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Medicina Aug 2022Tuberous sclerosis complex is an autosomal dominant genetic multisystemic disorder caused primarily by mutations in one of the two tumor suppressor genes TSC1 or TSC2,...
Tuberous sclerosis complex is an autosomal dominant genetic multisystemic disorder caused primarily by mutations in one of the two tumor suppressor genes TSC1 or TSC2, resulting in increased activation of the mTOR pathway. Regarding clinical manifestations, a wide range of phenotypic variability exists, with symptoms constellations that may differ in affected organs (brain, skin, heart, eyes, kidneys, lungs), age of presentation and severity, but usually with great impact in biopsychosocial aspects of health and in quality of life. Main clinical neurological features are epilepsy (frequently, antiepileptic drug-resistant epilepsy), neuropsychiatric disorders, and subependymal giant cell astrocytomas. Recently, many therapeutic strategies have developed, including preventive treatment of epilepsy, new options for treatment of epilepsy as cannabidiol, mTOR inhibitors, ketogenic diet, and a more precise epilepsy surgery. Subependymal giant cell astrocytomas may require surgical procedures or mTOR inhibitors treatment. mTOR inhibitors may also be useful for other comorbidities. To improve quality of life of patients with tuberous sclerosis complex, it is essential to be able to deliver an integrated approach by specialized multidisciplinary teams, coordinated with primary care physicians and health professionals, that include access to treatments, attention of psychosocial aspects, and an adequate health care transition from pediatric to adult care.
Topics: Adult; Astrocytoma; Child; Epilepsy; Humans; Quality of Life; Transition to Adult Care; Tuberous Sclerosis
PubMed: 36054862
DOI: No ID Found -
Clinical Neuropathology 2017Familial melanoma-astrocytoma syndrome is a tumor predisposition syndrome caused by inactivating germline alteration of the
CDKN2A tumor suppressor gene...Familial melanoma-astrocytoma syndrome: synchronous diffuse astrocytoma and pleomorphic xanthoastrocytoma in a patient with germline CDKN2A/B deletion and a significant family history.
Familial melanoma-astrocytoma syndrome is a tumor predisposition syndrome caused by inactivating germline alteration of the
CDKN2A tumor suppressor gene on chromosome 9p21. While some families with germlineCDKN2A mutations are prone to development of just melanomas, other families develop both melanomas, astrocytomas, and occasionally other nervous-system neoplasms including peripheral nerve sheath tumors and meningiomas. The histologic spectrum of the astrocytomas that arise as part of this syndrome is not well described, nor are the additional genetic alterations that drive these astrocytomas apart from the germlineCDKN2A inactivation. Herein, we report the case of a young man with synchronous development of a pleomorphic xanthoastrocytoma, diffuse astrocytoma, and paraspinal mass radiographically consistent with a peripheral nerve sheath tumor. His paternal family history is significant for melanoma, glioblastoma, and oral squamous cell carcinoma. Genomic profiling revealed that he harbors a heterozygous deletion in the germline of chromosome 9p21.3 encompassing theCDKN2A andCDKN2B tumor suppressor genes. Both the pleomorphic xanthoastrocytoma and diffuse astrocytoma were found to have homozygous deletion ofCDKN2A/B due to somatic loss of the other copy of chromosome 9p containing the remaining intact alleles. Additional somatic alterations includedBRAF p.V600E mutation in the pleomorphic xanthoastrocytoma andPTPN11 ,ATRX , andNF1 mutations in the diffuse astrocytoma. The presence of germlineCDKN2A/B inactivation together with the presence of multiple anatomically, histologically, and genetically distinct astrocytic neoplasms, both with accompanying somatic loss of heterozygosity for theCDKN2A/B deletion, led to a diagnosis of familial melanoma-astrocytoma syndrome. This remarkable case illustrates the histologic and genetic diversity that astrocytomas arising as part of this rare glioma predisposition syndrome can demonstrate. .Topics: Astrocytoma; Cyclin-Dependent Kinase Inhibitor p15; Cyclin-Dependent Kinase Inhibitor p16; Cyclin-Dependent Kinase Inhibitor p18; Humans; Male; Melanoma; Nervous System Neoplasms; Pedigree; Young Adult
PubMed: 28699883
DOI: 10.5414/NP301022 -
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 -
Cancer Research Dec 2009Mutations of the isocitrate dehydrogenase (IDH) metabolic enzymes IDH1 and IDH2 have been found to be frequent and early genetic alterations in astrocytomas and... (Review)
Review
Mutations of the isocitrate dehydrogenase (IDH) metabolic enzymes IDH1 and IDH2 have been found to be frequent and early genetic alterations in astrocytomas and oligodendrogliomas. All mutations identified to date affect a single amino acid located within the isocitrate binding site (R132 of IDH1 and the analogous R172 residue of IDH2). IDH1 and IDH2 mutations define a specific subtype of gliomas and may have significant utility for the diagnosis, prognosis, and treatment of patients with these tumors.
Topics: Astrocytoma; Central Nervous System Neoplasms; Glioblastoma; Humans; Isocitrate Dehydrogenase; Mutation
PubMed: 19996293
DOI: 10.1158/0008-5472.CAN-09-2650 -
Journal of Medical Case Reports Feb 2016Subependymal giant cell astrocytoma is a rare tumor that occurs in the wall of the lateral ventricle and foramen of Monro and, rarely, in the third ventricle. It is one... (Review)
Review
BACKGROUND
Subependymal giant cell astrocytoma is a rare tumor that occurs in the wall of the lateral ventricle and foramen of Monro and, rarely, in the third ventricle. It is one of the intracranial lesions found in tuberous sclerosis complex (which include subependymal nodules, cortical tubers, retinal astrocytoma and subependymal giant cell astrocytoma), but cases without such lesions have also been reported in the literature. It was described for the first time in 1908 by Vogt as part of the typical triad of tuberous sclerosis complex. At the 2012 Washington Consensus Conference, it was decided by the invited expert panel to document the definition of subependymal giant cell astrocytoma as a lesion at the caudothalamic groove with either a size of more than 1 cm in any direction or a subependymal lesion at any location that has shown serial growth on consecutive imaging regardless of size. Most subependymal giant cell astrocytomas will show avid enhancement after contrast administration; however, a growing subependymal lesion even in the absence of enhancement should be considered a subependymal giant cell astrocytoma.
CASE PRESENTATION
We report a case of subependymal giant cell astrocytoma in a 10-year-old white girl, who had no clinical symptoms of tuberous sclerosis. A computed tomography scan revealed a voluminous mass in her perilateral ventricle. An extemporaneous examination was in favor of a benign ganglioglioma tumor. After fixation in 10 % neutral-buffered formalin, embedding in paraffin and staining with hematoxylin, eosin and safran, the definitive diagnosis was subependymal giant cell astrocytoma.
CONCLUSIONS
Subependymal giant cell astrocytoma is a rare tumor of the central nervous system whose diagnosis is based on clinical, radiological, histological and immunohistochemical arguments. For its rarity, we must consider this diagnosis when faced with a mass near the foramen of Monro in the pediatric population even if there are no other features of tuberous sclerosis complex.
Topics: Astrocytoma; Cerebral Ventricle Neoplasms; Child; Female; Humans; Lateral Ventricles; Radiography; Seizures
PubMed: 26861567
DOI: 10.1186/s13256-016-0818-6 -
Cells Dec 2019High-grade astrocytomas are some of the most common and aggressive brain cancers, whose signs and symptoms are initially non-specific. Up to the present date, there are...
High-grade astrocytomas are some of the most common and aggressive brain cancers, whose signs and symptoms are initially non-specific. Up to the present date, there are no diagnostic tools to observe the early onset of the disease. Here, we analyzed the combination of blood serum proteins, which may play key roles in the tumorigenesis and the progression of glial tumors. Fifty-nine astrocytoma patients and 43 control serums were analyzed using Custom Human Protein Antibody Arrays, including ten targets: ANGPT1, AREG, IGF1, IP10, MMP2, NCAM1, OPN, PAI1, TGFβ1, and TIMP1. The decision tree analysis indicates that serums ANGPT1, TIMP1, IP10, and TGFβ1 are promising combinations of targets for glioma diagnostic applications. The accuracy of the decision tree algorithm was 73.5% (75/102), which correctly classified 79.7% (47/59) astrocytomas and 65.1% (28/43) healthy controls. The analysis revealed that the relative value of osteopontin (OPN) protein level alone predicted the 12-month survival of glioblastoma (GBM) patients with the specificity of 84%, while the inclusion of the IP10 protein increased model predictability to 92.3%. In conclusion, the serum protein profiles of ANGPT1, TIMP1, IP10, and TGFβ1 were associated with the presence of astrocytoma independent of its malignancy grade, while OPN and IP10 were associated with GBM patient survival.
Topics: Angiopoietin-1; Astrocytoma; Blood Proteins; Case-Control Studies; Chemokine CXCL10; Decision Trees; Disease Progression; Female; Glioblastoma; Humans; Male; Middle Aged; Neoplasm Grading; Osteopontin; Prognosis; Sensitivity and Specificity; Survival Analysis; Tissue Inhibitor of Metalloproteinase-1; Transforming Growth Factor beta1
PubMed: 31861636
DOI: 10.3390/cells9010016 -
Neuro-oncology Apr 1999Loss of function of the p53 tumor suppressor gene due to mutation occurs early in astrocytoma tumorigenesis in about 30-40% of cases. This is believed to confer a growth... (Review)
Review
Loss of function of the p53 tumor suppressor gene due to mutation occurs early in astrocytoma tumorigenesis in about 30-40% of cases. This is believed to confer a growth advantage to the cells, allowing them to clonally expand due to loss of the p53-controlled G1 checkpoint and apoptosis. Genetic instability due to the impaired ability of p53 to mediate DNA damage repair further facilitates the acquisition of new genetic abnormalities, leading to malignant progression of an astrocytoma into anaplastic astrocytoma. This is reflected by a high rate of p53 mutation (60-70%) in anaplastic astrocytomas. The cell cycle control gets further compromised in astrocytoma by alterations in one of the G1/S transition control genes, either loss of the p16/CDKN2 or RB genes or amplification of the cyclin D gene. The final progression process leading to glioblastoma multiforme seems to need additional genetic abnormalities in the long arm of chromosome 10; one of which is deletion and/or functional loss of the PTEN/MMAC1 gene. Glioblastomas also occur as primary (de novo) lesions in patients of older age, without p53 gene loss but with amplification of the epidermal growth factor receptor (EGFR) genes. In contrast to the secondary glioblastomas that evolve from astrocytoma cells with p53 mutations in younger patients, primary glioblastomas seem to be resistant to radiation therapy and thus show a poorer prognosis. The evaluation and design of therapeutic modalities aimed at preventing malignant progression of astrocytomas and glioblastomas should now be based on stratifying patients with astrocytic tumors according to their genetic diagnosis.
Topics: Alleles; Apoptosis; Astrocytoma; Brain Neoplasms; Cell Cycle; Cell Division; Cell Transformation, Neoplastic; Cyclin D; Cyclins; DNA Repair; Disease Progression; ErbB Receptors; Gene Amplification; Gene Expression Regulation, Neoplastic; Genes, Retinoblastoma; Genes, Tumor Suppressor; Genes, p16; Genes, p53; Glioblastoma; Humans; Loss of Heterozygosity; Mutation; PTEN Phosphohydrolase; Phosphoric Monoester Hydrolases; Prognosis; Tumor Suppressor Protein p53; Tumor Suppressor Proteins
PubMed: 11550308
DOI: 10.1093/neuonc/1.2.124 -
AJNR. American Journal of Neuroradiology Mar 1998We report the common characteristics of juvenile pilocytic astrocytomas revealed by proton MR spectroscopy. (Review)
Review
PURPOSE
We report the common characteristics of juvenile pilocytic astrocytomas revealed by proton MR spectroscopy.
METHODS
Eight children with pilocytic astrocytomas were studied with proton MR spectroscopy. The selected sampling volume was approximately 4 cm3, obtained from solid tumor. To localize the sampling volume, we used point-resolved spectroscopy (PRESS) and stimulated-echo acquisition mode (STEAM) techniques to acquire long- and short-TE spectra, respectively. Spectra from PRESS and STEAM sequences were processed using Lorentzian-to-Gaussian transformation and exponential apodization, respectively. For PRESS (2000/270) spectra, peaks of creatine, choline, N-acetylaspartate (NAA), and lactate resonances were integrated; for STEAM (2000/20) spectra, we measured the amplitude of the peaks at 3.2, 2.0, 1.3 and 0.9 ppm.
RESULTS
An elevated lactate doublet was observed in the PRESS spectra. The choline/NAA ratio was 3.40. The amplitude ratios of the lipid pattern (0.9, 1.3 and 2.0 ppm) to choline were all below one.
CONCLUSION
Despite the benign histology of the tumor, which generally lacks necrosis, a lactate signal was detected in all eight patients studied. A dominant lipid pattern was not observed.
Topics: Aspartic Acid; Astrocytoma; Brain Neoplasms; Child; Child, Preschool; Choline; Humans; Infant; Lactic Acid; Lipid Metabolism; Magnetic Resonance Spectroscopy; Protons
PubMed: 9541314
DOI: No ID Found -
ASN Neuro 2023Central nervous system tumors, especially astrocytomas, are the solid neoplasms with the highest incidence and mortality rates in childhood. The diagnosis is based on...
Central nervous system tumors, especially astrocytomas, are the solid neoplasms with the highest incidence and mortality rates in childhood. The diagnosis is based on histopathological characteristics, but molecular methods have been increasingly used. Translationally controlled tumor protein (TCTP) protein, encoded by the tumor protein, translationally controlled 1 () gene, is a multifunctional protein with an important physiological role in the cell cycle. Expression of this protein has been associated with several neoplasms, including astrocytomas in adults. However, the role of this protein in pediatric astrocytomas is largely unknown. We aim to evaluate in cases of pediatric astrocytomas, the frequency of polymorphisms in the gene and other genes associated with its molecular pathways, such as , , , and , correlating it with protein expression and clinical variables, in formalin-fixed, paraffin-embedded (FFPE) samples. These samples were submitted to genotyping and immunohistochemistry analyses. The most revealing results refer to the gene, rs117039649 [G/C], in which C polymorphic allele was observed only in the glioblastomas (= .028). The gene, rs3176334 [T/C] presented a homozygous polymorphic genotype only in high-grade astrocytomas, when infiltrating tumors were compared (= .039). The immunohistochemical expression of cytoplasmic MDM2 correlated with better survival rates in patients with glioblastoma (.018). The presence of polymorphisms in the and genes, as well as a specific correlation between MDM2 expression, suggests a likely association with risk in pediatric astrocytomas. This study sought the probable role involved in the TCTP pathway, and associated proteins, in the tumorigenesis of pediatric astrocytomas, and some could have potential impact as prognostic markers in these patients.
Topics: Child; Humans; Astrocytoma; Brain Neoplasms; Genotype; Glioblastoma; Polymorphism, Genetic; Tumor Protein, Translationally-Controlled 1
PubMed: 36714975
DOI: 10.1177/17590914231153481 -
Neuro-oncology Jun 2023Prognostic models for spinal cord astrocytoma patients are lacking due to the low incidence of the disease. Here, we aim to develop a fully automated deep learning (DL)...
BACKGROUND
Prognostic models for spinal cord astrocytoma patients are lacking due to the low incidence of the disease. Here, we aim to develop a fully automated deep learning (DL) pipeline for stratified overall survival (OS) prediction based on preoperative MR images.
METHODS
A total of 587 patients diagnosed with intramedullary tumors were retrospectively enrolled in our hospital to develop an automated pipeline for tumor segmentation and OS prediction. The automated pipeline included a T2WI-based tumor segmentation model and 3 cascaded binary OS prediction models (1-year, 3-year, and 5-year models). For the tumor segmentation model, 439 cases of intramedullary tumors were used to model training and testing using a transfer learning strategy. A total of 138 patients diagnosed with astrocytomas were included to train and test the OS prediction models via 10 × 10-fold cross-validation using CNNs.
RESULTS
The dice of the tumor segmentation model with the test set was 0.852. The results indicated that the best input of OS prediction models was a combination of T2W and T1C images and the tumor mask. The 1-year, 3-year, and 5-year automated OS prediction models achieved accuracies of 86.0%, 84.0%, and 88.0% and AUCs of 0.881 (95% CI 0.839-0.918), 0.862 (95% CI 0.827-0.901), and 0.905 (95% CI 0.867-0.942), respectively. The automated DL pipeline achieved 4-class OS prediction (<1 year, 1-3 years, 3-5 years, and >5 years) with 75.3% accuracy.
CONCLUSIONS
We proposed an automated DL pipeline for segmenting spinal cord astrocytomas and stratifying OS based on preoperative MR images.
Topics: Humans; Deep Learning; Retrospective Studies; Astrocytoma; Magnetic Resonance Imaging; Spinal Cord Neoplasms; Magnetic Resonance Spectroscopy
PubMed: 36562243
DOI: 10.1093/neuonc/noac280