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Case Reports in Oncology 2024Diffuse leptomeningeal glioneuronal tumor (DLGNT), a new addition to the 2016 World Health Organization (WHO) classification, is a rare childhood neoplasm presenting...
INTRODUCTION
Diffuse leptomeningeal glioneuronal tumor (DLGNT), a new addition to the 2016 World Health Organization (WHO) classification, is a rare childhood neoplasm presenting with disseminated leptomeningeal enhancement and an occasional intraparenchymal mass. Diagnosis is often impeded by infectious/immunological differentials, necessitating a biopsy to confirm the diagnosis. We report an adult male with DLGNT without hydrocephalus, which is rare in patients with cerebellar masses.
CASE PRESENTATION
A 56-year-old man presented with headaches, vertigo, diplopia, impaired hearing, and gait imbalance over 6 months. Magnetic resonance imaging showed a cystic right cerebellar mass with its leptomeningeal dissemination but without hydrocephalus. Cerebrospinal fluid analysis revealed elevated proteins with CD56-positive tumor cells. Cerebellar lesion biopsy verified the diagnosis of DLGNT (WHO Grade 3) with fusion and 1p deletion. Radiotherapy was prematurely aborted due to clinical deterioration. The patient was subsequently discharged to palliative home care and lost to follow-up.
CONCLUSION
We conducted the first review of all 34 adult DLGNT cases, including ours (one of the oldest), hitherto published in the literature. The majority presented with signs and symptoms of increased intracranial pressure. 52.0% of adult DLGNT patients were alive at follow-up. DLGNT should be considered in the differential diagnoses of diffuse leptomeningeal enhancement in imaging. Further studies comparing pediatric and adult subgroups of DLGNT are needed to evaluate histopathological prognosticators and standardize therapy for both subpopulations.
PubMed: 38404404
DOI: 10.1159/000536400 -
Neuro-oncology Advances 2024
PubMed: 38371225
DOI: 10.1093/noajnl/vdae006 -
BMC Cancer Feb 2024Glioma is a primary brain tumor and the assessment of its molecular profile in a minimally invasive manner is important in determining treatment strategies. Among the...
BACKGROUND
Glioma is a primary brain tumor and the assessment of its molecular profile in a minimally invasive manner is important in determining treatment strategies. Among the molecular abnormalities of gliomas, mutations in the isocitrate dehydrogenase (IDH) gene are strong predictors of treatment sensitivity and prognosis. In this study, we attempted to non-invasively diagnose glioma development and the presence of IDH mutations using multivariate analysis of the plasma mid-infrared absorption spectra for a comprehensive and sensitive view of changes in blood components associated with the disease and genetic mutations. These component changes are discussed in terms of absorption wavenumbers that contribute to differentiation.
METHODS
Plasma samples were collected at our institutes from 84 patients with glioma (13 oligodendrogliomas, 17 IDH-mutant astrocytoma, 7 IDH wild-type diffuse glioma, and 47 glioblastomas) before treatment initiation and 72 healthy participants. FTIR-ATR spectra were obtained for each plasma sample, and PLS discriminant analysis was performed using the absorbance of each wavenumber in the fingerprint region of biomolecules as the explanatory variable. This data was used to distinguish patients with glioma from healthy participants and diagnose the presence of IDH mutations.
RESULTS
The derived classification algorithm distinguished the patients with glioma from healthy participants with 83% accuracy (area under the curve (AUC) in receiver operating characteristic (ROC) = 0.908) and diagnosed the presence of IDH mutation with 75% accuracy (AUC = 0.752 in ROC) in cross-validation using 30% of the total test data. The characteristic changes in the absorption spectra suggest an increase in the ratio of β-sheet structures in the conformational composition of blood proteins of patients with glioma. Furthermore, these changes were more pronounced in patients with IDH-mutant gliomas.
CONCLUSIONS
The plasma infrared absorption spectra could be used to diagnose gliomas and the presence of IDH mutations in gliomas with a high degree of accuracy. The spectral shape of the protein absorption band showed that the ratio of β-sheet structures in blood proteins was significantly higher in patients with glioma than in healthy participants, and protein aggregation was a distinct feature in patients with glioma with IDH mutations.
Topics: Humans; Ataxia Telangiectasia Mutated Proteins; Blood Proteins; Brain Neoplasms; Glioma; Isocitrate Dehydrogenase; Mutation; Protein Aggregates; Spectroscopy, Fourier Transform Infrared; Amyloid
PubMed: 38365669
DOI: 10.1186/s12885-024-11970-y -
Journal of Neuro-oncology Mar 2024Various molecular profiles are needed to classify malignant brain tumors, including gliomas, based on the latest classification criteria of the World Health...
PURPOSE
Various molecular profiles are needed to classify malignant brain tumors, including gliomas, based on the latest classification criteria of the World Health Organization, and their poor prognosis necessitates new therapeutic targets. The Todai OncoPanel 2 RNA Panel (TOP2-RNA) is a custom-target RNA-sequencing (RNA-seq) using the junction capture method to maximize the sensitivity of detecting 455 fusion gene transcripts and analyze the expression profiles of 1,390 genes. This study aimed to classify gliomas and identify their molecular targets using TOP2-RNA.
METHODS
A total of 124 frozen samples of malignant gliomas were subjected to TOP2-RNA for classification based on their molecular profiles and the identification of molecular targets.
RESULTS
Among 55 glioblastoma cases, gene fusions were detected in 11 cases (20%), including novel MET fusions. Seven tyrosine kinase genes were found to be overexpressed in 15 cases (27.3%). In contrast to isocitrate dehydrogenase (IDH) wild-type glioblastoma, IDH-mutant tumors, including astrocytomas and oligodendrogliomas, barely harbor fusion genes or gene overexpression. Of the 34 overexpressed tyrosine kinase genes, MDM2 and CDK4 in glioblastoma, 22 copy number amplifications (64.7%) were observed. When comparing astrocytomas and oligodendrogliomas in gene set enrichment analysis, the gene sets related to 1p36 and 19q were highly enriched in astrocytomas, suggesting that regional genomic DNA copy number alterations can be evaluated by gene expression analysis.
CONCLUSIONS
TOP2-RNA is a highly sensitive assay for detecting fusion genes, exon skipping, and aberrant gene expression. Alterations in targetable driver genes were identified in more than 50% of glioblastoma. Molecular profiling by TOP2-RNA provides ample predictive, prognostic, and diagnostic biomarkers that may not be identified by conventional assays and, therefore, is expected to increase treatment options for individual patients with glioma.
Topics: Humans; Glioblastoma; Oligodendroglioma; Mutation; Glioma; Brain Neoplasms; Astrocytoma; Protein-Tyrosine Kinases; Biomarkers; Isocitrate Dehydrogenase
PubMed: 38363490
DOI: 10.1007/s11060-024-04563-z -
Acta Neurochirurgica Feb 2024Distant recurrence can occur by infiltration along white matter tracts or dissemination through the cerebrospinal fluid (CSF). This study aimed to clarify the clinical...
BACKGROUND
Distant recurrence can occur by infiltration along white matter tracts or dissemination through the cerebrospinal fluid (CSF). This study aimed to clarify the clinical features and mechanisms of recurrence in the dentate nucleus (DN) in patients with supratentorial gliomas. Based on the review of our patients, we verified the hypothesis that distant DN recurrence from a supratentorial lesion occurs through the dentato-rubro-thalamo-cortical (DRTC) pathway.
METHODS
A total of 380 patients with supratentorial astrocytoma, isocitrate dehydrogenase (IDH)-mutant (astrocytoma), oligodendroglioma, IDH mutant and 1p/19q-codeleted (oligodendroglioma), glioblastoma, IDH-wild type (GB), and thalamic diffuse midline glioma, H3 K27-altered (DMG), who underwent tumor resection at our department from 2009 to 2022 were included in this study. Recurrence patterns were reviewed. Additionally, clinical features and magnetic resonance imaging findings before treatment, at the appearance of an abnormal signal, and at further progression due to delayed diagnosis or after salvage treatment of cases with recurrence in the DN were reviewed.
RESULTS
Of the 380 patients, 8 (2.1%) had first recurrence in the DN, 3 were asymptomatic when abnormal signals appeared, and 5 were diagnosed within one month after the onset of symptoms. Recurrence in the DN developed in 8 (7.4%) of 108 cases of astrocytoma, GB, or DMG at the frontal lobe or thalamus, whereas no other histological types or sites showed recurrence in the DN. At the time of the appearance of abnormal signals, a diffuse lesion developed at the hilus of the DN. The patterns of further progression showed that the lesions extended to the superior cerebellar peduncle, tectum, tegmentum, red nucleus, thalamus, and internal capsule along the DRTC pathway.
CONCLUSION
Distant recurrence along the DRTC pathway is not rare in astrocytomas, GB, or DMG at the frontal lobe or thalamus. Recurrence in the DN developed as a result of the infiltration of tumor cells through the DRTC pathway, not dissemination through the CSF.
Topics: Humans; Cerebellar Nuclei; Oligodendroglioma; Glioma; Astrocytoma; Glioblastoma; Isocitrate Dehydrogenase
PubMed: 38353806
DOI: 10.1007/s00701-024-05981-8 -
Journal of Neuro-oncology Apr 2024Surgery for recurrent glioma provides cytoreduction and tissue for molecularly informed treatment. With mostly heavily pretreated patients involved, it is unclear...
PURPOSE
Surgery for recurrent glioma provides cytoreduction and tissue for molecularly informed treatment. With mostly heavily pretreated patients involved, it is unclear whether the benefits of repeat surgery outweigh its potential risks.
METHODS
Patients receiving surgery for recurrent glioma WHO grade 2-4 with the goal of tissue sampling for targeted therapies were analyzed retrospectively. Complication rates (surgical, neurological) were compared to our institutional glioma surgery cohort. Tissue molecular diagnostic yield, targeted therapies and post-surgical survival rates were analyzed.
RESULTS
Between 2017 and 2022, tumor board recommendation for targeted therapy through molecular diagnostics was made for 180 patients. Of these, 70 patients (38%) underwent repeat surgery. IDH-wildtype glioblastoma was diagnosed in 48 patients (69%), followed by IDH-mutant astrocytoma (n = 13; 19%) and oligodendroglioma (n = 9; 13%). Gross total resection (GTR) was achieved in 50 patients (71%). Tissue was processed for next-generation sequencing in 64 cases (91%), and for DNA methylation analysis in 58 cases (83%), while immunohistochemistry for mTOR phosphorylation was performed in 24 cases (34%). Targeted therapy was recommended in 35 (50%) and commenced in 21 (30%) cases. Postoperatively, 7 patients (11%) required revision surgery, compared to 7% (p = 0.519) and 6% (p = 0.359) of our reference cohorts of patients undergoing first and second craniotomy, respectively. Non-resolving neurological deterioration was documented in 6 cases (10% vs. 8%, p = 0.612, after first and 4%, p = 0.519, after second craniotomy). Median survival after repeat surgery was 399 days in all patients and 348 days in GBM patients after repeat GTR.
CONCLUSION
Surgery for recurrent glioma provides relevant molecular diagnostic information with a direct consequence for targeted therapy under a reasonable risk of postoperative complications. With satisfactory postoperative survival it can therefore complement a multi-modal glioma therapy approach.
Topics: Humans; Reoperation; Brain Neoplasms; Retrospective Studies; Neoplasm Recurrence, Local; Precision Medicine; Glioma
PubMed: 38334907
DOI: 10.1007/s11060-024-04595-5 -
Cureus Jan 2024Background Oligodendrogliomas, rare brain tumors in the frontal lobe's white matter, are reshaped by molecular markers like isocitrate dehydrogenase mutations and 1p/19q...
Background Oligodendrogliomas, rare brain tumors in the frontal lobe's white matter, are reshaped by molecular markers like isocitrate dehydrogenase mutations and 1p/19q co-deletion, influencing treatment outcomes. Despite the initial indolence, these tumors pose a significant risk, with a median survival of 10-12 years. Non-invasive alternatives, such as magnetic resonance imaging (MRI) for assessing T2-fluid-attenuated inversion recovery (FLAIR) mismatch and calcifications, provide insights into molecular subtypes and aid prognosis. Our study explored these features to predict the oligodendroglioma status and refine patient management to improve outcomes. Methods In this retrospective study, patient data identified patients with suspected central nervous system tumors undergoing MRI, revealing low-grade gliomas. Surgical biopsy and 1p/19q fluorescence in situ hybridization confirmed the co-deletion status. MRI was used to assess various morphological features. Statistical analyses included x2 tests, Fisher's exact tests, Kruskal-Wallis tests, and binary logistic regression models, with significance set at p < 0.05. Results Seventy-three patients (median age, 37 years) were stratified according to 1p/19q co-deletion. Most (61.6%) were 18-40 years old and mostly male (67.1%). Co-deletion cases, primarily frontal lobe lesions (67.6%), were unilateral (88.2%), with 55.9% non-circumscribed margins and 58.8% ill-defined contours. Smooth contrast enhancement and no necrosis were observed in 48.1% of 1p/19q co-deletion cases. Logistic regression analysis showed a significant association between ill-defined/irregular contours and 1p/19q co-deletion. Fisher's exact test confirmed this but raised concerns about the small sample size influencing the conclusions. Conclusions This study established a significant link between glioma tumor contour characteristics, particularly irregular and ill-defined contours, and the likelihood of 1p/19q co-deletion. Our findings underscore the clinical relevance of using tumor contours in treatment decisions and prognosis assessments.
PubMed: 38327950
DOI: 10.7759/cureus.51863 -
International Journal of Clinical and... 2024Diffuse glioma constitutes 28% of primary brain tumors. Until recently morphologic appearance was the only criterion for classifying these tumors. However, WHO 2016...
INTRODUCTION
Diffuse glioma constitutes 28% of primary brain tumors. Until recently morphologic appearance was the only criterion for classifying these tumors. However, WHO 2016 incorporates molecular information in the primary diagnosis of gliomas such as Isocitrate dehydrogenase 1 (IDH1), Alpha thalassemia/mental retardation syndrome X inked (ATRX) as well as 1p/19q codeletion on FISH. In a resource-limited setup where FISH is not available, Alpha internexin (INA) has been suggested as a surrogate IHC marker.
MATERIAL AND METHODS
Cross-sectional study conducted in the Department of Pathology for two years. Tissue blocks and clinical as well as radiological details were obtained from departmental archives. After assessing the morphologic details, routine IHC markers such as GFAP, Ki67 and P53 along with molecular markers like IDH-1, ATRX, and lNA were applied.
RESULTS
Out of 55 cases of diffuse glioma, 23 cases of astrocytoma and 32 cases of oligodendroglioma with an overall mean age of presentation of 41.49 ± 12.47 years. IDH-1 expression among diffuse glioma was 89.1% in our study. Alteration in the ATRX gene expression was observed in 95.7% of astrocytomas. 75% of oligodendrogliomas expressed INA with no significant difference in expression between the two grades. Based on the algorithmic approach using molecular surrogate markers, diffuse gliomas were categorized into six distinct groups. IDH-mutant, ATRX loss of expression astrocytoma and IDH-mutant, INA positive oligodendroglioma are two categories that do not require further molecular testing. This comprises 72.7% of the cases and these do not warrant further workup.
CONCLUSION
Implementation of combined phenotypic-genotypic diagnosis with the use of histomorphology and immunohistochemical surrogates for molecular genetic alterations will yield more homogeneous and narrowly defined diagnostic entities which will provide better prognostication and definitive treatment. It also is cost-effective in a resource-limited setup.
PubMed: 38322173
DOI: 10.62347/AJCP7971 -
Cureus Dec 2023Oligodendrogliomas are rare brain tumors arising from oligodendrocytes; there is a limited understanding of their pathogenesis, which leads to challenges in diagnosis,... (Review)
Review
Oligodendrogliomas are rare brain tumors arising from oligodendrocytes; there is a limited understanding of their pathogenesis, which leads to challenges in diagnosis, prognosis, and treatment. This study aimed to conduct a comprehensive bibliometric analysis of the oligodendroglioma literature to assess the current state of research, identify research trends, and elucidate implications for future research. The Lens database was used to retrieve journal articles related to "oligodendroglioma" without geographic or temporal restrictions. Year-on-year trends in publication and funding were analyzed. Global and gender equity were assessed using the NamsorApplication programming interface. Collaboration patterns were explored using network visualizations. Keyword analysis revealed the most prominent themes in oligodendroglioma research. Out of 9701 articles initially retrieved, 8381 scholarly journal articles were included in the final analysis. Publication trends showed a consistent increase until 2020, followed by a sharp decline likely due to the COVID-19 pandemic. Global representation revealed researchers from 86 countries, with limited participation from low and middle-income countries (LMICs). Gender inequity was evident, with 78.7% of researchers being male. Collaboration analysis revealed a highly interconnected research community. Prognosis, genetic aberrations (particularly "IDH" mutations), and therapeutic options (including chemotherapy and radiotherapy) emerged as dominant research themes. The COVID-19 pandemic impacted oligodendroglioma research funding and publication trends, highlighting the importance of robust funding mechanisms. Global and gender inequities in research participation underscore the need for fostering inclusive collaboration, especially in LMICs. The interconnected research community presents opportunities for knowledge exchange and innovation. Keyword analysis highlights current research trends and a shift to genetic and molecular understanding.
PubMed: 38283488
DOI: 10.7759/cureus.51161 -
Oncotarget Jan 2024Oligodendrocyte precursor markers have become of great interest to identify new diagnostic and therapeutic targets for diffuse gliomas, since state-of-the-art studies...
Oligodendrocyte precursor markers have become of great interest to identify new diagnostic and therapeutic targets for diffuse gliomas, since state-of-the-art studies point towards immature oligodendrocytes as a possible source of gliomagenesis. Brain enriched myelin associated protein 1 (BCAS1) is a novel marker of immature oligodendrocytes and was proposed to contribute to tumorigenesis in non-central nervous system tumors. However, BCAS1 role in diffuse glioma is still underexplored. This study analyzes the expression of BCAS1 in different tumor samples from patients with diffuse gliomas (17 oligodendrogliomas; 8 astrocytomas; 60 glioblastomas) and uncovers the molecular and ultrastructural features of BCAS1 cells by immunostaining and electron microscopy. Our results show that BCAS1 cells exhibit stellate or spherical morphology with similar ultrastructural features. Stellate and spherical cells were detected as isolated cells in all studied gliomas. Nevertheless, only stellate cells were found to be proliferative and formed tightly packed nodules with a highly proliferative rate in oligodendrogliomas. Our findings provide a comprehensive characterization of the BCAS1 cell population within diffuse gliomas. The observed proliferative capacity and distribution of BCAS1 stellate cells, particularly in oligodendrogliomas, highlight BCAS1 as an interesting marker, warranting further investigation into its role in tumor malignancy.
Topics: Humans; Oligodendroglioma; Brain Neoplasms; Glioma; Astrocytoma; Glioblastoma; Neoplasm Proteins
PubMed: 38275289
DOI: 10.18632/oncotarget.28553