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Acta Neuropathologica Jun 2015For nearly a century, the diagnosis and grading of oligodendrogliomas and oligoastrocytomas has been based on histopathology alone. Roughly 20 years ago, the first... (Review)
Review
For nearly a century, the diagnosis and grading of oligodendrogliomas and oligoastrocytomas has been based on histopathology alone. Roughly 20 years ago, the first glioma-associated molecular signature was found with complete chromosome 1p and 19q codeletion being particularly common in histologically classic oligodendrogliomas. Subsequently, this codeletion appeared to not only carry diagnostic, but also prognostic and predictive information, the latter aspect only recently resolved after carefully constructed clinical trials with very long follow-up times. More recently described biomarkers, including the non-balanced translocation leading to 1p/19q codeletion, promoter hypermethylation of the MGMT gene, mutations of the IDH1 or IDH2 gene, and mutations of FUBP1 (on 1p) or CIC (on 19q), have greatly enhanced our understanding of oligodendroglioma biology, although their diagnostic, prognostic, and predictive roles are less clear. It has therefore been suggested that complete 1p/19q codeletion be required for the diagnosis of 'canonical oligodendroglioma'. This transition to an integrated morphological and molecular diagnosis may result in the disappearance of oligoastrocytoma as an entity, but brings new challenges as well. For instance it needs to be sorted out how (histopathological) criteria for grading of 'canonical oligodendrogliomas' should be adapted, how pediatric oligodendrogliomas (known to lack codeletions) should be defined, which platforms and cut-off levels should ideally be used for demonstration of particular molecular aberrations, and how the diagnosis of oligodendroglioma should be made in centers/countries where molecular diagnostics is not available. Meanwhile, smart integration of morphological and molecular information will lead to recognition of biologically much more uniform groups within the spectrum of diffuse gliomas and thereby facilitate tailored treatments for individual patients.
Topics: Biomarkers, Tumor; Brain Neoplasms; Humans; Oligodendroglioma
PubMed: 25943885
DOI: 10.1007/s00401-015-1424-1 -
Journal of Veterinary Diagnostic... Sep 2022Ependymoma, one of the most common gliomas in cats, occurs most often in the lateral and third ventricles and has variable histologic patterns that often form rosettes...
Ependymoma, one of the most common gliomas in cats, occurs most often in the lateral and third ventricles and has variable histologic patterns that often form rosettes and pseudorosettes. Oligodendrocyte transcription factor (OLIG2) is expressed in oligodendrocyte precursor cells and mature oligodendrocytes. Although widely used as a diagnostic marker for most gliomas, OLIG2 is reported to have minimal immunolabeling in ependymomas. Here we characterize the OLIG2 immunolabeling pattern in 19 cases of feline ependymoma, which occurred predominantly in the lateral and third ventricles. Immunohistochemistry for GFAP was variable in 14 cases and was typically localized in the cytoplasmic processes of the neoplastic ependymal cells, especially in the rosettes and pseudorosettes. Nuclear OLIG2 immunolabeling was present in 17 cases and varied in intensity from weak (4 cases) to strong (13 cases). The distribution of OLIG2 immunolabeling within the neoplasms included none (2 cases), <25% (7 cases), 25-50% (6 cases), 51-75% (2 cases), and >75% (3 cases). OLIG2 immunolabeling intensity and distribution is widespread in feline ependymoma, in contrast to ependymomas in other species, and should not be relied upon as a specific marker for feline oligodendroglioma.
Topics: Animals; Brain Neoplasms; Cat Diseases; Cats; Ependymoma; Glioma; Immunohistochemistry; Oligodendroglioma
PubMed: 35762120
DOI: 10.1177/10406387221107898 -
AJNR. American Journal of Neuroradiology Oct 2022Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC) is a new, molecularly defined glioneuronal CNS tumor type. The objective of...
BACKGROUND AND PURPOSE
Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC) is a new, molecularly defined glioneuronal CNS tumor type. The objective of the present study was to describe MR imaging and clinical characteristics of patients with DGONC.
MATERIALS AND METHODS
Preoperative MR images of 9 patients with DGONC (median age at diagnosis, 9.9 years; range, 4.2-21.8 years) were reviewed.
RESULTS
All tumors were located superficially in the frontal/temporal lobes and sharply delineated, displaying little mass effect. Near the circle of Willis, the tumors encompassed the arteries. All except one demonstrated characteristics of low-to-intermediate aggressiveness with high-to-intermediate T2WI and ADC signals and bone remodeling. Most tumors ( 7) showed a homogeneous ground-glass aspect on T2-weighted and FLAIR images. On the basis of the original histopathologic diagnosis, 6 patients received postsurgical chemo-/radiotherapy, 2 were irradiated after surgery, and 1 patient underwent tumor resection only. At a median follow-up of 61 months (range, 10-154 months), 6 patients were alive in a first complete remission and 2 with stable disease 10 and 21 months after diagnosis. The only patient with progressive disease was lost to follow-up. Five-year overall and event-free survival was 100% and 86±13%, respectively.
CONCLUSIONS
This case series presents radiomorphologic characteristics highly predictive of DGONC that contrast with the typical aspects of the original histopathologic diagnoses. This presentation underlines the definition of DGONC as a separate entity, from a clinical perspective. Complete resection may be favorable for long-term disease control in patients with DGONC. The efficacy of nonsurgical treatment modalities should be evaluated in larger series.
Topics: Humans; Child; Oligodendroglioma; Glioma; Central Nervous System Neoplasms; Magnetic Resonance Imaging; Neoplasms, Neuroepithelial; Brain Neoplasms
PubMed: 36137663
DOI: 10.3174/ajnr.A7647 -
Cancer Medicine Aug 2023Oligodendroglioma is known for its relatively better prognosis and responsiveness to radiotherapy and chemotherapy. However, little is known about the evolution of...
BACKGROUND
Oligodendroglioma is known for its relatively better prognosis and responsiveness to radiotherapy and chemotherapy. However, little is known about the evolution of genetic changes as oligodendroglioma progresses.
METHODS
In this study, we evaluated gene evolution invivo during tumor progression based on deep whole-genome sequencing data (ctDNA). We analyzed longitudinal genomic data from six patients during tumor evolution, of which five patients developed distant recurrence.
RESULTS
Whole-exome sequencing demonstrated that the rate of shared mutations between the primary and recurrent samples was relatively low. In two cases, even well-known major driver mutations in CIC and FUBP1 that were detected in primary tumors were not detected in the relapse samples. Among these cases, two patients had a conversion from the IDH mutation in the originating state to the IDH1 wild state during the process of gene evolution under chemotherapy treatment, indicating that the cell phenotype and genetic characteristics of oligodendroglioma may change during tumor evolution. Two patients received long-term temozolomide (TMZ) treatment before the operation, and we found that recurrence tumors harbored mutations in the PI3K/AKT and Sonic hedgehog (SHh) signaling pathways. Hypermutation occurred with mutations in MMR genes in one patient, contributing to the rapid progression of the tumor.
CONCLUSION
Oligodendroglioma displayed great spatial and temporal heterogeneity during tumor evolution. The PI3K/AKT and SHh signaling pathways may play an important role in promoting treatment resistance and distant relapse during oligodendroglioma evolution. In addition, there was a tendency to increase the degree of tumor malignancy during evolution. Distant recurrence may be a later event duringoligodendroglioma progression.
CLINICALTRIALS
gov, Identifier: NCT05512325.
Topics: Humans; Oligodendroglioma; Brain Neoplasms; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Hedgehog Proteins; Neoplasm Recurrence, Local; Mutation; Genomics; Isocitrate Dehydrogenase; DNA-Binding Proteins; RNA-Binding Proteins
PubMed: 37533228
DOI: 10.1002/cam4.6327 -
International Journal of Molecular... Oct 2023The median survival time has been reported to vary between 5 and 8 years in low-grade (WHO grade 2) astrocytoma, and between 10 and 15 years for grade 2...
The median survival time has been reported to vary between 5 and 8 years in low-grade (WHO grade 2) astrocytoma, and between 10 and 15 years for grade 2 oligodendroglioma. Targeted alpha therapy (TAT), using the modified peptide vector [Bi]Bi/[Ac]Ac-DOTA-substance P, has been developed to treat glioblastoma (GBM), a prevalent malignant brain tumor. In order to assess the risk of late neurotoxicity, assuming that reduced tumor cell proliferation and invasion should directly translate into good responses in low-grade gliomas (LGGs), a limited number of patients with diffuse invasive astrocytoma (n = 8) and oligodendroglioma (n = 3) were offered TAT. In two oligodendroglioma patients, TAT was applied as a second-line treatment for tumor progression, 10 years after targeted beta therapy using [Y]Y-DOTA-substance P. The radiopharmaceutical was locally injected directly into the tumor via a stereotactic insertion of a capsule-catheter system. The activity used for radiolabeling was 2-2.5 GBq of Bismuth-213 and 17 to 35 MBq of Actinium-225, mostly applied in a single fraction. The recurrence-free survival times were in the range of 2 to 16 years (median 11 years) in low-grade astrocytoma (n = 8), in which TAT was administered following a biopsy or tumor debulking. Regarding oligodendroglioma, the recurrence-free survival time was 24 years in the first case treated, and 4 and 5 years in the two second-line cases. In conclusion, TAT leads to long-term tumor control in the majority of patients with LGG, and recurrence has so far not manifested in patients with low-grade (grade 2) astrocytomas who received TAT as a first-line therapy. We conclude that targeted alpha therapy has the potential to become a new treatment paradigm in LGG.
Topics: Humans; Oligodendroglioma; Substance P; Glioma; Astrocytoma; Glioblastoma; Brain Neoplasms
PubMed: 37958683
DOI: 10.3390/ijms242115701 -
Acta Neuropathologica Feb 2022Oligodendrogliomas are defined at the molecular level by the presence of an IDH mutation and codeletion of chromosomal arms 1p and 19q. In the past, case reports and...
Oligodendrogliomas are defined at the molecular level by the presence of an IDH mutation and codeletion of chromosomal arms 1p and 19q. In the past, case reports and small studies described gliomas with sarcomatous features arising from oligodendrogliomas, so called oligosarcomas. Here, we report a series of 24 IDH-mutant oligosarcomas from 23 patients forming a distinct methylation class. The tumors were recurrences from prior oligodendrogliomas or developed de novo. Precursor tumors of 12 oligosarcomas were histologically and molecularly indistinguishable from conventional oligodendrogliomas. Oligosarcoma tumor cells were embedded in a dense network of reticulin fibers, frequently showing p53 accumulation, positivity for SMA and CALD1, loss of OLIG2 and gain of H3K27 trimethylation (H3K27me3) as compared to primary lesions. In 5 oligosarcomas no 1p/19q codeletion was detectable, although it was present in the primary lesions. Copy number neutral LOH was determined as underlying mechanism. Oligosarcomas harbored an increased chromosomal copy number variation load with frequent CDKN2A/B deletions. Proteomic profiling demonstrated oligosarcomas to be highly distinct from conventional CNS WHO grade 3 oligodendrogliomas with consistent evidence for a smooth muscle differentiation. Expression of several tumor suppressors was reduced with NF1 being lost frequently. In contrast, oncogenic YAP1 was aberrantly overexpressed in oligosarcomas. Panel sequencing revealed mutations in NF1 and TP53 along with IDH1/2 and TERT promoter mutations. Survival of patients was significantly poorer for oligosarcomas as first recurrence than for grade 3 oligodendrogliomas as first recurrence. These results establish oligosarcomas as a distinct group of IDH-mutant gliomas differing from conventional oligodendrogliomas on the histologic, epigenetic, proteomic, molecular and clinical level. The diagnosis can be based on the combined presence of (a) sarcomatous histology, (b) IDH-mutation and (c) TERT promoter mutation and/or 1p/19q codeletion, or, in unresolved cases, on its characteristic DNA methylation profile.
Topics: Adult; Aged; Brain Neoplasms; Female; Humans; Isocitrate Dehydrogenase; Male; Middle Aged; Mutation; Oligodendroglioma; Sarcoma
PubMed: 34967922
DOI: 10.1007/s00401-021-02395-z -
Seizure Dec 1996Twelve cases with circling seizures are presented with their clinical, electroencephalographic and radiological findings. Four patients had symptomatic partial epilepsy,...
Twelve cases with circling seizures are presented with their clinical, electroencephalographic and radiological findings. Four patients had symptomatic partial epilepsy, five had cryptogenic partial epilepsy, and the remaining three had idiopathic generalized epilepsy. Three of the patients with symptomatic partial epilepsy had frontal lesion, and one had parito-occipital lesion. Turning direction had no lateralizing value in patients with partial epilepsy. Based on our study we conclude that circling seizures may occur in different epileptic syndromes and epilepsies. In cases with symptomatic partial epilepsy, lesions are mostly located in frontal lobes but also in parietooccipital areas.
Topics: Adult; Astrocytoma; Brain Neoplasms; Cerebral Cortex; Diagnostic Imaging; Dominance, Cerebral; Electroencephalography; Epilepsies, Partial; Epilepsy, Complex Partial; Epilepsy, Generalized; Female; Follow-Up Studies; Humans; Male; Middle Aged; Oligodendroglioma; Stereotyped Behavior
PubMed: 8952016
DOI: 10.1016/s1059-1311(96)80024-0 -
Folia Histochemica Et Cytobiologica 2008Brain gliomas are characterized by invasive growth and neovascularisation potential. Angiogenesis plays a major role in the progression of gliomas and its determination...
Brain gliomas are characterized by invasive growth and neovascularisation potential. Angiogenesis plays a major role in the progression of gliomas and its determination has a great prognostic value. The aim of the study was to assess the vascularisation of chosen brain gliomas and to estimate how it is correlated with tumour histological type, malignancy grade, location and size, and with age and sex of patients. Tumour vascularisation analysis was based on the determination of microvascular proliferation (MVP) and microvessel density (MVD). Microvascular proliferation was measured with immunohistochemical methods using mouse monoclonal antibodies to detect cell proliferation antigens. The following antibodies were used Ki-67 and PCNA (DAKO). Identification of vessels was performed by CD31 antibody and anti-human von Willebrand factor (DAKO). The highest microvascular proliferation and microvascular density were observed in multiform glioblastomas and the lowest in oligodendrogliomas. Significant correlation was observed between the vascularisation and malignancy grade.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cell Proliferation; Endothelial Cells; Female; Glioma; Humans; Immunohistochemistry; Male; Middle Aged; Neovascularization, Pathologic; Oligodendroglioma
PubMed: 18296266
DOI: 10.2478/v10042-008-0009-4 -
CNS Oncology 2015Oligodendroglioma (WHO Grade 2) and anaplastic oligodendroglioma (WHO Grade 3) are glial tumors composed of neoplastic cellular elements that resemble oligodendrocytes.... (Review)
Review
Oligodendroglioma (WHO Grade 2) and anaplastic oligodendroglioma (WHO Grade 3) are glial tumors composed of neoplastic cellular elements that resemble oligodendrocytes. The treatment of recurrent, alkylator refractory oligodendroglial tumors is challenging given the paucity of effective treatment and lack of randomized controlled trials on which to base therapy. Notwithstanding the lack of prospective, randomized data, treatment of oligodendroglial tumors with bevacizumab can be recommended tentatively recognizing that preliminary studies suggest efficacy. Somatic mutations of the isocitrate dehydrogenase enzymes (IDH1 and IDH2) appear to play a critical role in the pathogenesis of most oligodendroglial tumors and agents that target these mutations are a potential therapeutic option. Additionally, reversal of CpG island hypermethylated phenotype status through inhibition of DNA methyltransferase with an inhibitor such as decitabine may provide a target for future studies.
Topics: Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Brain Neoplasms; Humans; Isocitrate Dehydrogenase; Neoplasm Recurrence, Local; Oligodendroglioma; Vascular Endothelial Growth Factor A
PubMed: 26509217
DOI: 10.2217/cns.15.27 -
Seizure Apr 2012Carbamazepine is used to control seizures. Its common side effects are sleep disorders, anorexia, nausea, vomiting, polydipsia, irritability, ataxia, and diplopia....
Carbamazepine is used to control seizures. Its common side effects are sleep disorders, anorexia, nausea, vomiting, polydipsia, irritability, ataxia, and diplopia. Involvement of the immune system is rare, and few cases of decreased immunoglobulin levels have been reported. We describe a patient with low immunoglobulin levels due to carbamazepine use who presented with recurrent urinary tract infection. Intravenous immunoglobulin was administered, and immunoglobulin levels increased to safer levels after discontinuation of carbamazepine. Previous reports describe severe infection after carbamazepine-induced hypogammaglobulinemia. Therefore, in patients using antiepileptics, particularly carbamazepine, serum immunoglobulin levels should be checked in those with recurrent infections.
Topics: Adult; Agammaglobulinemia; Anticonvulsants; Brain Neoplasms; Carbamazepine; Humans; Male; Oligodendroglioma; Seizures; Urinary Tract Infections
PubMed: 22251925
DOI: 10.1016/j.seizure.2011.12.013