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Abstract The purpose of this pictorial essay is to describe the recommendations of the 2021 World Health Organization classification for adult-type and pediatric-type gliomas and to discuss the main modifications in relation to the previous (2016) classification, exemplified by imaging, histological, and molecular findings in nine patients followed at our institutions. In recent years, molecular biomarkers have gained importance in the diagnosis and classification of gliomas, mainly because they have been shown to correlate with the biological behavior and prognosis of such tumors. It is important for neuroradiologists to familiarize themselves with this new classification of central nervous system tumors, so that they can use this knowledge in evaluating and reporting the imaging examinations of patients with glioma.
Resumo O propósito deste ensaio iconográfico é descrever e discutir as novas recomendações da Organização Mundial da Saúde de 2021, referente aos gliomas dos tipos adulto e infantil, e suas principais diferenças com a classificação anterior (2016), exemplificadas com imagens de nove casos de pacientes atendidos nas nossas instituições. Recentemente, há uma crescente significância dos marcadores moleculares no diagnóstico e classificação dos gliomas e tumores do sistema nervoso central, principalmente pela correlação com o comportamento biológico e o prognóstico. É importante que os neurorradiologistas estejam familiarizados com a nova classificação dos tumores do sistema nervoso central para a prática clínica, na avaliação e emissão de laudos e opiniões nas imagens dos pacientes com gliomas.
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@#Introduction: Intracranial brain tumour like meningiomas and glioblastomas are most prevalent tumour. The metastasis to the brain is one of the major issues in the tumours of the central nervous system. The diagnosis of metastatic and primary brain tumour is incomprehensible with standard magnetic resonance imaging (MRI). The magnetic resonance spectroscopy (MRS) is basically performed in standard clinical setting for diagnosing and tracking the brain tumour. Method: It is a retrospective study containing 53 patients with MRS. The patients with metastatic tumour (n=10), glioblastomas (n=8) and meningiomas (n=20) are included in the study. Single voxel technique is applied in the tumour core to determine the metabolites. The tumour N-acetyl aspartate (NAA), Choline (Cho), Creatine (Cr), Lactate, Alanine and lipids were analysed. The ratios of NAA/Cr, Cho/NAA and Cho/Cr were recorded and compared between the three tumours. The metabolites were detected between short echo time (TE) to long echo time (TE) during MRS. Results: There is a sharp fall of NAA peak in metastatic tumour. The resonance of creatine, lactate and alanine is higher in glioblastomas. A high lipid mean value of 3.13(0.17) is seen in metastatic tumour. The ROC curve shows a low NAA/Cr specificity of 46.7%, high sensitivity of 83.3% in Cho/NAA and Cho/Cr ratio. Conclusion: The metabolic profiles of metastatic brain tumour, glioblastomas and meningioma illustrate a divergence in their description that will assist in planning therapeutic and surgical intervention of these tumours.
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BACKGROUND: There has been no practical guidelines for the management of patients with central nervous system (CNS) tumors in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, started to prepare guidelines for CNS tumors from February 2018. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. RESULTS: First, the maximal safe resection if feasible is recommended. After the diagnosis of a glioblastoma with neurosurgical intervention, patients aged ≤70 years with good performance should be treated by concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide chemotherapy (Stupp's protocol) or standard brain radiotherapy alone. However, those with poor performance should be treated by hypofractionated brain radiotherapy (preferred)±concurrent or adjuvant temozolomide, temozolomide alone (Level III), or supportive treatment. Alternatively, patients aged >70 years with good performance should be treated by hypofractionated brain radiotherapy+concurrent and adjuvant temozolomide or Stupp's protocol or hypofractionated brain radiotherapy alone, while those with poor performance should be treated by hypofractionated brain radiotherapy alone or temozolomide chemotherapy if the patient has methylated MGMT gene promoter (Level III), or supportive treatment. CONCLUSION: The KSNO's guideline recommends that glioblastomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to the individual comprehensive condition of the patient.
Subject(s)
Humans , Brain , Central Nervous System , Chemoradiotherapy , Diagnosis , Drug Therapy , Glioblastoma , Korea , RadiotherapyABSTRACT
Objective To investigate the feasibility of histogram analysis in differentiating brain high-grade glioblastomas,primary lymphoma from metastatic tumor.Methods 26 cases of brain high-grade glioblastomas,22 cases of primary lymphoma and 18 cases of metastatic tumor confirmed by postoperative pathological were analyzed retrospectively.Delineation of ROI and extraction of texture parameters were performing by using Mazda software.The histogram parameters,including Mean,Variance,Skewness,Kurtosis,Perc0.1%,Perc10%,Perc50%, Perc90% and Perc99% were analyzed statistically,and the ROC was then established.Results Mean,Perc0.1%,Perc10%and Perc50% exhibited statistically significant differences (P＜0.05).The best diagnostic parameters for differentiation between brain high-grade glioblastomas and primary lymphoma,primary lymphoma and metastatic tumor,and brain high-grade glioblastomas and metastatic tumor were Perc0.1%,Perc0.1%and Kurtosis.The AUC for these preferred diagnostic parameters were 0.937,0.879 and 0.7 1 8,respectively,with optimal thresholds of 50,70 and －0.43,sensitivity and specificity of 90.9% and 88.5%,77.3% and 88.9%,and 61.5% and 77.8%.Conclusion The histogram analysis of MRI images contributes to differentiate quantitatively between brain high-grade glioblastomas,primary lymphoma and metastatic tumor.
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OBJECTIVE Glioblastomas(GBM)are the most malignant brain tumors in humans and have a very poor prognosis. New therapeutics are urgently needed. Here, we reported 2-methoxy-6-acetyl-7-methyljuglone (MAM)-induced cell death in U87 and U251 glioma cancer cells. METHODS Cells were cultured and treated with MAM, the cell viability was determined by MTT assay and LDH assay. Intracellular reactive oxygen species (ROS) generation was observed by DCF fluorescence. The protein expression was determined by Western blotting. RESULTS MAM induced glioma cancer cell death without caspase activation. The cell death induced by MAM was attenuated by the pharmacological or genetic blockage of necroptosis signaling,including RIP1 inhibitor necrostatin-1s (Nec-1s)and siRNA-mediated gene silencing of RIP1 and RIP3,but was unaffected by caspase inhibitor z-vad-fmk or necrosis inhibitor 2-(1H-Indol-3-yl)-3-pentylamino-maleimide (IM54). MAM treated U87 and U251 glioma cancer cells induced RIP1/RIP3 complex formation, ROS level increased, ATP concentration decreased and loss of plasma membrane integrity, further confirmed this process was necroptosis.The essential role of ROS was confirmed by the protective effect of ROS scavenger NAC. Interestingly, MAM induced necroptosis both triggered by RIP1/RIP3 complex and ROS generation. Moreover, MAM induced necroptosis through cytosolic calcium (Ca2 +) accumulation and sustained c-Jun N-terminal kinase (JNK) activation. Both calcium chelator BAPTA-AM and JNK inhibitor SP600125 could attenuate cell death. Further, we found there exists a feedback loop between RIP1 and JNK activation.Finally,MAM induced necroptosis was inhibited by dicoumarol(a NQO1 inhibitor). Dicoumarol exposed glioma cancer cells were resistant to RIP1/RIP3 complex formation and ROS generation. MAM induced necroptosis was independent of MLKL. CONCLUSION MAM induced non-canonical necroptosis through the NQO1-dependent ROS and RIP1/RIP3 pathway.This study also provided new insights into the molecular regulation of necroptosis in human glioma cancer cells and a promising approach for GBM treatment.
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Objective To investigate the clinical effect of cisplatin combined with cisplatin and radiotherapy in the treatment of glioblastomas patients receiving surgery.Methods 68 cases of glioblastomas patients with surgery were divided into control group (n=36) and treatment group (n=32).The control group was treated with temozolomide and radiotherapy;the treatment group was treated with cisplatin combined with temozolomide and radiotherapy.Short-term efficacy,adverse reactions,and survival time were documented during following up in both groups.Results The efficiency in the treatment group (87.5％) was significantly higher than that in the control group (66.67％),P＜0.05.There were no significant difference of adverse reaction including bone marrow inhibition,digestive tract symptoms,and psychiatric symptoms among the two groups,P＞0.05.The medium survival time of the treatment group (26.0 month) was significantly longer than that of the control group (17.5 month),P ＜0.05.There was no significant difference of 1-year survival rate between the treatment group (81.25％) with control group (63.89％),P＞0.05;however,2-and 3-year survival rate in treatment group (52.13％,31.25％) were significantly higher than that in the control group (27.78％,11.11％),P＜0.05.1-year progression free survival (PFS) rate of treatment group (68.75％) was significantly higher that of control group (41.67％),P＜0.05.Conclusion Cisplatin combined with temozolomide and radiotherapy can significantly improve the treatment efficiency without leading to higher rate of adverse reactions and significantly improve the 2-,3-year survival rate as well as 1-year progression free survival (PFS) rate in patients with glioblastomas,it is worth being promoted in clinical application.
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This study aimed to evaluate the effects of volume adapted re-planning for radiotherapy (RT) after gross total resection (GTR) for glioblastoma. Nineteen patients with glioblastoma who underwent GTR and postoperative RT were analyzed. The volumes of the surgical cavity on computed tomography (CT) obtained one day after GTR (CT0), the first RT simulation CT (sim-CT1), and the second simulation CT for the boost RT plan (sim-CT2) were compared. The boost RT plan was based on the surgical cavity observed on the sim-CT2 (boost RTP2) and was compared with that based on the surgical cavity observed on the sim-CT1 (boost RTP1). The volume reduction ratios were 14.4%-51.3% (median, 29.0%) between CT0 and sim-CT1 and -7.9%-71.9% (median, 34.9%) between sim-CT1 and sim-CT2 (P < 0.001). The normal brain volumes in boost RTP1 were significantly reduced in boost RTP2, especially at high dose levels. Target volume in sim-CT2 which was not covered with the boost RTP1, developed in five cases (26.3%). The surgical cavity volume was reduced following surgery in patients with glioblastoma who underwent GTR. The application of volume-adapted re-planning during RT could decrease the irradiated volume of normal brain and prevent a target miss for boost RT.
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Brain Neoplasms/radiotherapy , Glioblastoma/radiotherapy , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Tomography, X-Ray ComputedABSTRACT
Diagnosis in neuroimaging involves the recognition of specific patterns indicative of particular diseases. Pareidolia, the misperception of vague or obscure stimuli being perceived as something clear and distinct, is somewhat beneficial for the physician in the pursuit of diagnostic strategies. Animals may be pareidolically recognized in neuroimages according to the presence of specific diseases. By associating a given radiological aspect with an animal, doctors improve their diagnostic skills and reinforce mnemonic strategies in radiology practice. The most important pareidolical perceptions of animals in neuroimaging are the hummingbird sign in progressive supranuclear palsy, the panda sign in Wilson's disease, the panda sign in sarcoidosis, the butterfly sign in glioblastomas, the butterfly sign in progressive scoliosis and horizontal gaze palsy, the elephant sign in Alzheimer's disease and the eye-of-the-tiger sign in pantothenate kinase-associated neurodegenerative disease.
O diagnóstico em neuroimagem envolve o reconhecimento de padrões específicos indicativos de doenças particulares. Pareidolia, é a perceção equivocada de algo claro e distinto a partir de um estímulo vago e obscuro, por vezes benéfico a quem interpreta exames de imagem na procura do diagnóstico. A este propósito, alguns animais podem pareidolicamente ser reconhecidos em neuroimagens associadas a determinadas doenças específicas, promovendo mais rapidez na habilidade diagnóstica e naturalmente reforçando estratégias mnemônicas individuais na prática do diagnóstico neuroradiológico. Alguns dos sinais de neuroimagens relacionados a percepções pareidolicas de animais são: o sinal do beja-flor na paralisia supra nuclear progressiva; o sinal do panda na doença de Wilson; o sinal do panda na sarcoisdose; o sinal da borboleta no glioblastoma; o sinal da borboleta no escoliose progressiva e paralisia do olhar horizontal; o sinal do elefante na doença de Alzheimeir; e o sinal do olho de tigre na doença degenerativa ligada a pantothenato kinase.
Subject(s)
Humans , Brain Diseases/diagnosis , Illusions , Perceptual Disorders/diagnosis , Illusions/psychology , Magnetic Resonance ImagingABSTRACT
Os gliomas são as neoplasias cerebrais primárias que mais freqüentemente acometem o Sistema Nervoso Central (SNC). Cerca de 50% dos casos de gliomas são neoplasias com fenótipo maligno, incluindo os glioblastomas. Os glioblastomas possuem grande capacidade de expansão e invasão do tecido cerebral adjacente, o que contribui para o seu prognóstico sombrio. O glutamato é o principal neurotransmissor excitatório do SNC, mas sob condições patológicas a ativação excessiva do sistema glutamatérgico provoca danos citotóxicos às células neurais. A toxicidade glutamatérgica está associada a uma série de doenças agudas e crônico-degenerativas que acometem o SNC. Os glioblastomas humanos são capazes de liberar quantidades tóxicas de glutamato sobre os tecidos adjacentes e esta liberação parece favorecer o crescimento e a expansão tumoral. A fim de avaliarmos se a progressão tumoral mediada pelo glutamato é desencadeada por elementos das vias de sinalização, investigamos o efeito do glutamato sobre o conteúdo e expressão do receptor do fator de crescimento epitelial (rEGF). Desta forma, os cultivos primários Gli1, Gli2 e Gli3, assim como a linhagem estabelecida U87MG, foram tratados com doses crescentes de glutamato (5-200 mM) por 48 horas e após o tratamento a viabilidade celular, os conteúdos de rEGF e de Akt foram avaliados. Os cultivos analisados apresentaram suscetibilidades distintas aos efeitos citotóxicos do glutamato, porém em todos os casos as doses efetivas foram muito superiores (valores de ICso de 45mM a 100mM) às concentrações tóxicas descritas para células neurais (valores de ICso de100uM a 1mM). A expressão protéica de rEGF e o conteúdo de Akt fosforilado aumentaram após o tratamento com 5mM de glutamato, sugerindo que a ativação dos receptores de EGF possam exercer função na via de sinalização desencadeada pelo glutamato. Após o término dos experimentos com glutamato dois dos três cultivos primários utilizados (Gli1 e Gli2) se mantiveram viáveis em cultivo por mais de 50 passagens, o que sugere estabilidade das alterações moleculares e a seleção de uma subpopulação especifica de células que pode ser denominada linhagem celular. Assim, em os à caracterização destas duas novas linhagens celulares derivadas de glioblastomas - Gli1 e Gli2. Para tal avaliamos as suas taxas de proliferação, morfologia celular, o perfil de cariótipo de ambas e os conteúdos de rEGF, Hsp70, 6, p53 e MMP2, marcadores relacionados à progressão tumoral. Em suma, os cultivos Gli1 e Gli2 demonstraram alterações cromossômicas e expressão de marcadores compatíveis com as anomalias descritas para a manifestação do fenótipo de glioblastomas. Igualmente, comparamos o crescimento destas linhagens glioblastomas cultivadas como monocamada com o cultivo tridimensional em esferóides multicelulares. Os resultados obtidos revelaram padrões de crescimento e conteúdos dos marcadores diferentes entre as condições de cultivo
The gliomas are the primary brain tumors that more frequntIy accomplished the Central Nervous System (CNS). About 50% of the glioma cases presented malignant phenotype, including glioblastomas. Glioblastoma are tumors with high capacity of proliferation and invasion through the adjacent healthy nervous tissue, which largely contributes for its poor prognosis. The glutamate is the main excitatory neurotransmitter of the CNS, but under pathological conditions the extreme activation of the glutamatergic system induces cytotoxic damages to the neural cells. The glutamatergic citotoxicity is associated with severaI acute and chronic-degenerative diseases of the CNS. Human glioblastomas are capable of release toxic amounts of glutamate on adjacent brain tissue and this release seems to favor tumoral growth and expansion. In order to evaluate if the tumoral progression mediated by glutamato is a product of the activation of elements 6f1he signaling pathways, we investigated the glutamate effect on the content and expression of EGFi . For this reason, the primary culture cells Gli1, Gli2 and Gli3, as well as the established cell line U-87MG, were treated with increasing doses of glutamate (5-200 mM) for 48 hours and after the treatment the cell viability, EGFr and Akt contents were evaluated. The studied cells presented distinct susceptibilities to the cytotoxic effects of glutamate, however in all the cell cultures the toxicity was revealed only with very high glutamate doses (values of ICso range from 45mM to 100mM) when compared to the described toxic concentrations for neural cells (ICso values range from 100uM to 1 mM). The EGFr protein expression and the phosphor-Akt content increased after the treatment with 5mM of glutamate, suggesting that the activation of the EGF receptors can have a role in the glutamate signaling pathways. After the conclusion of these set of experiments, twoof out three tested primary cultures remained viable in cell culture for more than 50 passages, which suggests stability of the molecular profile and the selection of a specific ce11 subpopulation that can be named by 0011 line. Thus, in order to characterize these two new glioblastoma cell lines (Gli1 and Gli2), we carry out a series of experiments. The experiments had included the evaluation of the cellular growth rate, the cellular morphology, the kariotype profile and the identification of molecular markers related to tumor progression (EGF, Hsp70, Ki76, p53 e MMP2). 80th glioblastoma cell lines had demonstrated chromosomic alterations and expression of molecular markers similar to those described for glioblastoma phenotype. Equally, we compared the growth of these cells in monolayer cultures to three-dimensional multicellular spheroids cultures. Accordingly the results demonstrated different standarts of growth and molecular markers between the culture conditions
Subject(s)
Male , Female , Humans , Brain Neoplasms , Glioblastoma/therapy , Glutamic Acid/adverse effects , Brazil , GliomaABSTRACT
Los glioblastomas multiformes (OMS grado IV) son las neoplasias más frecuentes y malignas del sistema nervioso central, una variante histológica de éstos, denominada, de células gigantes representa aproximadamente 1% de todos los tumores cerebrales y 5% de todos los glioblastomas. Presentamos el caso de un paciente de sexo femenino a quien se le diagnosticó y trató un glioblastoma de células gigantes de localización intra y paraventricular derecho. Se enfatiza la importancia de las características histológicas de este tumor en relación a su pronóstico.
Glioblastomas (WorldHealth Organization, (WHO), grade IV) are the most frequent and malignant neoplasms of the human nervous system, Giant cells glioblastomas, a subtype of these, account for less than 1% of all brain toumors and up to 5% of glioblastomas. We present the case of a female who was diagnosed and treated for a right intra and paraventricular giant cell glioblastoma. We enfatize the importance of histological features of this toumor related to its prognosis.