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Seminars in Oncology Aug 2014Diffuse astrocytomas (DAs) represent less than 10% of all gliomas. They are diffusely infiltrating World Health Organization (WHO) grade II neoplasms that have a median... (Review)
Review
Diffuse astrocytomas (DAs) represent less than 10% of all gliomas. They are diffusely infiltrating World Health Organization (WHO) grade II neoplasms that have a median survival in the range of 5-7 years, generally with a terminal phase in which they undergo malignant transformation to glioblastoma (GBM). The goals of treatment in addition to prolonging survival are therefore to prevent progression and malignant transformation, as well as optimally managing symptoms, primarily tumor-associated epilepsy. Available data suggest that the course of this disease is only minimally impacted by adjuvant therapies and that there does not seem to be much difference in terms of outcome of whether patients are treated in the adjuvant setting with irradiation or chemotherapy. We review the experience with chemotherapy as a treatment modality and offer some guidelines for its usage and discuss medical management of arising symptoms.
Topics: Antineoplastic Agents; Astrocytoma; Dacarbazine; Disease Progression; Humans; Neoplasm Grading; Nitrosourea Compounds; Prognosis; Supratentorial Neoplasms; Temozolomide
PubMed: 25173138
DOI: 10.1053/j.seminoncol.2014.06.013 -
G3 (Bethesda, Md.) Jul 2016Copy number alterations (CNA) are one of the driving mechanisms of glioma tumorigenesis, and are currently used as important biomarkers in the routine setting....
Copy number alterations (CNA) are one of the driving mechanisms of glioma tumorigenesis, and are currently used as important biomarkers in the routine setting. Therefore, we performed CNA profiling of 65 astrocytomas of distinct malignant grades (WHO grade I-IV) of Brazilian origin, using array-CGH and microsatellite instability analysis (MSI), and investigated their correlation with TERT and IDH1 mutational status and clinico-pathological features. Furthermore, in silico analysis using the Oncomine database was performed to validate our findings and extend the findings to gene expression level. We found that the number of genomic alterations increases in accordance with glioma grade. In glioblastomas (GBM), the most common alterations were gene amplifications (PDGFRA, KIT, KDR, EGFR, and MET) and deletions (CDKN2A and PTEN) Log-rank analysis correlated EGFR amplification and/or chr7 gain with better survival of the patients. MSI was observed in 11% of GBMs. A total of 69% of GBMs presented TERT mutation, whereas IDH1 mutation was most frequent in diffuse (85.7%) and anaplastic (100%) astrocytomas. The combination of 1p19q deletion and TERT and IDH1 mutational status separated tumor groups that showed distinct age of diagnosis and outcome. In silico validation pointed to less explored genes that may be worthy of future investigation, such as CDK2, DMRTA1, and MTAP Herein, using an extensive integrated analysis, we indicated potentially important genes, not extensively studied in gliomas, that could be further explored to assess their biological and clinical impact in astrocytomas.
Topics: Adolescent; Adult; Aged; Astrocytoma; Brain Neoplasms; Brazil; Child; Comparative Genomic Hybridization; Cyclin-Dependent Kinase Inhibitor p16; Cyclin-Dependent Kinase Inhibitor p18; ErbB Receptors; Female; Gene Dosage; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Isocitrate Dehydrogenase; Male; Microsatellite Instability; Middle Aged; Neoplasm Grading; Neoplasm Proteins; PTEN Phosphohydrolase; Proto-Oncogene Proteins c-kit; Proto-Oncogene Proteins c-met; Receptor, Platelet-Derived Growth Factor alpha; Telomerase; Tissue Array Analysis; Vascular Endothelial Growth Factor Receptor-2
PubMed: 27172220
DOI: 10.1534/g3.116.029884 -
Zhurnal Voprosy Neirokhirurgii Imeni N.... 2021To evaluate the possibilities of dynamic preoperative C-methionine (MET) PET/CT in differential diagnosis of various types of brain gliomas in adults.
OBJECTIVE
To evaluate the possibilities of dynamic preoperative C-methionine (MET) PET/CT in differential diagnosis of various types of brain gliomas in adults.
MATERIAL AND METHODS
The study included 74 patients aged 48±14 years with supratentorial gliomas: Grade IV - glioblastoma (GB, =33), Grade III - anaplastic oligodendroglioma (AOD, =10) and anaplastic astrocytoma (AA, =12), Grade II - diffuse astrocytoma (DA, =13) and oligodendroglioma (OD, =6). All patients underwent standard MRI and dynamic MET PET/CT within 20 minutes after intravenous injection of radiopharmaceutical. Then, we compared MRI and PET/CT data and comprehensively analyzed the early stages of time-activity curve using 2 parameters: the first pass peak (FPP) and the first peak of maximum uptake (Pmax).
RESULTS
We have significantly distinguished high-grade tumors (GB and AA+AOD) and certain benign gliomas (DA and OD) (<0.05). AUC was over 0.7 and 0.8 for FPP and Pmax in differential diagnosis of various gliomas, respectively. We found that difficulties in differential diagnosis of gliomas arise mainly if oligodendrogliomas are included in the control group.
CONCLUSION
Dynamic PET/CT with analysis of FPP and Pmax increases specificity of differential diagnosis of various gliomas compared to standard static imaging. These data are valuable for choice of optimal treatment strategy, as well as fundamental research of metabolic processes and vascularization of various tumors.
Topics: Adult; Astrocytoma; Brain; Brain Neoplasms; Diagnosis, Differential; Glioma; Humans; Methionine; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography
PubMed: 34156203
DOI: 10.17116/neiro2021850315 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2023To study the relationship of NMDA receptors expression activity with proliferative activity and genetic properties of anaplastic astrocytomas, as well as the survival of...
OBJECTIVE
To study the relationship of NMDA receptors expression activity with proliferative activity and genetic properties of anaplastic astrocytomas, as well as the survival of patients with this disease.
MATERIAL AND METHODS
To solve this problem, we compared the expression activity of the least studied NMDA receptors in the context under consideration, detected using immunofluorescent studies and polymerase chain reaction, with the results of histological and molecular studies, the proliferative activity of neoplasms, and the survival of patients.
RESULTS
The expression activity of NMDA receptors is higher in astrocytomas, grade 3, which do not carry mutations in and genes. In addition, the activity of NMDA receptors expression directly correlates with proliferative activity in the tumors. The activity of NMDA receptor expression has a significant impact on the prognosis of disease-free survival.
CONCLUSION
We have shown for the first time the significant role of NMDA receptors in the progression of diffuse astrocytomas, which can become the basis for creating new therapeutic and diagnostic tools.
Topics: Humans; Receptors, N-Methyl-D-Aspartate; Brain Neoplasms; Astrocytoma; Prognosis; Polymerase Chain Reaction; Mutation
PubMed: 36719124
DOI: 10.17116/jnevro202312301197 -
The Canadian Veterinary Journal = La... Sep 2017A miniature schnauzer dog presenting with hyphema and glaucoma of the right eye had a retinal neoplasm. Neoplastic cells stained positively for glial fibrillary acidic...
A miniature schnauzer dog presenting with hyphema and glaucoma of the right eye had a retinal neoplasm. Neoplastic cells stained positively for glial fibrillary acidic protein, vimentin, and S-100 and largely negatively for oligodendrocyte transcription factor 2 by immunohistochemistry. The clinical and histopathological features of canine retinal astrocytomas are discussed.
Topics: Animals; Astrocytoma; Dog Diseases; Dogs; Eye Neoplasms; Glial Fibrillary Acidic Protein; Immunohistochemistry; Retinal Diseases; Vimentin
PubMed: 28878413
DOI: No ID Found -
Journal of Neurological Surgery. Part... Jul 2015To describe our experience and the results obtained in performing transventricular brainstem biopsy with the use of flexible neuroendoscops.
OBJECTIVES
To describe our experience and the results obtained in performing transventricular brainstem biopsy with the use of flexible neuroendoscops.
METHODS
We identified patients who underwent a neuroendoscopic procedure with brainstem lesion biopsy to obtain histopathologic diagnosis and to treat obstructive hydrocephalus. All patients had follow-up examinations at months 1, 3, 6, and 12 postsurgery and then annually.
RESULTS
Seven patients had a transventricular biopsy of the brainstem performed. Of those, five were pediatric patients. The median age was 10 years (range: 3-26 years). Five of them were female and two male. Four patients presented with secondary obstructive hydrocephalus. The main clinical presentations were intracranial hypertension syndrome in four patients, motor neuron disease in four patients, two with decreased state of alertness, two with gait ataxia, and one with Parinaud syndrome. The types of tumors found in the histopathology and their location were one ventral (pons) and one aqueductal anaplastic astrocytoma, two ventral, one aqueductal, and one attached to the floor of the fourth ventricle pilocytic astrocytoma and one ventral low-grade astrocytoma. The route taken to approach the ventral tumors was made through premammillary fenestration. The tumors of the aqueduct and floor of the fourth ventricle were approached transaqueductally.
CONCLUSION
The use of flexible endoscops for biopsy of ventral, dorsal (tectum lamina quadrigemina), and diffuse brainstem tumors is a useful, effective, and safe procedure that also allows to treat obstructive hydrocephalus secondary to the tumors.
Topics: Adolescent; Astrocytoma; Biopsy; Brain Stem Neoplasms; Child; Child, Preschool; Endoscopes; Female; Follow-Up Studies; Glioma; Humans; Hydrocephalus; Magnetic Resonance Imaging; Male; Neuroendoscopy; Neurosurgical Procedures; Treatment Outcome; Young Adult
PubMed: 25798800
DOI: 10.1055/s-0034-1373661 -
Neuropathology and Applied Neurobiology Feb 2019Mutations of isocitrate dehydrogenase (IDH)1/2 affect almost all astrocytomas of WHO grade II and III. A subset of IDH-mutant astrocytic tumours progresses to IDH-mutant...
AIMS
Mutations of isocitrate dehydrogenase (IDH)1/2 affect almost all astrocytomas of WHO grade II and III. A subset of IDH-mutant astrocytic tumours progresses to IDH-mutant glioblastoma or presents with the histology of a glioblastoma at first presentation. We set out here to assess the molecular spectrum of IDH-mutant glioblastomas.
METHODS
We performed an integrated molecular analysis of a mono-centric cohort (n = 97); assessed through genome-wide DNA methylation analysis, copy-number profiling and targeted next generation sequencing using a neurooncology-tailored gene panel.
RESULTS
Of these 97 IDH-mutant glioblastomas, 68 had a glioblastoma at first presentation ('de novo' IDH-mutant glioblastoma) and 29 emerged from a prior low-grade lesion ('evolved' IDH-mutant glioblastoma). Unsupervised hierarchical clustering of DNA methylation data disclosed that IDH-mutant glioblastoma ('de novo' and 'evolved') formed a distinct group separate from other diffuse glioma subtypes. Homozygous deletions of CDKN2A/B were found to be associated with shorter survival.
CONCLUSIONS
This study demonstrates DNA methylation patterns in IDH-mutant glioblastoma to be distinct from lower-grade astrocytic counterparts but homogeneous within de novo and evolved IDH-mutant glioblastomas, and identifies CDKN2A as a marker for possible genetic sub-stratification.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Astrocytoma; Brain Neoplasms; Glioblastoma; Glioma; Humans; Isocitrate Dehydrogenase; Middle Aged; Mutation; Neoplasm Grading; Young Adult
PubMed: 30326163
DOI: 10.1111/nan.12523 -
PloS One 2017Astrocytomas are the most frequent primary brain tumors in adults, and despite aggressive treatment patients often experience recurrence. Survival decreases with...
Astrocytomas are the most frequent primary brain tumors in adults, and despite aggressive treatment patients often experience recurrence. Survival decreases with increasing tumor grade, and especially patients with grade IV glioblastoma have poor prognosis due to the aggressive character of this tumor. Matrix metalloproteinase-2 (MMP-2) is an extracellular matrix degrading enzyme which has been shown to play important roles in different cancers. The aim of this study was to investigate the expression and prognostic potential of MMP-2 in astrocytomas. Tissue samples from 89 patients diagnosed with diffuse astrocytoma, anaplastic astrocytoma and glioblastoma were stained immunohistochemically using a monoclonal MMP-2 antibody. The MMP-2 intensity in cytoplasm/membrane was quantified by a trained software-based classifier using systematic random sampling in 10% of the tumor area. We found MMP-2 expression in tumor cells and blood vessels. Measurements of MMP-2 intensity increased with tumor grade, and MMP-2 expression was found to be significantly higher in glioblastomas compared to normal brain tissue (p<0.001), diffuse astrocytomas (p<0.001) and anaplastic astrocytomas (p<0.05). MMP-2 expression was associated with shorter overall survival in patients with grade II-IV astrocytic tumors (HR 1.60; 95% CI 1.03-2.48; p = 0.036). In glioblastoma, high MMP-2 was associated with poorer prognosis in patients who survived longer than 8.5 months independent of age and gender (HR 2.27; 95% CI 1.07-4.81; p = 0.033). We found a positive correlation between MMP-2 and tissue inhibitor of metalloproteinases-1 (TIMP-1), and combined MMP-2 and TIMP-1 had stronger prognostic value than MMP-2 alone also when adjusting for age and gender (HR 2.78; 95% CI 1.30-5.92; p = 0.008). These findings were validated in bioinformatics databases. In conclusion, this study indicates that MMP-2 is associated with aggressiveness in astrocytomas and may hold an unfavorable prognostic value in patients with glioblastoma.
Topics: Adult; Aged; Astrocytoma; Brain Neoplasms; Cell Line, Tumor; Computational Biology; Extracellular Matrix; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Isocitrate Dehydrogenase; Male; Matrix Metalloproteinase 2; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Software; Tissue Inhibitor of Metalloproteinase-1; Treatment Outcome; Young Adult
PubMed: 28234925
DOI: 10.1371/journal.pone.0172234 -
Child's Nervous System : ChNS :... Sep 2023Pontine gliomas represent difficult to treat entity due to the location and heterogeneous biology varying from indolent low-grade gliomas to aggressive diffuse intrinsic...
Pontine gliomas represent difficult to treat entity due to the location and heterogeneous biology varying from indolent low-grade gliomas to aggressive diffuse intrinsic pontine glioma (DIPG). Making the correct tumor diagnosis in the pontine location is thus critical. Here, we report a case study of a 14-month-old patient initially diagnosed as histone H3 wild-type DIPG. Due to the low age of the patient, the MRI appearance of DIPG, and anaplastic astrocytoma histology, intensive chemotherapy based on the HIT-SKK protocol with vinblastine maintenance chemotherapy was administered. Rapid clinical improvement and radiological regression of the tumor were observed with nearly complete remission with durable effect and excellent clinical condition more than 6.5 years after diagnosis. Based on this unexpected therapeutic outcome, genome-wide DNA methylation array was employed and the sample was classified into the methylation class "Low-grade glioma, MYB(L1) altered." Additionally, RT-PCR revealed the presence of MYB::QKI fusion. Taken together, the histopathological classification, molecular-genetic and epigenetic features, clinical behavior, and pontine location have led us to reclassify the tumor as a pontine MYB-altered glioma. Our case demonstrates that more intensive chemotherapy can achieve long-term clinical effect in the treatment of MYB-altered pontine gliomas compared to previously used LGG-based regimens or radiotherapy. It also emphasizes the importance of a biopsy and a thorough molecular investigation of pontine lesions.
Topics: Humans; Infant; Brain Stem Neoplasms; Astrocytoma; Glioma; Histones; Pons
PubMed: 37165121
DOI: 10.1007/s00381-023-05976-3 -
Mymensingh Medical Journal : MMJ Jul 2023This cross-sectional study was carried out in the Department of Radiology and Imaging, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from...
This cross-sectional study was carried out in the Department of Radiology and Imaging, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from January 2015 to June 2016 in collaboration with Department of Neurosurgery and Department of Pathology of same hospital, to assess MRI findings of common IMSCTs and to find out the validity of MRI in the diagnosis of spinal ependymoma and astrocytoma, thereby differentiating these two common intramedullary entities. For this purpose, 40 patients aged from 15 to 60 years, who were diagnosed or suspected cases of having intramedullary spinal cord tumours were enrolled. These patients underwent preoperative MRI for evaluation of the spinal cord tumours during the study period in department of Radiology and Imaging. Also, patients were diagnosed by MRI as having IMSCTs incidentally was included. All of them were followed by histopathological examination of the same lesions after surgery. Among these 40 patients after exclusion for valid reason 28 cases were included as study population. MR images were obtained on a 1.5 Tesla (Avanto Magnatom, Siemens) unit with a spine surface coil. MRI findings were compared with histopathology after surgery keeping histopathology as gold standard. Out of 28 clinically and MRI diagnosed IMSCTs cases, 19 cases of ependymoma, 8 cases of astrocytoma and one diagnosed as hemangioblastoma by MRI. The mean age was 34.11±9.55 years, ranging from 15 to 56 years for ependymoma, 26.88±8.08 years ranging from 16 to 44 years for astrocytoma. Highest incidence (47.4%) was in between 31 to 40 years for ependymoma, 50.0% were in between 21-30 for Astrocytoma. On MRI majority 12(63.2%) of the cord ependymomas and majority 5(62.5%) of astrocytomas were in cervical region. While considering axial location ependymomas are mostly 17(89.5%) central and astrocytomas 5(62.5%) are eccentric in location. It was observed that out of 19 cases of ependymoma more than half 10(52.6%) had elongated shape, 12(63.1%) had well defined margin. Associated syringohydromyelia was present in 16(84.2%) cases. On T1WI 11(57.9%) and 8(42.1%) cases were iso and hypo respectively. On T2WI 14(73.7%) cases were hyper intense. After Gd-DTPA in most cases, 13(68.4%) cases showed diffuse enhancement. Noticeable and sizeable solid component observed among 13(68.4%) of the cases. Hemorrhage with cap sign was found in more than one third 7(36.8%) cases. Out of 8 cases of astrocytomas 4(50.0%) had lobulated shape, ill-defined margin 5(62.5%). T1WI: Iso 5(62.5%), hypo 3(37.5%), T2WI: hyper 5(62.5%), After Gd-DTPA: focal and heterogenous enhancement 3(37.5%) and rim enhancement 4(50.0%). Component: mixed 4(50.0%), cystic 3(37.5%) and solid 1(12.5%). Hemorrhage without cap sign 2(25.0%), associated syringohydromyelia 1(12.5%). In the case of evaluation of intramedullary ependymoma sensitivity of MRI in the present series is 94.44%, specificity 80.0%, Positive predictive value (PPV) 89.5%, Negative predictive value (NPV) 88.9% and accuracy 89.28%. In case of MRI evaluation of intramedullary astrocytoma sensitivity of MRI in the present study is 85.71%, specificity 90.47%, PPV 75%, NPV 95% and accuracy 89.2%. Thus present study shows MRI is a sensitive and effective noninvasive imaging modality in diagnosing common intramedullary spinal cord tumours.
Topics: Adult; Humans; Young Adult; Astrocytoma; Bangladesh; Cross-Sectional Studies; Ependymoma; Gadolinium DTPA; Magnetic Resonance Imaging; Spinal Cord Neoplasms; Spinal Neoplasms; Adolescent; Middle Aged
PubMed: 37391969
DOI: No ID Found