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Oligodendrogliomas are a rare diffuse astrocytic tumor, usually present in young adults, which depending on the pathogenic alterations can lead to major disabilities or even death. We present a case of a male patient in the fifth decade of life, who initially presented with an oligodendroglioma, and approximately one year after the first therapeutic intervention the condition recurred in the form of an anaplastic oligodendroglioma. We made a complete histopathological and immunohistochemical panel in order to have a final diagnosis with the greatest accuracy, thus making a comparison with the literature in order to assess the diagnosis and subsequent therapeutic conduct.

Objective: To review evidence-based data on spontaneous retrogression of low-grade gliomas with respect to interval till regression, type of glioma and patient outcome. Method: The systematic review comprised medical literature in English language published from January 1997 to January 2017 on Scopus, PubMed and Google Scholar databases to establish consensus about the possible mechanism of spontaneous regression, the role of therapeutic intervention and failure of management strategies in low-grade gliomas. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed during the review. Results: Of the 176 articles identified, 73(41.5%) were shortlisted for detailed assessment. Of them, 10(13.7%) were included; 5(50%) case reports and 5(50%) case series. There were 23 cases of spontaneous regression; 15(65.2%) males and 8(34.7%) females. The interval of regression varied from 3 months to 15.5 years, and the most commonly presenting low-grade glioma type was optic pathway glioma 11(47.4%). Conclusion: The phenomenon of regression was most evident in optic pathway glioma. Literature suggested that low-grade gliomas should undergo serial imaging before implying any therapeutic intervention. However, the evidence-based proof, large-scale experimental studies and ethical considerations are still required to standardise this strategy. Key Words: Pilocytic astrocytomas, Desmoplastic infantile ganglioglioma, DIG, Desmoplastic infantile astrocytomas, DIA, Diffuse astrocytoma, Spontaneous regression. Continuous...

Primary glioblastoma develops de novo without clinical or histological evidence of a low-grade precursor lesion, whereas secondary glioblastoma develops from a low-grade glioma. The present report describes an extraordinary case of IDH-wildtype secondary glioblastoma arising in IDH-mutant diffuse astrocytoma. A 31-year-old female had a surgical history of IDH-mutant diffuse astrocytoma on the left frontal lobe six years before. Magnetic resonance imaging revealed new infiltrative lesions in the left frontal lobe adjacent to the previous lesion. The patient underwent tumourectomy, and the new infiltrative lesion was diagnosed as glioblastoma. Interestingly, the IDH-1 (p.Arg132His) mutation was found in diffuse astrocytoma but not in glioblastoma based on next generation sequencing. ATRX (p.Gln1670Ter) and TP53 (p.His193Arg) mutations were found in both lesions. Additionally, the PTEN (p.His296Pro) mutation was identified only in glioblastoma. A well-accepted hypothesis is that the IDH mutation initiates in glial progenitor cells and causes secondary glioblastoma harboring the IDH mutation to develop from low grade glioma with IDH mutation. However, this case showed that the other genetic mutations can be initiated before the IDH mutation in glioma oncogenesis. Contrary to the previous hypothesis, this is the first case of IDH-wildtype secondary glioblastoma arising in IDH-mutant diffuse astrocytoma.

Background: More than half of Central Nervous System tumors are benign; however, they can cause substantial morbidity. The classification of central nervous system is vital for their varied outcomes and management. The objective of this study is to provide the histopathological spectrum of central nervous system tumors in a central hospital in Nepal.Methods: The present study is a retrospective cross-sectional study conducted at Department of Pathology, Kathmandu Model Hospital, Kathmandu, Nepal from January 2010 to December 2017 of 162 cases of clinically diagnosed cases of central nervous system tumors. All patients were classified according to the World Health Organization classification of central nervous system tumors. Results: Nine of these162 patients did not have any tumor. The most common categories of tumors were astrocytic and oligodendroglial tumors (39.2%), meningiomas (21.5%), cranial and para spinal tumors (15%), tumors of sellar region including pituitary adenoma (4.5%), and metastatic tumors (3.2%). Glioblastoma(51.6%) and diffuse astrocytoma (21.6%) were the most common astrocytic and oligodendroglial tumors. The most common site of tumors in the brain was frontal (14.37%) followed by temporal (10.45%) region in the brain and dorsal region in spine.Conclusions: This study gives the current scenario of the epidemiology and clinicohistopathological aspects of different brain tumors as encountered in a tertiary level hospital in Kathmandu.Keywords: Astrocytoma; central nervous system; cranial; meningioma; tumors.

A 39-year-old man had received boron neutron capture therapy (BNCT) for a grade II astrocytoma (compatible with diffuse astrocytoma, not otherwise specified in the WHO 2016 criteria). He returned to his previous work after surgery, but, 7 years later, he suddenly developed seizures, and his health condition deteriorated. Therefore, he underwent a second surgery. The mass removed in the second operation was mostly necrotic as a result of previous radiation treatment. He then showed no signs of recurrence and did not require any treatment other than antiepileptic drugs for 25 years. He was able to be employed by a listed company until the age of 65 years for light jobs as a physically handicapped individual. This case suggests the effectiveness of BNCT even for rather low-grade astrocytomas.

Neurofibromatosis type 1 (NF1) is one of the most common genetic neurocutaneous disorders, and it is well known to be associated with peripheral or central nervous system malignancies. The most common malignant tumors are malignant peripheral nerve sheath tumors (MPNSTs); MPNSTs are the most common cause of death in patients with NF1. Central nervous system malignancies rarely occur. So far, the occurrence of spinal cord malignancies is exceedingly rare. Herein, we report a rare case of a 69-year-old male with NF1 following tumor resection twice for cutaneous MPNSTs developing intramedullary diffuse astrocytoma in the conus medullaris, which initially presented with traumatic spinal cord injury associated with a compression fracture from fall. Contrast-enhanced magnetic resonance imaging and biopsy of the spinal cord were required to establish the final diagnosis.

Background Prognosis of low-grade glioma are currently determined by genetic markers that are limited in some countries. This study aimed to use clinical parameters to develop a nomogram to predict survival of patients with diffuse astrocytoma (DA) which is the most common type of low-grade glioma. Materials and Methods Retrospective data of adult patients with DA from three university hospitals in Thailand were analyzed. Collected data included clinical characteristics, neuroimaging findings, treatment, and outcomes. Cox’s regression analyses were performed to determine associated factors. Significant associated factors from the Cox regression model were subsequently used to develop a nomogram for survival prediction. Performance of the nomogram was then tested for its accuracy. Results There were 64 patients with DA with a median age of 39.5 (interquartile range [IQR] = 20.2) years. Mean follow-up time of patients was 42 months (standard deviation [SD] = 34.3). After adjusted for three significant factors associated with survival were age ≥60 years (hazard ratio [HR] = 5.8; 95% confidence interval [CI]: 2.09–15.91), motor response score of Glasgow coma scale < 6 (HR = 75.5; 95% CI: 4.15–1,369.4), and biopsy (HR = 0.45; 95% CI: 0.21–0.92). To predict 1-year mortality, sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the curve our nomogram was 1.0, 0.50, 0.45, 1.0, 0.64, and 0.75, respectively. Conclusions This study provided a nomogram predicting prognosis of DA. The nomogram showed an acceptable performance for predicting 1-year mortality.

Background Management of unresectable pediatric low-grade glioma and glioneuronal tumor (LGG/LGGNT) is controversial. There are no validated prognostic features to guide use of radiation therapy (RT). Our study aimed to identify negative prognostic features in patients treated with RT using clinicopathologic and molecular data and validate these findings in an external dataset. Methods Children with non-metastatic, biopsy-proven unresectable LGG/LGGNT treated with RT at a single institution between 1997 and 2017 were identified. Recursive partitioning analysis (RPA) was used to stratify patients into low- and high-risk prognostic groups based on overall survival (OS). CNS9702 data were used for validation. Results One hundred and fifty patients met inclusion criteria. Median follow-up was 11.4 years. RPA yielded low- and high-risk groups with 10-year OS of 95.6% versus 76.4% (95% CI: 88.7%–98.4% vs 59.3%–87.1%, P = 0.003), respectively. These risk groups were validated using CNS9702 dataset (n = 48) (4-year OS: low-risk vs high-risk: 100% vs 64%, P < 0.001). High-risk tumors included diffuse astrocytoma or location within thalamus/midbrain. Low-risk tumors included pilocytic astrocytoma/ganglioglioma located outside of the thalamus/midbrain. In the subgroup with known BRAF status (n = 49), risk stratification remained prognostic independently of BRAF alteration (V600E or fusion). Within the high-risk group, delayed RT, defined as RT after at least one line of chemotherapy, was associated with a further decrement in overall survival (P = 0.021). Conclusion A high-risk subgroup of patients, defined by diffuse astrocytoma histology or midbrain/thalamus tumor location, have suboptimal long-term survival and might benefit from timely use of RT. These results require validation.

OBJECTIVEThe authors aimed to investigate genetic alterations in low-grade gliomas (LGGs) in pediatric and young adult patients presenting with spontaneous hemorrhage.METHODSPatients younger than 30 years of age with a pathological diagnosis of World Health Organization (WHO) grade I or II glioma and who had undergone treatment at the authors’ institution were retrospectively examined. BRAF V600E, FGFR1 N546/K656, IDH1 R132, IDH2 R172, and KIAA1549-BRAF (K-B) fusion genetic alterations were identified, and the presence of spontaneous tumoral hemorrhage was recorded.RESULTSAmong 66 patients (39 with WHO grade I and 27 with grade II tumors), genetic analysis revealed K-B fusion in 18 (27.3%), BRAF V600E mutation in 14 (21.2%), IDH1/2 mutation in 8 (12.1%), and FGFR1 mutation in 4 (6.1%). Spontaneous hemorrhage was observed in 5 patients (7.6%); 4 of them had an FGFR1 mutation and 1 had K-B fusion. Univariate analysis revealed a statistically significant association of an FGFR1 mutation and a diencephalic location with spontaneous hemorrhage. Among 19 diencephalic cases including the optic pathway, hypothalamus, and thalamus, an FGFR1 mutation was significantly associated with spontaneous hemorrhage (p < 0.001). Four FGFR1 mutation cases illustrated the following results: 1) a 2-year-old female with pilomyxoid astrocytoma (PMA) harboring the FGFR1 K656E mutation presented with intraventricular hemorrhage (IVH); 2) a 6-year-old male with PMA harboring FGFR1 K656E and D652G mutations presented with intratumoral hemorrhage (ITH); 3) a 4-year-old female with diffuse astrocytoma harboring FGFR1 K656M and D652G mutations presented with IVH; and 4) a young adult patient with pilocytic astrocytoma with the FGFR1 N546K mutation presented with delayed ITH and IVH after 7 years of observation.CONCLUSIONSAlthough the mechanism remains unclear, the FGFR1 mutation is associated with spontaneous hemorrhage in pediatric and young adult LGG.

Diffuse astrocytic and oligodendroglial tumors are frequently associated with symptomatic epilepsy, and predictive seizure control is important for the improvement of patient quality of life. To elucidate the factors related to drug resistance of brain tumor-associated epilepsy from a pathological perspective. From January 2012 to October 2017, 36 patients diagnosed with diffuse astrocytic or oligodendroglial tumors were included. Assessment for seizure control was performed according to the Engel classification of seizures. Patient clinical, radiological, and pathological data were stratified based on the following 16 variables: age, sex, location of tumor, existence of the preoperative seizure, extent of resection, administration of temozolomide, radiation therapy, recurrence, Karnofsky performance scale, isocitrate dehydrogenase 1, 1p/19q co-deletion, Olig2, platelet-derived growth factor receptor alpha, p53, ATRX, and Ki67. These factors were compared between the well-controlled group and drug-resistant seizure group. Twenty-seven patients experienced seizures; of these, 14 cases were well-controlled, and 13 cases were drug-resistant. Neither clinical nor radiological characteristics were significantly different between these two groups, though p53 immunodetection levels were significantly higher, and the frequency of 1p/19q co-deletion was significantly lower in the group with drug-resistant seizures than in the well-controlled group. In the multivariate analysis, only one item was selected according to stepwise methods, and a significant difference was observed for p53 (OR, 21.600; 95% CI, 2.135-218.579; P = 0.009). Upregulation of p53 may be a molecular mechanism underlying drug resistant epilepsy associated with diffuse astrocytic and oligodendroglial tumors.

// Lubov Mitrofanova 1 , Anton Hazratov 1 , Boris Galkovsky 1 , Andrey Gorshkov 1 , 2 , Danila Bobkov 2 , 3 , Dmitry Gulyaev 4 and Evgeny Shlyakhto 5 1 Almazov National Medical Research Centre, Pathomorphology Research Laboratory, St. Petersburg, Russia 2 Smorodintsev Research Institute of Influenza, Laboratory of Intracellular Signaling and Transport, St. Petersburg, Russia 3 Institute of Cytology of the Russian Academy of Science, Laboratory of Cell Biology in Culture, St. Petersburg, Russia 4 Almazov National Medical Research Centre, Research Department of Neurosurgery, St. Petersburg, Russia 5 Almazov National Medical Research Centre, General Director, St. Petersburg, Russia Correspondence to: Lubov Mitrofanova, email: lubamitr@yandex.ru Keywords: telocytes; pericytes; confocal microscopy; primary culture of glioma telocytes; glioblastoma Received: June 05, 2019 Accepted: October 26, 2019 Published: January 28, 2020 ABSTRACT Telocytes (Tcs) and pericytes (Pcs) are two types of perivascular interstitial cell known to be widespread in various organs and tissues, including the brain. We postulated that Tcs and Pcs may be involved in glioblastoma (GBM) neovascularization. Objective Morphological study of Tc and Pc roles in GBM. Materials and Methods Samples from 15 GBM, 10 diffuse astrocytoma, as well as 5 control samples were studied. We used immunohistochemistry (IHC) with antibodies (Abs) to GFAP, Ki-67, CD117, NeuroD1, NG2, CD34, and SMA. Confocal laser scanning microscopy (CLSM) of 4 glioma tissue cultures and 4 GBM sections was performed with GFAP, CD117, CD34/connexin43, NeuroD1/connexin43, CD34/NG2 and CD13/CD117 Abs. Electron microscopy (EM) of GBM was performed in 4 cases. Results The presence of Tcs and Pcs was shown in GBM (IHC, EM, CLSM) and glioma cultures (CLSM). The Tc immunophenotype was CD117 + /CD34 + /connexin43 + /NeuroD1 + . The Pc immunophenotype was SMA + /NG2 + /CD13 + . The number of Tcs in GBM specimens was 10 times higher than in astrocytoma. We also identified CD13/CD117 and CD34/NG2 co-expressing cells in GBM blood vessels. Conclusion Four immunophenotypes were found in GBM vessels, corresponding to endotheliocytes, Pcs, Tcs, and a mixed Pc/Tc immunophenotype. These and forthcoming improvements in our understanding of the origin and function of Tcs, including their relationship with Pcs, are necessary steps in oncology. Study of these cell types (Tcs, Pcs) and their roles in brain tumor oncogenesis will likely enable improved targeted therapies and support development of new forms of anti-neoplastic drugs.

Experimental investigations have shown that drug abuse initiates a cascade of pathophysiological events including toxic and hypoxic-ischemic injury on neurons, microglia and astrocytes, which finally lead to widespread disturbances in the brain. There are many reports about the psychiatric and neurologic effects of multiple drug abuse, but only a few clinical studies reporting possible correlation between recreational illicit drugs and gliomas. In this paper we present the case of a 40 years-old male patient, with a long history (almost ten years) of multiple drug abuse, including cocaine, heroin, marijuana, ethnobotanical drugs and nicotine, who was diagnosed and surgically treated for a supratentorial secondary giant cell glioblastoma (sgcGB) developed in a diffuse astrocytoma NOS. Depending on the type of the illicit drug used by the patient and the moment of life he used them, the morphological features identified in the histological samples of our patient confirmed the gliomagenesis effect of chronic multiple drug abuse, but also its inhibitory effects on tumour cells growth. This was due to the fact that although the tumour was large in size and caused brain sub-falcine herniation, the patient reported the onset of seizures only late in the evolution. In conclusion, the diagnosis of a brain tumour should take into consideration not only patient's clinical and imaging data, but also his lifestyle, especially his addiction to recreational drugs.

Maffucci syndrome (MS) and Ollier disease (OD) are nonhereditary congenital diseases characterized by multiple enchondromas and/or chondrosarcomas. Recent studies have implicated somatic mosaic mutations of isocitrate dehydrogenase 1 or 2 (IDH1/2) as contributing to the pathogenesis of MS and OD. Occasionally, patients with these disorders may also present with central nervous system (CNS) tumors; however, detailed genetic analyses are limited. In this article, the authors report on a male patient with MS, harboring three CNS tumors that share a common genetic alteration. Over a 9-year period, three separate tumor resections were conducted for sellar, intraparenchymal brainstem, and osseous clival tumors. The histopathological diagnoses were pituitary adenoma, diffuse astrocytoma, and chondrosarcoma, respectively. Sanger sequencing revealed a common IDH1 R132C mutation among all three CNS tumors but not in blood DNA. Administering chemotherapy (nimustine) and subsequent radiation therapy to the brainstem glioma and the residual lesion in the clivus have kept the patient progression free for 18 months. This is the first report demonstrating an IDH1 mutation shared among three different CNS tumors in a single patient with MS. The findings support the hypothesis that in MS and OD, a single common IDH1 mutation triggers tumorigenesis in cells of different origins and locations in a somatic mosaic fashion.

Background Intratumoral heterogeneity is a hallmark of diffuse gliomas. DNA methylation profiling is an emerging approach in the clinical classification of brain tumors. The goal of this study is to investigate the effects of intratumoral heterogeneity on classification confidence. Methods We used neuronavigation to acquire 133 image-guided and spatially separated stereotactic biopsy samples from 16 adult patients with a diffuse glioma (7 IDH-wildtype and 2 IDH-mutant glioblastoma, 6 diffuse astrocytoma, IDH-mutant and 1 oligodendroglioma, IDH-mutant and 1p19q codeleted), which we characterized using DNA methylation arrays. Samples were obtained from regions with and without abnormalities on contrast-enhanced T1-weighted and fluid-attenuated inversion recovery MRI. Methylation profiles were analyzed to devise a 3-dimensional reconstruction of (epi)genetic heterogeneity. Tumor purity was assessed from clonal methylation sites. Results Molecular aberrations indicated that tumor was found outside imaging abnormalities, underlining the infiltrative nature of this tumor and the limitations of current routine imaging modalities. We demonstrate that tumor purity is highly variable between samples and explains a substantial part of apparent epigenetic spatial heterogeneity. We observed that DNA methylation subtypes are often, but not always, conserved in space taking tumor purity and prediction accuracy into account. Conclusion Our results underscore the infiltrative nature of diffuse gliomas and suggest that DNA methylation subtypes are relatively concordant in this tumor type, although some heterogeneity exists.

The prospect of using immunotherapy for IDH-mutant LGGs has been daunting given the immune-poor microenvironment and low mutational burden. We hypothesized that LGG-targeting T cells might still be present at low frequency and with limited regional infiltration into the tumor. To improve sensitivity, we combined high-density multi-region tumor sampling with high-throughput neoantigen-T cell screening for a patient with WHO Grade II diffuse astrocytoma who eventually progressed, at second recurrence, to anaplastic astrocytoma. We performed maximal-anatomic sampling from 10 distinct regions of the tumor at the initial resection, as well as single sampling at first recurrence, for exome-based prediction of clonal and subclonal expressed neoantigens, RNAseq-based estimation of regional immune cell composition, and T cell receptor (TCR) beta deep sequencing. Based on our predictions, we then generated a barcoded library of patient-specific peptide-HLA multimers loaded with predicted neopeptides. Using this library, neoantigen-specific CD8 T cells were captured and isolated from patient peripheral blood and subjected to single cell TCR sequencing. We screened patient-derived peripheral blood drawn two years after initial resection and identified five T cell clones recognizing three LGG neoepitopes. Two neoepitopes were derived from truncal, tumor-wide mutations, including a truncating splice-site mutation in TP53 and a missense mutation in MRPL46. Each of these neoepitopes were recognized by two distinct TCRs, consistent with TCR convergence. A third neoepitope was derived from a subclonal MRPL46 mutation. Using the TCR beta sequence as a molecular barcode, TCRs specific to the 2 clonal neoepitopes, but not the subclonal neoepitope, were detectable in the glioma and blood at initial resection, as well as in the recurrent glioma. In summary, we demonstrate the existence and persistence of neoantigen-targeting T cells within the blood and tumor of an IDH-mutant LGG patient. These findings suggest a feasible methodology to develop personalized T cell-based immunotherapies for IDH-mutant LGGs.

Background The present study tested the possible utility of fractal analysis from l-[methyl-11C]-methionine (MET) uptake in patients with newly diagnosed gliomas for differentiating glioma, especially in relation to isocitrate dehydrogenase 1 (IDH1) mutation status, and as compared with the conventional standardized uptake value (SUV) parameters. Methods Investigations of MET PET/CT were performed retrospectively in 47 patients with newly diagnosed glioma. Tumors were divided into three groups: lower grade glioma (IDH1-mutant diffuse astrocytoma and IDH1-mutant anaplastic astrocytoma), higher grade glioma (IDH1-wildtype diffuse astrocytoma and IDH1-wildtype anaplastic astrocytoma), and glioblastoma. The fractal dimension for tumor, maximum SUV (SUVmax) for tumor (T) and mean SUV for normal contralateral hemisphere (N) were calculated, and the tumor-to-normal (T/N) ratio was determined. Metabolic tumor volume (MTV) and total lesion MET uptake (TLMU) were also measured. Results There were significant differences in SUVmax (p = 0.006) and T/N ratio (p = 0.02) between lower grade glioma and glioblastoma. There were no significant differences among any of the three groups in MTV or TLMU. Significant differences were obtained in the fractal dimension between lower grade glioma and higher grade glioma (p = 0.006) and glioblastoma (p Conclusions The results of this preliminary study in a small patient population suggest that the fractal dimension using MET PET in patients with newly diagnosed gliomas is useful for differentiating glioma, especially in relation to IDH1 mutation status, which has not been possible with SUV parameters.

Gliomas are the most common type of the malignant brain tumor, which arise from glial cells. They make up about 40% of all primary brain tumors and around 70% of all primary malignant brain tumors. They can occur anywhere in the central nervous system (CNS) and have a poor prognosis. The average survival of glioma patients is approximately 6–15 months with poor aspects of life. In this edge, identification of proteins secreted by cancer cells is of special interest because it may provide a better understanding of tumor progression and provide early diagnosis of the diseases. Extracellular vesicles (EVs) were isolated from pooled plasma of healthy controls (n=03) and patients with different grades of glioma (Grade I or II or III, n=03 each). Nanoparticle tracking analysis, western blot, and flow cytometry were performed to determine the size, morphology, the concentration of glioma-derived vesicles and EV marker, CD63. Further, iTRAQ-based LC-MS/MS analysis of EV protein was performed to determine the differential protein abundance in extracellular vesicles across different glioma grades. We further verified galectin-3 binding protein (LGALS3BP) by ELISA in individual blood plasma and plasma-derived vesicles from control and glioma patients (n=40 each). Analysis by Max Quant identified 123 proteins from the pooled patient exosomes, out of which 34, 21, and 14 proteins were found to be differentially abundant by more than 1.3-fold in the different grades of glioma grade I, pilocytic astrocytoma; grade II, diffuse astrocytoma; grade III, anaplastic astrocytoma, respectively, in comparison with the control samples. A total of seven proteins—namely, CRP, SAA2, SERPINA3, SAA1, C4A, LV211, and KV112—showed differential abundance in all the three grades. LGALS3BP was seen to be upregulated across the different grades, and ELISA analysis from individual blood plasma and plasma-derived extracellular vesicles confirmed the increased expression of LGALS3BP in glioma patients (p

The pro-oncogene ETS-1 (E26 transformation-specific sequence 1) is a key regulator of the proliferation and invasion of cancer cells. The present work examined the correlation of the aberrant expression of ETS-1 with histological or clinical classification of astrocytoma: grade I (pilocytic astrocytoma), grade II (diffuse astrocytoma), grade III (anaplastic astrocytoma), and grade IV (glioblastoma multiforme). MicroRNA, miR-338-5p, was predicted by an online tool (miRDB) to potentially target the 3’ untranslated region of ETS-1; this was confirmed by multi-assays, including western blot experiments or the point mutation of the targeting sites of miR-338-5p in ETS-1’s 3’untralation region (3’UTR). The expression of miR-338-5p was negatively associated with that of ETS-1 in astrocytoma, and deficiency of miR-338-5p would mediate aberrant expression of ETS-1 in astrocytoma. Mechanistically, hypermethylation of miR-338-5p by DNA methyltransferase 1 (DNMT1) resulted in repression of miR-338-5p expression and the aberrant expression of ETS-1. Knockdown or deactivation of DNMT1 decreased the methylation rate of the miR-338-5p promoter, increased the expression of miR-338-5p, and repressed the expression of ETS-1 in astrocytoma cell lines U251 and U87. These results indicate that hypermethylation of the miR-338-5p promoter by DNMT1 mediates the aberrant expression of ETS-1 related to disease severity of patients with astrocytoma.

Background Detailed prevalence estimates of BRAFV600 mutations and BRAF inhibitor (BRAFi) treatment responses in V600-mutant glioma will inform trial development. Methods Our systematic review analyzed overall prevalence of BRAFV600 mutations in glioma and BRAFi treatment response. Results Based on 13 682 patients in 182 publications, the prevalence of BRAFV600 in epithelioid glioblastoma (eGBM) was 69% [95% CI: 45–89%]; pleomorphic xanthoastrocytoma (PXA): 56% [48–64%] anaplastic pleomorphic xanthoastrocytoma (aPXA): 38% [23–54%], ganglioglioma (GG): 40% [33–46%], and anaplastic ganglioglioma (aGG): 46% [18–76%]. Prevalence in astroblastoma was 24% [8–43%], desmoplastic infantile astrocytoma (DIA): 16% [0–57%], subependymal giant cell astrocytoma (SEGA): 8% [0–37%], dysembryoplastic neuroepithelial tumor (DNET): 3% [0–11%], diffuse astrocytoma (DA): 3% [0–9%], and pilocytic astrocytoma (PA): 3% [2–5%]. We reviewed 394 V600-mutant gliomas treated with BRAFi from 130 publications. One hundred and twenty-nine pediatric low-grade gliomas showed 4 (3.1%) complete response (CR); 53 (41.1%) partial response (PR); 64 (49.6%) stable disease (SD) and 8 (6.2%) progressive disease (PD). 25 pediatric high-grade gliomas showed CR; PR; SD; PD in 4 (16.0%); 10 (40.0%), 4 (16.0%); and 7 (28.0%) respectively. Thirty-nine adult low-grade gliomas showed CR; PR; SD; PD of 4 (10.3%); 17 (43.6%); 16 (41.0%) and 2 (5.1%) respectively. Ninety-seven adult high-grade gliomas showed CR; PR; SD; PD of 6 (6.2%); 31 (32.0%); 27 (27.8%); and 33 (34.0%) respectively. Conclusions BRAFV600 prevalence is highest in eGBM, PXA, aPXA, GG, aGG, and lower in astroblastoma, DIA, SEGA, DNET, DA, and PA. Our data provide the rationale for adjuvant clinical trials of BRAFi in V600-mutant glioma.

Background: Diffuse astrocytoma (DA) is a rare disease with inadequately understood epidemiological characteristics and prognosis. Identification of the factors associated with the survival in DA patients is therefore necessary. In this study, we aim to investigate the clinicopathological characteristics of DA to delineate factors influencing the survival of DA.Methods: A population-based cohort study was conducted, utilizing prospectively extracted data from the Surveillance, Epidemiology and End Results (SEER) database. Patients with histological diagnosis of DA in the SEER database from 1973 to 2017 were included.Results: A total of 799 participants with DA were included, consisting of 95.9% fibrillary astrocytoma and 4.1% protoplasmic variants. The average age of participants was 41.9 years, with 57.2% being male. The majority of the population was white (87.5%). More than half (53.9%) of the patients were married. DA arose mostly in the cerebrum (63.8%). Around 71.6% of the population had received surgical treatment. The overall 1-, 3-, 5-, and 10-year survival rate were 73.7, 55.2, 49.4, and 37.6%, respectively. Kaplan–Meier analysis showed that age at diagnosis, marital status, primary tumor site, tumor size, and surgery was possibly associated with cancer-specific survival (CSS) (p < 0.05). Multivariate Cox proportional hazard analysis indicated that surgery was a protective factor whereas older age, larger tumor size, and tumor in the brainstem were harmful factors for patients with DA. Moreover, a nomogram predicting 5- and 10-year survival probability for DA was developed.Conclusions: Age, primary tumor site, tumor size, and surgery were associated with the survival of patients with DA.

Pediatric low-grade gliomas (PLGGs) have excellent long-term survival, but death can occasionally occur. We reviewed all PLGG-related deaths between 1975 and 2019 at our institution: 48 patients were identified; clinical data and histology were reviewed; targeted exome sequencing was performed on available material. The median age at diagnosis was 5.2 years (0.4–23.4 years), at death was 13.0 years (1.9–43.2 years), and the overall survival was 7.2 years (0.0–33.3 years). Tumors were located throughout CNS, but predominantly in the diencephalon. Diagnoses included low-grade glioma, not otherwise specified (n = 25), pilocytic astrocytoma (n = 15), diffuse astrocytoma (n = 3), ganglioglioma (n = 3), and pilomyxoid astrocytoma (n = 2). Recurrence occurred in 42/48 cases, whereas progression occurred in 10. The cause of death was direct tumor involvement in 31/48 cases. Recurrent drivers included KIAA1549-BRAF (n = 13), BRAF(V600E) (n = 3), NF1 mutation (n = 3), EGFR mutation (n = 3), and FGFR1-TACC1 fusion (n = 2). Single cases were identified with IDH1(R132H), FGFR1(K656E), FGFR1 ITD, FGFR3 gain, PDGFRA amplification, and mismatch repair alteration. CDKN2A/B, CDKN2C, and PTEN loss was recurrent. Patients who received only chemotherapy had worse survival compared with patients who received radiation and chemotherapy. This study demonstrates that PLGG that led to death have diverse molecular characteristics. Location and co-occurring molecular alterations with malignant potential can predict poor outcomes.

Case Report Introduction Alice in Wonderland Syndrome (AIWS) is a rare neurological disorder that is characterised by unusual distortions to perception. The aetiology of AIWS is unclear, though it has been reported in a number of neurological conditions including infection (esp. EBV), CNS lesions, migraines and as a side effect to medications. This report outlines the case of a 72 year old gentleman who presented to hospital due to visual changes which he described as dysmetropsia (objects appeared distorted - thinner) and episodic chromatopsia. His chromatopsia was described as his entire visual field coloured with an orange hue, though this colour changed throughout the course of his admission. Movements appeared to occur in slow motion and movements of humans had a robotic appearance. Neurological examination was otherwise normal. These symptoms resolved after 2 days, and on subsequent examination his neurological and ophthalmological examinations were unremarkable. Results MRI brain revealed a right occipito-temporal T2 hyperintense lesion, initially interpreted as a subacute ischaemic infarct. Repeat MRI with contrast revealed a stable appearance of the lesion with areas of subtle contrast enhancement. PET scan showed reduced metabolic activity within the lesion with reduced FDG accumulation. Biopsy of the lesion identified features of a diffuse astrocytoma. Conclusions AIWS is a poorly recognised syndrome. Symptoms are not typical for an ischaemic event and alternative diagnosis should be investigated as an explanation for the cause of visual distortions.

Introduction Textiloma (Txm) is a nonmedical term that has been given to foreign body-related inflammatory pseudotumor arising from retained nonabsorbable cotton matrix that is either inadvertently or deliberately left behind during surgery, which may trigger an inflammatory reaction. This report describes a case of Txm mimicking a recurrent high-grade astrocytoma. Case Report We, here, present the case of a 69-year-old female with a 6-month history of progressive left-sided weakness. Neuroimaging studies revealed a large nonenhancing mass in the right frontoparietal lobe. Pathology reported a World Health Organization tumor classification grade II, diffuse astrocytoma. After surgical intervention, external beam radiation was given to the remaining areas of residual tumor. Routine magnetic resonance imaging (MRI) revealed a nodular area of contrast enhancement in the dorsal and inferior margin of the biopsy tract, growing between interval scans, and perfusion-weighted imaging parameters were elevated being clinically asymptomatic. She underwent a complete resection of this area of interest and pathology returned as a Txm with Surgicel fibers. Conclusion After treatment of a neoplasm, if unexpected clinical or imaging evidence of recurrence is present, a foreign body reaction to hemostatic material used during the initial surgery should be included in the differential diagnosis.

A study of Ki67 Labeling Index (LI) by immunohistochemistry was carried out in 47 CNS neoplasms. Astrocytic and oligodendroglial tumours were the most common group with glioblastoma, NOS and diffuse astrocytoma, NOS Grade II predominating. Ki67 LI of diffuse astrocytomas varied from 0.72 to 13.9% with a mean of 4.36%. In glioblastomas the Ki67 LIs varied from 5.96 to 22.4% with a mean of 12.3% which was comparable with various studies. 1 pleomorphic xanthoastrocytoma was reclassified as anaplastic type based on a high LI of 21.66%. All histological variants of ependymomas showed uniformly low Ki67 LIs. Grade I meningiomas show ed a mean Ki67 LI of 2.22% for benign, 5.85% for atypical Grade II and 30% in the anaplastic Grade III meningioma. Choroid plexus carcinoma and Non Hodgkins lymphomas showed very Ki67 LIs from 60 to 91%. The findings correlated well with WHO CNS tumour grade and helped to identify histologically defined lower grade tumours with potential for recurrence and progression. Keywords: CNS neoplasms, Gliomas, Proliferation markers, Ki67.

5-Aminolevulinic acid (5-ALA)–guided resection of gliomas in adults enables better delineation between tumor and normal brain, allowing improved resection and improved patients’ outcome. Recently, several reports were published regarding 5-ALA for resection of pediatric brain tumors. The aim of the study was to determine the intracellular fluorescence of protoporphyrin IX (PPIX) in pediatric brain tumors by hyperspectral imaging and to compare it with visually observed intraoperative fluorescence. 5-ALA was administered orally 4 h prior to surgery. During tumor resection, the surgeon assessed the fluorescence signal to be strong, weak, or absent. Subsequently, fluorescence intensity of tumor samples was measured via spectroscopy. In addition, clinical data, imaging, and laboratory data were analyzed. Eleven children (1–16 years) were operated. Tumor entities included three (n = 3) medulloblastomas, two (n = 2) pilocytic astrocytomas (PA), two (n = 2) anaplastic ependymomas and one (n = 1) diffuse astrocytoma, anaplastic astrocytoma (n = 1), pilomyxoid astrocytoma (n = 1) and anaplastic pleomorphic xanthoastrocytoma (n = 1). Strong fluorescence was visible in all anaplastic tumors and one PA; one PA demonstrated weak fluorescence. Visible fluorescence was strongly associated with intracellular fluorescence intensity and PPIX concentration (P

Optic pathway glioma (OPG) is a rare neoplasm that arises predominantly during childhood. Its location in a sensitive region involving the optic pathways, onset in young patients and controversial therapy choice make the management of OPG a challenge in paediatric neuro-oncology. In this study we assessed gastrin-releasing peptide receptor (GRPR)-targeted positron emission tomography (PET) imaging in children with OPG, and the application of a PET/MRI imaging-guided surgery navigation platform. Eight children (five boys, mean age 8.81 years, range 5–14 years) with suspicion of optic pathway glioma on MRI were recruited. Written informed consent was obtained from all patients and legal guardians. Brain PET/CT or PET/MRI acquisitions were performed 30 min after intravenous injection of 1.85 MBq/kg body weight of 68Ga-NOTA-Aca-BBN(7-14). Four patients also underwent 18F-FDG brain PET/CT for comparison. All patients underwent surgical resection within 1 week. All 11 lesions (100%) in the eight patients showed prominent 68Ga-NOTA-Aca-BBN(7-14) uptake with excellent contrast in relation to surrounding normal brain tissue. Tumour-to-background ratios (SUVmax and SUVmean) were significantly higher for 68Ga-NOTA-Aca-BBN(7-14) than for 18F-FDG (28.4 ± 5.59 vs. 0.47 ± 0.11 and 18.3 ± 4.99 vs. 0.35 ± 0.07, respectively). Fusion images for tumour delineation were obtained in all patients using the PET/MRI navigation platform. All lesions were pathologically confirmed as OPGs with positive GRPR expression, and 75% were pilocytic astrocytoma WHO grade I and 25% were diffuse astrocytoma WHO grade II. There was a positive correlation between the SUV of 68Ga-NOTA-Aca-BBN(7-14) and the expression level of GRPR (r2 = 0.56, P

Purpose To examine the occurrence of glioma-related preoperative seizures (GPS) and post-operative seizure control (PSC) with respect to patients characteristics including five commonly tested tumor molecular markers (TMMs). Methods A single-center retrospective cohort study of patients with glioma evaluated at the Mayo Clinic, Florida between 2016 and 2018. Results 68 adult patients (mean age = 51-years, 45-males) were included. 46 patients had GPS. 57 patients underwent intra-operative electrocorticography during awake craniotomy-assisted glioma resection. All patients underwent glioma resection (53, gross-total resection) with histologies of pilocytic astrocytoma (n = 2), diffuse astrocytoma (n = 4), oligodendroglioma (n = 14), anaplastic astrocytoma (n = 16), anaplastic oligodendroglioma (n = 1), and glioblastoma (n = 31). 31 (67%) patients had PSC (median follow-up = 14.5 months; IQR = 7–16.5 months). IDH1 mutation (IDH1mut) was present in 32, ARTX retention in 53, MGMT gene promotor methylation in 15, 1p/19q co-deletion in 15, and over-expression of p53 in 19 patients. Patients with IDH1mut were more likely to have GPS (p = 0.037) and PSC (p = 0.035) compared to patients with IDH1 wild-type. Patients with MGMT gene promoter methylation were also likely to have PSC (p = 0.032). GPS or PSC did not differ by age, sex, extent of surgery, glioma grade, location, and histopathological subtype, p53 expression, ARTX retention, or 1p/19q co-deletion status. Conclusions GPS and PSC may be associated with IDH1 mutation and MGMT gene promoter methylation status but not other glioma characteristics including tumor grade, location, or histopathology. Prospective studies with larger sample size are needed to clarify the exact mechanisms of GPS and PSC by the various TMMs to identify new treatment targets.

The use of [18F]fluoroethyl)-l-tyrosine ([18F]FET) positron emission tomography/computed tomography (PET/CT) has proven valuable in brain tumor management. This study aimed to investigate the prognostic value of radiotracer uptake in newly diagnosed grade II or III gliomas according to the current 2016 World Health Organization (WHO) classification. A total of 35 treatment-naive patients (mean age, 48 ± 17 years) with histologically proven WHO grade II or III gliomas as defined by the current 2016 WHO classification were included. Static PET/CT imaging was performed 20 min after intravenous [18F]FET injection. Images were assessed visually and semi-quantitatively using regions of interest for both tumor (SUVmax, SUVmean) and background (BKGmean) to calculate tumor-to-background (TBR) ratios. The association among histological results, molecular markers (including isocitrate dehydrogenase enzyme and methylguanine-DNA methyltransferase status), clinical features (age), and PET findings was tested and compared with outcome (progression-free [PFS] and overall survival [OS]). Fourteen patients presented with grade II (diffuse astrocytoma n = 10, oligodendroglioma n = 4) and 21 patients with grade III glioma (anaplastic astrocytoma n = 15, anaplastic oligodendroglioma n = 6). Twenty-seven out of the 35 patients were PET-positive (grade II n = 8/14, grade III n = 19/21), with grade III tumors exhibiting significantly higher amino acid uptake (TBRmean and TBRmax; p = 0.03 and p = 0.02, respectively). PET-negative lesions demonstrated significantly prolonged PFS (p = 0.003) as compared to PET-positive gliomas. PET-positive disease had a complementary value in prognostication in addition to patient age, glioma grade, and molecular markers. Amino acid uptake as assessed by [18F]FET-PET/CT imaging is useful as non-invasive read-out for tumor biology and prognosis in newly diagnosed, treatment-naive gliomas according to the 2016 WHO classification.

This paper reports on a case of pilocytic astrocytoma (PA), for which a diagnosis by conventional pathological diagnosis was difficult but an accurate diagnosis was possible by a new molecular diagnostic method. A 13-year-old girl whose tumor developed by a headache that gradually worsened, and a well-demarcated T2-hyperintense lesion was found in the left cerebellum by a magnetic resonance imaging while the apparent diffusion coefficient value was also high. While the finding was a typical PA, histological features of PA were not found in the surgical specimen. An initial diagnosis was anaplastic astrocytoma (AA), and the final diagnosis through a central review was diffuse astrocytoma (DA). On the other hand, using MethylationEPIC (850 K) array, an analysis by a DNA methylation-based tumor classifier tool as reported by Capper et al. showed that this case belonged to a methylation class of PA. The copy number profile calculated from the methylation array data showed hints of BRAF/KIAA1549 fusion and no other chromosomal alterations, which also supported the molecular diagnosis. The patient was treated with local radiotherapy concomitant with temozolomide based on the initial pathological diagnosis during the consultation, but maintenance temozolomide therapy was not done according to the final molecular diagnosis. The tumor showed no recurrence for 20 months. In this case, the integrated diagnostic approach based on histological and molecular findings was clinically significant to select proper adjuvant treatment. It is crucial that the usefulness and robustness of this new molecular diagnostic method be validated further.

Previous work in anaplastic astrocytoma (AA) demonstrated that the survival benefit from gross total resection (GTR) is modified by age and tumor location. Here, we determined the influence of age and tumor location on survival benefit from GTR in diffuse astrocytoma (DA).We used the Surveillance, Epidemiology, and End Results (SEER) database (1999-2010). We used Kaplan-Meier curves and Cox survival models to determine the survival benefit from GTR in populations stratified by age and tumor location. We determined the prevalence of the mutated isocitrate dehydrogenase (mIDH) using The Cancer Genome Atlas (TCGA).We identified 1980 patients with DA. For frontal DAs, GTR resulted in improved survival relative to subtotal resection in all ages (age ≤50 years hazard ratio [HR], 0.56; P = 0.002; age50 years HR, 0.41; P0.001). For nonfrontal DAs, only patients ≤50 years experienced improved survival with GTR (age ≤50 years HR, 0.55; P = 0.002; age50 years HR, 0.78; P = 0.114). For patients ≤50 years with frontal tumors, survival was comparable between DA and AA after GTR (75% survival DA: 80 months, AA: 89 months, P = 0.973). In TCGA, these tumors were nearly uniformly mIDH (DA: 98%; AA: 90%, P = 0.11). However, for patients ≤50 years with nonfrontal tumors, there was a survival difference after GTR (75% survival DA: 80 months, AA: 30 months, P = 0.001) despite comparable mIDH prevalence (DA: 82%, AA: 75%, P = 0.49).Age and tumor location modify the survival benefit derived from GTR in DA. Survival patterns in SEER imperfectly correlated with mIDH prevalence in TCGA, suggesting that tumor grade and mIDH status convey nonredundant prognostic information in select clinical contexts.

The authors describe a usual case of infiltrative low-grade glial neoplasm with a marked enhanced area which is difficult to diagnose. A 42-year-old man had the diffuse mass lesion partially with apparent enhancement in the right temporal lobe, the insular, and the basal ganglia regions. Final pathological diagnosis from the removed specimens was IDH-wildtype diffuse astrocytoma according to 2016 WHO classification, although it had unusual findings including gliomesenchymal reaction. The nodule-like enhancement was thought to be owing to the mesenchymal component. Several molecular analysis including pyrosequence analysis, Ion Torrent™ next-generation sequencing and multiplex ligation-dependent probe amplification analysis detected no genomic abnormality. IDH-wildtype diffuse astrocytoma is a heterogeneous category and has a minor subset with a silent genomic landscape like the present case.

The present study aimed to evaluate the impact caused by the 2016 World Health Organization (WHO) diagnostic classification of gliomas in 139 patients studied in Argentina. Formalin-fixed paraffin-embedded tissues were used for histological and immunohistochemical analysis [glial fibrillary acidic protein, KI67, synaptophysin and isocitrate dehydrogenase (IDH)1-R132H]. DNA from formalin-fixed paraffin-embedded tissues was used for molecular analysis: 1p/19q co-deletion and mutation status of the IDH gene. These experiments were performed by direct Sanger sequencing and multiplex ligation-dependent probe amplification. According to the new classification, diagnoses included oligodendroglioma IDH-mutant and 1p/19q co-deletion (4.20%), anaplastic oligodendroglioma IDH-mutant and 1p/19q co-deletion (2.52%), diffuse astrocytoma IDH-mutant (6.72%), diffuse astrocytoma IDH-wild type (1.68%), anaplastic astrocytoma IDH-mutant (5.04%), anaplastic astrocytoma IDH-wild type (8.40%), glioblastoma IDH-mutant (5.88%) and glioblastoma IDH-wild type (65.56%). Regarding tumor histology, 60% of oligodendrogliomas, 35% of astrocytoma and 100% of unclassified gliomas were re-classified, while glioblastomas maintained their initial classification. Additionally, the present study evaluated the prognostic value of the histological grade for the 2007 and 2016 WHO classifications of gliomas. The histological subgroup associated with longer overall survival (OS) was grade II glioma (OS-2007WHO, 35.6 months; and OS-2016WHO, 47.7 months). Glioblastoma was the subgroup associated with a poor outcome (OS-2007WHO, 10.4 months; and OS-2016WHO, 11.1 months). The present study evaluated the OS of tumor grade subgroups with respect to their IDH status. For all subgroups, IDH-mutant tumors were associated with an improved prognosis compared with IDH-wild type tumors. The results suggested that the incorporation of molecular biomarkers in the new WHO classification improves tumor characterization and prognostic value of the subgroups.

Robot-assisted brain tumor biopsy is becoming one of the most important innovative technologies in neurosurgical practice. The idea behind its engagement is to advance the safety and efficacy of the biopsy procedure, which is much in demand when planning the management of endocranial tumor pathology. Herein, we provide our earliest institutional experiences in utilizing this mesmerizing technology. Cranial robotic device was employed for stereotactic robot-assisted brain glioma biopsy in three consecutive patients from our series: an anaplastic isocitrate dehydrogenase (IDH) negative astrocytoma (WHO grade III) located in the right trigone region of the periventricular white matter; a low grade diffuse astrocytoma (WHO grade II) of bilateral thalamic region spreading into the right mesencephalic area; and an IDH-wildtype glioblastoma (WHO grade IV) of the right frontal lobe producing a contralateral midline shifting. Robot-assisted tumor biopsy was successfully performed to get tissue samples for histopathologic and immunohistochemical analysis. The adjacent tissue iatrogenic damage of the eloquent cortical areas was minimal, while the immediate postoperative recovery was satisfactory in all patients. In conclusion, considering the preliminary results of our early experiences, robot-assisted tumor biopsy was proven to be a feasible and accurate procedure when surgery for brain glioma was not an option. It may increase safety and precision, without expanding surgical time, being similarly effective when compared to standard stereotactic and manual biopsy. Using this method to provide accurate sampling for histopathologic and immunohistochemical analysis is a safe and easy way to determine management strategies and outcome of different types of brain glioma., Robotom potpomognuta tumorska biopsija postaje jednom od najvažnijih inovativnih tehnologija u neurokirurškom radu. Razlog njezine uporabe nalazi se u daljnjem poboljšanju sigurnosti, učinkovitosti i preciznosti biopsijske metode koja je osobito značajna u planiranju opskrbe endokranijske tumorske patologije. Ovim radom donosimo prva institucijska iskustva u primjeni ove začudne tehnologije pri biopsiji gliomskih tumora mozga. Kranijski robotički uređaj korišten je pri stereotaksijskoj robotom potpomognutoj tumorskoj biopsiji u tri susljedna slučaja iz naše serije, koja je uspješno učinjena radi uzimanja uzorka tumorskoga tkiva za patohistološku i imunohistokemijsku dijagnostiku u bolesnice s anaplastičkim izocitrat dehidrogenaza (IDH) negativnim astrocitomom (SZO st. III.) smještenim u periventrukulskoj bijeloj tvari desnoga trigonuma, u bolesnika s difuznim astrocitomom niskoga stupnja malignosti (SZO st. II.) smještenim obostrano u talamičkom području sa širenjem u desni mezencefalon, kao i u bolesnika s IDH-wildtype glioblastomom (SZO st. IV.) desnog čeonog režnja s pomakom središnjih tvorba. Jatrogena lezija pripadajućeg elokventnog moždanog korteksa bila je minimalna, dok je neposredni poslijeoperacijski oporavak bio uspješan u svih bolesnika. Uzimajući u obzir preliminarne rezultate našega početnog iskustva, zaključujemo kako je robotom potpomognuta tumorska biopsija dokazano izvodljiva i primjerena metoda u kirurgiji gliomskih tumora mozga kojom se može poboljšati sigurnost i preciznost bez produljenja vremena operacije, a koja je podjednako učinkovita u usporedbi sa standardnom stereotaksijskom i manualnom biopsijom. Uporaba navedene metode omogućuje precizno uzorkovanje tumorskoga tkiva za patohistološku i imunohistokemijsku analizu na siguran i lak način, što doprinosi odabiru strategije liječenja i predviđanju ishoda različitih tipova gliomskih tumora mozga.

To study energy metabolism in glial tumors using dynamic MR spectroscopy andThe study included 19 patients (9 women and 10 men) with newly diagnosed supratentorial glial tumors WHO Grade I-IV (diffuse astrocytoma - 4 cases, oligodendroglioma - 4 cases, anaplastic astrocytoma - 5 cases, glioblastoma - 6 cases). All patients underwent examination and surgical treatment at the Burdenko Neurosurgery Center. Dynamic MR spectroscopy andWe found multiple correlations between the ratio of bioorganic phosphate peaks and parameters of glucose uptake by tumor tissue. These relationships were more significant in patients with high-grade tumors: positive significant correlation between SUVtumor and PME/PCr ratio (RHigh-grade gliomas were characterized by higher glucose consumption, ATP release (intensification of energy metabolism) and faster cell membrane synthesis. These processes indicate enhanced proliferation of tumor cells (intensification of plastic metabolism).Изучить энергетический обмен в глиальных новообразованиях головного мозга методами магнитно-резонансной спектроскопии (МРС) и позитронно-эмиссионной томографии—компьютерной томографии (ПЭТ-КТ) сВ группу исследования включены 19 пациентов (9 женщин и 10 мужчин) с впервые выявленными супратенториальными глиальными опухолями WHO Grade I—IV (4 диффузные астроцитомы, 4 олигодендроглиомы, 5 анапластических астроцитом, 6 глиобластом), которые проходили обследование и хирургическое лечение в ФГАУ «НМИЦ нейрохирургии им. акад. Н.Н. Бурденко». Каждому пациенту выполнены МРС и ПЭТ-КТ сВыявлены множественные корреляции между соотношениями пиков биоорганических фосфатов и параметрами захвата глюкозы опухолевой тканью. Данные взаимосвязи более выражены в группе опухолей высокой степени злокачественности: положительные статистически значимые взаимосвязи между параметром SUVВ глиомах высокой степени злокачественности выявлена тенденция к увеличению потребления глюкозы, сопровождающаяся увеличением синтеза аденозинтрифосфата (интенсификация энергетического обмена), ускорением синтеза клеточных мембран, которые в совокупности отражают процессы усиления пролиферации опухолевых клеток (увеличение пластического обмена).

In previous studies, isocitrate dehydrogenase (IDH) mutations were associated with tumor-associated epilepsy (TAE) and venous thromboembolism (VTE). We examined the relationship between IDH mutations in grade II/III astrocytomas and TAE/VTE according to the 2016 World Health Organization classification. The clinical data of patients with newly diagnosed grade II/III gliomas who were treated at Tohoku University Hospital from January 2010 to December 2018 were reviewed. Associations between TAE or VTE and the clinical/biological characteristics, histology, and IDH1/2 mutational status in patients with grade II/III gliomas were evaluated. Of the initial 137 patients (290 hospitalizations), 117 patients (203 hospitalizations) were included in the TAE group and 124 patients (213 hospitalizations) were included in the VTE group. Seventy-eight patients (66.7%) in the TAE group were diagnosed with astrocytoma and 38/78 (48.3%) presented with TAE. According to the multivariable analysis, the IDH mutational status and male sex were associated independently with an increased risk of TAE (p

18F-DOPA PET-MRI was performed on a 38-year-old man referred for complementary imaging after a brain tumor was discovered, according to EANM/RANO recommendations. We performed a simultaneous PET with 3-T brain MRI, which revealed 2 high 18F-DOPA uptakes, with no multimodal MRI sign of aggressiveness. An awake surgery was performed and found a grade III anaplastic astrocytoma IDH1-R132L mutant, according to the 2016 WHO classification. This was probably the aggressive transition of a grade II diffuse astrocytoma. This case illustrates the added value of 18F-DOPA PET to multimodal MRI to distinguish low- and high-grade gliomas.

Purpose: The real impact of the Extent of Resection in respect to the 1p/19q codeletion status in determining the outcomes of Low Grade Glioma (LGG) patients is extensively debated. The aim of this paper is to retrospectively analyze the oncologic outcomes of a homogeneous cohort of LGG patients who underwent surgery by a single operator, first author of the present paper (GDA).Methods: A total of 66 patients suffering LGG who underwent craniotomy for tumor resection were operated on and retrospectively evaluated between 2008 and 2016 in a single center in which the operative theater was equipped with an Io-MRI system. We compared a subgroup of 37 patients suffering from Diffuse Astrocytoma to a second subgroup of 29 patients affected by Oligodendroglioma. Volumetric analyses of the Extent of Resection (EOR) were performed, PFS and OS were accurately recorded and used as endpoint variable, as well as the 1p/19q codeletion status of every patient included in the final cohort.Results: GTR produced a statistically significant survival advantage in respect to those associated with STR. This finding is confirmed even in patients suffering from Oligodendrogliomas (in the 1p/19q codeletion group 73.27 versus 101.73 months p=.0001). Similar findings were confimed for patients affected by Diffuse Astrocytomas(81.63 versus 60.44 months p < 0.012), despite the globally shorter survival.Conclusions: We can affirm that the EOR is an independent predictor of survival advantage. The 1p/19q codeletion is an independent prognostic factor significantly associated to a globally longer survival and a longer time to malignant transformation.

Grade 2 gliomas constitute a heterogeneous cohort of central nervous system (CNS) tumors of glial origin with variable clinical presentation and long-term outcomes. Despite inclusion into low grade gliomas, some of them may exhibit locally aggressive behavior and potential for malignant transformation into high grade gliomas. They usually impact children or young adults. Surgery is the primary treatment and extent of resection has prognostic implications. The World Health Organization (WHO) 2016 CNS classification has introduced several changes in the categorization of tumors with incorporation of molecular and genetic factors which has impact on prognosis as well as treatment decisions. Surgery is the main treatment modality—it relieves symptoms (most commonly seizures) and gives pathologic information to plan further adjuvant therapy. In astrocytic and oligodendroglial tumors, several randomized trials till date have defined the role of adjuvant therapy types, doses, timing, etc., to maximize survival. Incorporation of new molecular information for post hoc analysis of prior studies and stratification of future trials will help determine if data from randomized trials over last three decades still hold value. Since most of these tumors have potential for long-term survival, quality of life considerations are as important as local control in choosing between therapies.

To determine reproducible MRI parameters predictive of molecular subtype and risk stratification in glioma and develop a structured reporting system. All study patients were initially diagnosed with glioma, 141 from the Cancer Genome Atlas and 131 from our tertiary institution, as training and validation sets, respectively. Images were analyzed by three neuroradiologists with 1–7 years of experience. MRI features including contrast enhancement pattern, necrosis, margin, edema, T2/FLAIR mismatch, internal cyst, and cerebral blood volume higher than normal cortex were reported using a structured reporting system. The pathology was stratified into five risk types: (1) oligodendroglioma, isocitrate dehydrogenase [IDH]-mutant, 1p19q co-deleted; (2) diffuse astrocytoma, IDH-mutant, grade II–III; (3) glioblastoma, IDH-mutant, grade IV; (4) diffuse astrocytoma, IDH-wild, grade II–III; and (5) glioblastoma, IDH-wild, grade IV. Significant predictors were selected using multivariate logistic regression, and diagnostic performance was tested using a validation set. Reproducible imaging parameters exhibiting > 50% agreement across readers included the presence of necrosis, T2/FLAIR mismatch, internal cyst, and predominant contrast enhancement. In the validation set, prediction of risk type 5 exhibited the highest diagnostic performance with AUCs of 0.92 (reader 1) and 0.93 (reader 2) with predominant enhancement, followed by risk type 2 with AUCs of 0.95 and 0.95 with T2/FLAIR mismatch sign and no necrosis, and risk type 1 with AUCs of 0.84 and 0.83 with internal cyst or necrosis. Risk types 3 and 4 were difficult to visually predict. Imaging parameters with high reproducibility enabling prediction of IDH-wild-type glioblastoma, IDH-mutant/1p19q co-deletion oligodendroglioma, and IDH-mutant diffuse astrocytoma were identified. • Reproducible MRI parameters for determining molecular subtypes of glioma included the presence of necrosis, T2/FLAIR mismatch, internal cyst, and predominant contrast enhancement. • IDH-wild type glioblastoma, IDH-mutant/1p19q co-deletion oligodendroglioma, and IDH-mutant low-grade astrocytoma were identified using MRI parameters with high inter-reader reproducibility. • Identification of IDH-wild type low-grade glioma and IDH-mutant glioblastoma was difficult by visual analysis.