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Turkish Neurosurgery 2016Astroblastoma is a rare and distinct type of aggressive glial tumor for which there is much confusion regarding the diagnostic criteria. We present a case of... (Review)
Review
Astroblastoma is a rare and distinct type of aggressive glial tumor for which there is much confusion regarding the diagnostic criteria. We present a case of astroblastoma and review all relevant literature, aiming to discuss astroblastoma from the clinical, pathological, management, and prognostic points of view in an attempt to discover more of its secrets and to introduce a standard approach to its diagnosis and management.
Topics: Adult; Brain Neoplasms; Female; Humans; Male; Neoplasms, Neuroepithelial
PubMed: 27349390
DOI: 10.5137/1019-5149.JTN.9408-13.2 -
Brain Pathology (Zurich, Switzerland) May 2012The term long-term epilepsy associated tumor (LEAT) encompasses lesions identified in patients investigated for long histories (often 2 years or more) of drug-resistant... (Review)
Review
The term long-term epilepsy associated tumor (LEAT) encompasses lesions identified in patients investigated for long histories (often 2 years or more) of drug-resistant epilepsy. They are generally slowly growing, low grade, cortically based tumors, more often arising in younger age groups and in many cases exhibit neuronal in addition to glial differentiation. Gangliogliomas and dysembryoplastic neuroepithelial tumors predominate in this group. LEATs are further united by cyto-architectural changes that may be present in the adjacent cortex which have some similarities to developmental focal cortical dysplasias (FCD); these are now grouped as FCD type IIIb in the updated International League Against Epilepsy (ILAE) classification. In the majority of cases, surgical treatments are beneficial from both perspectives of managing the seizures and the tumor. However, in a minority, seizures may recur, tumors may show regrowth or recurrence, and rarely undergo anaplastic progression. Predicting and identifying tumors likely to behave less favorably are key objectives of the neuropathologist. With immunohistochemistry and modern molecular pathology, it is becoming increasingly possible to refine diagnostic groups. Despite this, some LEATs remain difficult to classify, particularly tumors with "non-specific" or diffuse growth patterns. Modification of LEAT classification is inevitable with the goal of unifying terminological criteria applied between centers for accurate clinico-pathological-molecular correlative data to emerge. Finally, establishing the epileptogenic components of LEAT, either within the lesion or perilesional cortex, will elucidate the cellular mechanisms of epileptogenesis, which in turn will guide optimal surgical management of these lesions.
Topics: Brain Neoplasms; Cerebral Cortex; Epilepsy; Glioma; Humans; Neuroglia; Neurons
PubMed: 22497610
DOI: 10.1111/j.1750-3639.2012.00582.x -
Deutsches Arzteblatt International Nov 2010Primary brain tumors are among the ten most common causes of cancer-related death. There is no screening test for them, but timely diagnosis and treatment improve the... (Review)
Review
BACKGROUND
Primary brain tumors are among the ten most common causes of cancer-related death. There is no screening test for them, but timely diagnosis and treatment improve the outcome. Ideally, treatment should be provided in a highly specialized center, but patients reach such centers only on the referral of their primary care physicians or other medical specialists from a wide variety of fields. An up-to-date account of basic knowledge in this area would thus seem desirable, as recent years have seen major developments both in the scientific understanding of these tumors and in clinical methods of diagnosis and treatment.
METHODS
Selective search of the pertinent literature (PubMed and Cochrane Library), including the guidelines of the German Societies of Neurosurgery, Neurology, and Radiotherapy.
RESULTS AND CONCLUSION
Modern neuroradiological imaging, in particular magnetic resonance imaging, can show structural lesions at high resolution and provide a variety of biological and functional information, yet it is still no substitute for histological diagnosis. Gross total resection of gliomas significantly improves overall survival. New molecular markers can be used for prognostication. Chemotherapy plays a major role in the treatment of various different kinds of glioma. The median survival, however, generally remains poor, e.g., 14.6 months for glio-blastoma.
Topics: Adult; Aged; Astrocytoma; Brain; Brain Neoplasms; Cell Movement; Child; Combined Modality Therapy; Cross-Sectional Studies; Disease Progression; Female; Glioblastoma; Glioma; Humans; Male; Middle Aged; Neoplasm Invasiveness; Prognosis; Survival Analysis
PubMed: 21124703
DOI: 10.3238/arztebl.2010.0799 -
AJNR. American Journal of Neuroradiology Aug 2022Glioneuronal tumors are characterized exclusively by neurocytic elements (neuronal tumors) or a combination of neuronal and glial features (mixed neuronal-glial tumors).... (Review)
Review
Glioneuronal tumors are characterized exclusively by neurocytic elements (neuronal tumors) or a combination of neuronal and glial features (mixed neuronal-glial tumors). Most of these tumors occur in young patients and are related to epilepsy. While ganglioglioma, dysembryoplastic neuroepithelial tumor, and desmoplastic infantile tumor are common glioneuronal tumors, anaplastic ganglioglioma, papillary glioneuronal tumor, rosette-forming glioneuronal tumor, gangliocytoma, and central neurocytoma are less frequent. Advances in immunohistochemical and molecular diagnostics have improved the characterization of these tumors and favored the description of variants and new subtypes, some not yet classified by the World Health Organization. Not infrequently, the histologic findings of biopsies of glioneuronal tumors simulate low-grade glial neoplasms; however, some imaging findings favor the correct diagnosis, making neuroimaging essential for proper management. Therefore, the aim of this review was to present key imaging, histopathology, immunohistochemistry, and molecular findings of glioneuronal tumors and their variants.
Topics: Humans; Child; Ganglioglioma; Neoplasms, Neuroepithelial; Central Nervous System Neoplasms; Brain Neoplasms; Neuroimaging
PubMed: 35512827
DOI: 10.3174/ajnr.A7465 -
Diagnostic Pathology Feb 2024This study aimed to investigate the clinicopathological characteristics, diagnostic indicators, and critical factors for the differential diagnosis of rosette-forming... (Review)
Review
BACKGROUND
This study aimed to investigate the clinicopathological characteristics, diagnostic indicators, and critical factors for the differential diagnosis of rosette-forming glioneuronal tumor (RGNT).
PATIENTS AND METHODS
This retrospective study included six surgically treated RGNT cases. We analyzed and summarized their clinical manifestations, radiological features, histological morphology, immunophenotype, and molecular genetic changes, supplemented with a literature review.
RESULTS
The patients comprised four males and two females with a mean age of 35 years. The tumors were located in the cerebellum (two cases); the fourth ventricle, quadrigeminal cistern, and third ventricle (one case each); and the fourth ventricle and brainstem (one case). Clinical manifestations included headaches in four cases, left eyelid ptosis in one case, and one asymptomatic case only identified during physical examination. Microscopically, the tumor cells were uniform in size and were marked by rosette-like or pseudorosette-like structures around the neuropil and blood vessels. Immunohistochemistry revealed biphasic patterns. The central neuropil components of the rosette-like structures around the neuropil and the pseudorosette structures of the perivascular regions expressed Syn, while the cells surrounding the rosettes expressed Olig2 and not GFAP. GFAP and S-100 were expressed in the glial components but not in the rosette or pseudorosette regions. The Ki-67 proliferation index was typically low. Molecular genetic analysis showed that the main molecular changes involved FGFR1 mutation accompanied by PIK3R1 mutation. None of the patients received chemoradiotherapy postoperatively. Follow-up durations varied between 4 and 23 months with no recorded recurrence or metastasis.
CONCLUSION
RGNT is a comparatively rare mixed glioneuronal tumor that occurs in the midline structures. Its morphology shows certain overlaps with other low-grade neuroepithelial tumors. Identifying the rosettes around the neuropil is critical for morphological diagnosis, and the molecular identification of FGFR1 mutations accompanied by PIK3R1 mutations can facilitate diagnosis.
Topics: Adult; Female; Humans; Male; Brain Neoplasms; Central Nervous System Neoplasms; Diagnosis, Differential; Fourth Ventricle; Mutation; Neoplasms, Neuroepithelial; Retrospective Studies
PubMed: 38388383
DOI: 10.1186/s13000-024-01465-6 -
Medicina (Kaunas, Lithuania) 2010Gliomatosis cerebri is a rare diffusely infiltrating glial tumor involving two or more lobes and is frequently is bilateral. Infiltrative extent of tumor is out of...
Gliomatosis cerebri is a rare diffusely infiltrating glial tumor involving two or more lobes and is frequently is bilateral. Infiltrative extent of tumor is out of proportion to histological and clinical features. We present a case in which finally the diagnosis of gliomatosis cerebri was made. In this case, computed tomography showed that midline structures were insignificantly shifted to the left, there was a mild dilatation of lateral ventricles more expressed on the right, and no pathologic changes of brain tissue density were found. On magnetic resonance tomography, T2W/SE and T2W/FLAIR images revealed zones of hyperintense signal, spreading with time, through several lobes of the brain with no enhancement on T1W images. Diagnosis of gliomatosis cerebri was suspected, stereotaxic biopsy was performed, and pathological examination revealed changes typical of diffuse glial tumor. In this article, changes typical of gliomatosis cerebri seen in other radiological methods such as computed tomography, magnetic resonance spectroscopy, dynamic contrast-enhanced T2*-weighted magnetic resonance, and positron emission tomography also are discussed.
Topics: Adrenal Cortex Hormones; Biopsy; Brain; Brain Neoplasms; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasms, Neuroepithelial; Tomography, X-Ray Computed
PubMed: 20679750
DOI: No ID Found -
Brain : a Journal of Neurology Apr 2022Unlike other tumours, the anatomical extent of brain tumours is not objectified and quantified through staging. Staging systems are based on understanding the anatomical...
Unlike other tumours, the anatomical extent of brain tumours is not objectified and quantified through staging. Staging systems are based on understanding the anatomical sequence of tumour progression and its relationship to histopathological dedifferentiation and survival. The aim of this study was to describe the spatiotemporal phenotype of the most frequent brain tumour entities, to assess the association of anatomical tumour features with survival probability and to develop a staging system for WHO grade 2 and 3 gliomas and glioblastoma. Anatomical phenotyping was performed on a consecutive cohort of 1000 patients with first diagnosis of a primary or secondary brain tumour. Tumour probability in different topographic, phylogenetic and ontogenetic parcellation units was assessed on preoperative MRI through normalization of the relative tumour prevalence to the relative volume of the respective structure. We analysed the spatiotemporal tumour dynamics by cross-referencing preoperative against preceding and subsequent MRIs of the respective patient. The association between anatomical phenotype and outcome defined prognostically critical anatomical tumour features at diagnosis. Based on a hypothesized sequence of anatomical tumour progression, we developed a three-level staging system for WHO grade 2 and 3 gliomas and glioblastoma. This staging system was validated internally in the original cohort and externally in an independent cohort of 300 consecutive patients. While primary CNS lymphoma showed highest probability along white matter tracts, metastases enriched along terminal arterial flow areas. Neuroepithelial tumours mapped along all sectors of the ventriculocortical axis, while adjacent units were spared, consistent with a transpallial behaviour within phylo-ontogenetic radial units. Their topographic pattern correlated with morphogenetic processes of convergence and divergence of radial units during phylo- and ontogenesis. While a ventriculofugal growth dominated in neuroepithelial tumours, a gradual deviation from this neuroepithelial spatiotemporal behaviour was found with progressive histopathological dedifferentiation. The proposed three-level staging system for WHO grade 2 and 3 gliomas and glioblastoma correlated with the degree of histological dedifferentiation and proved accurate in terms of survival upon both internal and external validation. In conclusion, this study identified specific spatiotemporal phenotypes in brain tumours through topographic probability and growth pattern assessment. The association of anatomical tumour features with survival defined critical steps in the anatomical sequence of neuroepithelial tumour progression, based on which a staging system for WHO grade 2 and 3 gliomas and glioblastoma was developed and validated.
Topics: Brain Neoplasms; Glioblastoma; Glioma; Humans; Neoplasms, Neuroepithelial; Phylogeny
PubMed: 34554211
DOI: 10.1093/brain/awab352 -
Acta Neuropathologica Sep 2023Malignant brain tumors, known as H3K27-altered diffuse midline glioma (DMG) and H3G34-mutant diffuse hemispheric glioma (DHG), can affect individuals of all ages and are...
Malignant brain tumors, known as H3K27-altered diffuse midline glioma (DMG) and H3G34-mutant diffuse hemispheric glioma (DHG), can affect individuals of all ages and are classified as CNS WHO grade 4. We comprehensively characterized 390 H3F3A-mutant diffuse gliomas (201 females, 189 males) arising in pediatric patients (under 20 years old) and adults (20 years and older) evaluated by the CGP program at Foundation Medicine between 2013 and 2020. We assessed information from pathology reports, histopathology review, and clinical data. The cohort included 304 H3K27M-mutant DMG (156 females, 148 males) and 86 H3G34-mutant DHG (45 females, 41 males). Median patient age was 20 years (1-74 years). The frequency of H3K27M-mutant DMG was similar in both pediatric and adult patients in our cohort-48.6% of the patients were over 20 years old, 31.5% over 30, and 18% over 40 at initial diagnosis. FGFR1 hotspot point mutations (N546K and K656E) were exclusively identified in H3K27M-mutant DMG tumors (64/304, 21%; p = 0.0001); these tend to occur in older patients (median age: 32.5 years) and mainly arose in the diencephalon. H3K27M-mutant DMG had higher rates of mutations in NF1 (31.0 vs 8.1%; p = 0.0001) and PIK3CA/PIK3R1 (27.9% vs 15.1%; p = 0.016) compared to H3G34-mutant DHG. However, H3G34-mutant DHG had higher rates of targetable alterations in cell-cycle pathway genes (CDK4 and CDK6 amplification; CDKN2A/B deletion) (27.0 vs 9.0%). Potentially targetable PDGFRA alterations were identified in ~ 20% of both H3G34-mutant DHG and H3K27M-mutant DMG. Overall, in the present study H3K27M-mutant DMG occurred at similar rates in both adult and patient patients. Through our analysis, we were able to identify molecular features characteristic of DMG and DHG. By identifying the recurrent co-mutations including actionable FGFR1 point mutations found in nearly one-third of H3K27M-mutant DMG in young adults, our findings can inform clinical translational studies, patient diagnosis, and clinical trial design.
Topics: Adult; Aged; Child; Female; Humans; Male; Young Adult; Brain Neoplasms; Genomics; Glioma; Histones; Mutation; World Health Organization; Infant; Child, Preschool; Adolescent; Middle Aged
PubMed: 37524847
DOI: 10.1007/s00401-023-02609-6 -
Frontiers in Immunology 2023Among all types of central nervous system cancers, glioma remains the most frequent primary brain tumor in adults. Despite significant advances in immunomodulatory...
INTRODUCTION
Among all types of central nervous system cancers, glioma remains the most frequent primary brain tumor in adults. Despite significant advances in immunomodulatory therapies, notably immune checkpoint inhibitors, their effectiveness remains constrained due to glioma resistance. The discovery of TMIGD2 (Transmembrane and Immunoglobulin Domain Containing 2) as an immuno-stimulatory receptor, constitutively expressed on naive T cells and most natural killer (NK) cells, has emerged as an attractive immunotherapy target in a variety of cancers. The expression profile of TMIGD2 and its significance in the overall survival of glioma patients remains unknown.
METHODS
In the present study, we first assessed TMIGD2 mRNA expression using the Cancer Genome Atlas (TCGA) glioma transcriptome dataset (667 patients), followed by validation with the Chinese Glioma Genome Atlas (CGGA) cohort (693 patients). Secondly, we examined TMIGD2 protein staining in a series of 25 paraffin-embedded blocks from Moroccan glioma patients. The statistical analysis was performed using GraphPad Prism 8 software.
RESULTS
TMIGD2 expression was found to be significantly higher in astrocytoma, IDH-1 mutations, low-grade, and young glioma patients. TMIGD2 was expressed on immune cells and, surprisingly, on tumor cells of glioma patients. Interestingly, our study demonstrated that TMIGD2 expression was negatively correlated with angiogenesis, hypoxia, G2/M checkpoint, and epithelial to mesenchymal transition signaling pathways. We also demonstrated that dendritic cells, monocytes, NK cells, gd T cells, and naive CD8 T cell infiltration correlates positively with TMIGD2 expression. On the other hand, Mantel-Cox analysis demonstrated that increased expression of TMIGD2 in human gliomas is associated with good overall survival. Cox multivariable analysis revealed that TMIGD2 is an independent predictor of a good prognosis in glioma patients.
DISCUSSION
Taken together, our results highlight the tight implication of TMIGD2 in glioma progression and show its promising therapeutic potential as a stimulatory target for immunotherapy.
Topics: Humans; Astrocytoma; Epithelial-Mesenchymal Transition; Glioma; Prognosis; Transcriptome
PubMed: 37261362
DOI: 10.3389/fimmu.2023.1173518 -
Annals of Palliative Medicine Jan 2021Gliomas represent the majority of malignant central nervous system tumors, with the most aggressive subtype, glioblastoma, accounting for almost 57% of this entity. Type... (Review)
Review
Gliomas represent the majority of malignant central nervous system tumors, with the most aggressive subtype, glioblastoma, accounting for almost 57% of this entity. Type of glioma and its incidence can vary depending on the age of presentation. In turn, outcomes can vary significantly based on the actual type of glioma (histologically and molecularly) and age of the patient, as well as various tumor specific factors such as size, location, comorbidities, etc. In the last decade we have been able to identify key molecular features that have provided us with greater insight into the behavior of these tumors, but the spectrum of treatment options remains limited. In addition, ultimate causes of death in patients with gliomas are variable and stochastic in nature. Given these complicated factors, prognostication for gliomas remains extremely difficult. This review aims to discuss prognostication in low grade versus high grade gliomas, variability in treatment of these tumors, clinical features of poor prognosis, and differences in prognostic understanding between patients, caregivers, and providers. We will also make some general recommendations where appropriate on how to approach this subject from a palliative care perspective.
Topics: Adult; Brain Neoplasms; Glioblastoma; Glioma; Humans; Prognosis
PubMed: 32787379
DOI: 10.21037/apm-20-640