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Indian Journal of Pathology &... May 2022The fifth edition of the World Health Organization (WHO) Classification of Tumors of the Central Nervous System (WHO CNS5) features several changes in the... (Review)
Review
A review of adult-type diffuse gliomas in the WHO CNS5 classification with special reference to Astrocytoma, IDH-mutant and Oligodendroglioma, IDH-mutant and 1p/19q codeleted.
The fifth edition of the World Health Organization (WHO) Classification of Tumors of the Central Nervous System (WHO CNS5) features several changes in the classification, diagnostic criteria, nomenclature, and grading of diffuse gliomas. Adult-type diffuse gliomas are genetically defined and include astrocytoma, isocitrate dehydrogenase (IDH)-mutant, oligodendroglioma, IDH-mutant and 1p/19q codeleted, and glioblastoma, IDH-wildtype. This review briefly discusses two tumor types: astrocytoma, IDH-mutant, and oligodendroglioma, IDH-mutant and 1p/19q codeleted, with emphasis on relevant changes in their classification and defining molecular genetic alterations. A simplified approach to the diagnosis of these tumors is provided.
Topics: Adult; Astrocytoma; Brain Neoplasms; Glioma; Humans; Isocitrate Dehydrogenase; Mutation; Oligodendroglioma; World Health Organization
PubMed: 35562130
DOI: 10.4103/ijpm.ijpm_34_22 -
BMC Cancer Apr 2021Astrocytoma is a common type of central nervous system tumor. In this study, we investigated the correlation between ST6GAL1 and CYP19A1 polymorphisms and the risk and...
BACKGROUND
Astrocytoma is a common type of central nervous system tumor. In this study, we investigated the correlation between ST6GAL1 and CYP19A1 polymorphisms and the risk and prognosis of astrocytoma.
METHODS
A total of 365 astrocytoma patients and 379 healthy controls were genotyped using the Agena MassARRAY system. The correlation between ST6GAL1 and CYP19A1 variants and astrocytoma risk was calculated using logistic regression. The survival rate of patients with astrocytoma was analyzed to evaluate prognosis.
RESULTS
We found that the ST6GAL1-rs2239611 significantly decreased the risk of astrocytoma in the codominant model (p = 0.044) and dominant model (p = 0.049). In stratified analyses, CYP19A1-rs2255192 might be associated with a higher risk of astrocytoma among the low-grade subgroup under recessive (p = 0.034) and additive (p = 0.030) models. However, CYP19A1-rs4646 had a risk-decreasing effect on the high-grade subgroup in the codominant model (p = 0.044). The results of Cox regression analysis showed that the CYP19A1-rs2239611 and -rs1042757 polymorphisms were significantly correlated with the prognosis of astrocytoma.
CONCLUSION
Our results suggest that ST6GAL1 and CYP19A1 genes may be a potential biomarker of genetic susceptibility and prognosis to astrocytoma in the Chinese Han population.
Topics: 3' Untranslated Regions; Adult; Alleles; Antigens, CD; Aromatase; Asian People; Astrocytoma; Case-Control Studies; China; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Prognosis; Risk Assessment; Risk Factors; Sialyltransferases; Survival Analysis
PubMed: 33836687
DOI: 10.1186/s12885-021-08110-1 -
Clinical Neurology and Neurosurgery Aug 2016Anaplastic pilocytic astrocytoma (APA) is an exceptionally rare type of high-grade glioma in adults. Establishing histopathological diagnosis is challenging and its... (Review)
Review
INTRODUCTION
Anaplastic pilocytic astrocytoma (APA) is an exceptionally rare type of high-grade glioma in adults. Establishing histopathological diagnosis is challenging and its clinical and radiological appearance insidious. By this case series and first literature review we investigated the various clinical, neuroradiological, and histopathological features of APA in adults.
METHODS
An in hospital screening of the database from the Institute of Pathology was conducted to identify cases of APA. Further, we performed a literature review in PubMed using the keywords "anaplastic/malignant/atypical AND pilocytic astrocytoma" and "anaplastic astrocytoma/glioblastoma AND Rosenthal fibers" and summarized the current knowledge about APA in adults.
RESULTS
Over the last decade we were able to identify 3 adult patients with APA in our hospital. According to the pertinent literature, the prognosis of APA in adults (documented survival of up to 10 years) appears to be better than in other high-grade gliomas. Few cases were associated with neurofibromatosis type 1, which seems to predispose for development of APA. Although molecular genetics is still of limited value for differentiation of APA from other high-grade glioma, advanced neuroimaging techniques such as magnetic resonance perfusion imaging and spectroscopy allow improved differential work-up. In particular, APA in adults has the ability to mimic various neurological diseases such as tumefactive demyelinating lesions, low-, or high-grade gliomas.
CONCLUSIONS
Although currently not explicitly recognized as a distinct clinico-pathologic entity it seems that adult APA behaves differently from conventional high-grade glioma and should be included in differential diagnostics to enable adequate patient care. However, further studies are needed to better understand this extremely rare disease.
Topics: Adult; Astrocytoma; Brain Neoplasms; Female; Humans; Male; Middle Aged
PubMed: 27341279
DOI: 10.1016/j.clineuro.2016.06.005 -
Molecular Medicine (Cambridge, Mass.) Mar 2022IDH-mutant astrocytoma and oligodendroglioma have an indolent natural history and are recognized as distinct entities of neoplasms. There is little knowledge on the...
BACKGROUND
IDH-mutant astrocytoma and oligodendroglioma have an indolent natural history and are recognized as distinct entities of neoplasms. There is little knowledge on the molecular differences between IDH-mutant astrocytoma and oligodendroglioma grade 2. Therefore, we investigated the multiomics and clinical data regarding these two types of tumors.
METHOD
In silico analyses were performed around mRNA, somatic mutations, copy number alternations (CNAs), DNA methylation, microRNA (miRNA), epigenetics, immune microenvironment characterization and clinical features of the two types of gliomas. A diagnostic model incorporating tumor purity was further established using machine learning algorithms, and the predictive value was evaluated by receiver operative characteristic curves.
RESULTS
Both types of gliomas shared chromosomal instability, and astrocytomas exhibited increased total CNAs compared to oligodendrogliomas. Oligodendrogliomas displayed distinct chromosome 4 (chr 4) loss, and subtyping of chr 7 gain/chr 4 loss (+ 7/- 4) presented the worst survival (P = 0.004) and progression-free interval (PFI) (P < 0.001). In DNA damage signatures, oligodendroglioma had a higher subclonal genome fraction (P < 0.001) and tumor purity (P = 0.001), and astrocytoma had a higher aneuploidy score (P < 0.001). Furthermore, astrocytomas exhibited inflamed immune cell infiltration, activated T cells and a potential response to immune checkpoint inhibitors (ICIs), while oligodendrogliomas were more homogeneous with increased tumor purity and decreased aggression. The tumor purity-involved diagnostic model exhibited great accuracy in identifying astrocytoma and oligodendroglioma.
CONCLUSION
This study addresses the similarities and differences between IDH-mutant astrocytoma and oligodendroglioma grade 2 and facilitates a deeper understanding of their molecular features, immune microenvironment, tumor purity and prognosis. The diagnostic tool developed using machine learning may offer support for clinical decisions.
Topics: Astrocytoma; Brain Neoplasms; Chromosome Deletion; Genomics; Glioma; Humans; Isocitrate Dehydrogenase; Mutation; Oligodendroglioma; Tumor Microenvironment
PubMed: 35287567
DOI: 10.1186/s10020-022-00454-z -
Glia Aug 2019Gliomas are a heterogenous group of malignant primary brain tumors that arise from glia cells or their progenitors and rely on accurate diagnosis for prognosis and...
Gliomas are a heterogenous group of malignant primary brain tumors that arise from glia cells or their progenitors and rely on accurate diagnosis for prognosis and treatment strategies. Although recent developments in the molecular biology of glioma have improved diagnosis, classical histological methods and biomarkers are still being used. The glial fibrillary acidic protein (GFAP) is a classical marker of astrocytoma, both in clinical and experimental settings. GFAP is used to determine glial differentiation, which is associated with a less malignant tumor. However, since GFAP is not only expressed by mature astrocytes but also by radial glia during development and neural stem cells in the adult brain, we hypothesized that GFAP expression in astrocytoma might not be a direct indication of glial differentiation and a less malignant phenotype. Therefore, we here review all existing literature from 1972 up to 2018 on GFAP expression in astrocytoma patient material to revisit GFAP as a marker of lower grade, more differentiated astrocytoma. We conclude that GFAP is heterogeneously expressed in astrocytoma, which most likely masks a consistent correlation of GFAP expression to astrocytoma malignancy grade. The GFAP positive cell population contains cells with differences in morphology, function, and differentiation state showing that GFAP is not merely a marker of less malignant and more differentiated astrocytoma. We suggest that discriminating between the GFAP isoforms GFAPδ and GFAPα will improve the accuracy of assessing the differentiation state of astrocytoma in clinical and experimental settings and will benefit glioma classification.
Topics: Animals; Astrocytoma; Biomarkers, Tumor; Central Nervous System Neoplasms; Glial Fibrillary Acidic Protein; Humans; Protein Isoforms
PubMed: 30667110
DOI: 10.1002/glia.23594 -
Diagnostic and Interventional Radiology... Nov 2021The reliability and reproducibility of T2-weighted imaging/ fluid-attenuated inversion recovery (T2/FLAIR) mismatch were investigated in the diagnosis of isocitrate...
PURPOSE
The reliability and reproducibility of T2-weighted imaging/ fluid-attenuated inversion recovery (T2/FLAIR) mismatch were investigated in the diagnosis of isocitrate dehydrogenase (IDH) mutant astrocytoma between WHO grade II and III diffuse hemispheric gliomas.
METHODS
WHO grade II and grade III diffuse hemispheric gliomas (n=133) treated in our institute were included in the study. Pathological findings and molecular markers of the cases were reviewed with the criteria of WHO 2016. The finding of mismatch between T2-weighted and FLAIR images in preoperative magnetic resonance imaging (MRI) of the cases was evaluated by two different radiologists. The readers reviewed MRIs independently, blinded to the histopathologic diagnosis or molecular subset of tumors. The cases were classified as IDH-mutant astrocytoma, oligodendroglioma and IDH-wildtype (IDH-wt) astrocytoma according to molecular and genetic features.
RESULTS
T2/FLAIR mismatch positivity was observed in 46 patients (34.6%). T2/FLAIR mismatch positivity was observed in 42 of 75 IDH-mutant astrocytomas (56%) and 4 of 43 oligodendrogliomas (9.30%), while it was not seen among IDH-wt astrocytomas (0/15, 0%). The T2/FLAIR mismatch ratio was significantly different between IDH-mutant astrocytomas (WHO grade II and grade III) and oligodendrogliomas (chi-square, p <0.05). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of T2/FLAIR mismatch in predicting IDH-mutant astrocytomas were 58.7%, 90.7%, 91.7%, 61.4%, and 70.3% respectively. Radiologist 1 diagnosed T2/FLAIR mismatch in 48 of 133 cases (36.1%) and Radiologist 2 in 66 of 133 cases (49.6%). The interrater agreement for the T2/FLAIR mismatch sign was 0.61 (p <0.05), 95% CI (0.55, 0.67).
CONCLUSION
T2/FLAIR mismatch appears to be an important MRI finding in distinguishing IDH-mutant astrocytomas from other diffuse hemispheric gliomas. However, it should be kept in mind that T2/FLAIR mismatch sign can be seen in a minority of oligodendrogliomas besides IDH-mutant astrocytomas.
Topics: Astrocytoma; Brain Neoplasms; Humans; Isocitrate Dehydrogenase; Magnetic Resonance Imaging; Mutation; Reproducibility of Results; Retrospective Studies
PubMed: 34792037
DOI: 10.5152/dir.2021.20624 -
Scientific Reports Jun 2021Astrocytoma is the most common glial tumour of the CNS. The most malignant form is grade IV Astrocytoma, also called Glioblastoma. Due to its heterogeneity,...
Astrocytoma is the most common glial tumour of the CNS. The most malignant form is grade IV Astrocytoma, also called Glioblastoma. Due to its heterogeneity, aggressiveness and lethal nature scientists are trying to find less invasive methods for early prediction of tumour onset, recurrence, response to therapy and patients' survival. Here, applying decision tree classification algorithm we performed astrocytoma specific protein profile analysis on serum proteins TIMP-1, active and latent form of TGF-β1, IP-10, ANGPT-1, OPN, and YKL-40 using enzyme-linked immunosorbent detection assay (ELISA). Results have demonstrated that astrocytoma specific profile consisted of three proteins-active form of TGF-β1, TIMP-1 and YKL-40 and was able to correctly classify 78.0% (103/132) of sample and 83.3% (60/72) of astrocytoma sample. Calculating decision tree algorithm associated with astrocytoma patient survival, prediction model reached an accuracy of 83.3% (60/72). All together these results indicate that glioma detection and prediction from patient serum using glioma associated proteins and applying mathematical classification tools could be achieved, and applying more comprehensive research further could be implemented in clinic.
Topics: Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; Case-Control Studies; Chitinase-3-Like Protein 1; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; Middle Aged; Prognosis; Survival Analysis; Tissue Inhibitor of Metalloproteinase-1; Transforming Growth Factor beta1
PubMed: 34162919
DOI: 10.1038/s41598-021-92328-3 -
Intractable & Rare Diseases Research Nov 2020Pilocytic astrocytomas are tumors of the central nervous system mostly during the first two decades of life. Although they are mostly common in the midline structures of...
Pilocytic astrocytomas are tumors of the central nervous system mostly during the first two decades of life. Although they are mostly common in the midline structures of children, pilocytic astrocytoma within the ventricular system of an adult is extremely rare. We report a case of a 38-year old woman with obstructive hydrocephalus secondary to a brain tumor within the third ventricle. On histological examination, the tumor exhibited biphasic growth pattern comprising compacted cellular areas with Rosenthal fibers and loose textured microcystic areas with eosinophilic granular bodies. Mitosis or necrosis was not present. Immunohistochemical studies demonstrated glial fibrillary acid protein (GFAP), Olig2, and ATRX positivity as well as NeuN and EMA negativity. Ki67 labeling index was less than 1%. Molecular studies revealed that there are no isocitrate dehydrogenase () gene mutation and mutation. This clinical presentation along with the histologic and molecular findings is consistent with a pilocytic astrocytoma arising in the third ventricle of this adult brain, which indicates that pilocytic astrocytoma can present as an intraventricular tumor in an adult patient and should be routinely included in the differential diagnosis of intraventricular brain neoplasm.
PubMed: 33139987
DOI: 10.5582/irdr.2020.03088 -
Laboratory Investigation; a Journal of... Jul 2022Pleomorphic xanthoastrocytomas (PXAs) are rare tumors accounting for less than 1% of astrocytomas. They commonly occur in young patients and have relatively favorable... (Review)
Review
Pleomorphic xanthoastrocytomas (PXAs) are rare tumors accounting for less than 1% of astrocytomas. They commonly occur in young patients and have relatively favorable prognosis. However, they are well known to have heterogenous morphology and biological behavior with the potential to recur and disseminate throughout the central nervous system, especially their anaplastic counterparts. Recent advances in the molecular characterization have discovered BRAFp.V600E mutations in conjunction with CDKN2A/B deletions and TERTp mutations to be the most frequent alterations in PXAs. These tumors can present a diagnostic challenge as they share overlapping histopathological, genomic as well as methylation profile with various other tumor types, particularly epithelioid glioblastomas (eGBs). This review provides the spectrum of evolution of PXAs from their genesis to recent molecular insights and attempts to review pathogenesis and relationship to other tumors that they mimic especially eGB. It is postulated based on evidence from literature that PXA and eGB are possibly related and not distinct entities, being two ends of a continuous spectrum of malignant progression (grade 2-grade 4) with anaplastic PXA (grade 3) lying in between. Future WHO classifications will have to possibly redefine these tumors using more confirmatory data from larger studies.
Topics: Astrocytoma; Brain Neoplasms; Glioblastoma; Humans; Mutation; Prognosis; Proto-Oncogene Proteins B-raf
PubMed: 35031693
DOI: 10.1038/s41374-021-00708-0 -
Journal of Neurosurgery. Case Lessons Mar 2022Treatment of pilocytic astrocytomas (PAs) in children can be challenging when they arise in deep midline structures because complete surgical resection may result in...
BACKGROUND
Treatment of pilocytic astrocytomas (PAs) in children can be challenging when they arise in deep midline structures because complete surgical resection may result in significant neurological injury. Laser interstitial thermal therapy (LITT) has provided an alternative treatment modality for lesions that may not be amenable to resection. However, many patients with PAs may be symptomatic from a compressive cyst associated with the PA, and LITT does not obviate the need for cystic decompression in these patients.
OBSERVATIONS
A 12-year-old male presented with left-sided weakness. Magnetic resonance imaging (MRI) revealed an enhancing mass with a large cyst involving the right thalamus and basal ganglia. The patient underwent a reservoir placement for cyst drainage and biopsy of the mass, revealing a pilocytic astrocytoma. He then underwent LITT followed by adjuvant chemotherapy. Sixteen months after LITT, follow-up MRI of the brain revealed no tumor growth.
LESSONS
This is the first case to describe reservoir placement to treat the cystic portion of a pilocytic astrocytoma followed by LITT and targeted chemotherapy. Reservoir placement reduced the cyst's mass effect and resolved the patient's symptoms, allowing for treatment options beyond resection.
PubMed: 36209402
DOI: 10.3171/CASE21363