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Archives of Pathology & Laboratory... Mar 2007Glioblastoma (GBM), the most common primary intracranial malignancy, is a morphologically diverse neoplasm with dismal prognosis despite multimodality therapy. Only 3... (Review)
Review
CONTEXT
Glioblastoma (GBM), the most common primary intracranial malignancy, is a morphologically diverse neoplasm with dismal prognosis despite multimodality therapy. Only 3 distinct morphologic variants of GBM are currently recognized by the current World Health Organization classification scheme, including GBM, giant cell GBM, and gliosarcoma. Additional variants, some of which have significant morphologic overlap with tumors that have more favorable prognosis and treatment response rates, particularly anaplastic oligodendroglioma, have been described since its publication in 2000 and may be included in the next classification.
OBJECTIVE
To summarize the morphologic and molecular genetic diversity of both well-established and novel GBM variants and outline our approach to these heterogeneous neoplasms and their distinction from other diffuse, high-grade gliomas.
DATA SOURCES
Published literature and our own experience in an active academic diagnostic surgical neuropathology practice were reviewed.
CONCLUSIONS
Precise subclassification of GBM is required for accurate prognostication and appropriate treatment planning.
Topics: Astrocytoma; Brain Neoplasms; Glioblastoma; Gliosarcoma; Humans; Oligodendroglioma
PubMed: 17516742
DOI: 10.5858/2007-131-397-G -
Acta Neuropathologica Feb 2022Oligodendrogliomas are defined at the molecular level by the presence of an IDH mutation and codeletion of chromosomal arms 1p and 19q. In the past, case reports and...
Oligodendrogliomas are defined at the molecular level by the presence of an IDH mutation and codeletion of chromosomal arms 1p and 19q. In the past, case reports and small studies described gliomas with sarcomatous features arising from oligodendrogliomas, so called oligosarcomas. Here, we report a series of 24 IDH-mutant oligosarcomas from 23 patients forming a distinct methylation class. The tumors were recurrences from prior oligodendrogliomas or developed de novo. Precursor tumors of 12 oligosarcomas were histologically and molecularly indistinguishable from conventional oligodendrogliomas. Oligosarcoma tumor cells were embedded in a dense network of reticulin fibers, frequently showing p53 accumulation, positivity for SMA and CALD1, loss of OLIG2 and gain of H3K27 trimethylation (H3K27me3) as compared to primary lesions. In 5 oligosarcomas no 1p/19q codeletion was detectable, although it was present in the primary lesions. Copy number neutral LOH was determined as underlying mechanism. Oligosarcomas harbored an increased chromosomal copy number variation load with frequent CDKN2A/B deletions. Proteomic profiling demonstrated oligosarcomas to be highly distinct from conventional CNS WHO grade 3 oligodendrogliomas with consistent evidence for a smooth muscle differentiation. Expression of several tumor suppressors was reduced with NF1 being lost frequently. In contrast, oncogenic YAP1 was aberrantly overexpressed in oligosarcomas. Panel sequencing revealed mutations in NF1 and TP53 along with IDH1/2 and TERT promoter mutations. Survival of patients was significantly poorer for oligosarcomas as first recurrence than for grade 3 oligodendrogliomas as first recurrence. These results establish oligosarcomas as a distinct group of IDH-mutant gliomas differing from conventional oligodendrogliomas on the histologic, epigenetic, proteomic, molecular and clinical level. The diagnosis can be based on the combined presence of (a) sarcomatous histology, (b) IDH-mutation and (c) TERT promoter mutation and/or 1p/19q codeletion, or, in unresolved cases, on its characteristic DNA methylation profile.
Topics: Adult; Aged; Brain Neoplasms; Female; Humans; Isocitrate Dehydrogenase; Male; Middle Aged; Mutation; Oligodendroglioma; Sarcoma
PubMed: 34967922
DOI: 10.1007/s00401-021-02395-z -
Arquivos de Neuro-psiquiatria Feb 2020Central nervous system (CNS) gliosarcoma (GSM) is a rare primary neoplasm characterized by the presence of glial and sarcomatous components. (Review)
Review
BACKGROUND
Central nervous system (CNS) gliosarcoma (GSM) is a rare primary neoplasm characterized by the presence of glial and sarcomatous components.
OBJECTIVE
In this report, we describe the clinical and neuroimaging aspects of three cases of GSM and correlate these aspects with pathological findings. We also provide a brief review of relevant literature.
METHODS
Three patients were evaluated with magnetic resonance imaging (MRI), and biopsies confirmed the diagnosis of primary GSM, without previous radiotherapy.
RESULTS
The analysis of conventional sequences (T1, T1 after contrast injection, T2, Fluid attenuation inversion recovery, SWI and DWI/ADC map) and advanced (proton 1H MR spectroscopy and perfusion) revealed an irregular, necrotic aspect of the lesion, peritumoral edema/infiltration and isointensity of the solid component on a T2-weighted image. These features were associated with irregular and peripheral contrast enhancement, lipid and lactate peaks, increased choline and creatine levels in proton spectroscopy, increased relative cerebral blood volume (rCBV) in perfusion, multifocality and drop metastasis in one of the cases.
CONCLUSION
These findings are discussed in relation to the general characteristics of GSM reported in the literature.
Topics: Brain Neoplasms; Gliosarcoma; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy
PubMed: 32022137
DOI: 10.1590/0004-282X20190158 -
Cureus Jul 2022Gliosarcoma is a rare subtype of glioblastoma, isocitrate dehydrogenase (IDH) wildtype. This biphasic tumor has two components. The first one is glial and usually...
Gliosarcoma is a rare subtype of glioblastoma, isocitrate dehydrogenase (IDH) wildtype. This biphasic tumor has two components. The first one is glial and usually represented by glioblastoma. The second is a sarcomatous component usually represented by nonspecific spindle cell sarcoma. Rarely, different glial tumors could represent the non-sarcomatous component, including oligodendroglioma and ependymoma. There were only two reported cases in the literature with glioneuronal components (both were anaplastic ganglioglioma) as the non-sarcomatous component. This work reports a gliosarcoma in the right frontal lobe of a 13-year-old female with a glioneuronal tumor representing the non-sarcomatous component and a rhabdomyosarcoma representing the sarcomatous component. The child lived for only six months after the resection of the tumor. The short survival attests to the dismal prognosis of gliosarcoma regardless of the nature of the non-sarcomatous component.
PubMed: 35959193
DOI: 10.7759/cureus.26695 -
Journal of Neurosurgery. Case Lessons May 2023Gliosarcoma is a rare and highly malignant cancer of the central nervous system with the ability to metastasize. Secondary gliosarcoma, or the evolution of a spindle...
BACKGROUND
Gliosarcoma is a rare and highly malignant cancer of the central nervous system with the ability to metastasize. Secondary gliosarcoma, or the evolution of a spindle cell-predominant tumor after the diagnosis of a World Health Organization grade IV glioblastoma, has also been shown to metastasize. There is little information on metastatic secondary gliosarcoma.
OBSERVATIONS
The authors present a series of 7 patients with previously diagnosed glioblastoma presenting with recurrent tumor and associated metastases with repeat tissue diagnosis consistent with gliosarcoma. The authors describe the clinical, imaging, and pathological characteristics in addition to carrying out a systematic review on metastases in secondary gliosarcoma.
LESSONS
The present institutional series and the systematic review of the literature show that metastatic secondary gliosarcoma is a highly aggressive disease with a poor prognosis.
PubMed: 37218733
DOI: 10.3171/CASE232 -
Scientific Reports Sep 2021Gliosarcoma is an aggressive brain tumor with histologic features of glioblastoma (GBM) and soft tissue sarcoma. Despite its poor prognosis, its rarity has precluded...
Gliosarcoma is an aggressive brain tumor with histologic features of glioblastoma (GBM) and soft tissue sarcoma. Despite its poor prognosis, its rarity has precluded analysis of its underlying biology. We used a multi-center database to characterize the genomic landscape of gliosarcoma. Sequencing data was obtained from 35 gliosarcoma patients from Genomics Evidence Neoplasia Information Exchange (GENIE) 5.0, a database curated by the American Association of Cancer Research (AACR). We analyzed genomic alterations in gliosarcomas and compared them to GBM (n = 1,449) and soft tissue sarcoma (n = 1,042). 30 samples were included (37% female, median age 59 [IQR: 49-64]). Nineteen common genes were identified in gliosarcoma, defined as those altered in > 5% of samples, including TERT Promoter (92%), PTEN (66%), and TP53 (60%). Of the 19 common genes in gliosarcoma, 6 were also common in both GBM and soft tissue sarcoma, 4 in GBM alone, 0 in soft tissue sarcoma alone, and 9 were more distinct to gliosarcoma. Of these, BRAF harbored an OncoKB level 1 designation, indicating its status as a predictive biomarker of response to an FDA-approved drug in certain cancers. EGFR, CDKN2A, NF1, and PTEN harbored level 4 designations in solid tumors, indicating biological evidence of these biomarkers predicting a drug-response. Gliosarcoma contains molecular features that overlap GBM and soft tissue sarcoma, as well as its own distinct genomic signatures. This may play a role in disease classification and inclusion criteria for clinical trials. Gliosarcoma mutations with potential therapeutic indications include BRAF, EGFR, CDKN2A, NF1, and PTEN.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Brain Neoplasms; Cyclin-Dependent Kinase Inhibitor p16; Databases, Factual; ErbB Receptors; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Glioblastoma; Gliosarcoma; Humans; Male; Middle Aged; Mutation; Neurofibromin 1; PTEN Phosphohydrolase; Prognosis; Proto-Oncogene Proteins B-raf; Telomerase; Tumor Suppressor Protein p53
PubMed: 34504233
DOI: 10.1038/s41598-021-97454-6 -
Neuropsychiatric Disease and Treatment 2022To investigate the clinical, imaging, and pathological features of gliosarcoma.
OBJECTIVE
To investigate the clinical, imaging, and pathological features of gliosarcoma.
METHODS
The clinical data of 14 patients with gliosarcoma confirmed by surgery and pathology at our hospital between 2010 and 2021 were analyzed retrospectively, and the relevant literature was reviewed.
RESULTS
In all 14 cases, the gliosarcoma was located in the supratentorial brain parenchyma and involved a single lesion. There were more male patients (64.3%) than female patients (35.7%), and 57.1% of all the patients were 40-60 years of age. The prognosis of all 14 patients was poor, and the average survival time was approximately seven months. The computed tomography findings revealed mostly mixed density lesions, and some cases were complicated with bleeding. The magnetic resonance imaging revealed irregularly shaped mass lesions of different sizes, with uneven or circular enhancement. Cystic degeneration and necrosis could be seen in all the masses, some of which showed signs of bleeding and were surrounded by different degrees of edema and space-occupying effects. The pathological examination revealed that the tumors had bidirectional differentiation of the glial and sarcoma components, while the immunohistochemistry examination revealed glial fibrillary acidic protein-positive and reticular fiber-positive staining in the sarcoma.
CONCLUSION
The clinical manifestations of gliosarcoma are nonspecific, but imaging reveals that the condition has certain characteristics, typically consisting of a huge supratentorial mass, with an irregular heterogeneous periphery or obvious mass-like augmentation after enhancement. The final diagnosis depends on the results of a pathological examination.
PubMed: 36387942
DOI: 10.2147/NDT.S386616 -
Journal of Neuro-oncology Apr 2018Gliosarcoma is a rare histopathologic variant of glioblastoma traditionally associated with a poor prognosis. While gliosarcoma may represent a distinct clinical entity... (Comparative Study)
Comparative Study
Gliosarcoma is a rare histopathologic variant of glioblastoma traditionally associated with a poor prognosis. While gliosarcoma may represent a distinct clinical entity given its unique histologic composition and molecular features, its relative prognostic significance remains uncertain. While treatment of gliosarcoma generally encompasses the same standardized approach used in glioblastoma, supporting evidence is limited given its rarity. Here, we characterized 32 cases of gliosarcoma and retrospectively evaluated survival relative to 451 glioblastoma patients diagnosed during the same era within the same institution. Overall, we identified 22 primary gliosarcomas, representing 4.7% of WHO Grade IV primary glioblastomas, and 10 secondary gliosarcomas. With median age of 62, patients were predominately Caucasian (87.5%) and male (65.6%). Tumors with available molecular profiling were primarily MGMT-unmethylated (87.5%), IDH-1-preserved (100%) and EGFR wild-type (100%). Interestingly, while no significant median survival difference between primary gliosarcoma and glioblastoma was observed across the entire cohort (11.0 vs. 14.8 months, p = 0.269), median survival was worse for gliosarcoma specifically among patients who received modern temozolomide-based (TMZ) chemoradiotherapy (11.0 vs. 17.3 months, p = 0.006). Matched-pair analysis also trended toward worse median survival among gliosarcomas (11.0 vs. 19.6 months, log-rank p = 0.177, Breslow p = 0.010). While adjuvant radiotherapy (HR 0.206, p = 0.035) and TMZ-based chemotherapy (HR 0.531, p = 0.000) appeared protective, gliosarcoma emerged as a significantly poor prognostic factor on multivariate analysis (HR 3.27, p = 0.012). Collectively, our results suggest that gliosarcoma may still portend worse prognosis even with modern trimodality therapy.
Topics: Adult; Aged; Biomarkers, Tumor; Brain Neoplasms; Female; Glioblastoma; Gliosarcoma; Humans; Male; Middle Aged; Prognosis; Retrospective Studies; Survival Analysis
PubMed: 29264835
DOI: 10.1007/s11060-017-2718-z -
ArXiv Jun 2023Histological staining of tissue biopsies, especially hematoxylin and eosin (H&E) staining, serves as the benchmark for disease diagnosis and comprehensive clinical...
Histological staining of tissue biopsies, especially hematoxylin and eosin (H&E) staining, serves as the benchmark for disease diagnosis and comprehensive clinical assessment of tissue. However, the process is laborious and time-consuming, often limiting its usage in crucial applications such as surgical margin assessment. To address these challenges, we combine an emerging 3D quantitative phase imaging technology, termed quantitative oblique back illumination microscopy (qOBM), with an unsupervised generative adversarial network pipeline to map qOBM phase images of unaltered thick tissues (i.e., label- and slide-free) to virtually stained H&E-like (vH&E) images. We demonstrate that the approach achieves high-fidelity conversions to H&E with subcellular detail using fresh tissue specimens from mouse liver, rat gliosarcoma, and human gliomas. We also show that the framework directly enables additional capabilities such as H&E-like contrast for volumetric imaging. The quality and fidelity of the vH&E images are validated using both a neural network classifier trained on real H&E images and tested on virtual H&E images, and a user study with neuropathologists. Given its simple and low-cost embodiment and ability to provide real-time feedback in vivo, this deep learning-enabled qOBM approach could enable new workflows for histopathology with the potential to significantly save time, labor, and costs in cancer screening, detection, treatment guidance, and more.
PubMed: 37396611
DOI: No ID Found