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Acta Neuropathologica Jun 2015Diffusely infiltrating astrocytomas include diffuse astrocytomas WHO grade II and anaplastic astrocytomas WHO grade III and are classified under astrocytic tumours... (Review)
Review
Diffusely infiltrating astrocytomas include diffuse astrocytomas WHO grade II and anaplastic astrocytomas WHO grade III and are classified under astrocytic tumours according to the current WHO Classification. Although the patients generally have longer survival as compared to those with glioblastoma, the timing of inevitable malignant progression ultimately determines the prognosis. Recent advances in molecular genetics have uncovered that histopathologically diagnosed astrocytomas may consist of two genetically different groups of tumours. The majority of diffusely infiltrating astrocytomas regardless of WHO grade have concurrent mutations of IDH1 or IDH2, TP53 and ATRX. Among these astrocytomas, no other genetic markers that may distinguish grade II and grade III tumours have been identified. Those astrocytomas without IDH mutation tend to have a distinct genotype and a poor prognosis comparable to that of glioblastomas. On the other hand, diffuse astrocytomas that arise in children do not harbour IDH/TP53 mutations, but instead display mutations of BRAF or structural alterations involving MYB/MYBL1 or FGFR1. A molecular classification may thus help delineate diffusely infiltrating astrocytomas into distinct pathogenic and prognostic groups, which could aid in determining individualised therapeutic strategies.
Topics: Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; Humans; Neuroimaging
PubMed: 25975377
DOI: 10.1007/s00401-015-1439-7 -
Veterinary Pathology Sep 2022This case series describes the clinical and pathological findings of intracranial neoplasms in cattle, a rare entity. Data and archived tissues from 24 intracranial...
This case series describes the clinical and pathological findings of intracranial neoplasms in cattle, a rare entity. Data and archived tissues from 24 intracranial tumors were reviewed and investigated by immunohistochemistry for S100, glial fibrillary acidic protein, synaptophysin, pancytokeratin, vimentin, neuron-specific enolase, oligodendrocyte transcription factor 2, and isocitrate dehydrogenase 1. Ages of affected cattle ranged from 6 months to 14 years (5.7 ± 3.6 years; mean ± SD). Predominant clinical signs were altered mental state, central vestibular dysfunction, and cerebellar incoordination. Twelve gliomas, all high grade, were the most common tumors observed: oligodendrogliomas (n = 6), astrocytomas (n = 4), and undefined gliomas (n = 2). The oligodendrogliomas were located in the brainstem and extended into the ventricles, whereas all astrocytomas were located in the forebrain. Isocitrate dehydrogenase 1 gene mutation as described in humans was not detected. The 5 meningiomas exhibited microcystic, chordoid, atypical, papillary, and anaplastic subtypes. Metastatic carcinomas (n = 4) were the only secondary tumor type present, and these were located at the level of the medulla with infiltration of cranial nerves and in one case leptomeningeal carcinomatosis. In addition, 2 medulloblastomas and 1 choroid plexus carcinoma were diagnosed. Immunohistochemistry for vimentin and pancytokeratin was particularly useful to distinguish meningiomas and choroid plexus carcinoma (positive for vimentin only) from mestastatic carcinomas (positive for cytokeratin only) as all showed a papillary growth pattern. Overall, the morphological features were comparable with other species and the human and canine classifications could be applied.
Topics: Animals; Astrocytoma; Brain Neoplasms; Carcinoma; Cattle; Cattle Diseases; Choroid Plexus Neoplasms; Glioma; Isocitrate Dehydrogenase; Meningeal Neoplasms; Meningioma; Oligodendroglioma; Retrospective Studies; Vimentin
PubMed: 35638647
DOI: 10.1177/03009858221100433 -
Neurobiology of Disease Jan 2016Glioblastoma (GBM, Grade IV astrocytoma) is the most common and most aggressive of the primary malignant brain tumors in adults. Hypoxia is a distinct feature in GBM and... (Review)
Review
Glioblastoma (GBM, Grade IV astrocytoma) is the most common and most aggressive of the primary malignant brain tumors in adults. Hypoxia is a distinct feature in GBM and plays a significant role in tumor progression, resistance to treatment and poor outcomes. This review considers the effects of hypoxia on astrocytic tumors and the mechanisms that contribute to tumor progression and therapeutic resistance, with a focus on the vascular changes, chemotaxic signaling pathways and metabolic alterations involved.
Topics: Animals; Astrocytoma; Brain Neoplasms; Humans; Hypoxia
PubMed: 26094595
DOI: 10.1016/j.nbd.2015.06.007 -
The Canadian Journal of Neurological... Sep 2023
Topics: Humans; Astrocytoma; Brain Neoplasms
PubMed: 35860980
DOI: 10.1017/cjn.2022.274 -
The Journal of Maternal-fetal &... Dec 2022To describe the ultrasonographic appearance of congenital anaplastic astrocytoma, so as to provide diagnostic clues for it. An updated review of the literature was also... (Review)
Review
OBJECTIVES
To describe the ultrasonographic appearance of congenital anaplastic astrocytoma, so as to provide diagnostic clues for it. An updated review of the literature was also carried out.
RESULTS
There was a case of fetal anaplastic astrocytoma detected by ultrasound at 37 + 1 weeks of gestation. It showed that a hypoechoic mass was located in the left hemisphere with a relatively clear margin and subtle color flows. Prenatal magnetic resonance imaging (MRI) which was taken subsequently confirmed the result of ultrasound. Intratumoral hemorrhage was observed in later follow-up and further confirmed by histological examination. The fetus was delivered vaginally at 39 + 6 weeks. The infant died 2 h after delivery due to respiration failure. The histological examination confirmed an anaplastic astrocytoma.
CONCLUSIONS
Congenital anaplastic astrocytoma commonly detected by ultrasound has a relatively better perinatal prognosis, especially compared with glioblastoma. Prenatal ultrasonography diagnosis accurately is of critical importance. The anaplastic astrocytoma should be considered in cases in which fetal images reveal a heterogeneous echogenic mass in the brain, especially in the presence of intratumoral hemorrhage, subtle color flow, and relatively clear margin.
Topics: Female; Humans; Pregnancy; Glioblastoma; Brain Neoplasms; Astrocytoma; Prenatal Diagnosis; Fetus; Ultrasonography, Prenatal; Magnetic Resonance Imaging; Hemorrhage
PubMed: 33969782
DOI: 10.1080/14767058.2021.1918668 -
Brain Pathology (Zurich, Switzerland) Jan 2021Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytoma predominantly affecting children and young adults. We performed comprehensive genomic characterization on a...
Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytoma predominantly affecting children and young adults. We performed comprehensive genomic characterization on a cohort of 67 patients with histologically defined PXA (n = 53, 79%) or anaplastic PXA (A-PXA, n = 14, 21%), including copy number analysis (ThermoFisher Oncoscan, n = 67), methylation profiling (Illumina EPIC array, n = 43) and targeted next generation sequencing (n = 32). The most frequent alterations were CDKN2A/B deletion (n = 63; 94%) and BRAF p.V600E (n = 51, 76.1%). In 7 BRAF p.V600 wild-type cases, alternative driver alterations were identified involving BRAF, RAF1 and NF1. Downstream phosphorylation of ERK kinase was uniformly present. Additional pathogenic alterations were rare, with TERT, ATRX and TP53 mutations identified in a small number of tumors, predominantly A-PXA. Methylation-based classification of 46 cases utilizing a comprehensive reference tumor allowed assignment to the PXA methylation class in 40 cases. A minority grouped with the methylation classes of ganglioglioma or pilocytic astrocytoma (n = 2), anaplastic pilocytic astrocytoma (n = 2) or control tissues (n = 2). In 9 cases, tissue was available from matched primary and recurrent tumors, including 8 with anaplastic transformation. At recurrence, two tumors acquired TERT promoter mutations and the majority demonstrated additional non-recurrent copy number alterations. Methylation class was preserved at recurrence. For 62 patients (92.5%), clinical follow-up data were available (median follow-up, 5.4 years). Overall survival was significantly different between PXA and A-PXA (5-year OS 80.8% vs. 47.6%; P = 0.0009) but not progression-free survival (5-year PFS 59.9% vs. 39.8%; P = 0.05). WHO grade remained a strong predictor of overall survival when limited to 38 cases defined as PXA by methylation-based classification. Our data confirm the importance of WHO grading in histologically and epigenetically defined PXA. Methylation-based classification may be helpful in cases with ambiguous morphology, but is largely confirmatory in PXA with well-defined morphology.
Topics: Adolescent; Adult; Aged; Astrocytoma; Brain Neoplasms; Child; Child, Preschool; Cohort Studies; DNA Methylation; Female; Humans; Male; Middle Aged; Neoplasm Grading; Young Adult
PubMed: 32619305
DOI: 10.1111/bpa.12874 -
Journal of Neuropathology and... Apr 2021Numerous recent studies have demonstrated that the vast majority of IDH-wildtype astrocytomas with WHO grade II/III histology have clinical outcomes equivalent to...
Numerous recent studies have demonstrated that the vast majority of IDH-wildtype astrocytomas with WHO grade II/III histology have clinical outcomes equivalent to IDH-wildtype glioblastomas. This has called into question the existence of an IDH-wildtype lower-grade astrocytoma (LGA) category, and the cIMPACT-NOW study group has suggested 3 molecular features which, if present, warrant upgrading IDH-wildtype LGA to glioblastoma: EGFR amplification, 7+/10-, and TERT promoter mutation. Herein, we evaluate the clinical, histologic, and molecular features of IDH-wildtype low-grade astrocytomas, defined here as infiltrative adult astrocytoma lacking histologic features of glioblastoma (microvascular proliferation and/or necrosis), IDH1/2 mutation, and all 3 of the cIMPACT-NOW update 3 factors. Compared with their counterparts with cIMPACT-NOW features of glioblastoma (LGA-C+; n = 108), IDH-wildtype LGAs lacking these features (LGA-C0; n = 36) occur in significantly younger patients, are more frequently WHO grade II, have less total copy number variation distributed across the entire genome, less frequent homozygous deletion of CDKN2A, less frequent PTEN and PIK3CA alterations, and more frequent NF1 alterations. These results suggest that although rare, a "true" IDH-wildtype LGA category does exist, and has distinct clinical and molecular features consistent with relatively beneficial clinical outcomes in these patients.
Topics: Astrocytoma; DNA Copy Number Variations; Glioblastoma; Homozygote; Humans; Necrosis; Sequence Deletion; Vascular Diseases
PubMed: 33829259
DOI: 10.1093/jnen/nlab023 -
Zhurnal Voprosy Neirokhirurgii Imeni N.... 2023Anaplastic astrocytoma (AA) is a rare intracerebral tumor. Therefore, the number of studies devoted to risk factors of overall and disease-free survival is small. This...
UNLABELLED
Anaplastic astrocytoma (AA) is a rare intracerebral tumor. Therefore, the number of studies devoted to risk factors of overall and disease-free survival is small. This single-center clinical study is devoted to various factors influencing prognosis of treatment in this group of patients.
MATERIAL AND METHODS
A retrospective study included 389 patients diagnosed with grade 3 astrocytoma. We analyzed dependence of overall and disease-free survival from the following factors: gender, age of onset of disease, tumor extent, surgery, neurological disorders before and after surgery (NANO grading system), Ki67 index, postoperative radio- and chemotherapy (number courses, treatment regimens).
RESULTS
Significant risk factors for overall and disease-free survival were spread and volume of tumor, postoperative neurological aggravation, Ki67 index, IDH mutation, radio- and chemotherapy. Age, frontal lobe tumor and disease manifestation variant were significant only for overall, but not for disease-free survival.
CONCLUSION
This study was based on material of one of the largest clinical series of patients with AA operated on in one center in «molecular» era. Our results are consistent with previous data. Analysis of tumor biology and risk factors for IDH-negative AA without molecular signs of glioblastoma may be perspective.
Topics: Humans; Disease-Free Survival; Ki-67 Antigen; Retrospective Studies; Astrocytoma; Prognosis; World Health Organization
PubMed: 37650276
DOI: 10.17116/neiro20238704146 -
Clinical Neurology and Neurosurgery Aug 2016Anaplastic pilocytic astrocytoma (APA) is an exceptionally rare type of high-grade glioma in adults. Establishing histopathological diagnosis is challenging and its... (Review)
Review
INTRODUCTION
Anaplastic pilocytic astrocytoma (APA) is an exceptionally rare type of high-grade glioma in adults. Establishing histopathological diagnosis is challenging and its clinical and radiological appearance insidious. By this case series and first literature review we investigated the various clinical, neuroradiological, and histopathological features of APA in adults.
METHODS
An in hospital screening of the database from the Institute of Pathology was conducted to identify cases of APA. Further, we performed a literature review in PubMed using the keywords "anaplastic/malignant/atypical AND pilocytic astrocytoma" and "anaplastic astrocytoma/glioblastoma AND Rosenthal fibers" and summarized the current knowledge about APA in adults.
RESULTS
Over the last decade we were able to identify 3 adult patients with APA in our hospital. According to the pertinent literature, the prognosis of APA in adults (documented survival of up to 10 years) appears to be better than in other high-grade gliomas. Few cases were associated with neurofibromatosis type 1, which seems to predispose for development of APA. Although molecular genetics is still of limited value for differentiation of APA from other high-grade glioma, advanced neuroimaging techniques such as magnetic resonance perfusion imaging and spectroscopy allow improved differential work-up. In particular, APA in adults has the ability to mimic various neurological diseases such as tumefactive demyelinating lesions, low-, or high-grade gliomas.
CONCLUSIONS
Although currently not explicitly recognized as a distinct clinico-pathologic entity it seems that adult APA behaves differently from conventional high-grade glioma and should be included in differential diagnostics to enable adequate patient care. However, further studies are needed to better understand this extremely rare disease.
Topics: Adult; Astrocytoma; Brain Neoplasms; Female; Humans; Male; Middle Aged
PubMed: 27341279
DOI: 10.1016/j.clineuro.2016.06.005 -
Acta Neuropathologica Jun 2015Pilocytic astrocytomas (PAs) were recognized as a discrete clinical entity over 70 years ago. They are relatively benign (WHO grade I) and have, as a group, a 10-year... (Review)
Review
Pilocytic astrocytomas (PAs) were recognized as a discrete clinical entity over 70 years ago. They are relatively benign (WHO grade I) and have, as a group, a 10-year survival of over 90%. Many require merely surgical removal and only very infrequently do they progress to more malignant gliomas. While most show classical morphology, they may present a spectrum of morphological patterns, and there are difficult cases that show similarities to other gliomas, some of which are malignant and require aggressive treatment. Until recently, almost nothing was known about the molecular mechanisms involved in their development. The use of high-throughput sequencing techniques interrogating the whole genome has shown that single abnormalities of the mitogen-activating protein kinase (MAPK) pathway are exclusively found in almost all cases, indicating that PA represents a one-pathway disease. The most common mechanism is a tandem duplication of a ≈2 Mb-fragment of #7q, giving rise to a fusion between two genes, resulting in a transforming fusion protein, consisting of the N-terminus of KIAA1549 and the kinase domain of BRAF. Additional infrequent fusion partners have been identified, along with other abnormalities of the MAP-K pathway, affecting tyrosine kinase growth factor receptors at the cell surface (e.g., FGFR1) as well as BRAF V600E, KRAS, and NF1 mutations among others. However, while the KIAA1549-BRAF fusion occurs in all areas, the incidence of the various other mutations identified differs in PAs that develop in different regions of the brain. Unfortunately, from a diagnostic standpoint, almost all mutations found have been reported in other brain tumor types, although some retain considerable utility. These molecular abnormalities will be reviewed, and the difficulties in their potential use in supporting a diagnosis of PA, when the histopathological findings are equivocal or in the choice of individualized therapy, will be discussed.
Topics: Astrocytoma; Central Nervous System Neoplasms; Genetic Predisposition to Disease; Humans; Models, Molecular; Molecular Biology; Neuroimaging
PubMed: 25792358
DOI: 10.1007/s00401-015-1410-7