-
Acta Medica Academica Apr 2021This review focuses on adult gliomas, highlighting the most relevant biomarkers in the diagnosis of these tumours and the use of DNA methylation arrays to complement... (Review)
Review
This review focuses on adult gliomas, highlighting the most relevant biomarkers in the diagnosis of these tumours and the use of DNA methylation arrays to complement conventional molecular diagnostic techniques. The discovery and characterisation of diagnostic and prognostic biomarkers in brain tumours has significantly changed the neuropathological landscape over the last decade. These include mutations in the IDH1 and IDH2 genes in astrocytomas and oligodendrogliomas, histone H3 K27M mutations in midline gliomas, or BRAF mutations in a range of low-grade and high-grade glial and glioneuronal tumours. Other biomarkers of relevance are mutations in the TERT promoter, the ATRX gene, and genomic alterations such as 1p/19q codeletion, EGFR amplification, and chromosome 7 gain and 10 loss. The development of DNA methylation profiling and algorithmic classification of brain tumours has further enhanced the diagnostic abilities of neuropathologists. Methylation profiling is particularly useful for the diagnostic workup of biopsies with an inconclusive molecular test results, small samples, or samples with indistinctive low-grade or high-grade histology. This technology has become indispensable for the risk stratification of ependymal tumours, medulloblastomas and meningiomas. CONCLUSION: This review highlights the importance of an integrated approach to brain tumour diagnostics and gives a balanced view of the relevance and choice of conventional and molecular techniques in the workup of adult gliomas in diagnostic neuropathology practice.
Topics: Adult; Glioma; Humans; Isocitrate Dehydrogenase; Neuropathology; Oligodendroglioma; Pathology, Molecular
PubMed: 34075762
DOI: 10.5644/ama2006-124.324 -
Neuro-oncology Dec 2022IDH-mutant gliomas are separate based on the codeletion of the chromosomal arms 1p and 19q into oligodendrogliomas IDH-mutant 1p/19q-codeleted and astrocytomas...
BACKGROUND
IDH-mutant gliomas are separate based on the codeletion of the chromosomal arms 1p and 19q into oligodendrogliomas IDH-mutant 1p/19q-codeleted and astrocytomas IDH-mutant. While nuclear loss of ATRX expression excludes 1p/19q codeletion, its limited sensitivity prohibits to conclude on 1p/19q status in tumors with retained nuclear ATRX expression.
METHODS
Employing mass spectrometry based proteomic analysis in a discovery series containing 35 fresh frozen and 72 formalin fixed and paraffin embedded tumors with established IDH and 1p/19q status, potential biomarkers were discovered. Subsequent validation immunohistochemistry was conducted on two independent series (together 77 oligodendrogliomas IDH-mutant 1p/19q-codeleted and 92 astrocytomas IDH-mutant).
RESULTS
We detected highly specific protein patterns distinguishing oligodendroglioma and astrocytoma. In these patterns, high HIP1R and low vimentin levels were observed in oligodendroglioma while low HIP1R and high vimentin levels occurred in astrocytoma. Immunohistochemistry for HIP1R and vimentin expression in 35 cases from the FFPE discovery series confirmed these findings. Blinded evaluation of the validation cohorts predicted the 1p/19q status with a positive and negative predictive value as well as an accuracy of 100% in the first cohort and with a positive predictive value of 83%; negative predictive value of 100% and an accuracy of 92% in the second cohort. Nuclear ATRX loss as marker for astrocytoma increased the sensitivity to 96% and the specificity to 100%.
CONCLUSIONS
We demonstrate that immunohistochemistry for HIP1R, vimentin, and ATRX predict 1p/19q status with 100% specificity and 95% sensitivity and therefore, constitutes a simple and inexpensive approach to the classification of IDH-mutant glioma.
Topics: Humans; Oligodendroglioma; Isocitrate Dehydrogenase; Immunohistochemistry; Vimentin; Brain Neoplasms; Proteomics; Mutation; Glioma; Astrocytoma; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 19; Microfilament Proteins; Adaptor Proteins, Signal Transducing
PubMed: 35511748
DOI: 10.1093/neuonc/noac111 -
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 -
Scientific Reports Aug 2022Oligodendrogliomas are typically associated with the most favorable prognosis among diffuse gliomas. However, many of the tumors progress, eventually leading to patient...
Oligodendrogliomas are typically associated with the most favorable prognosis among diffuse gliomas. However, many of the tumors progress, eventually leading to patient death. To characterize the changes associated with oligodendroglioma recurrence and progression, we analyzed two recurrent oligodendroglioma tumors upon diagnosis and after tumor relapse based on whole-genome and RNA sequencing. Relapsed tumors were diagnosed as glioblastomas with an oligodendroglioma component before the World Health Organization classification update in 2016. Both patients died within 12 months after relapse. One patient carried an inactivating POLE mutation leading to a clearly hypermutated progressed tumor. Strikingly, both relapsed tumors carried focal chromosomal rearrangements in PTPRD and CNTNAP2 genes with associated decreased gene expression. TP53 mutation was also detected in both patients after tumor relapse. In The Cancer Genome Atlas (TCGA) diffuse glioma cohort, PTPRD and CNTNAP2 expression decreased by tumor grade in oligodendrogliomas and PTPRD expression also in IDH-mutant astrocytomas. Low expression of the genes was associated with poor overall survival. Our analysis provides information about aggressive oligodendrogliomas with worse prognosis and suggests that PTPRD and CNTNAP2 expression could represent an informative marker for their stratification.
Topics: Astrocytoma; Biomarkers; Biomarkers, Tumor; Brain Neoplasms; Glioma; Humans; Isocitrate Dehydrogenase; Membrane Proteins; Mutation; Neoplasm Recurrence, Local; Nerve Tissue Proteins; Oligodendroglioma; Receptor-Like Protein Tyrosine Phosphatases, Class 2
PubMed: 35982066
DOI: 10.1038/s41598-022-14977-2 -
Pathologica Dec 2022Glioneuronal tumours (GNT) are uncommon neoplasms, characterised by glial and neuronal differentiation. In the 5th edition of the World Health Organization (WHO)... (Review)
Review
Glioneuronal tumours (GNT) are uncommon neoplasms, characterised by glial and neuronal differentiation. In the 5th edition of the World Health Organization (WHO) Classification, they are grouped under the heading "Glioneuronal and neuronal tumours", which comprises fourteen different tumours, among which the diffuse glioneuronal tumour with oligodendroglioma-like cells and nuclear clusters (DGONC), myxoyd glioneuronal tumour (MGT) and multinodular and vacuolating neuronal tumour (MNVNT) are new types. MGT and MNVNT are classified WHO grade 1 and may be recognised and diagnosed by peculiar clinical-pathological features. DGONC was not assigned a WHO grade and was only provisionally included among GNT, due to the possibility that it rather represents an embryonal tumour type or subtype. Although the histopathological characteristics may be useful for its identification, the specific methylation profile is an essential diagnostic criterion for DGONC.
Topics: Humans; Central Nervous System Neoplasms; Neuroglia; Neurons; World Health Organization; Brain Neoplasms
PubMed: 36534423
DOI: 10.32074/1591-951X-819 -
Radiology Case Reports Apr 2023Oligodendroglioma, the third most common glioma, accounts for 5% of primary brain tumors and around 20% of all glial neoplasms. They are quite uncommon in children....
Oligodendroglioma, the third most common glioma, accounts for 5% of primary brain tumors and around 20% of all glial neoplasms. They are quite uncommon in children. Here, we aimed to show an unusual case of a 9-year-old boy developing a huge anaplastic oligodendroglioma. A high-grade astrocytoma-like supratentorial tumor was discovered by a sophisticated brain scan employing magnetic resonance imaging. The tumor was identified by histopathology as an anaplastic oligodendroglioma. Anaplastic oligodendroglioma should be considered while making the differential diagnosis of high-grade astrocytoma notwithstanding its rarity.
PubMed: 36815147
DOI: 10.1016/j.radcr.2023.01.059 -
Surgical Neurology International 2022Oligodendrogliomas are generally low-grade glial neoplasms commonly occurring in a cortical or subcortical location and frequently contain coarse calcifications. Tumors...
BACKGROUND
Oligodendrogliomas are generally low-grade glial neoplasms commonly occurring in a cortical or subcortical location and frequently contain coarse calcifications. Tumors with 1p and 19q codeletions behave atypically and are more likely to have ill-defined margins and tend to have calcification. Very rarely, diffuse pattern and gliomatosis type of infiltrative nature of oligodendrogliomas have been described in sporadic case reports.
CASE DESCRIPTION
In this article, we present a case of a 31-year-old male who had diffuse multifocal oligodendroglioma with rare features of extensive callosal and brainstem involvement on imaging.
CONCLUSION
Rare cases of oligodendrocytic gliomatosis cerebri or oligodendrogliomatosis with diffuse white matter spread of these tumors usually lead to a detrimental course of neurological status and a poor prognosis in these patients.
PubMed: 36324958
DOI: 10.25259/SNI_589_2022 -
CNS Oncology 2015Radiotherapy has been a longstanding treatment option for low-grade glioma. Improvements in tumor control and radiation-related toxicity may be attributed to advances in... (Review)
Review
Radiotherapy has been a longstanding treatment option for low-grade glioma. Improvements in tumor control and radiation-related toxicity may be attributed to advances in neuroimaging as well as radiotherapy planning and delivery. The discovery of various molecular prognostic factors have aided in patient selection for radiotherapy. These prognostic and predictive factors may also play a key role in determining which patients are likely to benefit most from combined systemic therapy and radiation.
Topics: Brain Neoplasms; Combined Modality Therapy; Humans; Neuroimaging; Oligodendroglioma; Radiotherapy Dosage; Radiotherapy, Computer-Assisted
PubMed: 26477980
DOI: 10.2217/cns.15.25 -
CNS Oncology 2015Oligodendroglial tumors are chemosensitive with a favorable prognosis compared with other histological subtypes. The genetic hallmark of co-deletion of 1p and 19q... (Review)
Review
Oligodendroglial tumors are chemosensitive with a favorable prognosis compared with other histological subtypes. The genetic hallmark of co-deletion of 1p and 19q determines both treatment response and prognosis. While this test now forms part of routine histopathology diagnosis in many laboratories, alternative noninvasive imaging biomarkers of tumor genotype remain an attractive proposition. This review will focus on imaging biomarkers of molecular genetics in oligodendroglial tumors.
Topics: Brain Neoplasms; Chromosome Deletion; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 9; Humans; Neuroimaging; Oligodendroglioma
PubMed: 26478219
DOI: 10.2217/cns.15.37 -
Folia Neuropathologica 2021This study has assessed the diagnostic ability of oligodendrocyte-2 (Olig2), CD99, and epithelial membrane antigen (EMA) immunohistochemical stains to diagnose...
INTRODUCTION
This study has assessed the diagnostic ability of oligodendrocyte-2 (Olig2), CD99, and epithelial membrane antigen (EMA) immunohistochemical stains to diagnose oligodendroglial-like neoplasms as central neurocytoma, ependymoma, or oligodendroglioma.
MATERIAL AND METHODS
An immunohistochemistry (IHC) panel of Olig2, EMA, and CD99 was performed on 18 central neurocytomas, 46 ependymomas, and 28 oligodendrogliomas. A quantitative labelling index of stained tumor cells was assessed using a scoring system, and its diagnostic predictability was evaluated with multinomial logistic regression.
RESULTS
Significant differences in IHC expression patterns were observed between all tumor groups (p < 0.001). The labeling indices of the histochemical expression of Olig2, EMA, and CD99 were related to diagnostic predictability. Olig2 was unlikely to differentiate ependymoma from central neurocytoma (p = 0.154), while EMA and CD99 were significant in diagnosing these two tumors (p < 0.05). Olig2 was a specific marker of oligodendroglioma, differentiating it from ependymoma and central neurocytoma (p 0.05), but CD99 significantly differentiated ependymoma from oligodendroglioma (p = 0.022). These labelling indices were used to re-assess the diagnostic accuracy, regardless of tumor location and histology, and yielded significantly different tumor diagnoses.
CONCLUSIONS
The IHC panel of Olig2, EMA, and CD99 should be used to differentiate oligodendroglial-like neoplasms. Olig2 is a specific IHC marker to diagnose oligodendroglioma and differentiate it from ependymoma and central neurocytoma. Lack of Olig2 expression rules out oligodendroglioma and suggests the diagnosis of ependymoma rather than central neurocytoma if the EMA labelling index shows diffuse/partial expression. CD99 is considered a sensitive marker for ependymoma but not central neurocytoma.
Topics: 12E7 Antigen; Biomarkers, Tumor; Brain Neoplasms; Ependymoma; Humans; Mucin-1; Neurocytoma; Oligodendrocyte Transcription Factor 2; Oligodendroglia; Oligodendroglioma
PubMed: 34628794
DOI: 10.5114/fn.2021.108526