) which shares some clinicopathologic aspects with other CNS tumors, especially ependymoma. To further clarify the nature of astroblastoma, we performed clinicopathologic and molecular genetic studies on eight cases of astroblastoma. The median age of the patients was 14.5 years, ranging from 5 to 60 years, and seven of the patients were female. All tumors arose in the cerebral hemisphere and radiologically appeared to be well-bordered, nodular tumors often associated with cystic areas and contrast-enhancement. Six of the seven patients with prognosis data survived without recurrences during the follow-up periods ranging from six to 76 months. One patient had multiple recurrences and died six years later. All tumors exhibited salient microscopic features, such as being well demarcated from the surrounding brain tissue, perivascular arrangement of epithelioid tumor cells (represented by "astroblastic" pseudorosettes, trabecular alignment, and pseudopapillary patterns), and hyalinized blood vessels. Immunoreactivity for GFAP, S-100 protein, Olig2, and EMA was variably demonstrated in all tumors, and IDH1 R132H and L1CAM were negative. Array comparative genomic hybridization revealed numerous heterozygous deletions on chromosome X in the four tumors studied, and break-apart fluorescence in situ hybridization demonstrated rearrangement of MN1 in five tumors with successful testing. The characteristic clinicopathologic and genetic findings support the idea that astroblastoma is distinct from other CNS tumors, in particular, ependymoma. In addition, MN1 rearrangement and aberrations of chromosome X may partly be involved in the pathogenesis of astroblastoma.
Topics: Adolescent; Adult; Biomarkers, Tumor; Brain; Brain Neoplasms; Child; Child, Preschool; Chromosomes, Human, X; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms, Neuroepithelial; Prognosis; Proto-Oncogene Proteins B-raf; Trans-Activators; Tumor Suppressor Proteins; Young Adult
PubMed: 28990708
DOI: 10.1111/bpa.12565 -
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 -
World Neurosurgery Jul 2019An updated and comprehensive review on dysembryoplastic neuroepithelial tumor (DNET) focusing on differential diagnosis, atypical presentation, seizure outcome, and risk... (Review)
Review
OBJECTIVE
An updated and comprehensive review on dysembryoplastic neuroepithelial tumor (DNET) focusing on differential diagnosis, atypical presentation, seizure outcome, and risk of malignant transformation.
METHODS
A PubMed/MEDLINE-based literature search has been performed using "dysembryoplastic neuroepithelial tumor" as a keyword. Two treated cases characterized by an atypical presentation have been reviewed.
RESULTS
Of 1162 articles, 200 relevant studies have been selected. DNET is a benign mixed neuronal-glial tumor causing drug-resistant epilepsy primarily in children and young adults. The typical radiological pattern is a magnetic resonance imaging (MRI) T1-hypointense, T2-, and fluid-attenuated inversion-recovery hyperintense multicystic lesion involving the cerebral cortex with no edema. Contrast enhancement may be present and a focal cortical dysplasia is commonly associated with it. MRI diffusion, perfusion, and spectroscopy have a paramount role in the differential diagnosis. The "specific glioneuronal elements" are pathognomonic. They are positive for S100 protein, synaptofisin, neuronal nuclei, oligodendrocyte transcription factor, neurite outgrowth inhibitor, and microtubule-associated protein 2, but negative for glial fibrillary acidic protein. As opposed to v-myb avian myeloblastosis viral oncogene homolog, isocitrate dehydrogenase-1/isocitrate dehydrogenase-2 mutation and codeletion 1p-19q, fibroblast growth factor receptor 1 and BRAF V600E mutations are present. The effectiveness of surgery on seizure outcome has been established. Rare malignant transformations have been reported, especially in extra-temporal and complex forms.
CONCLUSIONS
Advanced MRI techniques are fundamental in the differential diagnosis for DNET versus other low-grade gliomas. Immuno-phenotype assessment and search for fibroblast growth factor receptor 1 and BRAF V600E mutations limit the risk of misdiagnoses. A gross total tumor removal is generally associated with a seizure-free outcome. Recurrences and malignant transformations may rarely follow, legitimizing MRI surveillance in cases of subtotal tumor resection.
Topics: Aged; Brain Neoplasms; Female; Humans; Middle Aged; Neoplasms, Neuroepithelial
PubMed: 30981794
DOI: 10.1016/j.wneu.2019.04.056