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Hiroko Ohgaki - One of the best experts on this subject based on the ideXlab platform.
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correlation among pathology genotype and patient outcomes in glioblastoma
Journal of Neuropathology and Experimental Neurology, 2006Co-Authors: Taku Homma, Pierluigi Di Patre, Salvatore Vaccarella, Silvia Franceschi, Takao Fukushima, Yasuhiro Yonekawa, Hiroko OhgakiAbstract:Abstract Glioblastomas are histologically and genetically heterogeneous.We have investigated to what extent histologic features reflect thegenetic profile and whether they are predictive of clinical outcome.Key histologic characteristics, including major cell types (smallcell, nonsmall cell), other components such as oligodendroglialcomponents, Gemistocytes, multinucleated giant cells, as well asnecrosis and microvascular proliferation, of 420 cases of glioblas-toma within a population-based study (1) were reassessed andcorrelated with patients_ clinical outcome and key genetic alter-ations. EGFR amplification and p16 INK4a homozygous deletionwere significantly more frequent in small cell glioblastomas than innonsmall cell glioblastomas (EGFR, 46% vs 26%, p = 0.0002;p16 INK4a 39% vs 25%, p = 0.0167). Multivariate analyses withadjustment for age and gender showed that small cell glioblastomashad frequent EGFR amplification and p16 INK4a deletion butinfrequent PTEN mutations. An oligodendroglial component wasdetected in 20% of glioblastomas; these patients were significantlyyounger (54.4 T 13.6 vs 59.2 T 13.8 years; p = 0.0049) and survivedlonger (10.3 T 8.3 vs 8.2 T 8.4 months; p = 0.0647). However,multivariate analyses with adjustment for age and gender did notshow the presence of an oligodendroglial component to bepredictive of longer survival. After adjustment for age and gender,LOH 1p was associated with longer survival (hazard ratio, 0.7; 95%confidence interval [CI], 0.5Y1.0), whereas LOH 10q was associ-ated with shorter survival (hazard ratio, 1.4; 95% CI, 1.0Y1.8) ofpatients with glioblastoma. Glioblastomas containing Q5% multi-nucleated giant cells showed more frequent TP53 mutation andinfrequent EGFR amplification than those containing <5% multi-nucleated giant cells (TP53, 45% vs 24%, p = 0.0001; EGFR, 24%vs 42%, p = 0.0005). Vascular proliferation was observed in allglioblastomas, whereas large ischemic and/or pseudopalisadingnecrosis was observed in 366 of 420 (87%) cases. Glioblastomaswith necrosis were associated with older age (59.2 T 13.3 vs 51.6 T15.3 years; p = 0.0001) and shorter survival (7.9 T 6.8 vs 12.9 T14.2 months; p = 0.0017). Multivariate analyses with adjustment forageandgenderconfirmedthisobservation(hazardratio,1.5;95%CI,1.1Y2.0). Multivariate analysis with adjustment for age and gendershowed that necrosis was significantly associated with wild-type TP53and absence of an oligodendroglial component. These results suggestthat some histologic features in g lioblastomas are associated withspecific genetic alterations and with clinical outcome.Key Words: EGFR amplification, Glioblastoma, LOH 1p, LOH19q, Necrosis, Oligodendroglial component, p16
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Correlation among pathology, genotype, and patient outcomes in glioblastoma.
Journal of neuropathology and experimental neurology, 2006Co-Authors: Taku Homma, Pierluigi Di Patre, Salvatore Vaccarella, Silvia Franceschi, Takao Fukushima, Yasuhiro Yonekawa, Hiroko OhgakiAbstract:Abstract Glioblastomas are histologically and genetically heterogeneous.We have investigated to what extent histologic features reflect thegenetic profile and whether they are predictive of clinical outcome.Key histologic characteristics, including major cell types (smallcell, nonsmall cell), other components such as oligodendroglialcomponents, Gemistocytes, multinucleated giant cells, as well asnecrosis and microvascular proliferation, of 420 cases of glioblas-toma within a population-based study (1) were reassessed andcorrelated with patients_ clinical outcome and key genetic alter-ations. EGFR amplification and p16 INK4a homozygous deletionwere significantly more frequent in small cell glioblastomas than innonsmall cell glioblastomas (EGFR, 46% vs 26%, p = 0.0002;p16 INK4a 39% vs 25%, p = 0.0167). Multivariate analyses withadjustment for age and gender showed that small cell glioblastomashad frequent EGFR amplification and p16 INK4a deletion butinfrequent PTEN mutations. An oligodendroglial component wasdetected in 20% of glioblastomas; these patients were significantlyyounger (54.4 T 13.6 vs 59.2 T 13.8 years; p = 0.0049) and survivedlonger (10.3 T 8.3 vs 8.2 T 8.4 months; p = 0.0647). However,multivariate analyses with adjustment for age and gender did notshow the presence of an oligodendroglial component to bepredictive of longer survival. After adjustment for age and gender,LOH 1p was associated with longer survival (hazard ratio, 0.7; 95%confidence interval [CI], 0.5Y1.0), whereas LOH 10q was associ-ated with shorter survival (hazard ratio, 1.4; 95% CI, 1.0Y1.8) ofpatients with glioblastoma. Glioblastomas containing Q5% multi-nucleated giant cells showed more frequent TP53 mutation andinfrequent EGFR amplification than those containing
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Genetic evidence of the neoplastic nature of Gemistocytes in astrocytomas.
Acta neuropathologica, 2001Co-Authors: Rui Manuel Reis, Paul Kleihues, Akira Hara, Hiroko OhgakiAbstract:Gemistocytic astrocytoma is characterized by a predominance of large astrocytes with plump processes and massive accumulation of glial fibrillary acidic protein (Gemistocytes). This histological variant of low-grade diffuse astrocytoma (WHO grade II) is prone to more rapid progression to anaplastic astrocytoma and glioblastoma than the ordinary fibrillary astrocytoma. The biological basis of this unfavorable prognosis is unclear, since Gemistocytes themselves have low proliferative activity, even if present in anaplastic astrocytomas or glioblastomas. This has raised the question of whether Gemistocytes are neoplastic cells or dysplastic reactive astrocytes. In this study, Gemistocytes and non-gemistocytic neoplastic cells were separated by laser-assisted microdissection from six gemistocytic astrocytomas carrying TP53 mutations. In all cases, identical TP53 mutations were identified in both cell types, indicating that Gemistocytes are indeed neoplastic cells. Their lack of proliferative activity may indicate terminal differentiation.
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p53 and pten gene mutations in gemistocytic astrocytomas
Acta Neuropathologica, 1998Co-Authors: Kunihiko Watanabe, Paul Kleihues, Aurelia Peraud, Catherine Gratas, Susumu Wakai, Hiroko OhgakiAbstract:The gemistocytic astrocytoma is a histological variant of diffuse astrocytomas and is characterised by the presence of large, GFAP-expressing neoplastic astrocytes (Gemistocytes) and a tendency towards rapid progression to glioblastoma. In this study, we analyzed 28 gemistocytic astrocytomas (mean fraction of Gemistocytes, 35.0 ± 9.9%) for mutations in the p53 and PTEN(MMAC1) tumour suppressor genes. Single strand conformation polymorphism (SSCP), followed by direct DNA sequencing of p53 exons 5–8, revealed a mutation in 23 of 28 (82%) cases. Regional analysis of four tumours revealed identical p53 mutations in gemistocytic and fibrillary tumour areas. In contrast, none of 15 gemistocytic astrocytomas (WHO Grade II) and only two of 11 (18%) anaplastic gemistocytic astrocytomas (WHO Grade III) contained a PTEN mutation. Of these, one was a 1 bp deletion in codon 345 and the other a 1 bp insertion in intron 4. Differential PCR did not reveal homozygous PTEN deletion in any of the tumours analysed. These results indicate that p53 mutations are a genetic hallmark of gemistocytic astrocytomas, whilst PTEN mutations are absent in low-grade and rare in anaplastic gemistocytic astrocytomas.
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Role of Gemistocytes in astrocytoma progression.
Laboratory investigation; a journal of technical methods and pathology, 1997Co-Authors: Kunihiko Watanabe, Yasuhiro Yonekawa, Osamu Tachibana, Paul Kleihues, Hiroko OhgakiAbstract:The presence of Gemistocytes in low-grade astrocytomas is regarded as a sign of poor prognosis because the majority of gemistocytic astrocytomas rapidly progress to anaplastic astrocytoma or glioblastoma. To elucidate the role of Gemistocytes in astrocytoma progression, we assessed the fraction of neoplastic Gemistocytes, bcl-2 expression, p53 mutations, p53 immunoreactivity (PAb 1801), and proliferative activity (MIB-1) in 40 low-grade astrocytomas (World Health Organization (WHO) Grade II) with histologically proven progression to anaplastic astrocytoma (WHO Grade III) or glioblastoma (WHO Grade IV). Astrocytoma progression took significantly less time in patients with a low-grade astrocytoma containing more than 5% Gemistocytes (35 months) than in those with lesions containing less than 5% Gemistocytes (64 months; p = 0.038). All 11 astrocytomas with more than 5% Gemistocytes contained a p53 mutation, whereas the incidence of p53 mutations in astrocytomas with less than 5% Gemistocytes was 61% (p = 0.017). In low-grade astrocytomas, the p53 labeling index (Ll) of Gemistocytes (7.4%) was significantly higher than in all tumor cells (3.2%, p = 0.0014). Gemistocytes showed a significantly higher bcl-2 expression than all tumor cells, with a mean bcl-2 LI of 15.6% versus 2.7% in low-grade astrocytomas (p = 0.0004), 20.9% versus 3.0% in anaplastic astrocytoma (p = 0.002), and 30.2% versus 5.2% in glioblastomas (p = 0.0002). In contrast, Gemistocytes showed a significantly lower proliferating activity than the mean of all tumor cells, with a mean MIB-1 LI of 0.5% versus 2.6% in low-grade astrocytomas, 1.5% versus 11.6% in anaplastic astrocytoma, and 1.7% versus 16.6% in glioblastomas (p < 0.0001). These data show that low-grade astrocytomas with a significant fraction of Gemistocytes progress more rapidly and typically carry a p53 mutation. The vast majority of Gemistocytes are, however, in a nonproliferative state (G o Phase of the cell cycle), which suggests terminal differentiation. Their accumulation within astrocytomas may be due to bcl-2-mediated escape from apoptosis.
Lynn S. Ashby - One of the best experts on this subject based on the ideXlab platform.
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Predicting Progressive Gangliogliomas: Early Identification Of Those At Risk In A Sample Of 156 Consecutive Patients Treated At The Barrow Neurological Institute (S22.004)
Neurology, 2014Co-Authors: Glynnis Zieman, Christopher Dardis, Andrea Gomes, Adrienne C. Scheck, Jennifer M. Eschbacher, Lynn S. AshbyAbstract:Objective: Early identification of ganglioglioma patients at risk for malignant progression. Background: Gangliogliomas are biphasic tumors comprised of neoplastic neuronal and glial cells. Lesions occur in children and adults anywhere in the neuraxis, most commonly in the temporal lobe. Low grade gangliogliomas are indolent and considered to be curable with gross total resection. Anaplastic variants are less common. Patient characteristics, along with histopathological and immunohistochemical analyses, correlate with outcome. However, early identification of patients at risk for malignant progression remains a clinical challenge. Methods: A retrospective analysis was performed of 156 patients with gangliogliomas diagnosed between 1983 and 2013. Histopathological and radiographic data were reviewed for 115 adults (18 years or greater) and 41 children. Extent of resection was determined by neuroimaging. Tumor registry provided follow-up and survival data. Pathological criteria included: Neu-N, GFAP, presence of Rosenthal fibers, eosinophilic granular bodies, perivascular lymphocytic inflammation, bi- or multinuclear ganglion cells, fibrillary astrocytes, Gemistocytes, mitotic figures, calcification, cortical dysplasia, and elevated MIB-1/Ki67. Results: Median ages for children and adults were 11 and 29 years, respectively. Tumors were located in the temporal lobe in 26.5% of children, 31.5% of adults. In 108 subjects with survival data, there were 11 anaplastic tumors with MST of only 3.7 years. In the non-anaplastic group, MST has not been reached (12 deaths in 97 subjects). Age in the adult was a poor prognostic variable (p
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predicting progressive gangliogliomas early identification of those at risk in a sample of 156 consecutive patients treated at the barrow neurological institute s22 004
Neurology, 2014Co-Authors: Glynnis Zieman, Christopher Dardis, Andrea Gomes, Adrienne C. Scheck, Jennifer M. Eschbacher, Lynn S. AshbyAbstract:Objective: Early identification of ganglioglioma patients at risk for malignant progression. Background: Gangliogliomas are biphasic tumors comprised of neoplastic neuronal and glial cells. Lesions occur in children and adults anywhere in the neuraxis, most commonly in the temporal lobe. Low grade gangliogliomas are indolent and considered to be curable with gross total resection. Anaplastic variants are less common. Patient characteristics, along with histopathological and immunohistochemical analyses, correlate with outcome. However, early identification of patients at risk for malignant progression remains a clinical challenge. Methods: A retrospective analysis was performed of 156 patients with gangliogliomas diagnosed between 1983 and 2013. Histopathological and radiographic data were reviewed for 115 adults (18 years or greater) and 41 children. Extent of resection was determined by neuroimaging. Tumor registry provided follow-up and survival data. Pathological criteria included: Neu-N, GFAP, presence of Rosenthal fibers, eosinophilic granular bodies, perivascular lymphocytic inflammation, bi- or multinuclear ganglion cells, fibrillary astrocytes, Gemistocytes, mitotic figures, calcification, cortical dysplasia, and elevated MIB-1/Ki67. Results: Median ages for children and adults were 11 and 29 years, respectively. Tumors were located in the temporal lobe in 26.5% of children, 31.5% of adults. In 108 subjects with survival data, there were 11 anaplastic tumors with MST of only 3.7 years. In the non-anaplastic group, MST has not been reached (12 deaths in 97 subjects). Age in the adult was a poor prognostic variable (p<0.0001). Mitotic figures worsened prognosis (p<0.005). Elevated MIB-1 predicted shorter survival (p<0.005), with improved survival when labelling index <2% (p<0.002). Further immunohistochemistry is in progress. Conclusions: Age predicts survival in adults, not children. Tumor location and MR enhancement are not prognostic. Risk of malignant transformation is related to glial features. Continuing immunohistochemical analysis includes MIB-1/Ki-67, CD34, MGMT and IDH1, as well as 1p19q deletion status for oligodendroglial or mixed features. Disclosure: Dr. Zieman has nothing to disclose. Dr. Dardis has nothing to disclose. Dr. Gomes has nothing to disclose. Dr. Scheck has nothing to disclose. Dr. Eschbacher has nothing to disclose. Dr. Ashby has nothing to disclose.
Glynnis Zieman - One of the best experts on this subject based on the ideXlab platform.
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Predicting Progressive Gangliogliomas: Early Identification Of Those At Risk In A Sample Of 156 Consecutive Patients Treated At The Barrow Neurological Institute (S22.004)
Neurology, 2014Co-Authors: Glynnis Zieman, Christopher Dardis, Andrea Gomes, Adrienne C. Scheck, Jennifer M. Eschbacher, Lynn S. AshbyAbstract:Objective: Early identification of ganglioglioma patients at risk for malignant progression. Background: Gangliogliomas are biphasic tumors comprised of neoplastic neuronal and glial cells. Lesions occur in children and adults anywhere in the neuraxis, most commonly in the temporal lobe. Low grade gangliogliomas are indolent and considered to be curable with gross total resection. Anaplastic variants are less common. Patient characteristics, along with histopathological and immunohistochemical analyses, correlate with outcome. However, early identification of patients at risk for malignant progression remains a clinical challenge. Methods: A retrospective analysis was performed of 156 patients with gangliogliomas diagnosed between 1983 and 2013. Histopathological and radiographic data were reviewed for 115 adults (18 years or greater) and 41 children. Extent of resection was determined by neuroimaging. Tumor registry provided follow-up and survival data. Pathological criteria included: Neu-N, GFAP, presence of Rosenthal fibers, eosinophilic granular bodies, perivascular lymphocytic inflammation, bi- or multinuclear ganglion cells, fibrillary astrocytes, Gemistocytes, mitotic figures, calcification, cortical dysplasia, and elevated MIB-1/Ki67. Results: Median ages for children and adults were 11 and 29 years, respectively. Tumors were located in the temporal lobe in 26.5% of children, 31.5% of adults. In 108 subjects with survival data, there were 11 anaplastic tumors with MST of only 3.7 years. In the non-anaplastic group, MST has not been reached (12 deaths in 97 subjects). Age in the adult was a poor prognostic variable (p
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predicting progressive gangliogliomas early identification of those at risk in a sample of 156 consecutive patients treated at the barrow neurological institute s22 004
Neurology, 2014Co-Authors: Glynnis Zieman, Christopher Dardis, Andrea Gomes, Adrienne C. Scheck, Jennifer M. Eschbacher, Lynn S. AshbyAbstract:Objective: Early identification of ganglioglioma patients at risk for malignant progression. Background: Gangliogliomas are biphasic tumors comprised of neoplastic neuronal and glial cells. Lesions occur in children and adults anywhere in the neuraxis, most commonly in the temporal lobe. Low grade gangliogliomas are indolent and considered to be curable with gross total resection. Anaplastic variants are less common. Patient characteristics, along with histopathological and immunohistochemical analyses, correlate with outcome. However, early identification of patients at risk for malignant progression remains a clinical challenge. Methods: A retrospective analysis was performed of 156 patients with gangliogliomas diagnosed between 1983 and 2013. Histopathological and radiographic data were reviewed for 115 adults (18 years or greater) and 41 children. Extent of resection was determined by neuroimaging. Tumor registry provided follow-up and survival data. Pathological criteria included: Neu-N, GFAP, presence of Rosenthal fibers, eosinophilic granular bodies, perivascular lymphocytic inflammation, bi- or multinuclear ganglion cells, fibrillary astrocytes, Gemistocytes, mitotic figures, calcification, cortical dysplasia, and elevated MIB-1/Ki67. Results: Median ages for children and adults were 11 and 29 years, respectively. Tumors were located in the temporal lobe in 26.5% of children, 31.5% of adults. In 108 subjects with survival data, there were 11 anaplastic tumors with MST of only 3.7 years. In the non-anaplastic group, MST has not been reached (12 deaths in 97 subjects). Age in the adult was a poor prognostic variable (p<0.0001). Mitotic figures worsened prognosis (p<0.005). Elevated MIB-1 predicted shorter survival (p<0.005), with improved survival when labelling index <2% (p<0.002). Further immunohistochemistry is in progress. Conclusions: Age predicts survival in adults, not children. Tumor location and MR enhancement are not prognostic. Risk of malignant transformation is related to glial features. Continuing immunohistochemical analysis includes MIB-1/Ki-67, CD34, MGMT and IDH1, as well as 1p19q deletion status for oligodendroglial or mixed features. Disclosure: Dr. Zieman has nothing to disclose. Dr. Dardis has nothing to disclose. Dr. Gomes has nothing to disclose. Dr. Scheck has nothing to disclose. Dr. Eschbacher has nothing to disclose. Dr. Ashby has nothing to disclose.
Din-e Shan - One of the best experts on this subject based on the ideXlab platform.
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Hemichorea-hemiballism associated with hyperintense putamen on T1-weighted MR images: an update and a hypothesis.
Acta neurologica Taiwanica, 2004Co-Authors: Din-e ShanAbstract:In 1998 some patients with hyperglycemia-related hemichorea-hemiballism have been reported with a hyperintense putamen on T1-weighted MR images, presumably resulting from petechial hemorrhage. I questioned this explanation from my experience because (1) the areas of hyperintense lesions and their time evolutions did not match with those of the high density lesions on CT, (2) these hyperintense lesions persisted for years, and (3) the hyperintense lesions extended inferiorly to the midbrain. Therefore, a biopsy was performed in one patient and disclosed a fragment of gliotic brain tissue with abundant Gemistocytes, which I proposed was sufficient to explain the shortening of T1 relaxation time. In addition, because two of our patients were associated with cortical infarcts and without hyperglycemia, I have suggested that cerebral ischemia might be a more important cause. In 1999 Fujioka et al reproduced the MR finding in animals 7 days after 15-minute occlusion of the middle cerebral artery. Therefore, both studies have suggested that the MRI finding resulted from a progressive pathological reaction in an incomplete infarction. In 2003 Fujioka et al further reported that the hyperintensity on T1-weighted MR images after mild ischemia may involve a paramagnetic effect resulting from tissue manganese accumulation in reactive astrocytes.
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Delayed Ischemic Hyperintensity of T1-Weighted MRI
Stroke, 2000Co-Authors: Din-e ShanAbstract:To the Editor: Fujioka et al1 reported 4 cases of transient internal carotid artery–middle cerebral artery occlusion; serial MRI revealed hyperintensity on T1-weighted (T1W) imaging in the caudoputamen in all patients and in the cerebral cortex in 2 patients. In the companion article,2 Fujioka et al reproduced the MRI finding in rats by 15-minute middle cerebral artery occlusion but not by 60-minute occlusion. Histological examination revealed that this specific ischemic change on MRI corresponded to selective neuronal death and gliosis with preservation of the macroscopic structure of the brain. I have previously reported3 10 cases with similar MRI finding; these patients presented not only with sudden hemispheric stroke followed by rapid improvement but also with hemichorea-hemiballism. A biopsy from the hyperintense putamen in one of my patients revealed a fragment of gliotic brain tissue with abundant Gemistocytes. It is interesting that in both my studies and those of Fujioka et al similar conclusions were obtained. First, the MRI finding corresponded with an incomplete infarction. This was demonstrated not only by the relative preservation of the macroscopic structure of the brain in both studies but also by the presence of patchy lesions intermixing with relatively normal brain tissue in the biopsy specimen of my patient. Second, Fujioka’s study confirmed my hypothesis that the MRI finding was related more to vascular compromise than to petechial hemorrhage or hyperglycemia, as had been proposed in patients with hemichorea-hemiballism. Third, while Fujioka et al demonstrated the delayed appearance of the ischemic hyperintensity of the T1W MRI, the onset of …
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Hemichorea-hemiballism: an explanation for MR signal changes.
AJNR. American journal of neuroradiology, 1998Co-Authors: Din-e Shan, Chen Chang, Hung-chi Pan, Michael Mu-huo TengAbstract:PURPOSE Some cases of hemichorea-hemiballism (HCHB) are associated with a hyperintense putamen on T1-weighted MR images, the cause of which remains unclear. Our purpose was to determine the cause and significance of these MR signal changes. METHODS We analyzed the clinical and neuroimaging findings in 10 patients with HCHB, focusing on locations of the hyperintense lesions on T1-weighted images, comparing them with those on CT scans, and evaluating their changes after years of follow-up. A biopsy was performed in one patient. RESULTS Seven patients had hyperglycemia and two had cortical infarcts. HCHB recurred in four patients. A hyperintense putamen preceded the occurrence of HCHB in two patients. T1-weighted MR images revealed hyperintense lesions limited to the ventral striatum in six patients. Hyperintense lesions extended to the level of the midbrain in one patient and persisted for as long as 6 years in another patient. T2-weighted MR images revealed slit-shaped cystic lesions in the lateral part of the putamina 2 to 6 years after the onset of symptoms in two patients. A biopsy specimen from the hyperintense putamen in one patient revealed a fragment of gliotic brain tissue with abundant Gemistocytes. Proton MR spectroscopy of the specimen showed an increase in lactic acid, acetate, and lipids, and a decrease in N-acetylaspartate and creatine, suggesting the presence of pronounced energy depletion and neuronal dysfunction. CONCLUSION Gemistocytes are sufficient to explain the shortening of T1 relaxation time. Our investigation suggests that neurons in the ventral striatum and striatonigral pathway may play a critical role in generating ballism.
Jennifer M. Eschbacher - One of the best experts on this subject based on the ideXlab platform.
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Predicting Progressive Gangliogliomas: Early Identification Of Those At Risk In A Sample Of 156 Consecutive Patients Treated At The Barrow Neurological Institute (S22.004)
Neurology, 2014Co-Authors: Glynnis Zieman, Christopher Dardis, Andrea Gomes, Adrienne C. Scheck, Jennifer M. Eschbacher, Lynn S. AshbyAbstract:Objective: Early identification of ganglioglioma patients at risk for malignant progression. Background: Gangliogliomas are biphasic tumors comprised of neoplastic neuronal and glial cells. Lesions occur in children and adults anywhere in the neuraxis, most commonly in the temporal lobe. Low grade gangliogliomas are indolent and considered to be curable with gross total resection. Anaplastic variants are less common. Patient characteristics, along with histopathological and immunohistochemical analyses, correlate with outcome. However, early identification of patients at risk for malignant progression remains a clinical challenge. Methods: A retrospective analysis was performed of 156 patients with gangliogliomas diagnosed between 1983 and 2013. Histopathological and radiographic data were reviewed for 115 adults (18 years or greater) and 41 children. Extent of resection was determined by neuroimaging. Tumor registry provided follow-up and survival data. Pathological criteria included: Neu-N, GFAP, presence of Rosenthal fibers, eosinophilic granular bodies, perivascular lymphocytic inflammation, bi- or multinuclear ganglion cells, fibrillary astrocytes, Gemistocytes, mitotic figures, calcification, cortical dysplasia, and elevated MIB-1/Ki67. Results: Median ages for children and adults were 11 and 29 years, respectively. Tumors were located in the temporal lobe in 26.5% of children, 31.5% of adults. In 108 subjects with survival data, there were 11 anaplastic tumors with MST of only 3.7 years. In the non-anaplastic group, MST has not been reached (12 deaths in 97 subjects). Age in the adult was a poor prognostic variable (p
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predicting progressive gangliogliomas early identification of those at risk in a sample of 156 consecutive patients treated at the barrow neurological institute s22 004
Neurology, 2014Co-Authors: Glynnis Zieman, Christopher Dardis, Andrea Gomes, Adrienne C. Scheck, Jennifer M. Eschbacher, Lynn S. AshbyAbstract:Objective: Early identification of ganglioglioma patients at risk for malignant progression. Background: Gangliogliomas are biphasic tumors comprised of neoplastic neuronal and glial cells. Lesions occur in children and adults anywhere in the neuraxis, most commonly in the temporal lobe. Low grade gangliogliomas are indolent and considered to be curable with gross total resection. Anaplastic variants are less common. Patient characteristics, along with histopathological and immunohistochemical analyses, correlate with outcome. However, early identification of patients at risk for malignant progression remains a clinical challenge. Methods: A retrospective analysis was performed of 156 patients with gangliogliomas diagnosed between 1983 and 2013. Histopathological and radiographic data were reviewed for 115 adults (18 years or greater) and 41 children. Extent of resection was determined by neuroimaging. Tumor registry provided follow-up and survival data. Pathological criteria included: Neu-N, GFAP, presence of Rosenthal fibers, eosinophilic granular bodies, perivascular lymphocytic inflammation, bi- or multinuclear ganglion cells, fibrillary astrocytes, Gemistocytes, mitotic figures, calcification, cortical dysplasia, and elevated MIB-1/Ki67. Results: Median ages for children and adults were 11 and 29 years, respectively. Tumors were located in the temporal lobe in 26.5% of children, 31.5% of adults. In 108 subjects with survival data, there were 11 anaplastic tumors with MST of only 3.7 years. In the non-anaplastic group, MST has not been reached (12 deaths in 97 subjects). Age in the adult was a poor prognostic variable (p<0.0001). Mitotic figures worsened prognosis (p<0.005). Elevated MIB-1 predicted shorter survival (p<0.005), with improved survival when labelling index <2% (p<0.002). Further immunohistochemistry is in progress. Conclusions: Age predicts survival in adults, not children. Tumor location and MR enhancement are not prognostic. Risk of malignant transformation is related to glial features. Continuing immunohistochemical analysis includes MIB-1/Ki-67, CD34, MGMT and IDH1, as well as 1p19q deletion status for oligodendroglial or mixed features. Disclosure: Dr. Zieman has nothing to disclose. Dr. Dardis has nothing to disclose. Dr. Gomes has nothing to disclose. Dr. Scheck has nothing to disclose. Dr. Eschbacher has nothing to disclose. Dr. Ashby has nothing to disclose.