Journal articles on the topic 'Glioma diagnosis'
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Cherkasova, Olga, Yan Peng, Maria Konnikova, Yuri Kistenev, Chenjun Shi, Denis Vrazhnov, Oleg Shevelev, Evgeny Zavjalov, Sergei Kuznetsov, and Alexander Shkurinov. "Diagnosis of Glioma Molecular Markers by Terahertz Technologies." Photonics 8, no. 1 (January 16, 2021): 22. http://dx.doi.org/10.3390/photonics8010022.
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This review considers glioma molecular markers in brain tissues and body fluids, shows the pathways of their formation, and describes traditional methods of analysis. The most important optical properties of glioma markers in the terahertz (THz) frequency range are also presented. New metamaterial-based technologies for molecular marker detection at THz frequencies are discussed. A variety of machine learning methods, which allow the marker detection sensitivity and differentiation of healthy and tumor tissues to be improved with the aid of THz tools, are considered. The actual results on the application of THz techniques in the intraoperative diagnosis of brain gliomas are shown. THz technologies’ potential in molecular marker detection and defining the boundaries of the glioma’s tissue is discussed.
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Lee, Ian, Lisa Scarpace, Rachel Hunt, Kevin Nelson, Darshana Patil, Vineet Datta, Dadasaheb Akolkar, et al. "PATH-64. PROSPECTIVE, BLINDED PLASMA BASED ANALYSIS FOR DIAGNOSIS OF NEWLY DIAGNOSED GLIOMA." Neuro-Oncology 21, Supplement_6 (November 2019): vi157—vi158. http://dx.doi.org/10.1093/neuonc/noz175.659.
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Abstract INTRODUCTION In patients with newly diagnosed intracerebral lesions, gliomas are often suspected. However, other conditions such as multiple sclerosis, abscess or lymphoma are possible, as well. Furthermore, biopsy can be challenging due to eloquent and/or deep location within the brain. In this prospective, blinded study, analysis of plasma isolated cell-free DNA and exosome mRNA and miRNA from newly diagnosed glioma patients and from cancer-free volunteers was used to predict disease. METHODS Plasma was drawn from 52 patients with newly diagnosed gliomas (28 high grade glioma (HGG), 10 low grade (LGG)) and 14 patients without documented history of cancer and recent MRI brain which was negative for brain tumor. High quality DNA and RNA was isolated and sequenced using Next Generation Sequencing and Digital Droplet PCR was used for detection and verification of trace molecular artifacts. Multianalyte processing yielded data that was harmonized and interpreted through an Artificial Intelligence based algorithm to assess for possible glioma and to assign grade in a blinded fashion. EGFRvIII, TP53 and IDH1 mutations were also analyzed and compared to molecular testing from tumor specimens. RESULTS 66% (25 of 38) of glioma patients were correctly diagnosed as having a malignancy. 43% of HGG and 60% of LGG patients were correctly graded. Of the 14 normal controls, 6 were concluded to be cancer-free. IDH1, EGFRvIII, and TP53 mutation had concordance of 64% (21/33), 82% (14/17) and 36% (5/14), respectively. CONCLUSIONS Analysis of plasma cell free tumor derived DNA and RNA was relatively sensitive for detecting glioma in treatment naïve patients. In contrast, this analysis was not specific in ruling out malignancy in the normal control patients. Given this profile, in patients with newly diagnosed intracerebral lesions suspicious for glioma, this may be a useful screening test to determine the need for more invasive testing, i.e. biopsy/resection.
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Nechipay, E. A., M. B. Dolgushin, A. I. Pronin, E. A. Kobyakova, and L. M. Fadeeva. "Dynamic Contrast Enhanced MRI in Glioma Diagnosis." Medical Visualization, no. 4 (August 28, 2017): 88–96. http://dx.doi.org/10.24835/1607-0763-2017-4-88-96.
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The aim: to examine the possibility of using dynamic contrast enhanced magnetic resonance imaging (DCE MRI) in clarifying the diagnosis of glial brain tumors and the differentiation between them on the basis of the malignancy degree. In this regard, the authors evaluated the effectiveness of perfusion parameters (Ktrans, Kep, Ve and iAUC).Materials and methods.The study included examination of 54 patients with an established presence of brain glial tumors. Glioma Grade I–II diagnosed in 13 (24.1%) and glioma Grade III–IV in 41 (75.9%) cases. Morphological verification of the diagnosis obtained as a result of either surgical removal of the tumor or stereotactic biopsy was achieved in 31 (57.4%) patients: glial tumors Grade I–II identified in 6 (19.4%), and glioma Grade III–IV – 25 (80.6%) cases. Results. According to DCE increasing of the malignancy degree of glial tumors is followed by increasing of all perfusion parameters: thus, the lowest values of Ktrans, Kep, Ve and iAUC were identified in low grade gliomas (0.026 min−1, 0.845 min−1, 0.024 and 1.757, respectively), the highest in gliomas Grade III–IV (0.052 min−1 1.083 min−1, 0.06 and 2.694, respectively). The most informative parameters with sensi tivity 90% and specificity 100% in the differential diagnosis of gliomas Grade I-II and Grade III-IV are Ktrans (cut-off = 0.16 min−1) and Ve (cut-off = 0.13).Conclusion.DCE MRI can be used in differential diagnosis of glial brain tumors of different malignancy grade.
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Zhao, Shiguang. "BIOM-63. DIAGNOSIS AND PROGNOSTIC SIGNIFICANCE OF CIRCULATING miR-2276-5p IN PLASMA OF GLIOMA PATIENTS." Neuro-Oncology 22, Supplement_2 (November 2020): ii15. http://dx.doi.org/10.1093/neuonc/noaa215.060.
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Abstract Circulating microRNAs (miRNAs) in plasma have the potential to become diagnostic and prognostic biomarkers for various cancers. This study hopes to use plasma circulating miRNAs as biomarkers for diagnosis and prognosis of glioma patients. METHOD: In this study, the plasma circulating miRNAs of 124 patients with glioma and 36 controls was collected to detect the relative expression of miR-2276-5p, and the specificity and sensitivity of the diagnosis were verified by ROC curve. The follow-up survival status was analyzed by cox regression analysis. RESULT: In the GSE 139031 database, it was found that the expression of circulating miR-2276-5p in plasma of glioma patients was significantly lower than that of patients with non-gliomas. Using our plasma samples, and it is indicated that the expression of circulating miR-2276-5p in plasma is lower than that of healthy patients, and compared with low-grade gliomas, patients with high-grade gliomas have a lower expression of circulating miR-2276-5p. ROC curve analysis found that the AUC value was 0.851. The low expression of circulating miR-2276-5p in plasma of glioma patients indicates a poor prognosis of glioma patients, After univariate and multifactorial cox regression analysis, which can be used as an independent prognostic risk factor for glioma patients (P< 0.05). CONCLUSION: The expression of circulating miR-2276-5p in plasma of glioma patients was significantly lower than that of the control group, compared with low-grade gliomas, patients with high-grade gliomas have a lower expression of circulating miR-2276-5p. The lower the relative expression of circulating miR-2276-5p indicated that glioma patients had a worse prognosis.
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Yin, Luxin, and Liwei Zhang. "Correlation Between MRI Findings and Histological Diagnosis of Brainstem Glioma." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 40, no. 3 (May 2013): 348–54. http://dx.doi.org/10.1017/s0317167100014293.
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Objective:In most studies, treatment decisions of brainstem glioma are based solely on MRI features and do not incorporate a histopathological diagnosis. In the current study, we sought to compare MRI characteristics with histopathological findings of bainstem glioma.Methods:From April 2003 through April 2012, 150 patients were diagnosed with brainstem gliomas by MRI and microsurgically treated in Tiantan Hospital, Beijing, China. All the MRI and histopathological findings of these patients were respectively reviewed.Results:Of the 150 patients, 65 were female and 85 were male, 120 were adults and 30 were children (age < 18 years), 108 were low-grade glioma (72.0%), 35 were high-grade glioma (23.3%). The accuracy of the MRI diagnosis for brainstem glioma was 95.3%. Data analysis of the MRI findings revealed that a focal lesion was associated with a more favorable histopathological diagnosis in intrinsic (P=0.005) and exophytic (P=0.001) brainstem glioma patients. In the intrinsic diffuse type, tumors without enhancement had more favorable pathological findings (P=0.009).Conclusions:To our knowledge, this is the largest case series of this nature reported in the literature to date. The results of this study suggest that MRI features of brainstem gliomas could predict some pathological features and guide prognosis, choice of biopsy and treatment modalities. The pathology of tumors with a focal appearance on MRI was associated with a prognosis that was significantly better than their diffuse counterparts. For the intrinsic diffuse gliomas, non-enhancing tumors had pathology suggestive of a favorable prognosis.
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Du, Peng, Hongyi Chen, Kun Lv, and Daoying Geng. "A Survey of Radiomics in Precision Diagnosis and Treatment of Adult Gliomas." Journal of Clinical Medicine 11, no. 13 (June 30, 2022): 3802. http://dx.doi.org/10.3390/jcm11133802.
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Glioma is the most common primary malignant tumor of the adult central nervous system (CNS), which mostly shows invasive growth. In most cases, surgery is often difficult to completely remove, and the recurrence rate and mortality of patients are high. With the continuous development of molecular genetics and the great progress of molecular biology technology, more and more molecular biomarkers have been proved to have important guiding significance in the individualized diagnosis, treatment, and prognosis evaluation of glioma. With the updates of the World Health Organization (WHO) classification of tumors of the CNS in 2021, the diagnosis and treatment of glioma has entered the era of precision medicine in the true sense. Due to its ability to non-invasively achieve accurate identification of glioma from other intracranial tumors, and to predict the grade, genotyping, treatment response, and prognosis of glioma, which provides a scientific basis for the clinical application of individualized diagnosis and treatment model of glioma, radiomics has become a research hotspot in the field of precision medicine. This paper reviewed the research related to radiomics of adult gliomas published in recent years and summarized the research proceedings of radiomics in differential diagnosis, preoperative grading and genotyping, treatment and efficacy evaluation, and survival prediction of adult gliomas.
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Ogawa, Tomoya, Keisuke Miyake, Takeshi Fujimori, Daisuke Ogawa, Masaki Okada, Tetsuhiro Hatakeyama, Masanobu Okauchi, Atsushi Shindo, Masahiko Kawanishi, and Takashi Tamiya. "NI-15 THE USEFULNESS OF PET IMAGING IN MOLECULAR DIAGNOSIS OF GLIOMA." Neuro-Oncology Advances 1, Supplement_2 (December 2019): ii28. http://dx.doi.org/10.1093/noajnl/vdz039.127.
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Abstract OBJECTIVE After WHO 2016 Classification of Tumors of the Central Nervous System have published, molecular diagnosis became part of the diagnostic criteria. In this study, we investigated the correlation between PET images and molecular diagnosis of glioma. METHODS We performed retrospective review of newly diagnosed supratentorial glioma patients who preoperatively underwent all four PET examinations (18F-FDG, 11C-MET, 18F-FLT and 18F-FMISO) from April 2009 to March 2019. The standardized uptake value (SUV) from the accumulation of each PET tracers, TNR (tumor to contralateral normal tissue ratio) of 18F-FDG,11C-MET and 18F-FLT, TBR (tumor to blood values ratio) of 18F-FMISO were measured. We investigated the correlation between these PET images and molecular diagnosis of glioma. RESULTS Data from total of 79 patients which were 42 cases of IDH wild type glioblastoma, 2 cases of IDH mutated glioblastoma, 9 cases of IDH wild type astrocytoma, 13 cases of IDH mutated astrocytoma and 13 cases of IDH mutated and 1p/19q co-deleted oligodendroglioma were included in this study. Both TNR of 11C-MET(p<0.01) and 18F-FLT(p<0.01), and also TBR of 18F-FMISO(p<0.01) in IDH wild type gliomas showed significantly higher than IDH mutated gliomas. In WHO Gr2-3 gliomas, only TNR of 18F-FLT showed a significant difference between IDH wild type gliomas and IDH mutated gliomas(p<0.01). TNR of 18F-FLT(p<0.01) and TBR of 18F-FMISO(p<0.01) in 1p/19q co-deleted gliomas were significantly lower than gliomas without 1p/19q co-deletion, but there were no significant differences in WHO Gr2-3 gliomas. Among IDH mutated gliomas, TNR of 11C-MET in 1p/19q co-deleted gliomas showed significantly higher uptake than gliomas without 1p/19q co-deletion(p<0.05). CONCLUSION Preoperative PET evaluation of each PET tracers may be useful for the molecular diagnosis of glioma.
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Cheng, Chuandong, Ying Ji, Tiantian Han, Xiaomin Li, Yahui Huang, Weijie Sun, Guanghua Lu, Wanglong Deng, Ran Ding, and Fanfeng Bu. "MAPK pathway alteration may be a new integrated diagnosis term." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e14022-e14022. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e14022.
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e14022 Background: The 2016 CNS WHO classification is the first to include molecular factors to classify in glioma. We are in the age of glioma subgroups, in which the category depended on the histological and molecular composition, providing more clinical behavior, prognosis, and therapeutic targets hints. The most well-known molecular modifications are IDH1/2 mutation, ATRX variant, TP53 variant, BRAF mutation or fusion, 1p/19q co-deletions. However, there is a diagnostic term“NOS” in the 2016 CNS WHO classification，which indicates that a tumor could not be placed into a more specific WHO category. Here, our analysis of the MAPK pathway may suggest a new subtype. Methods: Targeted next-generation DNA sequence of the 131-genes panel was performed on gliomas in 119 patients. We measured the somatic variations in the MAPK pathway after filtering known driver mutations. The analysis of genomic alterations was performed using a two-sided Fisher exact test. Results: 90/119（75.6%）were excluded due to known driver mutations. 29/119(24.4%) were classified in NOS with a typical “single MAPK pathway alteration” and different histological characteristics and WHO grade. The median age at diagnosis was 35 years (4-79) in our gliomas. The most frequent mutations were NF1(10/29), FGFR1(7/29), KRAS (6/29), BRAF (3/29), PTPN11(2/29), although there are other gene mutations like FGFR2, FGFR3, AKT1, MAP2K1. According to cIMPACT-NOW update 4, our pediatric gliomas ( < 30 years, n = 14) could be identified as “diffuse glioma, other MAPK pathway alteration.” Our adult gliomas have a higher frequency of NF1 mutations（8/15 vs. 2/14, p = 0.05), a lower KRAS (1/15 vs. 5/14) and FGFR1 (2/15 vs. 5/14) mutations than children. Conclusions: Our result suggests that MAPK pathway alteration may be a new integrated diagnosis term in all ages of glioma. Moreover, KRAS and FGFR1 may be associated with pediatric gliomas. NF1 is more common in adult gliomas.
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Galijasevic, Malik, Ruth Steiger, Stephanie Mangesius, Julian Mangesius, Johannes Kerschbaumer, Christian Franz Freyschlag, Nadja Gruber, Tanja Janjic, Elke Ruth Gizewski, and Astrid Ellen Grams. "Magnetic Resonance Spectroscopy in Diagnosis and Follow-Up of Gliomas: State-of-the-Art." Cancers 14, no. 13 (June 29, 2022): 3197. http://dx.doi.org/10.3390/cancers14133197.
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Preoperative grade prediction is important in diagnostics of glioma. Even more important can be follow-up after chemotherapy and radiotherapy of high grade gliomas. In this review we provide an overview of MR-spectroscopy (MRS), technical aspects, and different clinical scenarios in the diagnostics and follow-up of gliomas in pediatric and adult populations. Furthermore, we provide a recap of the current research utility and possible future strategies regarding proton- and phosphorous-MRS in glioma research.
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Chaudhary, Reeta, Nishi Tandon, Andleeb Zehra, Jyoti Jaiswal, Nirupma Lal, and Bandhul Tiwari. "HIGH GRADE GLIOMA IN A 2 1/2 YEAR OLD: A CASE REPORT." Era's Journal of Medical Research 9, no. 1 (June 2022): 114–16. http://dx.doi.org/10.24041/ejmr2022.18.
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Gliomas are the tumor of glial cells found in Central nervous System. High Grade Gliomas are rare in pediatric age group. Definitive diagnosis is made by histopathological examination. A 2 ½ year old male admitted with the complaint of abnormal tonic-clonic body movements along with headache, nausea, vomiting and fever. CT scan showed a poorly circumscribed hypodense lesion involving frontoparietal region. Surgery was performed and specimen sent for histopathological examination. Histopathological examination showed mfeatures of high grade glioma like microvascular proliferation, necrosis and haemorrhage. Cerebral tumors are the most common childhood neoplastic tumors. Gliomas are generally classified into low grade glioma and high grade glioma. High Grade glioma is rare in pediatric age group. Most commonly they present in supra tentorial compartment. The most common cerebral cortex involved are frontal lobe followed by parietal and temporal. Clinical signs and symptoms of High grade gliomas are seizure, headache, nausea, vomiting and visual disturbances. CT scan showed a poorly circumscribed hypodense lesion involving left frontoparietal region mainly. Definitive diagnosis of high grade glioma is by histopathological examination. Histopathological examination showed hypercellular heterogeneous tumor lying on a fibrillary background. Areas of microvascular proliferation along with necrosis and haemorrhage are also seen. Surgical resection followed by chemotherapy and local radiotherapy are the present recommendation. High grade gliomas are rare pediatric tumor associated with poor outcome. Surgery was performed due to neurological worsening, which was unsuccessful and patient died. Diagnosis was confirmed on histopathological examination. Poor prognosis and high morbidity even after evolution of treatment, demands further research to improve the prognosis and reduce morbidities.
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Wang, Lei, Zhengtao Yu, Shaiqi Sun, Jun Peng, Rongjun Xiao, Shengpan Chen, Xiaokun Zuo, Quan Cheng, and Ying Xia. "Long non-coding RNAs: potential molecular biomarkers for gliomas diagnosis and prognosis." Reviews in the Neurosciences 28, no. 4 (May 24, 2017): 375–80. http://dx.doi.org/10.1515/revneuro-2016-0066.
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AbstractThe current grade classification system of gliomas is based on the histopathological features of these tumors and has great significance in defining groups of patients for clinical assessment. However, this classification system is also associated with a number of limitations, and as such, additional clinical assessment criteria are required. Long non-coding RNAs (lncRNAs) play a critical role in cellular functions and are currently regarded as potential biomarkers for glioma diagnosis and prognosis. Therefore, the molecular classification of glioma based on lncRNA expression may provide additional information to assist in the systematic identification of glioma. In the present paper, we review the emerging evidence indicating that specific lncRNAs may have the potential for use as key novel biomarkers and thus provide a powerful tool for the systematic diagnosis of glioma.
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Kan, Liyen Katrina, Kate Drummond, Martin Hunn, David Williams, Terence J. O'Brien, and Mastura Monif. "Potential biomarkers and challenges in glioma diagnosis, therapy and prognosis." BMJ Neurology Open 2, no. 2 (August 2020): e000069. http://dx.doi.org/10.1136/bmjno-2020-000069.
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Gliomas are the most common central nervous system malignancies and present with significant morbidity and mortality. Treatment modalities are currently limited to surgical resection, chemotherapy and radiotherapy. Increases in survival rate over the previous decades are negligible, further pinpointing an unmet clinical need in this field. There is a continual struggle with the development of effective glioma diagnostics and therapeutics, largely due to a multitude of factors, including the presence of the blood–brain barrier and significant intertumoural and intratumoural heterogeneity. Importantly, there is a lack of reliable biomarkers for glioma, particularly in aiding tumour subtyping and measuring response to therapy. There is a need for biomarkers that would both overcome the complexity of the disease and allow for a minimally invasive means of detection and analysis. This is a comprehensive review evaluating the potential of current cellular, proteomic and molecular biomarker candidates for glioma. Significant hurdles faced in glioma diagnostics and therapy are also discussed here.
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Alfaro, Clint M., Valentina Pirro, Michael F. Keating, Eyas M. Hattab, R. Graham Cooks, and Aaron A. Cohen-Gadol. "Intraoperative assessment of isocitrate dehydrogenase mutation status in human gliomas using desorption electrospray ionization–mass spectrometry." Journal of Neurosurgery 132, no. 1 (January 2020): 180–87. http://dx.doi.org/10.3171/2018.8.jns181207.
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OBJECTIVEThe authors describe a rapid intraoperative ambient ionization mass spectrometry (MS) method for determining isocitrate dehydrogenase (IDH) mutation status from glioma tissue biopsies. This method offers new glioma management options and may impact extent of resection goals. Assessment of the IDH mutation is key for accurate glioma diagnosis, particularly for differentiating diffuse glioma from other neoplastic and reactive inflammatory conditions, a challenge for the standard intraoperative diagnostic consultation that relies solely on morphology.METHODSBanked glioma specimens (n = 37) were analyzed by desorption electrospray ionization–MS (DESI-MS) to develop a diagnostic method to detect the known altered oncometabolite in IDH-mutant gliomas, 2-hydroxyglutarate (2HG). The method was used intraoperatively to analyze tissue smears obtained from glioma patients undergoing resection and to rapidly diagnose IDH mutation status (< 5 minutes). Fifty-one tumor core biopsies from 25 patients (14 wild type [WT] and 11 mutant) were examined and data were analyzed using analysis of variance and receiver operating characteristic curve analysis.RESULTSThe optimized DESI-MS method discriminated between IDH-WT and IDH-mutant gliomas, with an average sensitivity and specificity of 100%. The average normalized DESI-MS 2HG signal was an order of magnitude higher in IDH-mutant glioma than in IDH-WT glioma. The DESI 2HG signal intensities correlated with independently measured 2HG concentrations (R2 = 0.98). In 1 case, an IDH1 R132H–mutant glioma was misdiagnosed as a demyelinating condition by frozen section histology during the intraoperative consultation, and no resection was performed pending the final pathology report. A second craniotomy and tumor resection was performed after the final pathology provided a diagnosis most consistent with an IDH-mutant glioblastoma. During the second craniotomy, high levels of 2HG in the tumor core biopsies were detected.CONCLUSIONSThis study demonstrates the capability to differentiate rapidly between IDH-mutant gliomas and IDH-WT conditions by DESI-MS during tumor resection. DESI-MS analysis of tissue smears is simple and can be easily integrated into the standard intraoperative pathology consultation. This approach may aid in solving differential diagnosis problems associated with low-grade gliomas and could influence intraoperative decisions regarding extent of resection, ultimately improving patient outcome. Research is ongoing to expand the patient cohort, systematically validate the DESI-MS method, and investigate the relationships between 2HG and tumor heterogeneity.
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Sharma, Gaurav, Shashi Kant Jain, and Virendra Deo Sinha. "Peripheral Inflammatory Blood Markers in Diagnosis of Glioma and IDH Status." Journal of Neurosciences in Rural Practice 12, no. 01 (January 2021): 088–94. http://dx.doi.org/10.1055/s-0040-1721166.
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Abstract Objective Gliomas are the most common intracranial tumors. Histopathology and neuroimaging are the main modalities used for diagnosis and treatment response monitoring. However, both are expensive and insensitive methods and can cause neurological deterioration. This study aimed to develop a minimally invasive peripheral inflammatory biomarker for diagnosis of glioma, its grade, and isocitrate dehydrogenase (IDH) status. Materials and Methods Patients undergoing surgery for glioma, acoustic neuroma, and meningioma between January 2019 and December 2019 were included. Preoperative neutrophil/lymphocyte ratio (NLR), derived NLR (dNLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), eosinophil/lymphocyte ratio (ELR), and prognostic nutritional index (PNI) were calculated. Histopathology and immunohistochemistry (IHC) staining were done postoperatively. Results A total of 154 patients of glioma, 36 patients of acoustic neuroma, 58 patients of meningioma, and 107 healthy controls were included. dNLR showed the maximum area under the curve (AUC) (0.656639) for diagnosis of glioma from other tumors and among combinations. dNLR +NLR showed the maximum AUC (0.647865). Maximum AUC for glioblastoma multiforme (GBM) versus other grades and among combinations was shown by NLR (0.83926). NLR + dNLR had the maximum AUC (0.764794). NLR showed significant p value in differentiating IDH wild from IDH mutant GBM. Conclusion dNLR has the maximum diagnostic value in diagnosing glioma from other tumors. NLR (AUC = 0.83926) showed the highest accuracy for GBM diagnosis and may be a parameter in predicting the grade of glioma; also, it has maximum diagnostic value in differentiating IDH wild GBM from IDH mutant GBM. These peripheral inflammatory parameters may prove to be sensitive and cost-effective markers for glioma diagnosis, predicting grade of glioma, monitoring of treatment response, and in predicting recurrence.
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den Hartog, Sanne J., Anja van der Kolk, Annette Bruggink, Tatjana Seute, Pieter Wesseling, and Joyce Wilbers. "Pathology-proven extradural (“distant”) metastases of gliomas in adults in the Netherlands between 1971 and 2018: a systematic case series." Neuro-Oncology Practice 8, no. 3 (January 22, 2021): 317–24. http://dx.doi.org/10.1093/nop/npab006.
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Abstract Background Diffuse gliomas are the most frequent primary tumors originating in the central nervous system parenchyma. Although the majority of these tumors are highly malignant, extradural metastases (EDM) are extremely rare. We aimed to perform a systematic review of patients with pathology-proven EDM of diffuse gliomas in the Netherlands. Methods From the Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands information on all cases with EDM between 1971 and October 2018 was retrieved. Patients aged < 18 years or with a diagnosis of ependymoma or continuous tumor growth from intradural to extradural were excluded. Demographics, initial tumor diagnosis, treatment characteristics, location of the EDM, and survival data were collected. IDH1 R132H immunohistochemistry was performed on cases in which a paraffin block of the metastatic tumor could be retrieved. Results Twenty-five patients with diffuse glioma and pathology-proven EDM were identified. Median age at diagnosis of glioma was 46 years (IQR: 35-59); 21 patients (84%) were male. Histopathologic diagnosis was glioblastoma in 17 patients (68%) and lower-grade tumor in eight patients. In 3 out of 12 patients of which a paraffin block could be retrieved immunohistochemistry revealed an IDH1-mutant glioma. Most frequent EDM locations were bone/bone marrow (14/25 patients; 56%), and lymph nodes (6/25 patients; 24%). Conclusion EDM of diffuse glioma are rare. They occur most frequently in patients with glioblastoma, however, they can also originate from lower-grade, IDH-mutant gliomas. In daily practice, EDM of diffuse glioma should be considered in patients with tumefactive lesions of the bone or lymph nodes.
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Persaud-Sharma, Dharam, Joseph Burns, Jeran Trangle, Grettel Castro, Noel Barengo, Sabyasachi Moulik, and Juan Manuel Lozano. "Demographic Variation in the Frequency of Gliomas in Florida." Medicina 55, no. 1 (January 4, 2019): 5. http://dx.doi.org/10.3390/medicina55010005.
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Background and objectives: Glial brain cancers affect nearly 20,000 individuals in the United States (USA) annually. SEER database data exploring the relationship between race and gliomas is now available and have shown that cerebral gliomas occur at a higher frequency in Caucasian men. However, such analyses did not include demographic data specific to the state of Florida. This study assessed the association between race and glial vs. non-glial Central Nervous System (CNS) cancers in Florida, USA. Materials and Methods: This case-control study utilized the Florida Cancer Data Registry (FCDS), in which race was considered the exposure and development of glioma as the measured outcome. The sample was comprised of patients in Florida diagnosed with brain tumors from 1981 to 2013. Relative racial frequencies were compared between patients with glial brain tumors and those with other CNS tumors. Data was analyzed using logistic regression in order to determine any associations between race and frequency of diagnosis adjusting for several confounders (age, sex, smoking status, year of diagnosis, and insurance status). Results: Between 1981 and 2013 a total of 14,092 patients meeting the inclusion and exclusion criteria were diagnosed in Florida with a primary brain tumor. Being of non-white race was associated with 60% decreased odds of glioma diagnosis compared to the reference white population (adjusted OR 0.4, 95% CI 0.34–0.47). Secondary findings include associations between increasing age and male sex with increased odds of glioma diagnosis. Decreased adjusted odds of glioma diagnosis were found with former smoking status (reference non-smokers), diagnosis between 2001 and 2010 (reference 1981–1990), and Medicaid or Medicare insurance (reference private insurance). Hispanic ethnicity, current smoking status, no insurance/self-pay, and geographical location (urban vs. rural) all had no association with glioma diagnosis. Conclusions: These findings are consistent with and help reinforce previous studies utilizing national databases (SEER) which also showed increasing odds of glioma diagnosis in older white males. Various potential explanations for these findings include genetic predisposition, lifestyle and behavioral factors, and socioeconomic status, including access to healthcare. Future research aims at identifying potential genetic etiologies.
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Fujioka, Yutaka, Nobuhiro Hata, Yojiro Akagi, Daisuke Kuga, Ryusuke Hatae, Yuhei Sangatsuda, Yuhei Michiwaki, et al. "Molecular diagnosis of diffuse glioma using a chip-based digital PCR system to analyze IDH, TERT, and H3 mutations in the cerebrospinal fluid." Journal of Neuro-Oncology 152, no. 1 (January 8, 2021): 47–54. http://dx.doi.org/10.1007/s11060-020-03682-7.
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Abstract Purpose Conventional genetic analyzers require surgically obtained tumor tissues to confirm the molecular diagnosis of diffuse glioma. Recent technical breakthroughs have enabled increased utilization of cell-free tumor DNA (ctDNA) in body fluids as a reliable resource for molecular diagnosis in various cancers. Here, we tested the application of a chip-based digital PCR system for the less invasive diagnosis (i.e., liquid biopsy) of diffuse glioma using the cerebrospinal fluid (CSF). Methods CSF samples from 34 patients with diffuse glioma were collected from the surgical field during craniotomy. Preoperative lumbar CSF collection was also performed in 11 patients. Extracted ctDNA was used to analyze diagnostic point mutations in IDH1 R132H, TERT promoter (C228T and C250T), and H3F3A (K27M) on the QuantStudio® 3D Digital PCR System. These results were compared with their corresponding tumor DNA samples. Results We detected either of the diagnostic mutations in tumor DNA samples from 28 of 34 patients. Among them, we achieved precise molecular diagnoses using intracranial CSF in 20 (71%). Univariate analyses revealed that the World Health Organization (WHO) grade (p = 0.0034), radiographic enhancement (p = 0.0006), and Mib1 index (p = 0.01) were significant predictors of precise CSF-based molecular diagnosis. We precisely diagnosed WHO grade III or IV diffuse gliomas using lumbar CSF obtained from 6 (87%) of 7 patients with tumors harboring any mutation. Conclusion We established a novel, non-invasive molecular diagnostic method using a chip-based digital PCR system targeting ctDNA derived from CSF with high sensitivity and specificity, especially for high-grade gliomas.
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Liu, Xiaoxue, Jianrui Li, Qiang Xu, Qirui Zhang, Xian Zhou, Hao Pan, Nan Wu, Guangming Lu, and Zhiqiang Zhang. "RP-Rs-fMRIomics as a Novel Imaging Analysis Strategy to Empower Diagnosis of Brain Gliomas." Cancers 14, no. 12 (June 7, 2022): 2818. http://dx.doi.org/10.3390/cancers14122818.
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Rs-fMRI can provide rich information about functional processes in the brain with a large array of imaging parameters and is also suitable for investigating the biological processes in cerebral gliomas. We aimed to propose an imaging analysis method of RP-Rs-fMRIomics by adopting omics analysis on rs-fMRI with exhaustive regional parameters and subsequently estimating its feasibility on the prediction diagnosis of gliomas. In this retrospective study, preoperative rs-fMRI data were acquired from patients confirmed with diffuse gliomas (n = 176). A total of 420 features were extracted through measuring 14 regional parameters of rs-fMRI as much as available currently in 10 specific narrow frequency bins and three parts of gliomas. With a randomly split training and testing dataset (ratio 7:3), four classifiers were implemented to construct and optimize RP-Rs-fMRIomics models for predicting glioma grade, IDH status and Karnofsky Performance Status scores. The RP-Rs-fMRIomics models (AUROC 0.988, 0.905, 0.801) were superior to the corresponding traditional single rs-fMRI index (AUROC 0.803, 0.731, 0.632) in predicting glioma grade, IDH and survival. The RP-Rs-fMRIomics analysis, featuring high interpretability, was competitive for prediction of glioma grading, IDH genotype and prognosis. The method expanded the clinical application of rs-fMRI and also contributed a new imaging analysis for brain tumor research.
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Gupta, Mihir, Evan Burns, Nicholas Georgantas, Julia Thierauf, Naema Nayyar, Ryan Burns, Jose Velarde, et al. "BIOM-54. A RAPID GENOTYPING PANEL FOR SENSITIVE AND SPECIFIC SEGREGATION OF CNS PATHOLOGIES." Neuro-Oncology 22, Supplement_2 (November 2020): ii13. http://dx.doi.org/10.1093/neuonc/noaa215.051.
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Abstract Primary central nervous system lymphoma (PCNSL) remains challenging to diagnose due to nonspecific clinical and radiologic features and low diagnostic yields of cerebrospinal fluid (CSF) studies. We sought to characterize the diagnostic approach of suspected PCNSL, in order to improve clinical workflow. We first reviewed 1,007 new brain lesions of unknown etiology that included PCNSL in the radiologic differential diagnosis. The most common final diagnoses included high-grade glioma (28.2%) and PCNSL (14.6%). Diagnostic biopsies were frequently performed for high-grade glioma (100%) and PCNSL (94.4%), while CSF was frequently sampled for PCNSL (78.7%). We next identified 159 patients with an established new diagnosis of PCNSL. CSF studies were non-diagnostic in 86.7% of cases, whereas biopsy was positive in 93%. However, intraoperative histopathology was inconclusive for PNCSL in 54.5%, likely contributing to 22% of patients undergoing surgical resection. These challenges resulted in 12 days median time to treatment initiation, and readmission for further workup or treatment initiation in 27% of patients. These results indicated the need for a rapid, sensitive and specific platform to segregate PCNSL and glioma using CSF and tissue samples. We developed a qPCR-based assay to genotype the MYD88 L265P hotspot mutation from CSF and plasma within 80 minutes of sample acquisition. Results were concordant with orthogonal DNA sequencing in extracts from 87 archived specimens, with detection limits of 490pg of input genomic DNA and 0.15% mutant allele frequency. When performed simultaneously with assays for TERT promoter, IDH1/2, H3F3A and BRAF point mutations, the resulting panel accurately segregated PCNSL and adult diffuse glioma molecular diagnoses in 87 archived specimens and 19 prospective liquid biopsies, including cases of lymphoma and glioma. We propose that inclusion of targeted analysis of these mutually exclusive recurrent molecular alterations characterizing gliomas and PCNSL will facilitate rapid, sensitive diagnosis from solid and liquid biopsies.
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Billard, P., C. Guerriau, C. Carpentier, F. Juillard, N. Grandin, P. Lomonte, P. Kantapareddy, et al. "OS02.6.A The TeloDIAG: How telomeric parameters can help in glioma rapid diagnosis and liquid biopsies approaches." Neuro-Oncology 23, Supplement_2 (September 1, 2021): ii5—ii6. http://dx.doi.org/10.1093/neuonc/noab180.015.
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Abstract BACKGROUND The integration of molecular markers into the WHO 2016 classification has clarified the complex diagnosis of gliomas. Among these biomarkers, the TERT promoter mutation and the loss of ATRX (ATRX loss) are mutually exclusive alterations associated with re-activation of telomerase or alternative lengthening of telomeres (ALT), respectively. Strangely, 25% of gliomas display neither or both these alterations, a situation referred to as abnormal telomere maintenance mechanism (aTMM). MATERIAL AND METHODS To investigate the TMM actually involved in gliomas, the C-circle (CC) assay was adapted to tumor (FFPE and frozen) samples. RESULTS We constructed a CC-based algorithm able to identify the TMM of 284 gliomas with either TERT or ATRX alteration, with a sensitivity of 100% and a specificity of 97.3%, and succeeded in deciphering the TMM involved in 122 aTMM gliomas. Additionally, the combination of the TMM, the mutational status of the Isocitrate dehydrogenase 1/2 (IDH) gene, and the histological grading was used as base for a new classification: TeloDIAG. Six subtypes are defined in this classification: tOD, tLGA, tGBM_IDHmt, tGBM, and tAIV, corresponding to oligodendroglioma, IDHmt low grade astrocytoma, IDHmt glioblastoma, and IDHwt glioblastoma, respectively, the last class gathers ALT+ IDHwt glioma. The TeloDIAG diagnosis is 99% concordant with the WHO classification for glioma displaying typical molecular characteristics (N=312). It modified the classification of 38% (N=156) discordant tumors, such as IDHwt Astrocytoma, aTMM tumors, or gliomas with unexpected TMM (e.g. TERTwt oligodendroglioma, ATRX loss GBM). Interestingly, 20% (N=69) of TERTwt, ATRXwt, or IDHwt GBM were actually tAIV, which is remarkable as tAIV-glioma patients’ survival tended to be longer (21.2 months) than tGBM patients’ survival (16.5 months). Importantly, CC in blood sampled from IDHmt astrocytoma patients was detected with a sensitivity of 56% and a specificity of 95% (N = 206). CONCLUSION In sum, the TeloDIAG is a new, simple, and efficient tool helping in glioma diagnosis and a promising option for liquid biopsy
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Zhang, Xiaoming, Mengyuan Jiang, Shenfeng Tang, Chaoshi Niu, and Shanshan Hu. "Comprehensive bioinformatic analysis of key genes and signaling pathways in glioma." JUSTC 52, no. 9 (2022): 3. http://dx.doi.org/10.52396/justc-2022-0010.
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The identification of specific survival-related differentially expressed genes (DEGs) is a method for uncovering therapeutic approaches for various cancers, including glioma. However, the key target genes associated with the occurrence and development of gliomas remain unknown. In this study, we performed bioinformatics analysis on 17 GSE datasets and identified DEGs correlated with glioma. A total of 74 mutual-DEGs with downregulated expression in gliomas compared with that in normal brain tissues were found in 17 datasets. These DEGs were related to GABAergic synaptic transmission, chloride transmembrane transport, glutamate secretion, and gamma-aminobutyric acid signaling pathway. Gamma-aminobutyric acid type A receptor subunit gamma 2 (GABRG2) was identified as a hub gene in the protein-protein interaction network. GABRG2 exhibited lower expression in IDH wild-type astrocytoma than that in IDH mutant astrocytoma and indicated poor prognosis in glioma patients. GABRG2 may contribute to the progression of glioma by affecting GABA receptor-related pathways and is a potential biomarker for the diagnosis and treatment of glioma.
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Kobayashi, Yusuke, Yosuke Sato, Takashi Kon, Daisuke Tanioka, Katsuyoshi Shimizu, and Tohru Mizutani. "HGG-29. A CASE OF CIRCUMSCRIBED HIGH-GRADE ASTROCYTOMA WITH ATRX AND CDKN2A/B ALTERNATIONS WHO WAS INITIALLY DIAGNOSED AS GLIOBLASTOMA AND HAS 20 YEARS SURVIVAL." Neuro-Oncology 22, Supplement_3 (December 1, 2020): iii349. http://dx.doi.org/10.1093/neuonc/noaa222.312.
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Abstract Pediatric high-grade gliomas are rare and often hard to classify, which grow locally and show longer survival than diffuse high-grade gliomas in adults. We report a case of circumscribed high-grade astrocytoma who was initially diagnosed as glioblastoma and has 20 years survival. A 7-year-old girl suffered from epileptic seizure due to a left occipital lobe tumor. The tumor was resected in another hospital and diagnosed as glioblastoma. The tumor disappeared after extended local irradiation and chemotherapy using nimustine hydrochloride (ACNU) and cisplatin (CDDP). Eighteen years after initial onset, first recurrence was confirmed as the intra-tumoral hemorrhage. The tumor was resected and diagnosed as anaplastic oligoastrocytoma. After 6 courses of temozolomide (TMZ), the tumor disappeared. Twenty years after initial onset, the second local recurrence was confirmed. Although gamma knife and TMZ was performed, the tumor did not disappear. The tumor was surgically resected. Histopathology showed localized growth with some infiltration and mitosis but lacked pseudopallisading and microvascular proliferation. The tumor was diagnosed as circumscribed high-grade astrocytoma. Immunostaining revealed ATRX nuclear loss and CDKN2A / B homozygous deletion. After 10 courses of TMZ, the third local recurrence was confirmed. The tumor was completely removed and has not occurred recurrence more than 3 months after the last operation. Circumscribed high-grade glioma is expected to survive longer than invasive glioma. Pediatric gliomas should differ from adult gliomas in the genes of tumorigenesis. Care should be taken for its diagnosis and treatments. We also need a new classification based on histology and gene profile. HGG-30, ANALYSIS OF PEDIATRIC GLIOMAS IN OUR INSTITUTE Kaoru Tamura, Mai Fujioka, Masae Kuroha, Motoki Inaji, Yoji Tanaka, Tadashi Nariai, and Taketoshi Maehara; Tokyo Medical and Dental University, Tokyo, Japan. PURPOSE: Recent advances in genetic interrogation of pediatric glioma increase the importance of molecular diagnosis using surgical specimen. However, surgical resection may be avoided to preserve quality of life, especially in brain stem glioma cases. We retrospectively examined diagnosis and treatment of pediatric gliomas in our hospital. METHODS: This study includes 14 consecutive glioma patients under the age of 18 who underwent initial treatment at our hospital from 2000 to 2019. Histopathological diagnosis, clinical course and molecular status such as IDH, H3F3A and BRAF were analyzed. RESULTS: 5 patients (1 pilocytic astrocytoma (PA), 3 diffuse astrocytomas, 1 oligodendroglioma were treated only by surgical resection (group A). 7 patients (1 PA, 1 anaplastic oligodendroglioma, 2 diffuse midline gliomas and 3 glioblastomas (GBM)) received radiation and/or chemotherapy after surgical resection (group B). 2 diffuse intrinsic pontine gliomas (DIPG) received radiation and chemotherapy without surgical resection (Group C). No IDH mutation was observed in all pathological specimen obtained cases. BRAF alteration was observed in all PA cases. 1 case of GBM had BRAF V600Emutation and the other had H3K27M mutation. During a median of 7.7 years of follow-up, group A patients have no recurrence. Group B includes various diagnosis and prognosis. 2 group C patients diagnosed DIPG by MRI showed different clinical courses. CONCLUSION: Pediatric gliomas include diverse biological subgroups and show broad range of clinical behavior. Since pediatric glioma has a low incidence and a wide variety of genetic mutations, multicenter study is important to improve the treatment of pediatric glioma.
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Gao, Huasong, Bin Yu, Yaohua Yan, Jianhong Shen, Sanhu Zhao, Jianhong Zhu, Wenxin Qin, and Yilu Gao. "Correlation of expression levels of ANXA2, PGAM1, and CALR with glioma grade and prognosis." Journal of Neurosurgery 118, no. 4 (April 2013): 846–53. http://dx.doi.org/10.3171/2012.9.jns112134.
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Object Biomarkers for the diagnosis and prognosis of gliomas are lacking. To elucidate new diagnostic and prognostic targets, a routine method is used to evaluate differences between the protein profile of normal and tumor cells. The object of the current study was to investigate novel differentially expressed proteins and their roles in gliomas. Methods Differences in the protein profile were compared using 2D polyacrylamide gel electrophoresis using C6 glioma cells and rat astrocytes. The mRNA and protein expression of ANXA2, PGAM1, and CALR were analyzed in glioma tissues and normal brain tissues. The expression of ANXA2 in the U87 glioma cell line was interrupted using short interfering RNA duplexes, and the role of ANXA2 in the migration and invasiveness of glioma cells was assessed. The expression of ANXA2, PGAM1, and CALR was examined further by immunohistochemical analysis using 130 glioma samples obtained in patients, and their prognostic roles in gliomas were evaluated using Kaplan-Meier and Cox regression analyses. Results Significantly higher expression levels of ANXA2 and PGAM1 and a lower level of CALR were found in glioma samples than in the normal brain samples. ANXA2, PGAM1, and CALR expression correlated with the grade and survival of patients with gliomas. Multivariate analysis further revealed that ANXA2 was an independent prognostic marker for glioma. After ANXA2 expression was suppressed using short interfering RNA, U87 cells had decreased migratory and invasive capabilities in vitro. Conclusions Protein expression alterations in ANXA2, PGAM1, and CALR were found in gliomas, and ANXA2 provided a novel prognostic value.
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Kitano, Yotaro, Kosuke Aoki, Takao Yasui, Kazuya Motomura, Fumiharu Ohka, Kuniaki Tanahashi, Masaki Hirano, et al. "PATH-36. MACHINE LEARNING TO DETECT GLIOMAS IN URINE-BASED LIQUID BIOPSY." Neuro-Oncology 21, Supplement_6 (November 2019): vi151. http://dx.doi.org/10.1093/neuonc/noz175.632.
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Abstract BACKGROUND Diffuse gliomas are the most common primary malignant brain tumors, whose overall prognosis is quite dismal. Tumor-cell-secreted extracellular vesicles (EVs) participate in physiological and pathological processes and have potential applications to diagnostics of malignant tumors including diffuse gliomas. Because urine is less invasive to collect, development of early diagnosis based on urine EVs is eagerly awaited. In this study, we captured urine EVs of patients with gliomas efficiently with the nanowire device and compared expression profile of microRNAs (miRNAs) within urine EVs with that of healthy donors to identify diagnostic accuracy by a machine learning algorithm. METHODS 62 patients with diffuse gliomas, including 27 glioblastoma and 35 lower grade gliomas, and 100 healthy donors were analyzed, along with orthotopic transplant mouse model. Urinary EVs were obtained with the nanowire device which could collect EVs more efficiently than the conventional ultracentrifugation method (Yasui et.al., Science Adv.2017). Machine learning methods were performed to select the miRNAs which could distinguish patients with gliomas from healthy control. RESULTS More than 2400 miRNAs were obtained from all urine samples. We identified miRNA panels that provided high diagnostic accuracy of diffuse gliomas (92.5%). There were 440 miRNAs whose expression increased by more than 1.5 fold (p< 0.05) as compared to healthy donor samples (glioma-upregulated miRNAs), whereas the expression of 87 miRNAs decreased to less than 2/3-fold (p< 0.05) (glioma-downregulated miRNAs). Mouse miRNAs which were homologous to glioma-upregulated and -downregulated miRNAs showed significantly high and low level expressions, respectively, in glioma mouse models as compared to normal control mice, confirming the reliability of urine miRNA-based diagnosis. Furthermore, some of these glioma-upregulated miRNAs has been reported to be involved in tumor progression. CONCLUSIONS miRNAs obtained from urine could be biomarkers for detection of gliomas by machine learning and some of these could be associated with tumor progression.
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Im, Sanghyuk, Jonghwan Hyeon, Eunyoung Rha, Janghyeon Lee, Ho-Jin Choi, Yuchae Jung, and Tae-Jung Kim. "Classification of Diffuse Glioma Subtype from Clinical-Grade Pathological Images Using Deep Transfer Learning." Sensors 21, no. 10 (May 17, 2021): 3500. http://dx.doi.org/10.3390/s21103500.
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Diffuse gliomas are the most common primary brain tumors and they vary considerably in their morphology, location, genetic alterations, and response to therapy. In 2016, the World Health Organization (WHO) provided new guidelines for making an integrated diagnosis that incorporates both morphologic and molecular features to diffuse gliomas. In this study, we demonstrate how deep learning approaches can be used for an automatic classification of glioma subtypes and grading using whole-slide images that were obtained from routine clinical practice. A deep transfer learning method using the ResNet50V2 model was trained to classify subtypes and grades of diffuse gliomas according to the WHO’s new 2016 classification. The balanced accuracy of the diffuse glioma subtype classification model with majority voting was 0.8727. These results highlight an emerging role of deep learning in the future practice of pathologic diagnosis.
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Kosmopoulos, Marinos, Anthos Christofides, Dimitrios Drekolias, Phaedon D. Zavras, Antonios N. Gargalionis, and Christina Piperi. "Critical Role of IL-8 Targeting in Gliomas." Current Medicinal Chemistry 25, no. 17 (May 22, 2018): 1954–67. http://dx.doi.org/10.2174/0929867325666171129125712.
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Background: Glioma is a heterogeneous, highly complicated central nervous system (CNS) tumor with uncertain mechanism of initiation and progression, resulting in an unfavorable outcome. An extended network of cytokines is recognized as a major regulator of glioma pathogenesis, either promoting or inhibiting glioma progression based on their type and specificity. Interleukin-8 (IL-8) has been revealed as a critical regulator of CNS function and development with participation in many CNS disorders including gliomas. Objective: The aim of the present review is to address the role of IL-8 in glioma pathogenesis focusing on the implicated molecular pathways as well as on its potential targeting for glioma therapy. Methods and Results: PubMed-Medline, SCOPUS, and Google Scholar databases were searched for pre-clinical and clinical studies related to IL-8 implication in gliomagenesis and IL-8 targeting strategies for gliomas. Literature data indicate that IL-8 participates in glioma angiogenesis and cell migration and it can serve as a potential biomarker, for early diagnosis, follow-up and response to therapy. Conclusion: Several promising approaches that target directly or indirectly IL-8 effects in gliomas are currently in progress while more-in-depth studies are needed to validate its biomarker role and elucidate the underlying molecular mechanisms.
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Kanamori, Masayuki, Atsuo Kikuchi, Mika Watanabe, Ichiyo Shibahara, Ryuta Saito, Yoji Yamashita, Yukihiko Sonoda, Toshihiro Kumabe, Shigeo Kure, and Teiji Tominaga. "Rapid and sensitive intraoperative detection of mutations in the isocitrate dehydrogenase 1 and 2 genes during surgery for glioma." Journal of Neurosurgery 120, no. 6 (June 2014): 1288–97. http://dx.doi.org/10.3171/2014.3.jns131505.
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Object Intraoperative diagnosis is important in determining the strategies during surgery for glioma. Because the mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes have diagnostic, prognostic, and predictive values, the authors assessed the feasibility and significance of a simplified method for the intraoperative detection of IDH1 and IDH2 gene mutations. Methods Rapid DNA extraction, amplification with conventional polymerase chain reaction (PCR) or co-amplification at lower denaturation temperature PCR (COLD-PCR), and fluorescence melting curve analysis with adjacent hybridization probes were performed for the intraoperative detection of IDH1 and IDH2 mutations in 18 cases of suspected nonneoplastic lesions and low- and high-grade gliomas and in 3 cases of radiation necrosis. Results DNA extraction for detection of the mutation took 60–65 minutes. The results of this assay showed complete correlation with that of Sanger sequencing. The sensitivity for detection of mutations in a background of wild-type genes was 12.5% and 2.5% in conventional PCR and COLD-PCR, respectively. The diagnosis of glioma was established in 3 of 5 cases in which definitive diagnosis was not obtained using frozen sections, and information was obtained for the discrimination of glioblastoma or glioblastoma with an oligodendroglioma component from anaplastic glioma or secondary glioblastoma. This assay also detected a small fraction of tumor cells with IDH1 mutation in radiation necrosis. Conclusions These methods provide important information for establishing the differential diagnosis between low-grade glioma and nonneoplastic lesions and the diagnosis for subtypes of high-grade glioma. Although tumor cells in radiation necrosis were detected with a high sensitivity, further investigation is necessary for clinical application in surgery for recurrent glioma.
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Cheng, Tong, Manyu Xu, Hui Zhang, Bing Lu, Xiaojing Zhang, Ziheng Wang, and Jianfei Huang. "KLHDC8A Expression in Association with Macrophage Infiltration and Oxidative Stress Predicts Unfavorable Prognosis for Glioma." Oxidative Medicine and Cellular Longevity 2022 (September 19, 2022): 1–14. http://dx.doi.org/10.1155/2022/2694377.
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Background. The tumor immune microenvironment (TME) is associated with cancer progression and immune escape. Although KLHDC8A has been reported in glioma in vitro, the expression and clinical significance of this gene in clinical samples are unknown. Methods. The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases were used to evaluate the mRNA expression level of KLHDC8A and its significance in the glioma TME. Tissue microarray-based multiple immunohistochemical staining was conducted to determine KLHDC8A protein levels and characterize the immune signature of tumor-infiltrating immune cells in gliomas. Results. Tumor cells and tumor-associated macrophages expressed KLHDC8A. The expression of KLHDC8A was higher in glioma tissues than in normal brain tissues and was associated with patient clinical characteristics. Gliomas exhibited a high abundance of macrophages, neutrophils, regulatory T cells, and the immune checkpoint PD-L1, as well as high KLHDC8A expression. Cox regression analysis showed that KLHDC8A+CD68+ macrophages and KLHDC8A predicted unfavorable survival in patients with glioma. Finally, protein-protein interaction network analysis showed that the KLHDC8A expression was associated with hypoxia and oxidative stress. Conclusions. KLHDC8A is a potential marker for the clinical diagnosis of glioma. The immune characteristics of macrophages play a crucial role in predicting patients with glioma, providing a new avenue for targeted glioma therapy.
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Piazza, Amedeo, Paolo Rosa, Luca Ricciardi, Antonella Mangraviti, Luca Pacini, Antonella Calogero, Antonino Raco, and Massimo Miscusi. "Circulating Exosomal-DNA in Glioma Patients: A Quantitative Study and Histopathological Correlations—A Preliminary Study." Brain Sciences 12, no. 4 (April 14, 2022): 500. http://dx.doi.org/10.3390/brainsci12040500.
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Glial neoplasms are a group of diseases with poor prognoses. Not all risk factors are known, and no screening tests are available. Only histology provides certain diagnosis. As already reported, DNA transported by exosomes can be an excellent source of information shared by cells locally or systemically. These vesicles seem to be one of the main mechanisms of tumor remote intercellular signaling used to induce immune deregulation, apoptosis, and both phenotypic and genotypic modifications. In this study, we evaluated the exosomal DNA (exoDNA) concentration in blood samples of patients affected by cerebral glioma and correlated it with histological and radiological characteristics of tumors. From 14 patients with diagnosed primary or recurrent glioma, we obtained MRI imaging data, histological data, and preoperative blood samples that were used to extract circulating exosomal DNA, which we then quantified. Our results demonstrate a relationship between the amount of circulating exosomal DNA and tumor volume, and mitotic activity. In particular, a high concentration of exoDNA was noted in low-grade gliomas. Our results suggest a possible role of exoDNAs in the diagnosis of brain glioma. They could be particularly useful in detecting early recurrent high-grade gliomas and asymptomatic low-grade gliomas.
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Arcella, Antonietta, Fiona Limanaqi, Rosangela Ferese, Francesca Biagioni, Maria Antonietta Oliva, Marianna Storto, Mirco Fanelli, Stefano Gambardella, and Francesco Fornai. "Dissecting Molecular Features of Gliomas: Genetic Loci and Validated Biomarkers." International Journal of Molecular Sciences 21, no. 2 (January 20, 2020): 685. http://dx.doi.org/10.3390/ijms21020685.
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Recently, several studies focused on the genetics of gliomas. This allowed identifying several germline loci that contribute to individual risk for tumor development, as well as various somatic mutations that are key for disease classification. Unfortunately, none of the germline loci clearly confers increased risk per se. Contrariwise, somatic mutations identified within the glioma tissue define tumor genotype, thus representing valid diagnostic and prognostic markers. Thus, genetic features can be used in glioma classification and guided therapy. Such copious genomic variabilities are screened routinely in glioma diagnosis. In detail, Sanger sequencing or pyrosequencing, fluorescence in-situ hybridization, and microsatellite analyses were added to immunohistochemistry as diagnostic markers. Recently, Next Generation Sequencing was set-up as an all-in-one diagnostic tool aimed at detecting both DNA copy number variations and mutations in gliomas. This approach is widely used also to detect circulating tumor DNA within cerebrospinal fluid from patients affected by primary brain tumors. Such an approach is providing an alternative cost-effective strategy to genotype all gliomas, which allows avoiding surgical tissue collection and repeated tumor biopsies. This review summarizes available molecular features that represent solid tools for the genetic diagnosis of gliomas at present or in the next future.
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Aguiar, Guilherme Brasileiro de, Karla Helena Picoli Natário, Heitor Castelo Branco Rodrigues Alves, Thays Filizzola Borges, and Marcus André Acioly. "Hemorragia cerebral espontânea como manifestação inicial de glioma multicêntrico / Spontaneous cerebral haemorrhage as an initial manifestation of multicentric glioma." Arquivos Médicos dos Hospitais e da Faculdade de Ciências Médicas da Santa Casa de São Paulo 64, no. 2 (May 27, 2019): 169. http://dx.doi.org/10.26432/1809-3019.2019.64.2.169.
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Introdução / Objetivos: Os gliomas multicêntricos são neoplasias malignas raras e importantes no diagnóstico diferencial de lesões cerebrais múltiplas. São representados por lesões múltiplas, localizadas em lobos ou hemisférios cerebrais distintos, com ausência de contiguidade entre as lesões e de vias de disseminação anatômica ou formações satélites. Apresentam manifestação clínica heterogênea a depender da área cometida. A ressonância magnética é o recurso utilizado para investigação diagnóstica, onde pode-se avaliar a ausência de contiguidade entre as lesões. O objetivo do presente estudo é relatar o caso de um paciente adulto portador de glioma multicêntrico, cuja manifestação inicial se deu após episódio de hemorragia tumoral. Relato de caso: paciente masculino de 62 anos, sem diagnóstico de lesão cerebral conhecida, foi diagnosticado com hemorragia cerebral espontânea. Após algumas semanas, tal hemorragia revelou tratar-se de glioma multicêntrico, confirmado por biopsia. Resultados: após a biopsia, com a confirmação do diagnóstico, o paciente foi encaminhado para tratamento adjuvante. No entanto, faleceu por progressão da doença. Conclusão: Os gliomas multicêntricos são raros e apresentam sintomatologia semelhante aos demais processos neoplásicos cerebrais, sendo que manifestações hemorrágicas são incomuns nesse tipo de neoplasia.Descritores: Glioma, Glioblastoma, Neoplasias encefálicas, Diagnóstico por imagemAbstractIntroduction / Purpose: Multicentric gliomas are rare malignant neoplasms and important in the differential diagnosis of multiple brain lesions. They are represented by multiple lesions, located in distinct lobes or cerebral hemispheres, with absence of contiguity between the lesions and of anatomical dissemination pathways or satellite formations. They present heterogeneous clinical manifestation depending on the committed area. Magnetic resonance imaging is the resource used for diagnostic investigation, in which the absence of contiguity between the lesions can be evaluated. The objective of this paper is to report the case of an adult patient with multicentric glioma, whose initial manifestation occurred after an episode of tumor hemorrhage. Case report: A 62-year-old male patient, without a known brain injury diagnosis, was diagnosed with spontaneous cerebral hemorrhage. After a few weeks, such bleeding revealed to be multicenter, biopsy-confirmed glioma. Results: After biopsy, with confirmation of diagnosis, the patient was referred for adjuvant treatment. However, he died of disease progression. Conclusion: Multicentric gliomas are rare and present similar symptomatology to other brain neoplastic processes, and hemorrhagic manifestations are uncommon in this type of neoplasia.Keywords: Glioma, Glioblastoma, Brain Neoplasms, Diagnostic Imaging
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Guo, Geng, Cheng-liang Zhong, Yang Liu, Xing-gang Mao, Zheng Zhang, Ji Jin, Jing Liu, et al. "Overexpression of FRAT1 Is Associated with Malignant Phenotype and Poor Prognosis in Human Gliomas." Disease Markers 2015 (2015): 1–8. http://dx.doi.org/10.1155/2015/289750.
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Glioma is the most common malignancy of the central nervous system. Approximately 40 percent of intracranial tumors are diagnosed as gliomas. Difficulties in treatment are associated closely with the malignant phenotype, which is characterized by excessive proliferation, relentless invasion, and angiogenesis. Although the comprehensive treatment level of brain glioma is continuously progressing, the outcome of this malignancy has not been improved drastically. Therefore, the identification of new biomarkers for diagnosis and therapy of this malignancy is of significant scientific and clinical value. FRAT1 is a positive regulator of the Wnt/β-catenin signaling pathway and is overexpressed in many human tumors. In the present study, we investigated the expression status of FRAT1 in 68 patients with human gliomas and its correlation with the pathologic grade, proliferation, invasion, angiogenesis, and prognostic significance. These findings suggest that FRAT1 may be an important factor in the tumorigenesis and progression of glioma and could be explored as a potential biomarker for pathological diagnosis, an indicator for prognosis, and a target for biological therapy of malignancy.
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Xuan, Chengmin, Mingwei Jin, Lei Wang, Shengbai Xue, Qi An, Qingzeng Sun, Lei Wang, and Yong Gao. "PART1 and hsa-miR-429-Mediated SHCBP1 Expression Is an Independent Predictor of Poor Prognosis in Glioma Patients." BioMed Research International 2020 (April 13, 2020): 1–12. http://dx.doi.org/10.1155/2020/1767056.
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Gliomas are the most common primary brain tumors. Because of their high degree of malignancy, patient survival rates are unsatisfactory. Therefore, exploring glioma biomarkers will play a key role in early diagnosis, guiding treatment, and monitoring the prognosis of gliomas. We found two lncRNAs, six miRNAs, and nine mRNAs that were differentially expressed by analyzing genomic data of glioma patients. The diagnostic value of mRNA expression levels in gliomas was determined by receiver operating characteristic (ROC) curve analysis. Among the nine mRNAs, the area under the ROC curve values of only CEP55 and SHCBP1 were >0.7, specifically 0.834 and 0.816, respectively. Additionally, CEP55 and SHCBP1 were highly expressed in glioma specimens and showed increased expression according to the glioma grade, and outcomes of high expression patients were poor. CEP55 was enriched in the cell cycle, DNA replication, mismatch repair, and P53 signaling pathway. SHCBP1 was enriched in the cell cycle, DNA replication, ECM receptor interaction, and P53 signaling pathway. Age, grade, IDH status, chromosome 19/20 cogain, and SHCBP1 were independent factors for prognosis. Our findings suggest the PART1-hsa-miR-429-SHCBP1 regulatory network plays an important role in gliomas.
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Dunbar, Erin, and Anthony T. Yachnis. "Glioma Diagnosis: Immunohistochemistry and Beyond." Advances in Anatomic Pathology 17, no. 3 (May 2010): 187–201. http://dx.doi.org/10.1097/pap.0b013e3181d98cd9.
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D’Haene, Nicky, Bárbara Meléndez, Oriane Blanchard, Nancy De Nève, Laetitia Lebrun, Claude Van Campenhout, and Isabelle Salmon. "Design and Validation of a Gene-Targeted, Next-Generation Sequencing Panel for Routine Diagnosis in Gliomas." Cancers 11, no. 6 (June 4, 2019): 773. http://dx.doi.org/10.3390/cancers11060773.
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The updated 2016 World Health Organization (WHO) classification system for gliomas integrates molecular alterations and histology to provide a greater diagnostic and prognostic utility than the previous, histology-based classification. The increasing number of markers that are tested in a correct diagnostic procedure makes gene-targeted, next-generation sequencing (NGS) a powerful tool in routine pathology practice. We designed a 14-gene NGS panel specifically aimed at the diagnosis of glioma, which allows simultaneous detection of mutations and copy number variations, including the 1p/19q-codeletion and Epidermal Growth Factor Receptor (EGFR) amplification. To validate this panel, we used reference mutated DNAs, nontumor and non-glioma samples, and 52 glioma samples that were previously characterized. The panel was then prospectively applied to 91 brain lesions. A specificity of 100% and sensitivity of 99.4% was achieved for mutation detection. Orthogonal methods, such as in situ hybridization and immunohistochemical techniques, were used for validation, which showed high concordance. The molecular alterations that were identified allowed diagnosis according to the updated WHO criteria, and helped in the differential diagnosis of difficult cases. This NGS panel is an accurate and sensitive method, which could replace multiple tests for the same sample. Moreover, it is a rapid and cost-effective approach that can be easily implemented in the routine diagnosis of gliomas.
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Yamasaki, Fumiyuki, Takeshi Takayasu, Ryo Nosaka, Vishwa Jeet Amatya, Aidos Doskaliyev, Yuji Akiyama, Atsushi Tominaga, Yukio Takeshima, Kazuhiko Sugiyama, and Kaoru Kurisu. "Magnetic resonance spectroscopy detection of high lipid levels in intraaxial tumors without central necrosis: a characteristic of malignant lymphoma." Journal of Neurosurgery 122, no. 6 (June 2015): 1370–79. http://dx.doi.org/10.3171/2014.9.jns14106.
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OBJECT The differentiation of malignant lymphomas from gliomas or malignant gliomas by conventional MRI can be difficult. The authors studied Gd-enhanced MR images to obtain a differential diagnosis between malignant lymphomas and gliomas without central necrosis or cystic changes and investigated the diagnostic value of single-voxel proton MR spectroscopy (1H-MRS) using different parameters, including lipid levels. METHODS This was a retrospective study of patients with primary malignant CNS lymphoma (n = 17) and glioma (n = 122 [Grades I, II, III, and IV in 10, 30, 33, and 49 patients, respectively]) who were treated between 2007 and 2013. The authors focused on 15 patients with homogeneously enhanced primary malignant CNS lymphomas and 7 homogeneously enhanced gliomas. Images of all the included tumors were acquired with 1H-MRS at 3 T, and the diagnoses were histologically confirmed. RESULTS Using a short echo time 1H-MRS, large lipid peaks were observed in all 17 patients with a malignant lymphoma, in 39 patients (79.6%) with a Grade IV glioma, and in 10 patients (30.3%) with a Grade III glioma. A focus on homogeneously enhanced tumors revealed large lipid peaks in 15 malignant lymphomas that were free of central necrosis on Gd-enhanced T1-weighted images. Conversely, in the 7 homogeneously enhanced gliomas (glioblastoma and anaplastic astrocytoma, n = 2 each; anaplastic oligodendroglioma, diffuse astrocytoma, and pilomyxoid astrocytoma, n = 1 each), lipid peaks were small or absent. CONCLUSIONS Large lipid peaks on 1H-MRS images of tumors without central necrosis were characteristic of malignant lymphomas. Conversely, small or absent lipid peaks in intraaxial tumors without central necrosis were strongly suggestive of glioma.
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Ren, Jinhong, Peilan Jia, Hongxia Feng, Xiuhua Li, Jinghui Zhao, and Yunxia Sun. "Involvement of poly(ADP-ribose) polymerase-1 in Chinese patients with glioma: a potential target for effective patient care." International Journal of Biological Markers 33, no. 1 (July 27, 2017): 68–72. http://dx.doi.org/10.5301/ijbm.5000267.
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Objective: We aimed to evaluate the genetic variation of poly(ADP-ribose) polymerase-1 (PARP-1) in the development of gliomas among Chinese individuals. Materials and methods: Patients with a confirmed diagnosis of glioma and healthy individuals with no clinical symptoms of glioma were enrolled at Liaocheng People’s Hospital, China. Genetic polymorphisms were studied in plasma samples by polymerase chain reaction-restriction fragment length polymorphism assay. Cytokine levels were measured routinely in serum samples by sandwich ELISA technique. Results: A total of 120 Chinese patients with gliomas and 120 healthy Chinese individuals were included. We found that patients with the GG genotype (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.46-4.38, p<0.001) and carriers of the G allele (OR 11.5, 95% CI 6.31-21.3, p<0.0001) were at high risk of developing glioma. A del/ins polymorphism of the NF-κB1 gene (OR 4.27, 95% CI 2.43-7.50, p<0.001) was also found to be associated with glioma. In addition, significantly increased cytokine levels were observed in patients with glioma (p<0.05). Conclusions: Our findings showed that PARP-1 polymorphisms are involved in the development of glioma in Chinese individuals. Also serum cytokine levels can be considered among the potential risk factors for developing glioma.
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Verma, Kavita, Satya Raj Negi, and Sanjay Garhwal. "To study histopathological features, GFAP staining and Ki 67/ MIB-1 labelling index in diagnoses and histological grading of gliomas." Indian Journal of Forensic and Community Medicine 8, no. 2 (July 15, 2021): 115–19. http://dx.doi.org/10.18231/j.ijfcm.2021.023.
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: A group of tumors that develops in the brain and spinal cord is called glioma. Histologically gliomas are classified into astrocytoma, ependymoma, oligodendroglioma, brain stem glioma and oligoastrocytoma. The present study was conducted to study histological grading of gliomas and correlate it with patient’s age, sex, GFAP staining, role of the Ki-67/MIB-1 labelling indices (PIs). The present retrospective study was conducted on 50 biopsies received. All specimens were subjected to immunohistochemistory for GFAP and MIB-1 and correlated with WHO grading for glioma.: High incidence of glial tumours was seen in the 3 and 4 decade with slight male predominance (60%), with commonest site being frontal lobe. Glioblastomas (Grade IV) constitute the most common glial tumour. A statistically significant correlation was observed between GFAP staining and Ki-67/MIB-1 with histological grading.: The study can prove helpful in diagnosis and histological grading of gliomas and in planning treatment protocols and strategies.
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Jones, Pamela S., Gavin P. Dunn, Fred G. Barker, William T. Curry, Fred H. Hochberg, and Daniel P. Cahill. "Molecular genetics of low-grade gliomas: genomic alterations guiding diagnosis and therapeutic intervention. 11th Annual Frye-Halloran Brain Tumor Symposium." Neurosurgical Focus 34, no. 2 (February 2013): E9. http://dx.doi.org/10.3171/2012.12.focus12349.
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Object The authors' goal was to review the current understanding of the underlying molecular and genetic mechanisms involved in low-grade glioma development and how these mechanisms can be targets for detection and treatment of the disease and its recurrence. Methods On October 4, 2012, the authors convened a meeting of researchers and clinicians across a variety of pertinent medical specialties to review the state of current knowledge on molecular genetic mechanisms of low-grade gliomas and to identify areas for further research and drug development. Results The meeting consisted of 3 scientific sessions ranging from neuropathology of IDH1 mutations; CIC, ATRX, and FUBP1 mutations in oligodendrogliomas and astrocytomas; and IDH1 mutations as therapeutic targets. Sessions consisted of a total of 10 talks by international leaders in low-grade glioma research, mutant IDH1 biology and its application in glioma research, and treatment. Conclusions The recent discovery of recurrent gene mutations in low-grade glioma has increased the understanding of the molecular mechanisms involved in a host of biological activities related to low-grade gliomas. Understanding the role these genetic alterations play in brain cancer initiation and progression will help lead to the development of novel treatment modalities than can be personalized to each patient, thereby helping transform this now often-fatal malignancy into a chronic or even curable disease.
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Barritault, Marc, Thiébaud Picart, Delphine Poncet, Tanguy Fenouil, Anne d’Hombres, Mathieu Gabut, Jacques Guyotat, et al. "Avoiding New Biopsies by Identification of IDH1 and TERT Promoter Mutation in Nondiagnostic Biopsies From Glioma Patients." Neurosurgery 87, no. 4 (February 28, 2020): E513—E519. http://dx.doi.org/10.1093/neuros/nyaa025.
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Abstract BACKGROUND Biopsies in patients with a suspected glioma are occasionally nondiagnostic. OBJECTIVE To explore the utility of molecular testing in this setting by determining whether IDH1 and TERT promoter (pTERT) mutations could be detected in nondiagnostic biopsies from glioma patients. METHODS Using SNaPshot polymerase chain reaction, we retrospectively assessed IDH1 and pTERT mutation status in nondiagnostic biopsies from 28 glioma patients. RESULTS The nondiagnostic biopsy (needle biopsy n = 25, open or endoscopic biopsy n = 3) consisted of slight glial cell hypercellularity, hemorrhage, and/or necrosis. After another biopsy (n = 23) or a subsequent surgical resection (n = 5) the diagnosis was an IDH1-wildtype (WT) pTERT-mutant glioma (glioblastoma n = 16, astrocytoma n = 4), an IDH1-mutant pTERT-mutant oligodendroglioma (n = 1), an IDH1-mutant pTERT-WT astrocytoma (n = 1), and an IDH1-WT pTERT-WT glioblastoma (n = 6). An IDH1 mutation was identified in the nondiagnostic biopsies of the 2 IDH-mutant gliomas, and a pTERT mutation in the nondiagnostic biopsies of 16 out of the 21 of pTERT mutant-gliomas (76%). Overall, an IDH1 and/or a pTERT mutation were detected in 17 out of 28 (61%) of nondiagnostic biopsies. Retrospective analysis of the nondiagnostic biopsies based on these results and on imaging characteristics suggested that a new biopsy could have been avoided in 6 patients in whom a diagnosis of “molecular glioblastoma” could have been done with a high level of confidence. CONCLUSION In the present series, IDH1 and pTERT mutations could be detected in a high proportion of nondiagnostic biopsies from glioma patients. Molecular testing may facilitate the interpretation of nondiagnostic biopsies in patients with a suspected glioma.
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Chen, Zhen, Ning Li, Changtao Liu, and Shiwei Yan. "Deep Convolutional Neural Network-Based Brain Magnetic Resonance Imaging Applied in Glioma Diagnosis and Tumor Region Identification." Contrast Media & Molecular Imaging 2022 (May 24, 2022): 1–10. http://dx.doi.org/10.1155/2022/4938587.
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The aim of this study was to explore the application value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) based on a convolutional neural network (CNN) algorithm in glioma diagnosis and tumor segmentation. 66 patients with gliomas who were diagnosed and treated in the hospital were selected as the research objects. The patients were rolled into the high-grade glioma group (HGG, 46 cases) and the low-grade glioma group (LGG, 20 cases) according to the World Health Organization glioma grading standard. All patients received a conventional plain scan and a DCE-MRI. Parameters such as volume transfer constant (Ktrans), rate constant (Kep), extracellular volume (Ve), and mean plasma volume (Vp) were calculated, and the parameters of patients of each grade were analyzed. The efficacy of each parameter in diagnosing glioma was analyzed through a receiver operating characteristic curve. All images were segmented by the CNN algorithm. The CNN algorithm showed good performance in DCE-MRI image segmentation. The mean, standard deviation, kurtosis, and skewness of Ktrans and Ve, the standard deviation and skewness of Kep, and the mean and standard deviation of Vp were statistically considerable in differentiating HGG and LGG P < 0.05 . ROC analysis showed that the standard deviation of Ktrans (0.885) had the highest diagnostic accuracy in distinguishing HGG and LGG. The values of Ktrans, Ve, and Vp were positively correlated with Ki-67 (r = 0.346, P = 0.014; r = 0.335, P = 0.017; r = 0.323, P = 0.022). In summary, the CNN-based DCE-MRI technology had high application value in glioma diagnosis and tumor segmentation.
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Ross, Jennifer, Adriana Olar, and Christine Fuller. "A Pediatric Case of Diffuse Glioma Diagnosed at Autopsy." Academic Forensic Pathology 7, no. 4 (December 2017): 657–66. http://dx.doi.org/10.23907/2017.056.
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Sudden death from an undiagnosed primary intracranial neoplasm is extremely uncommon and even rarer in the pediatric population. Gliomatosis cerebri (GC) represents a growth pattern demonstrable by a variety of gliomas, predominating in adults. Herein we present a rare occurrence of diagnosis of a pediatric glioma with a GC pattern of infiltration at autopsy and compare the immunohistochemical results and molecular characteristics in this tumor to the small amount of published knowledge available about pediatric diffuse gliomas with widespread brain invasion.
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Yogendran, Lalanthica, Mark Rudolf, Drew Yeannakis, Kathleen Fuchs, and David Schiff. "QOL-09. NAVIGATING DISABILITY INSURANCE FOR PATIENTS DIAGNOSED WITH LOW-GRADE GLIOMA." Neuro-Oncology 24, Supplement_7 (November 1, 2022): vii242. http://dx.doi.org/10.1093/neuonc/noac209.936.
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Abstract Central nervous system tumors and their treatments can cause neurologic, cognitive, and psychiatric symptoms that restrict a patient’s ability to work. In the United States, a diagnosis of high-grade glioma (grade 3 or 4) medically qualifies a patient for disability benefits through Social Security. Low-grade gliomas can be similarly debilitating, with at least 50% of patients presenting with one or more cognitive deficits and 80% of patients with tumor-related epilepsy. In light of these serious symptoms, it is unsurprising at least half of patients with low-grade glioma do not return to work within one year of diagnosis. Yet a diagnosis of low-grade glioma does not in and of itself qualify patients for disability benefits; the burden of proof is substantially higher. Thus, patients with low-grade glioma require special attention as they seek disability benefits. Here, we outline the process of medical documentation to support disability benefits, Security Disability Insurance (SSDI) and Supplemental Security Income (SSI). We provide a template to assist providers in facilitating the application process for patients with low-grade glioma seeking disability benefits. The provider’s role is not to simply “declare” a patient disabled, but rather to provide comprehensive documentation regarding the patient’s diagnosis, treatment, response to treatment, symptoms, and functional status in the medical record. As cognitive symptoms and seizures are two key sources of disability in low-grade glioma patients, referrals to neuropsychology and epileptology, among other sub-specialties, are key to improve patient care and bolster documentation of the patient’s symptoms in these domains. Likewise, connecting patients with social workers and disability claims representatives can assist them in navigating the complicated application process. Providers are better able to help their patients navigate the disability application process when they understand how disability evaluations work and what key information evaluators seek.
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Vuckovic, Nada, Dejan Vuckovic, Dragan Dankuc, and Ljiljana Jovancevic. "Nasal glioma." Archive of Oncology 14, no. 1-2 (2006): 57–59. http://dx.doi.org/10.2298/aoo0602057v.
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Congenital midline nasal masses are rather rare anomalies that occur in about one in 20 000- 40 000 live births. Nasal gliomas account for approximately 5% of all congenital nasal swellings. The most common are dermoid/epidermoid tumors, nasal cerebral heterotopias (nasal gliomas), and nasal encephaloceles, with clinical significance that some of them have an actual or potential central nervous system connection. We present a case of an 8-year-old boy who complained of slight hearing loss dating 2 month before. Anterior rhinoscopy showed an oval, elastic, smooth, uncompressible mass, at the upper third of the nasal septum, unchanged in size on the Valsalva test. The mass causes breathing difficulties on that left naris. Clinical diagnosis was hemangioma. In the histopathologic laboratory, on gross examination, the mass measured 1.0 x 0.7 x 0.5 cm, was well demarcated, smooth, elastic, homogeneous, firm and whitish-gray in color. On cut section, the mass was homogenous, firm whitish gray in color. It consisted of astrocytic neuroglial cells with fibrous connective tissue and covered by the normal respiratory mucosa. The diagnosis of a nasal glioma was made.
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Wakabayashi, Toshihiko, Jun Yoshida, Hisao Seo, Kyoto Kazo, Yoshiharu Murata, Nobuo Matsui, and Naoki Kageyama. "Characterization of neuroectodermal antigen by a monoclonal antibody and its application in CSF diagnosis of human glioma." Journal of Neurosurgery 68, no. 3 (March 1988): 449–55. http://dx.doi.org/10.3171/jns.1988.68.3.0449.
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✓ Monoclonal antibodies were produced by immunization of the human glioma cell line SK-MG-4. One of the antibodies, designated G-22, reacted with 18 of 20 glioma cell lines, two melanoma cell lines, and three lung cancer cell lines, but not with 39 cell lines derived from sarcoma, carcinoma, or hematopoietic tumors. The antigen was expressed in the brain of human fetuses in early gestation (9 weeks) but not in late gestation (8 months) or in normal adult brain, suggesting that the antibody recognizes neural differentiation antigens expressed by neuroectodermal origin. A high incidence of positive antigens has been observed in gliomas but not in the other neural tumors, such as ependymomas, meningiomas, and neuroblastomas. Thus, the antigen defined by the G-22 monoclonal antibody could be defined as glioma-associated antigen. Pulse-labeling with tritiated leucine and subsequent immunoprecipitation of the solubilized cell membrane revealed that the antigen recognized by this antibody had a molecular weight of 67 kD on sodium dodecyl sulfate-poly-acrylamide gel electrophoresis (SDS-PAGE). It was shown by dot-blot enzyme-linked immunospecific assay (ELISA) that the antigen could be detected in the cerebrospinal fluid (CSF) from patients with gliomas. From analysis of affinity chromatography and SDS-PAGE, the antigen present in the CSF had a molecular weight similar to that of a 1% Nonidet P-40 (NP-40) extract from a glioma cell line. When the antigen in CSF was quantitatively assayed by ELISA, the mean antigen level (expressed as optical density at 450 nm) in the CSF of seven patients was 0.8 ± 0.28 (mean ± standard deviation), which was significantly higher than the 0.38 ± 0.14 level observed in the CSF of 15 patients with nonglioma brain tumors and the 0.23 ± 0.09 level in the CSF of four patients without brain tumors. These results indicate that the monoclonal antibody G-22 is useful for the diagnosis of glioma.
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Praska, Corinne, Thomas Kollmeyer, Emily Barr Fritcher, Jesse Voss, Michelle McKenna, Jessica Balcom, Amber Pryzbylski, et al. "PATH-45. CLINICAL UTILITY OF COMBINED NEXT GENERATION SEQUENCING AND CHROMOSOMAL MICROARRAY ANALYSIS FOR THE DIAGNOSIS AND MANAGEMENT OF ADULT GLIOMAS." Neuro-Oncology 22, Supplement_2 (November 2020): ii174. http://dx.doi.org/10.1093/neuonc/noaa215.725.
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Abstract BACKGROUND Molecular parameters have been incorporated into the 2016 WHO Classification of CNS Tumors and subsequent cIMPACT-NOW updates to facilitate clinical management of glioma patients. However, there have been few reports of the overall clinical utility of comprehensive genetic testing in adult glioma patients. We report the results of sequencing and chromosomal microarray analysis of adult gliomas seen at the Mayo Clinic and through the Mayo Clinic Laboratories (MCL) reference practice. METHODS A consecutive series of 379 Mayo Clinic adult glioma patients were consented to receive targeted next generation sequencing and chromosomal microarray analysis, regardless of standard clinical ordering practices. Known diagnostic, prognostic, and predictive alterations were annotated for each case. These results were compared to the larger MCL reference practice of 2400 adult glioma samples that received one or both tests clinically. RESULTS Of the consecutive Mayo Clinic cases, 67% had alterations that fell into at least one of the diagnostic, prognostic, and/or predictive categories. Molecular testing generated diagnostic, prognostic, and predictive information in 44%, 34%, and 36% of cases, respectively. Diagnostically, molecular testing mainly aided in arriving at a final integrated diagnosis, and only a small number of cases (n= 5; 1%) had a change in diagnosis. The consecutive cases represent the typical distribution of adult glioma types (47% IDH-wildtype glioblastoma/astrocytoma, 22% IDH-mutant astrocytoma/glioblastoma, 13% IDH-mutant 1p/19q-codeleted oligodendroglioma, and 18% other tumor types). The MCL practice is enriched in tumors with atypical molecular patterns (37% IDH-wildtype glioblastoma/astrocytoma, 17% IDH-mutant astrocytoma/glioblastoma, 18% IDH-mutant 1p/19q-codeleted oligodendroglioma, and 29% other tumor types). CONCLUSIONS Molecular testing provides useful diagnostic, prognostic, and predictive information for the clinical management of adult glioma patients. While the current guidelines for ordering molecular testing are effective for diagnostic purposes, additional prognostic and predictive information can be gleaned from comprehensive molecular testing of adult gliomas.
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Calin, V. L., G. E. D. Petrescu, M. Mihailescu, F. M. Brehar, M. Lisievici, B. Comanescu, N. Tarba, M. R. Gorgan, T. Savopol, and M. G. Moisescu. "P04.17 Differential diagnosis of gliomas using Digital Holographic Microscopy." Neuro-Oncology 21, Supplement_3 (August 2019): iii32—iii33. http://dx.doi.org/10.1093/neuonc/noz126.112.
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Abstract BACKGROUND The clinical course and prognostic of gliomas depend on the tumor histological and molecular features. The histopathological diagnosis requests well-trained specialists and multi-step operational procedures for sample preparation. Faster and more objective protocols should be implemented in support of pathologists. The Quantitative Phase Imaging based methods are biologically proved to be efficient in revealing, without any labeling, important characteristics of the living specimens having different structural complexity. We used Digital Holographic Microscopy (DHM) to acquire QPIs and to analyze glioma samples in order to discriminate glioma tissues of various malignancy grades. MATERIAL AND METHODS Grade II glioma (GM) and grade IV glioblastoma (GBM) tissues were collected from patients who underwent surgery. For each sample, two consecutive slices were fixed with formalin, embedded in paraffin and cut at 4 µm thickness. One slice was stained using hematoxylin and eosin (H&E) and the other slice was left unstained. The pathologist diagnosed H&E slides as GM or GBM and the corresponding unstained slides were accordingly labeled. Holograms of unstained sections were acquired using a LyncéeTec DHM®-R1000 digital holographic microscope (at 664.5 nm). QPIs were reconstructed using the Koala dedicated software, and then the distribution of the phase shift values in the image was characterized by various statistical parameters (mean, variance, kurtosis, skewness, energy, entropy). RESULTS A total of 78 images were analyzed, 33 for grade II gliomas and 45 for grade IV glioblastomas, the areas being randomly selected, as the tissue is highly homogeneous. Lower values of Mean, Variance and Energy and higher values of Kurtosis and Entropy were found for GM compared to GBM (Mann-Whitney test was performed for proofing the statistically significance). No statistical difference was observed for Skewness. As the thickness of the samples was constant, variations of these parameters may be attributed to different distributions of the refractive index within the samples, which in turn is directly related to the protein content and structural features of the tissue. CONCLUSION The analyze of unstained biopsies of glioma tumors based on DHM could be used for faster and more accurate diagnosis, offering efficient optical markers to distinguish between levels of malignancy with high statistical confidence. Our findings can be further exploited for automatic evaluation and classification of malignant tissues, parameters provided by QPIs being used as classifiers for a supervised machine algorithm. This method can be adapted for fresh samples, being thus a promising method for intraoperative diagnostic.
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Alenda, Cristina, Estefanía Rojas, and Luis M. Valor. "FFPE samples from cavitational ultrasonic surgical aspirates are suitable for RNA profiling of gliomas." PLOS ONE 16, no. 7 (July 22, 2021): e0255168. http://dx.doi.org/10.1371/journal.pone.0255168.
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During surgical procedures for gliomas, tissue material obtained from cavitational ultrasonic surgical aspirators (CUSAs) is generally discarded but can actually exceed the amount and quality of certain tumour core resections (TCRs). Despite reports indicating the suitability of CUSA-derived material for diagnosis and research, its use is still marginal. We extended these conclusions to formalin-fixed, paraffin-embedded (FFPE) samples, the most common format for archival tumour tissue in anatomical pathology departments, by conducting for the first time RNA-seq analysis in CUSA aspirates. We compared the molecular diagnosis of somatic mutations used in the clinical routine and the gene expression profiles of fixed solid material from CUSA aspirates and TCRs from the same patients in selected gliomas encompassing grades II to IV. Despite the characteristic heterogeneity of gliomas, we found substantial similarities between the corresponding aspirates and TCRs that included transcriptional signatures associated with glioma subtypes. Based on these results, we confirmed that CUSA-fixed biomaterials from glioma surgeries are appropriate for downstream applications and biomarkers screening.
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Murillo, Jennifer, Elizabeth Anyanda, and Jason Huang. "EPID-10. GLIOMA INCIDENCE AND SURVIVAL BY INCOME LEVEL IN THE UNITED STATES GENERAL POPULATION AGES AND ABOVE FROM 2000-2018." Neuro-Oncology 23, Supplement_6 (November 2, 2021): vi87—vi88. http://dx.doi.org/10.1093/neuonc/noab196.343.
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Abstract Gliomas are the most common primary malignant brain tumor in the United States with previous studies showing the incidence varied by age, sex, and race or ethnicity. Survival after diagnosis has also been shown to vary by these factors. Also, socioeconomic status and its association with various cancers have also been studied at length over time. PURPOSE: The purpose of our research was to quantify the differences in incidence and survival rates of gliomas in 15 years and older by income level. METHODS: This population-based study obtained incidence and survival data from the Incidence-SEER Research Database the general population. Average age incidence were generated by glioma groups and grouped by income levels. Survival rates were generated by overall glioma diagnosis grouped by observed survival at 12, 24, 36, 48 and 60 months and by again by income levels. The analysis included 94,207 patients with glioma diagnosed in those aged 15 years or older. RESULTS: Overall, 94, 207 patients diagnosed with glioma were analyzed. Of these, 1,089 (1.16%) fell into the < $35k group, 1,684 (1.79%) in the $35k-$40k group, 3,473 (3.69%) in the $40k-$45k group, 5,647 (5.99%) in the $45k-$50k group, 7,138 (7.58%) in the $50k-$55k group, 6,468 (6.87%) in the $55k-$60k group, 15,348 (16.29%) in the $60k-$65k group, 13,216 (14.03%) in the $65k-$70k group, 9,035 (9.59%) in the $70k-$75k group, and 31,109 (33.02%) fell in > $75k group. The data was also broken further down into survivability showing average survival. CONCLUSION: Incidence of glioma and 12, 24, 36, 48 and 60 month survival rates after diagnosis vary significantly by income level with higher income level greater than $75,000+ having higher incidence and higher survival rates compared with lower income levels. Further research is needed to help determine risk factors and barriers to care to help reveal health disparities.
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Hervás-Corpión, Irati, Andrea Gallardo-Orihuela, Inmaculada Catalina-Fernández, Irene Iglesias-Lozano, Olga Soto-Torres, Noelia Geribaldi-Doldán, Samuel Domínguez-García, et al. "Potential Diagnostic Value of the Differential Expression of Histone H3 Variants between Low- and High-Grade Gliomas." Cancers 13, no. 21 (October 20, 2021): 5261. http://dx.doi.org/10.3390/cancers13215261.
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Glioblastoma (GB) is the most aggressive form of glioma and is characterized by poor prognosis and high recurrence despite intensive clinical interventions. To retrieve the key factors underlying the high malignancy of GB with potential diagnosis utility, we combined the analysis of The Cancer Gene Atlas and the REMBRANDT datasets plus a molecular examination of our own collection of surgical tumor resections. We determined a net reduction in the levels of the non-canonical histone H3 variant H3.3 in GB compared to lower-grade astrocytomas and oligodendrogliomas with a concomitant increase in the levels of the canonical histone H3 variants H3.1/H3.2. This increase can be potentially useful in the clinical diagnosis of high-grade gliomas, as evidenced by an immunohistochemistry screening of our cohort and can be at least partially explained by the induction of multiple histone genes encoding these canonical forms. Moreover, GBs showing low bulk levels of the H3.1/H3.2 proteins were more transcriptionally similar to low-grade gliomas than GBs showing high levels of H3.1/H3.2. In conclusion, this study identifies an imbalanced ratio between the H3 variants associated with glioma malignancy and molecular patterns relevant to the biology of gliomas, and proposes the examination of the H3.3 and H3.1/H3.2 levels to further refine diagnosis of low- and high-grade gliomas in future studies.