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Neurocirugia (English Edition) 2022Diffuse astrocytoma (WHO grade II) has classically been considered a slow growing tumour, typically affecting young adults, with tendency for late malignant conversion....
Diffuse astrocytoma (WHO grade II) has classically been considered a slow growing tumour, typically affecting young adults, with tendency for late malignant conversion. We describe a case of early atypical malignant transformation of diffuse astrocytoma seventeen months after complete surgical removal, as an intraventricular high-grade glioma (HGG). Retrospective laboratory findings for the presence of IDH 1/2 (isocitrate dehydrogenase) mutations were negative. There is growing evidence that IDH-wildtype (wt) astrocytomas behave more aggressively, therefore identifying IDH-mutation status should be mandatory in order to determine disease prognosis and guide treatment course.
Topics: Astrocytoma; Brain Neoplasms; Genotype; Humans; Isocitrate Dehydrogenase; Retrospective Studies; Young Adult
PubMed: 34998489
DOI: 10.1016/j.neucie.2020.09.001 -
Neurologic Clinics Aug 2018In the 2016 WHO classification of diffuse glioma, the diagnosis of an (anaplastic) oligodendroglioma requires the presence of both an IDH mutation (mt) and 1p/19q... (Review)
Review
In the 2016 WHO classification of diffuse glioma, the diagnosis of an (anaplastic) oligodendroglioma requires the presence of both an IDH mutation (mt) and 1p/19q codeletion, whereas (anaplastic) astrocytoma are divided in IDH wild-type and IDHmt tumors. Standard of care for grade II and III glioma consists of resection. For patients with tumors that require postoperative treatment, radiotherapy and chemotherapy are recommended. Trials in newly diagnosed grade II and III glioma have shown survival benefit of the addition of chemotherapy to radiotherapy compared with initial treatment with radiotherapy alone; both temozolomide and PCV have been shown to improve survival.
Topics: Astrocytoma; Brain Neoplasms; Humans; Oligodendroglioma
PubMed: 30072066
DOI: 10.1016/j.ncl.2018.04.005 -
Acta Neuropathologica Sep 2009Separation of pilocytic astrocytoma from diffuse astrocytomas frequently poses problems mostly related to small sample size. Precise classification and grading are...
Separation of pilocytic astrocytoma from diffuse astrocytomas frequently poses problems mostly related to small sample size. Precise classification and grading are essential due to different therapeutic strategies prompted by diagnoses of pilocytic astrocytoma WHO grade I, diffuse astrocytomas WHO grade II or anaplastic astrocytoma WHO grade III. Recently, genomic aberrations with a high specificity for distinct glioma entities have been described. Pilocytic astrocytomas carry a duplication at chromosome band 7q34 containing a BRAF-KIAA1549 gene fusion in the majority of cases. IDH1 mutations are observed very frequently in adult astrocytomas and IDH2 mutations have been reported in some astrocytomas. We examined a series of 120 astrocytomas including 70 pilocytic astrocytomas WHO grade I and 50 diffuse astrocytomas WHO grade II for both, BRAF-KIAA1549 fusion with a newly developed FISH assay and mutations in IDH1 and IDH2 by direct sequencing. Pilocytic astrocytomas contained the BRAF fusion in 49 cases (70%) but neither IDH1 nor IDH2 mutations. Astrocytomas WHO grade II exhibited IDH1 mutations in 38 cases (76%) but neither IDH2 mutations nor BRAF fusions. Thus, combined molecular analysis of BRAF and IDH1 is a sensitive and highly specific approach to separate pilocytic astrocytoma from diffuse astrocytoma.
Topics: Adolescent; Adult; Aged; Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; Child; Child, Preschool; Diagnosis, Differential; Female; Humans; In Situ Hybridization, Fluorescence; Isocitrate Dehydrogenase; Male; Middle Aged; Mutation; Proto-Oncogene Proteins B-raf; Tissue Array Analysis
PubMed: 19543740
DOI: 10.1007/s00401-009-0550-z -
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 -
Indian Journal of Pathology &... May 2022Low-grade gliomas are the most common primary central nervous system (CNS) neoplasms in the pediatric age group. The majority of these tumors are circumscribed, while... (Review)
Review
Low-grade gliomas are the most common primary central nervous system (CNS) neoplasms in the pediatric age group. The majority of these tumors are circumscribed, while diffuse low-grade gliomas are relatively rare. The pediatric type diffuse low-grade gliomas (pDLGG) have a distinctly different biological behavior, molecular profile, and clinical outcome as compared to their adult counterpart. In the 5 edition of World Health Organization (WHO) CNS classification, pDLGGs are subclassified into four distinct histomolecular entities, namely, (i) diffuse astrocytoma, MYB- or MYBL1-altered, (ii) angiocentric glioma, (iii) polymorphous low-grade neuroepithelial tumor of the young (PLNTY), and (iv) diffuse low-grade glioma, MAPK pathway-altered. Although the molecular profile, to a great extent, aligns with the morphological features, it is not specific. Many of the molecular alterations described in pDLGG have therapeutic implications with the availability of newer targeted therapies. A wide range of testing platforms are available for routine assessment of these molecular alterations in clinical laboratories, though WHO does not recommend any particular method.
Topics: Astrocytoma; Brain Neoplasms; Child; Glioma; Humans; Mutation; World Health Organization
PubMed: 35562133
DOI: 10.4103/ijpm.ijpm_1043_21 -
British Journal of Neurosurgery Oct 2023Primary glioblastoma develops without clinical or histological evidence of a low-grade precursor lesion, whereas secondary glioblastoma develops from a low-grade...
Primary glioblastoma develops 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 -wildtype secondary glioblastoma arising in -mutant diffuse astrocytoma. A 31-year-old female had a surgical history of -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 -1 (p.Arg132His) mutation was found in diffuse astrocytoma but not in glioblastoma based on next generation sequencing. (p.Gln1670Ter) and (p.His193Arg) mutations were found in both lesions. Additionally, the (p.His296Pro) mutation was identified only in glioblastoma. A well-accepted hypothesis is that the mutation initiates in glial progenitor cells and causes secondary glioblastoma harboring the mutation to develop from low grade glioma with mutation. However, this case showed that the other genetic mutations can be initiated before the mutation in glioma oncogenesis. Contrary to the previous hypothesis, this is the first case of -wildtype secondary glioblastoma arising in -mutant diffuse astrocytoma.
Topics: Female; Humans; Adult; Glioblastoma; Brain Neoplasms; Isocitrate Dehydrogenase; Astrocytoma; Glioma; Mutation
PubMed: 33095064
DOI: 10.1080/02688697.2020.1837733 -
No Shinkei Geka. Neurological Surgery Oct 2020The 2016 World Health Organization brain tumor classification update may change the clinical approach toward treatment of diffuse astrocytoma(DA). Thus, more information...
The 2016 World Health Organization brain tumor classification update may change the clinical approach toward treatment of diffuse astrocytoma(DA). Thus, more information about such cases is required. We report a case of DA, which was previously diagnosed as oligoastrocytoma. The tumor showed malignant progression after long-term temozolomide monotherapy. A 78-year-old woman presented with forgetfulness and decreased activity 12 years ago. MRI identified a T2-hyperintense lesion in the right frontal lobe. Histological diagnosis following partial resection was oligoastrocytoma. The residual tumor shrank after 65 courses of maintenance temozolomide monotherapy, which was terminated five years ago. The remaining lesion started enlarging gradually two years ago, showing enhancement on post-contrast T1WI and hyperintensity on arterial spin labeling, indicating malignant progression. The patient underwent maximum resection. The primary and the recurrent tumors were histologically reviewed. The former comprised of oligodendroglial and astrocytic tumor cells positive for mutations and negative for mutations. The Ki67 index was 2.6%. Using the MethylationEPIC array, we generated a copy number profile and confirmed that the 1p/19q status was intact. The patient was ultimately diagnosed with -mutant DA. The recurrent tumor showed marked proliferation of atypical glial cells with microvascular proliferation and the same immunophenotype as the primary tumor, with a Ki67 index of 13.1%. Thus, it was diagnosed as an -mutant anaplastic astrocytoma and was treated with postoperative radiochemotherapy. Currently, multimodal therapy selection may be performed during initial treatment. Thus, an integrated diagnostic approach based on both histological and molecular findings is essential to identify the optimal treatment.
Topics: Aged; Astrocytoma; Brain Neoplasms; Female; Humans; Isocitrate Dehydrogenase; Neoplasm Recurrence, Local; Temozolomide
PubMed: 33071231
DOI: 10.11477/mf.1436204300 -
World Neurosurgery Feb 2022In 2016, the World Health Organization revised its guidelines to retain only gemistocytic astrocytoma (GemA) as a distinct variant of diffuse astrocytoma (DA). In the...
BACKGROUND
In 2016, the World Health Organization revised its guidelines to retain only gemistocytic astrocytoma (GemA) as a distinct variant of diffuse astrocytoma (DA). In the past, grade II GemAs were linked with a worse prognosis than DA. However, it is unclear how consistently the tumor subtype has been diagnosed over time. We used more recent data to compare outcomes between grade II GemA and DA.
METHODS
Patients with grade II DA and GemA were extracted from the Surveillance, Epidemiology, and End Results database between 1973 and 2016. Kaplan-Meier curves estimated survival differences across different eras, with a focus on patients diagnosed between 2000 and 2016, and propensity score matching was used to balance baseline characteristics between DA and GemA cohorts.
RESULTS
Of 2467 patients with grade II astrocytoma diagnosed between 2000 and 2016, 132 (5.35%) had GemA, and 2335 (94.65%) had DA. At baseline, marked demographic and treatment differences were noted between tumor subtypes, including age at diagnosis and female sex. GemA patients did not have worse survival compared with DA patients at baseline (P = 0.349) or after propensity score matching (P = 0.497). Multivariate Cox models found that surgical extent of resection was associated with a survival benefit for DA patients, and both DA and GemA patients >65 years old had dramatically inferior survival.
CONCLUSIONS
Our data suggest that the impact of GemA versus DA histopathology depends more on the decade of queried data rather than patient-specific demographics. Using more recent longitudinal data, we found that grade II GemA and DA tumors did not have significant differences in survival. These data may prove useful for clinicians counseling patients with grade II GemA.
Topics: Aged; Astrocytoma; Brain Neoplasms; Female; Humans; Prognosis; Proportional Hazards Models; World Health Organization
PubMed: 34844008
DOI: 10.1016/j.wneu.2021.11.089 -
PloS One 2023This study compared the dynamic susceptibility contrast (DSC) magnetic resonance imaging parameters and apparent diffusion coefficient (ADC) between pilocytic...
Dynamic susceptibility contrast perfusion-weighted and diffusion-weighted magnetic resonance imaging findings in pilocytic astrocytoma and H3.3 and H3.1 variant diffuse midline glioma, H3K27-altered.
OBJECTIVE
This study compared the dynamic susceptibility contrast (DSC) magnetic resonance imaging parameters and apparent diffusion coefficient (ADC) between pilocytic astrocytoma (PA) and diffuse midline glioma, H3K27-altered (DMG) variants.
METHODS
The normalized relative cerebral blood volume (nrCBV), normalized relative flow (nrCBF), percentile signal recovery (PSR), and normalized mean ADC (nADCmean) of 23 patients with midline PAs (median age, 13 years [range, 1-71 years]; 13 female patients) and 40 patients with DMG (8.5 years [1-35 years]; 19 female patients), including 35 patients with H3.3- and five patients with H3.1-mutant tumors, treated between January 2016 and May 2022 were statistically compared.
RESULTS
DMG had a significantly lower nADCmean (median: 1.48 vs. 1.96; p = 0.00075) and lower PSR (0.97 vs. 1.23, p = 0.13) but higher nrCBV and nrCBF (1.66 vs. 1.17, p = 0.058, respectively, and 1.87 vs. 1.19, p = 0.028, respectively) than PA. The H3.3 variant had a lower nADCmean than the H3.1 variant (1.46 vs. 1.80, p = 0.10).
CONCLUSION
DMG had lower ADC and PSR and higher rCBV and rCBF than PA. The H3.3 variant had a lower ADC than the H3.1 variant. Recognizing the differences and similarities in the DSC parameters and ADC between these tumors may help presurgical diagnosis.
Topics: Humans; Female; Adolescent; Brain Neoplasms; Astrocytoma; Diffusion Magnetic Resonance Imaging; Magnetic Resonance Imaging; Perfusion
PubMed: 37450487
DOI: 10.1371/journal.pone.0288412 -
Journal of Cancer Research and... 2022Malignant transformation (MT) of low-grade astrocytoma (LGA) produces a poor prognosis in benign tumors. Currently, variables linked with MT of LGA have proven...
BACKGROUND
Malignant transformation (MT) of low-grade astrocytoma (LGA) produces a poor prognosis in benign tumors. Currently, variables linked with MT of LGA have proven equivocal. The present study aims to evaluate the risk variables, indicating that LGA gradually differentiates to malignant astrocytoma.
METHODS
Retrospective cohort analysis of LGA patients was performed. Both univariate and multivariate studies were used to discover variables connected to MT using the Cox regression method. As a result, the cumulative incidence of MT for each covariate survival curve was built after the final model.
RESULTS
In the current study, 115 individuals with LGA were included in the analysis, and MT was found in 16.5% of cases. In the case of MT, 68.4% of patients progressed to glioblastoma, whereas 31.6% progressed to anaplastic astrocytoma. Significant factors included supratentorial tumor (hazard ratio (HR) 3.41, 95% CI 1.18-12.10), midline shift > 5 mm (HR 7.15, 95% CI 2.28-34.33), and non-total resection as follows: subtotal resection (HR 5.09, 95% CI 0.07-24.02), partial resection (HR 1.61, 95% CI 1.09-24.11), and biopsy (HR 2.80, 95% CI 1.18-32.52).
CONCLUSION
In individuals with LGA, MT dramatically altered the disease's natural history to a poor prognosis. The present study's analysis of the clinical features of patients indicated supratentorial LGA, a midline shift greater than 5 mm, and the degree of resection as risk factors for MT. The more extensive the resection, the greater the reduction in tumor load and MT. In addition, more molecular study is necessary to elucidate the pathophysiology of MT.
Topics: Humans; Retrospective Studies; Brain Neoplasms; Astrocytoma; Glioblastoma; Cell Transformation, Neoplastic
PubMed: 36412420
DOI: 10.4103/jcrt.JCRT_1469_20