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Folia Neuropathologica 2016Pilocytic astrocytomas (PAs) are the most frequent primary astroglial tumours affecting children and adolescents. They occur sporadically or in association with a... (Review)
Review
Pilocytic astrocytomas (PAs) are the most frequent primary astroglial tumours affecting children and adolescents. They occur sporadically or in association with a genetically determined syndrome - neurofibromatosis type 1. Classic PA usually manifests as a well-circumscribed, often cystic, slowly growing tumour, which corresponds to WHO grade I. The majority of pilocytic tumours arise along the neuraxis, predominantly in the cerebellum. They are associated with favourable long-term outcome or spontaneous regression, even after incomplete resection. However, the behaviour and prognosis might also be related to tumour histology and location. Pilomyxoid astrocytoma (PMA) represents a variant of classical PA with more invasive growth and increased risk of recurrences and dissemination. Typically, PAs exhibit distinct histology with biphasic architecture of loose, microcystic and compact, fibrillary areas. However, some tumours arise in an uncommon location and display heterogeneous histopathological appearance. The morphological pattern of PA can mimic some other glial neoplasms, including oligodendroglioma, pleomorphic xanthoastrocytoma, ependymoma or diffuse astrocytoma. Not infrequently, the advanced degenerative changes, including vascular fibrosis, and recent and old haemorrhages, may mimic vascular pathology. Sometimes, the neoplastic piloid tissue can resemble reactive gliosis, related to long-standing non neoplastic lesions. Not infrequently, PA exhibits histological features typical for anaplasia, including necrosis, mitoses and glomeruloid vascular proliferation that can suggest a diffuse high-grade glioma. However, even those PAs that lack distinct histological features of anaplasia can behave unpredictably, in a more aggressive manner, with leptomeningeal spreading. Genetic alterations resulting in aberrant signalling of the mitogen-activated protein kinase (MAPK) pathway have been considered to underlie the development of PAs. The most commonly identified KIAA1549-BRAF fusion is important for appropriate tumour molecular diagnosis. In this paper we summarize the clinicopathological presentation of PAs, with emphasis on their heterogeneous morphology, based on our own experience in the field of surgical neuropathology and the literature data. Diagnosis of pilocytic tumours requires careful analysis of clinical, histopathological and molecular features to avoid misinterpretation of these benign neoplastic lesions.
Topics: Animals; Astrocytes; Astrocytoma; Brain Neoplasms; Glioma; Humans; Mitogen-Activated Protein Kinases; Neoplasm Recurrence, Local
PubMed: 27764513
DOI: 10.5114/fn.2016.62530 -
European Review For Medical and... 2015Glioblastoma (GBM) is a very lethal form of human brain cancer, which is characterized by rapid diffuse, infiltrative growth and high level of cellular heterogeneity.... (Review)
Review
Glioblastoma (GBM) is a very lethal form of human brain cancer, which is characterized by rapid diffuse, infiltrative growth and high level of cellular heterogeneity. Such cancer patients usually survive for one year under treatment. Recently, the role of small non-coding RNA known as microRNAs (miRNA), have been suggested to be involved in the pathogenesis of glioblastoma, as miRNAs play a critical role in the tumor-forming processes. The change in expression levels of several miRNAs has been found in GBM patients within last 10 years. It is evident now that impairment of miRNA regulation is one of the key mechanisms in GBM pathogenesis. The miRNA deregulation is involved in many processes, such as cell proliferation, cell cycle regulation, apoptosis, invasion, glioma stem cell behavior, and angiogenesis. GBM is also known as Grade IV astrocytoma, a rare disease with an incidence of 2-3 cases per 100,000 people in Europe and North America, and 50% with GBM die within 1 year, while 90% within 3 years. The treatments of GBM involve chemotherapy, radiation and surgery. The median survival with standard radiation and chemotherapy with Temozolomide is 1 year and 3 months, and median survival without treatment is four and a half months. In this article, symptoms of GBM, treatments, the role of miRNAs, gene expressions, types of miRNAs, neoplasms and glioblastomas, the miRNA biogenesis pathways, deregulation of miRNAs, and care of GBM have been described.
Topics: Brain Neoplasms; Europe; Female; Glioblastoma; Humans; MicroRNAs; Middle Aged; North America; Survival Analysis
PubMed: 26004603
DOI: No ID Found -
Radiation Oncology (London, England) May 2022We sought to clarify the optimal follow-up, therapeutic strategy, especially the role of reirradiation, and the diagnostic impact of isocitrate dehydrogenase (IDH) 1 and...
BACKGROUND
We sought to clarify the optimal follow-up, therapeutic strategy, especially the role of reirradiation, and the diagnostic impact of isocitrate dehydrogenase (IDH) 1 and 2 mutation status in patients with radiation-induced glioma (RIG).
METHODS
We retrospectively reviewed the clinical characteristics and treatment outcomes of 11 patients with high-grade glioma who satisfied Cahan's criteria for RIG in our database during 2001-2021. IDH 1/2 mutations were analyzed by Sanger sequencing and/or pyrosequencing.
RESULTS
The RIGs included glioblastoma with IDH 1/2 wild-type (n = 7), glioblastoma not otherwise specified (n = 2), anaplastic astrocytoma with IDH1/2 wild-type (n = 1), and anaplastic astrocytoma not otherwise specified (n = 1). The median period from primary disease and RIG diagnosis was 17 years (range: 9-30 years). All patients underwent tumor removal or biopsy, 5 patients postoperatively received reirradiation combined with chemotherapy, and 6 patients were treated with chemotherapy alone. The median progression-free and survival times were 11.3 and 28.3 months. The median progression-free survival time of patients treated with reirradiation and chemotherapy (n = 5) tended to be longer than that of patients that received chemotherapy alone (n = 6) (17.0 vs 8.1 months). However, the median survival time was similar (29.6 vs 27.4 months). Local recurrence was observed in 5 patients treated with chemotherapy alone, whereas in 2 patients among 4 patients treated with reirradiation and chemotherapy. None of the patients developed radiation necrosis. In one case, the primary tumor was diffuse astrocytoma with IDH2 mutant, and the secondary tumor was glioblastoma with IDH 1/2 wild-type. Based on the difference of IDH2 mutation status, the secondary tumor with IDH 1/2 wild-type was diagnosed as a de novo tumor that was related to the previous radiation therapy.
CONCLUSIONS
RIG can occur beyond 20 years after successfully treating the primary disease using radiotherapy; thus, cancer survivors should be informed of the long-term risk of developing RIG and the need for timely neuroimaging evaluation. Reirradiation combined with chemotherapy appears to be feasible and has favorable outcomes. Determining the IDH1/2 mutational status is useful to establish RIG diagnosis when the primary tumor is glioma.
Topics: Astrocytoma; Brain Neoplasms; Glioblastoma; Glioma; Humans; Isocitrate Dehydrogenase; Re-Irradiation; Retrospective Studies
PubMed: 35505351
DOI: 10.1186/s13014-022-02054-x -
Brain Tumor Pathology Apr 2019Many breakthroughs have been made in the past decade regarding our knowledge of the biological basis of the diffuse gliomas, the most common primary central nervous... (Review)
Review
Many breakthroughs have been made in the past decade regarding our knowledge of the biological basis of the diffuse gliomas, the most common primary central nervous system (CNS) tumors. These tumors as a group are aggressive, associated with high mortality, and have a predilection for adults. However, a subset of CNS glial and glioneuronal tumors are characterized by a more circumscribed pattern of growth and occur more commonly in children and young adults. They tend to be indolent, but our understanding of anaplastic changes in these tumors continues to improve as diagnostic classifications evolve in the era of molecular pathology and more integrated and easily accessible clinical databases. The presence of anaplasia in pleomorphic xanthoastrocytomas and gangliogliomas is assigned a WHO grade III under the current classification, while the significance of anaplasia in pilocytic astrocytomas remains controversial. Recent data highlight the association of the latter with aggressive clinical behavior, as well as the presence of molecular genetic features of both pilocytic and diffuse gliomas, with the recognition that the precise terminology remains to be defined. We review the current concepts and advances regarding histopathology and molecular understanding of pilocytic astrocytomas, pleomorphic xanthoastrocytomas, and gangliogliomas, with a focus on their anaplastic counterparts.
Topics: Anaplasia; Astrocytoma; Brain Neoplasms; Carcinoma; Central Nervous System Neoplasms; Ganglioglioma; Glioma; Humans; Neuroglia; Proto-Oncogene Proteins B-raf
PubMed: 30859342
DOI: 10.1007/s10014-019-00336-z -
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 -
Open Veterinary Journal Apr 2019An increased rate of diffuse gliomas, including glioblastoma, has been noted in livestock farmers in Western countries. Some researchers have suggested that a zoonotic... (Review)
Review
Baseballs, tennis balls, livestock farm manure, the IDH1 mutation, endothelial cell proliferation and hypoxic pseudopalisading (granulomatous) necrosis: subspecies and the epidemiology, cellular metabolism and histology of diffuse gliomas, including glioblastoma.
An increased rate of diffuse gliomas, including glioblastoma, has been noted in livestock farmers in Western countries. Some researchers have suggested that a zoonotic virus or bacteria present in the livestock animal's feces or manure may be a possible etiologic factor. subspecies (MAP), the cause of a chronic enteropathy in domestic livestock and a probable zoonosis, is heavily excreted in an infected animal's feces or manure, contaminating soil and ground on the animal's farm. Once excreted in an animal's feces, MAP lasts indefinitely in a dormant but viable form, and easily spreads outside farms to the surrounding environment. MAP's presence throughout the soil in countries where MAP infection of domestic livestock is extensive and long-standing may explain the increased rates of glioblastoma in tennis and baseball players who handle balls coated with MAP-contaminated dirt. MAP infection is consistent with glioblastoma's two defining histopathologic characteristics: endothelial cell proliferation and pseudopalisading necrosis. MAP is a non-tuberculous or atypical mycobacterium, which can cause hypoxic necrotizing granulomas, granulomas that resemble areas of pseudopalisading necrosis. There are known bacterial causes of endothelial cell proliferation. Almost unique amongst intracellular bacteria, MAP's variant isocitrate dehydrogenase 1 (IDH1) enzyme, a type 2-oxoglutarate ferredoxin oxidoreductase, can use a host cell's cytosolic α-ketoglutarate in its own Krebs or tricarboxylic acid cycle. MAP's ability to use a host cell's α-ketoglutarate may explain the survival advantage of the cytosolic IDH1 enzyme mutation for patients with diffuse gliomas including glioblastoma, astrocytoma, and oligdendroglioma, a mutation that results in a reduced supply of cytosolic α-ketoglutarate. MAP may therefore be one possible infectious cause of glioblastoma and the other histologic categories of diffuse glioma.
Topics: Animals; Glioblastoma; Glioma; Humans; Mycobacterium avium subsp. paratuberculosis; Paratuberculosis
PubMed: 31086759
DOI: 10.4314/ovj.v9i1.2 -
Neurologia Medico-chirurgica 2013World Health Organization grade II gliomas (GIIGs) include diffuse astrocytoma, oligodendroglioma, and oligoastrocytoma. GIIG is a malignant brain tumor for which the... (Comparative Study)
Comparative Study Review
World Health Organization grade II gliomas (GIIGs) include diffuse astrocytoma, oligodendroglioma, and oligoastrocytoma. GIIG is a malignant brain tumor for which the treatment outcome can still be improved. Review of previous clinical trials found the following: (1) GIIG increased in size by 3-5 mm per year when observed or treated with surgery alone; (2) after pathological diagnosis, the survival rate was increased by early aggressive tumor removal at an earlier stage compared to observation alone; (3) although the prognosis after total tumor removal was significantly better than that after partial tumor removal, half of the patients relapsed within 5 years; (4) comparing postoperative early radiotherapy (RT) and non-early RT after relapse, early RT prolonged progression-free survival (PFS) but did not affect overall survival (OS); (5) local RT of 45 to 64.8 Gy did not impact PFS or OS; (6) in patients with residual tumors, RT combined with chemotherapy (procarbazine plus lomustine plus vincristine) prolonged PFS compared with RT alone but did not affect OS; and (7) poor prognostic factors included astrocytoma, non-total tumor removal, age ≥40 years, largest tumor diameter ≥4-6 cm, tumor crossing the midline, and neurological deficit. To improve treatment outcomes, surgery with functional brain mapping or intraoperative magnetic resonance imaging or chemoradiotherapy with temozolomide is important. In this review, current knowledge regarding GIIG is described and treatment strategies are explored.
Topics: Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Chemoradiotherapy, Adjuvant; Combined Modality Therapy; Cranial Irradiation; Craniotomy; Early Medical Intervention; Glioma; Humans; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm, Residual; Oligodendroglioma; Randomized Controlled Trials as Topic; Survival Rate
PubMed: 23883553
DOI: 10.2176/nmc.53.429 -
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 -
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 -
Diagnostic and Interventional Radiology... Nov 2021The reliability and reproducibility of T2-weighted imaging/ fluid-attenuated inversion recovery (T2/FLAIR) mismatch were investigated in the diagnosis of isocitrate...
PURPOSE
The reliability and reproducibility of T2-weighted imaging/ fluid-attenuated inversion recovery (T2/FLAIR) mismatch were investigated in the diagnosis of isocitrate dehydrogenase (IDH) mutant astrocytoma between WHO grade II and III diffuse hemispheric gliomas.
METHODS
WHO grade II and grade III diffuse hemispheric gliomas (n=133) treated in our institute were included in the study. Pathological findings and molecular markers of the cases were reviewed with the criteria of WHO 2016. The finding of mismatch between T2-weighted and FLAIR images in preoperative magnetic resonance imaging (MRI) of the cases was evaluated by two different radiologists. The readers reviewed MRIs independently, blinded to the histopathologic diagnosis or molecular subset of tumors. The cases were classified as IDH-mutant astrocytoma, oligodendroglioma and IDH-wildtype (IDH-wt) astrocytoma according to molecular and genetic features.
RESULTS
T2/FLAIR mismatch positivity was observed in 46 patients (34.6%). T2/FLAIR mismatch positivity was observed in 42 of 75 IDH-mutant astrocytomas (56%) and 4 of 43 oligodendrogliomas (9.30%), while it was not seen among IDH-wt astrocytomas (0/15, 0%). The T2/FLAIR mismatch ratio was significantly different between IDH-mutant astrocytomas (WHO grade II and grade III) and oligodendrogliomas (chi-square, p <0.05). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of T2/FLAIR mismatch in predicting IDH-mutant astrocytomas were 58.7%, 90.7%, 91.7%, 61.4%, and 70.3% respectively. Radiologist 1 diagnosed T2/FLAIR mismatch in 48 of 133 cases (36.1%) and Radiologist 2 in 66 of 133 cases (49.6%). The interrater agreement for the T2/FLAIR mismatch sign was 0.61 (p <0.05), 95% CI (0.55, 0.67).
CONCLUSION
T2/FLAIR mismatch appears to be an important MRI finding in distinguishing IDH-mutant astrocytomas from other diffuse hemispheric gliomas. However, it should be kept in mind that T2/FLAIR mismatch sign can be seen in a minority of oligodendrogliomas besides IDH-mutant astrocytomas.
Topics: Astrocytoma; Brain Neoplasms; Humans; Isocitrate Dehydrogenase; Magnetic Resonance Imaging; Mutation; Reproducibility of Results; Retrospective Studies
PubMed: 34792037
DOI: 10.5152/dir.2021.20624