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Radiation-induced sarcoma (RIS) of the central nervous system is an uncommon late complication of radiation therapy. We report a case of a 47-year-old male patient who underwent surgery followed by irradiation and chemotherapy with temozolomide for a frontal lobe gliosarcoma and presented 43 months later with a recurrent tumor in the same location with interval growth in the size of the lesion. Histology from surgical resection of the recurrent tumor revealed embryonal rhabdomyosarcoma (RMS). Adjacent brain parenchyma showed radiation-induced changes. There was no evidence of gliosarcoma at recurrence. In addition to the rarity of sarcomas arising following irradiation for glial tumors, this case represents one of the first reports of an intracerebral RMS arising in this setting.

Introduction: It is reported that migraine may be a risk factor for brain cancers. Since one of the best ways to assess this possible relationship is to study the molecular mechanism, here the common central dysregulated proteins between these diseases are investigated via network analysis. Methods: The dysregulated proteins of migraine and gliosarcoma are extracted from the STRING database and interacted via Cytoscape software, version 3.7.2. to form two separate networks. Central nodes of the networks are compared to find the common central district proteins. First neighbors of the common central proteins are studied. Results: The number of 11 hub bottlenecks was identified for each of the migraine and gliosarcoma cancer networks. Albumin (ALB) and interleukin 6 (IL6) were introduced as common differentially expressed central proteins. Kininogen 1 (KNG1), vascular endothelial growth factor A (VEGFA), and neurofibromatosis type I (NF1) the first neighbors of ALB-IL6 were connected to the central nodes of networks of the two studied diseases. Conclusion: ALB and IL6 can be considered molecular links between migraine and brain cancers.

Mismatch repair-deficient (MMRD) brain tumors are rare among primary brain tumors and can be induced by germline or sporadic mutations. Here, we report 13 MMRD-associated (9 sporadic and 4 Lynch syndrome) primary brain tumors to determine clinicopathological and molecular characteristics and biological behavior. Our 13 MMRD brain tumors included glioblastoma (GBM) IDH-wildtype (n = 9) including 1 gliosarcoma, astrocytoma IDH-mutant WHO grade 4 (n = 2), diffuse midline glioma (DMG) H3 K27M-mutant (n = 1), and pleomorphic xanthoastrocytoma (PXA) (n = 1). Next-generation sequencing using a brain tumor-targeted gene panel, microsatellite instability (MSI) testing, Sanger sequencing for germline MMR gene mutation, immunohistochemistry of MMR proteins, and clinicopathological and survival analysis were performed. There were many accompanying mutations, suggesting a high tumor mutational burden (TMB) in 77%, but TMB was absent in one case of GBM, IDH-wildtype, DMG, and PXA, respectively. MSH2, MLH1, MSH6, and PMS2 mutations were found in 31%, 31%, 31% and 7% of patients, respectively. MSI-high and MSI-low were found in 50% and 8% of these gliomas, respectively and 34% was MSI-stable. All Lynch syndrome-associated GBMs had MSI-high. In addition, 77% (10/13) had histopathologically multinucleated giant cells. The progression-free survival tended to be poorer than the patients with no MMRD gliomas, but the number and follow-up duration of our patients were insufficient to get statistical significance. In the present study, we found that the most common MMRD primary brain tumor was GBM IDH-wildtype. The genetic profile of MMRD GBM was different from that of conventional GBM. MMRD gliomas with TMB and MSI-H may be sensitive to immunotherapy but resistant to temozolomide. Our findings can help develop better treatment options., The authors examined 13 mismatch repair-deficient (MMRD)-associated primary brain tumors to determine molecular characteristics and biological behavior. MMRD occurred after chemotherapy and radiotherapy in two cases. The genetic profile of MMRD glioblastoma was different from that of conventional glioblastoma. Half of the MMRD-gliomas and all Lynch syndrome-associated GBMs were high in microsatellite instability. These tumors had high mutational burdens and tended to have shorter progression-free survival than glioma without MMRD.

BACKGROUND: Astrocytic tumors are the most common primary brain tumors. Glioblastoma is the most common astrocytic tumor representing the highest World Health Organization (WHO) grade (WHO grade IV) with poor prognosis and short survival time. Anaplastic lymphoma kinase (ALK) has a role in embryonic central nervous system development. ALK receptor is thought to contribute to nervous system function, repair, and metabolic homeostasis and is expressed in high-grade tumors like anaplastic large cell lymphoma that makes it a potential target for therapeutic intervention. AIM: This work aimed to examine the immunohistochemical expression of ALK in astrocytic tumors and its correlation with age, sex, clinical presentation, location, laterality, recurrence, and WHO grade to implicate possible therapeutic potential. METHODS: This retrospective study was conducted on sixty cases of archived, formalin-fixed, paraffin-embedded tissue blocks that included different subtypes and grades of astrocytic tumors. Immunohistochemistry using ALK monoclonal antibody was performed using a standard avidin-biotin-peroxidase system. RESULTS: Of the sixty cases, 57 (95%) cases were negative for ALK, while three (5%) cases are positive for ALK; all showed the strong intensity of expression. No statistically significant association was found between ALK expression and astrocytic tumors in addition to other clinical variables of the studied tumors. CONCLUSIONS: Most cases of astrocytic tumors showed negative ALK expression apart from three positive cases seen in higher WHO grades, especially gliosarcoma. The high number of negative cases for ALK in our study group suggests that ALK expression is not associated with a prognostic significance toward astrocytic tumors whatever its grade.

Background An open-label, non-comparative study assessed the efficacy and safety of nivolumab in Japanese patients with first recurrence glioblastoma. Methods Patients with first recurrence of histologically confirmed World Health Organization Grade IV glioma, after treatment with temozolomide and radiotherapy, received nivolumab 3 mg/kg every 2 weeks until confirmed disease progression (Response Assessment in Neuro-Oncology criteria) or toxicity. Primary endpoint was 1-year overall survival rate assessed by Bayesian approach. The prespecified efficacy criterion was that the Bayesian posterior probability threshold for exceeding the 1-year overall survival of bevacizumab (34.5%) from the Japanese phase 2 study (JO22506) would be 93%. Results Of the 50 enrolled patients, 44 (88.0%) had recurrent malignant glioma (glioblastoma, gliosarcoma), and of these, 26 (59.1%) had at least one measurable lesion at baseline. The Bayesian posterior mean 1-year overall survival (90% Bayesian credible intervals) with nivolumab was 54.4% (42.27–66.21), and the Bayesian posterior probability of exceeding the threshold of the 1-year overall survival rate of bevacizumab (34.5%) was 99.7%. Median (90% confidence interval) overall and progression-free survival was 13.1 (10.4–17.7) and 1.5 (1.4–1.5) months, respectively. One partial response was observed (objective response rate 1/26 evaluable patients [3.8%]). Treatment-related adverse event rates were 14.0% for Grade 3–4 and 2.0% for Grade 5; most adverse events resolved and were manageable. Conclusions The 1-year overall survival with nivolumab monotherapy in Japanese patients with glioblastoma met the prespecified efficacy criterion. The safety profile of nivolumab was consistent with that observed in other tumor types. Clinical Trial Registration JapicCTI-152967.

Objective Gliosarcomas (GS) comprise ~ 2 - 8% of glioblastomas and are associated with a similar poor prognosis. GS have rarely been found with a primitive neuroectodermal component (PNET). We present a case of gliosarcoma with PNET features (GS-PNET) that mimicked a neuroendocrine carcinoma on initial biopsy. Materials and methods A 68-year-old male presented with 2 weeks of increasing headaches and difficulties with reading, writing, and word-finding. He was found to have a left-sided parieto-occipital heterogeneously enhancing mass. Results Pathologic analysis after surgical resection initially diagnosed a poorly differentiated carcinoma with neuroendocrine features, and adjuvant therapy was guided by this diagnosis as well as systemic imaging, which was suggestive of gastrointestinal primary malignancy with central nervous system (CNS) metastasis. Subsequent progression and re-resection established a diagnosis of GS with PNET component. Genomic profiling showed shared PTEN, TERT promotor, and TP53 mutations in the original and recurrent tumors. Conclusion There have only been 5 previously reported cases of GS-PNET, to our knowledge, with this case representing the first with comprehensive molecular profiling. The case also highlights the importance of further work-up of presumed metastatic carcinoma with indeterminate immunostaining and/or suspected non-epithelioid component.

Gliosarcoma, a variant of glioblastoma, is a rare and aggressive tumor of the central nervous system (CNS) composed of glial and sarcomatous tissues. Up to now, there are only 2 reported cases of gliosarcoma of the optical pathway. We report a case from March 2018 of a 53-year-old male patient presented with 6 months’ of right fronto-orbital pulsatile headache, behavior changes, and visual loss. The MRI study showed an expansile optic pathway lesion involving the chiasm and right optic nerve. The diagnosis of gliosarcoma was obtained by open brain biopsy and immunohistochemical analysis. Although gliosarcoma is rare, it should be considered a differential diagnosis even in optic pathway tumors in older patients. The experience of the neuropathologist with a trained eye can be the differential in the accurate diagnostic process. Optic pathway, Gliosarcoma, Glioblastoma, Magnetic resonance imaging

Gliosarcomas are a rare subtype of glioblastomas associated with high rates of malignancy-associated venous thromboembolism (VTE). VTE risk is further increased in hypercoagulable patients upon discontinuing pharmacologic anticoagulation for surgery. We present a 60-year old obese male with history of hypercoagulability on apixaban who developed extensive thrombosis following resection of a gliosarcoma. Prior to temporal lobe resection, apixaban was discontinued and an IVC filter placed. On postoperative day 4, imaging revealed thrombosis above the IVC filter extending to the bilateral common, internal and external iliac, and femoral veins, requiring immediate anticoagulation and suction thrombectomy. Clinicians must balance the risk of VTE and intracerebral hemorrhage following neurosurgical. While withholding pharmacologic VTE is standard, hypercoagulable patients may benefit from pharmacologic prophylaxis postoperatively. Patients with multiple risk factors including malignancies with high rates VTE, like gliosarcomas, medical and hematological conditions, including idiopathic erythrocytosis, and history of VTE may benefit from earlier pharmacologic prophylaxis.

Background Gliosarcoma (GSM) is a distinct and aggressive variant of glioblastoma multiforme (GBM) with worse prognosis and few treatment options. It is often managed with the same treatment modalities with temozolomide (TMZ) as in GBM. However, the therapeutic benefits on GSM from such treatment regimen is largely unknown. Patient-derived xenograft (PDX) models have been used widely to model tumor progression, and subsequently to validate biomarkers and inform potential therapeutic regimens. Here, we report for the first time the successful development of a PDX model of secondary GSM. Methods Tissue obtained from a tumor resection revealed a secondary GSM arising from GBM. The clinical, radiological, and histopathological records of the patient were retrospectively reviewed. Samples obtained from surgery were cultured ex vivo and/or implanted subcutaneously in immunocompromised mice. Histopathological features between the primary GBM, secondary GSM, and GSM PDX are compared. Results In explant culture, the cells displayed a spindle-shaped morphology under phase contrast microscopy, consistent with the sarcomatous component. GSM samples were subcutaneously engrafted into immunocompromised mice after single-cell suspension. Xenografts of serial passages showed enhanced growth rate with increased in vivo passage. We did not observe any histopathological differences between the secondary GSM and its serial in vivo passages of PDX tumors. Conclusions Our PDX model for GSM retained the histopathological characteristics of the engrafted tumor from the patient. It may provide valuable information to facilitate molecular and histopathological modelling of GSM and be of significant implication in future research to establish precise cancer medicine for this highly malignant tumor.

Non-small cell lung cancer (NSCLC) commonly presents with metastasis to the brain. When brain metastases are treated with stereotactic radiosurgery (SRS), longitudinal imaging to monitor treatment response may identify radiation necrosis, metastasis progression, and/or another primary brain malignancy. A 60-year-old female with metastatic NSCLC involving the brain underwent treatment with systemic therapy and SRS. While some brain metastases resolved, two remaining sites evolved to resemble radiation necrosis on magnetic resonance imaging and spectroscopy. One of those sites was later confirmed to be radiation necrosis after receding with steroids and bevacizumab. The other lesion continued to enlarge and was then surgically resected, pathologically proven to be a gliosarcoma. When scan findings diverge among multiple treated disease sites, imaging should be cautiously interpreted in conjunction with clinical information as well as early surgical consultation for biopsy consideration, especially when there is suspicion of unusual or superimposed pathologies.

Objective: Gliosarcoma - regarded as a rare variant of glioblastoma - has been observed in approximately 2% of patients with malignant gliomas. While treatment and outcome of patients with gliosarcoma has received more attention over the past decade, only few studies compared differences in primary[for full text, please go to the a.m. URL], 71. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 9. Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie

Background Extraneural metastasis of glioma is a rare event, often occurring in patients with advanced disease. Genomic alterations associated with extraneural glioma metastasis remain incompletely understood. Methods Ten patients at Memorial Sloan Kettering Cancer Center diagnosed with extraneural metastases of glioblastoma (9 patients) and gliosarcoma (1 patient) from 2003 to 2018 were included in our analysis. Patient characteristics, clinical course, and genomic alterations were evaluated. Results Patient age at diagnosis ranged from 14 to 73, with 7 men and 3 women in this group. The median overall survival from initial diagnosis and from diagnosis of extraneural metastasis was 19.6 months (range 11.2 to 57.5 months) and 5 months (range 1 to 16.1 months), respectively. The most common site of extraneural metastasis was bone, with other sites being lymph nodes, dura, liver, lung, and soft tissues. All patients received surgical resection and radiation, and 9 patients received temozolomide, with subsequent chemotherapy appropriate for individual cases. 1 patient had an Ommaya and then ventriculoperitoneal shunt placed, and 1 patient underwent craniectomy for cerebral edema associated with a brain abscess at the initial site of resection. Genomic analysis of primary tumors and metastatic sites revealed shared and private mutations with a preponderance of tumor suppressor gene alterations, illustrating clonal evolution in extraneural metastases. Conclusions Several risk factors emerged for extraneural metastasis of glioblastoma and gliosarcoma, including sarcomatous dedifferentiation, disruption of normal anatomic barriers during surgical resection, and tumor suppressor gene alterations. Next steps with this work include validation of these genomic markers of glioblastoma metastases in larger patient populations and the development of preclinical models. This work will lead to a better understanding of the molecular mechanisms of metastasis to develop targeted treatments for these patients.

Gliosarcoma is a variant of glioblastoma with equally poor prognosis and characterized by mixed glial and mesenchymal pathology. Metastasis is not uncommon but the involvement of the spinal cord is rare, and comprehensive genetic characterization of spinal gliosarcoma is lacking. We describe a patient initially diagnosed with a low-grade brain glioma via biopsy, followed by adjuvant radiation and temozolomide treatment. Nearly 2 years after diagnosis, she developed neurological deficits from an intradural, extramedullary tumor anterior to the spinal cord at T4, which was resected and diagnosed as gliosarcoma. Whole-exome sequencing (WES) of this tumor revealed a hypermutated phenotype, characterized by somatic mutations in key DNA mismatch repair (MMR) pathway genes, an abundance of C>T transitions within the identified somatic single nucleotide variations, and microsatellite stability, together consistent with temozolomide-mediated hypermutagenesis. This is the first report of a hypermutator phenotype in gliosarcoma, which may represent a novel genomic mechanism of progression from lower grade glioma.

Gliosarcoma (GSM) is a rare central nervous system tumor. Clinical management of it is similar to glioblastoma (GBM). However, due to a few comparative studies exist, uncertainty and disagreements remain in the literatures. To assess the available evidence on the value of different treatments and to carry out an up-to-date evaluation to summarize the evidence for the optimal treatment in GSM patients. Free words were used to search for the relevant studies without language limitations in electronic databases including PubMed, Ovid EMBASE, Cochrane Central Register of Controlled Trials from inception to September 15, 2019. Pooled hazard ratio (HR) with 95% confidence interval (CI) were calculated using a random-effects model. The main endpoint was all-cause mortality. Overall, 10 studies published between 2008 and 2018 including 803 patients were selected for the meta-analysis. Temozolomide (TMZ)-dominated chemotherapy was associated with a reduced risk of overall survival (OS), with HR 0.49 (95% CI 0.37-0.66). The pooled HR of OS was 0.40 (95% CI 0.29-0.56) between radiotherapy and without radiotherapy. The pooled HR (0.52, 95% CI 0.32-0.85) indicated gross total resection (GTR) had a positive impact on OS in GSM. In patients with GSM, survival benefits as currently performed are associated with TMZ-dominated chemotherapy and high-dose radiotherapy. Our systematic review and meta-analysis also demonstrate GTR is associated with a reduction in all-cause mortality in patients with primary GSM.

The clinical implications of plasmatic cell-free and tumor DNA (cfDNA and ctDNA) are challenging in glioblastoma. This prospective study included 52 consecutive newly diagnosed glioblastoma (n = 49) or gliosarcoma (n = 3) patients treated with concomitant temozolomide and radiotherapy (RT-TMZ), followed by a TMZ maintenance phase. Plasma samples were collected at baseline, before RT-TMZ (pre-RT-TMZ) and at the end of adjuvant TMZ, or at the time of progression in cases of progressive disease (PD). The cfDNA concentration was measured with a fluorometric method, and ctDNA was detected using targeted droplet digital PCR. The main objectives were to analyze the associations between cfDNA and ctDNA measurements during the course of treatment with PD and survival. There was a significant decrease in median cfDNA concentration from baseline to pre-RT-TMZ—19.4 versus 9.7 ng/mL (p p = 0.037), respectively, while no difference was observed for nonprogressive patients. Neither the cfDNA concentration at baseline nor its kinetics correlated with survival. ctDNA was detected in 2 patients (3.8%) and only in gliosarcoma subtypes.Trial registration ClinicalTrial, NCT02617745. Registered 1 December 2015, https://clinicaltrials.gov/ct2/show/NCT02617745?term=glioplak&draw=2&rank=1.

A heterogeneous group of CNS tumors are characterized by mixed neuroepithelial and mesenchymal features. Glial tumors manifesting this phenomenon are referred to as gliosarcoma. These tumors are usually mistaken for cerebral metastases or meningioma at operation. Their histological studies have revealed an admixture of gliomatous and sarcomatous tissues, which leads to a biphasic pattern. The mesenchymal component can present in different forms such as fibrosarcoma, undifferentiated pleomorphic sarcoma, chondro-osteogenic, and myogenic differentiation, as well as angiosarcomatous and liposarcomatous types. Squamous differentiation, adenoid formations and glandular structures may also be displayed. Herein, we report a rare case who was admitted to the emergency room with decreased consciousness resembling methadone poisoning. Clinical work-up showed a temporoparietal mass on radiological investigation. Histopathological evaluation of the brain mass revealed a gliosarcoma with adenoid formations and a mesenchymal component, which manifested as chondrosarcomatous differentiation. Immunohistochemical studies confirmed the histologic diagnosis through positivity for EMA, GFAP, S100, and vimentin expression in different components.

Introduction: Gliosarcoma is a rare histopathologic variant of glioblastoma traditionally associated with a poor prognosis.We present two cases of Gliosarcoma treated in our department. Discussion: Gliosarcoma (GSM) is a variant of glioblastoma (GBM), the most common primary malignant brain tumor that occurs in adults. GSM is characterized by its biphasic components: the gliomatous and sarcomatous components and categorized into primary and secondary GSM. Intrinsic to the brain parenchyma, GSM is usually managed by gross total resection, and radiotherapy with/without chemotherapy. Conclusion: Despite the notable advances and improvement in overall survival (OS), a consensus on the optimal treatment for GSM patients is unclear.

Well-circumscribed intra-axial CNS tumors encompass a wide variety of gliomas and glioneuronal tumors, usually corresponding to WHO grades I and II. Nonetheless, sometimes high-grade 'diffuse' gliomas such as gliosarcoma and giant cell glioblastoma can be relatively circumscribed but are often found to have foci of diffuse infiltration on careful examination, harboring distinct molecular alterations. These tumors are excluded from the discussion in this chapter with the current review emphasizing on lower-grade entities to include a brief description of their histology and associated molecular findings. Like elsewhere in brain biopsy evaluation, imaging is crucial and acts as a surrogate to gross examination. Given the circumscribed nature of these tumors, surgery alone is the mainstay treatment in most entities.

Primary intracranial gliosarcoma is a rare malignant brain tumour, and the most effective treatment for gliosarcoma remains unclear. This study aimed to identify risk factors for progression-free survival (PFS) and overall survival (OS) in these cases. This retrospective single-centre study evaluated 103 patients (median age, 51 years; 67 men [65%]) with primary intracranial gliosarcoma between 2006 and 2017. Treatments included surgery (GTR, 63 patients; STR, 39 patients; biopsy, 1 patient), radiotherapy (adjuvant, 76 patients; exclusive treatment, 1 patient), and chemotherapy (adjuvant temozolomide, 52 patients; adjuvant nimustine/teniposide, 19 patients; adjuvant bevacizumab, 1 patient; exclusive nimustine/teniposide treatment, 1 patient). The median OS was 13.3 months, and the median PFS was 9.1 months. In the multivariate analyses, the poor prognostic factors were ependymal lining enhancement of the lateral ventricle (PFS, HR 2.406, p = 0.005; OS, HR 2.946, p = 0.009) and enhancement in the motor functional cortex (PFS, HR 2.892, p = 0.002; OS, HR 2.639, p = 0.009). Good OS was predicted by adjuvant radiotherapy alone (HR 0.071, p

Background Targeting vascular endothelial growth factor (VEGF) alone does not improve overall survival (OS) in recurrent glioblastoma (rGBM). The angiopoiein (Ang)-TIE2 system may play a role in tumor survival under VEGF inhibition. We conducted a phase 2, double-blinded, placebo-controlled trial of bevacizumab plus trebananib (a novel Fc fusion protein that sequesters Ang1/Ang2) over bevacizumab alone in rGBM. Methods Patients ≥18 years of age with a Karnofsky performance status ≥70 and GBM or variants in first or second relapse were randomized to bevacizumab 10 mg/kg every 2 weeks plus trebananib 15 mg/kg every week or bevacizumab plus placebo. The primary endpoint was 6-month progression-free survival (PFS). Results After an initial 6-patient lead-in cohort confirmed the safety of combining bevacizumab and trebananib, 115 eligible patients were randomized to the control (n = 58) or experimental treatment (n = 57). In the control arm, 6-month PFS was 41.1%, median survival time was 11.5 months (95% CI, 8.4-14.2 months), median PFS was 4.8 months (95% CI, 3.8-7.1 months), and radiographic response (RR) was 5.9%. In the experimental arm, 6-month PFS was 22.6%, median survival time was 7.5 months (95% CI, 6.8-10.1 months), median PFS was 4.2 months (95% CI, 3.7-5.6 months), and RR was 4.2%. The rate of severe toxicities was not significantly different between arms. Conclusion The combination of bevacizumab and trebananib was well tolerated but did not significantly improve 6-month PFS rate, PFS, or OS for patients with rGBM over bevacizumab alone. The shorter PFS in the experimental arm with a hazard ratio of 1.51 (P = .04) suggests that the addition of trebananib to bevacizumab is detrimental.

Purpose: Glioblastoma (GBM) has the highest fatality rate among primary malignant brain tumors. GBMs with synchronous multiple foci (multiple GBMs) is rarely diagnosed in the clinical scenario. This study aims to compare the clinical characteristics between multiple and single GBMs and to identify factors associated with the survival of GBM and evaluate their effects. Methods: We retrospectively reviewed the medical records of patients with primary GBM in a referral medical center in Taiwan who were diagnosed between 2005 and 2016. They were identified from the cancer registry database of the center and followed from the date of diagnosis to october 2018. The primary endpoint of this study was overall survival (OS), and the independent factors for survival were identified through Cox regressions. Results: A total of 48 patients were identified, of whom 44 GBM (92%) and 4 gliosarcoma (GSM) (8%). Preoperative images showed five (10%) patients had multiple brain lesions. GSM showed a high ratio of multiple lesions (50%) than patients with GBM (5%) (p = 0.05). Those with multiple lesions had significantly worse median OS of 8.2 months compared to patients with a single lesion (16 months, p = 0.03). We found that multiple GBMs was a predictor of worse survival (hazard ratio [HR] = 3.57, 95% confidence interval [95%CI]: 1.26–10.13) after adjusting for other significant predictor of radiotherapy (HR = 0.47, 95%CI: 0.23–0.96). Conclusion: Patients with multiple GBMs had worse survival compared to those with single GBM. GBM patients without post-operative radiotherapy were also a predictor of worse survival. Keywords: Glioblastoma, Gliosarcoma, Multiple brain lesions, Radiotherapy, Survival

Background: Glioblastoma (GBM) is the most common primary intracranial malignancy. Previous studies found incidence of GBM varies substantially by age, sex, race and ethnicity, and survival also varies by country, ethnicity, and treatment. Gliosarcoma (GSM) and giant cell glioblastoma (GC-GBM) are different histologic variants of GBM with distinct clinico-pathologic entities. We conducted a study to compare epidemiology, survival, and prognostic factors among the three.Methods: We identified GBM patients diagnosed between 2000 and 2016 using the Taiwan Cancer Registry and followed them using the death registry. Survival was compared among conventional GBM and two histologic variants. The potential confounding factors evaluated in this study included registered year, age, sex, and treatment modality (resection, radiotherapy, and chemotherapy).Results: We enrolled 3,895 patients, including 3,732 (95.8%) with conventional GBM, 102 (2.6%) with GSM, and 61 (1.6%) with GC-GBM. GC-GBM patients had younger mean age at diagnosis (49.5 years) than conventional GBM patients (58.7 years) and GSM patients (61.3 years) (p < 0.01). The three groups had similar sex distributions (p = 0.29). GC-GBM had a longer median survival [18.5, 95% confidence interval (CI): 15.8–25.3 months] than conventional GBM (12.5, 95%CI: 12.0–13.0 months) and GSM (12.8, 95%CI: 9.2–16.2 months), and the differences in overall survival did not attain statistical significance (p = 0.08, log-rank test). In univariate analysis, GC-GBM had better survival than conventional GBM, but the hazard ratio (0.91) did not reach statistical significance (95%CI: 0.69–1.20) in the multivariate analysis. Young ages (≤ 40 years), female sex, resection, radiotherapy, and chemotherapy were factors associated with better survival in overall GBMs. In subtype analyses, these factors remained statistically significant for conventional GBM, as well as radiotherapy for GSM.Conclusion: Our analysis found conventional GBM and its variants shared similar poor survival. Factors with age ≤ 40 years, female sex, resection, radiotherapy, and chemotherapy were associated with better prognosis in conventional GBM patients.

Objective: To identify optimal machine-learning methods for the radiomics-based differentiation of gliosarcoma (GSM) from glioblastoma (GBM). Materials and Methods: This retrospective study analyzed cerebral magnetic resonance imaging (MRI) data of 83 patients with pathologically diagnosed GSM (58 men, 25 women; mean age, 50.5 ± 12.9 years; range, 16-77 years) and 100 patients with GBM (58 men, 42 women; mean age, 53.4 ± 14.1 years; range, 12-77 years) and divided them into a training and validation set randomly. Radiomics features were extracted from the tumor mass and peritumoral edema. Three feature selection and classification methods were evaluated in terms of their performance in distinguishing GSM and GBM: the least absolute shrinkage and selection operator (LASSO), Relief, and Random Forest (RF); and adaboost classifier (Ada), support vector machine (SVM), and RF; respectively. The area under the receiver operating characteristic curve (AUC) and accuracy (ACC) of each method were analyzed. Results: Based on tumor mass features, the selection method LASSO + classifier SVM was found to feature the highest AUC (0.85) and ACC (0.77) in the validation set, followed by Relief + RF (AUC = 0.84, ACC = 0.72) and LASSO + RF (AUC = 0.82, ACC = 0.75). Based on peritumoral edema features, Relief + SVM was found to have the highest AUC (0.78) and ACC (0.73) in the validation set. Regardless of the method, tumor mass features significantly outperformed peritumoral edema features in the differentiation of GSM from GBM (P < 0.05). Furthermore, the sensitivity, specificity, and accuracy of the best radiomics model were superior to those obtained by the neuroradiologists. Conclusion: Our radiomics study identified the selection method LASSO combined with the classifier SVM as the optimal method for differentiating GSM from GBM based on tumor mass features.

Background The authors report a case of a woman aged 33 years who suffered from the combination of primary gliosarcoma and arteriovenous malformation as the first clinical presentation of intracranial hemorrhage. Case Description Subsequently, gene examination rarely finds BRAF V600E mutation in the surgical specimen. The lesion was not completely identified with magnetic resonance imaging and digital subtraction angiography. Conclusions This case illustrates the occult and unusual feature of gliosarcoma. The pathogenesis of such coexistence might be related to underlying genetic alterations.

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. Resumo Introdução: O gliossarcoma (GSM) do sistema nervoso central (SNC) é uma neoplasia primária rara, caracterizada pela presença de componentes gliais e sarcomatosos. Objetivo: Nosso objetivo é descrever os aspectos clínicos e de neuroimagem de três casos com este diagnóstico e correlacioná-los com os achados patológicos. Também foi realizada uma breve revisão da literatura relevante. Métodos: Três pacientes foram avaliados por ressonância magnética (RM), e biópsias confirmaram o diagnóstico de GSM primário, sem radioterapia prévia. Resultados: Foram analisadas as sequências convencionais (T1, T1 após injeção de contraste, T2, FLAIR-fluid attenuation inversion recovery, SWI, DWI/mapa ADC) e as sequências avançadas (espectroscopia de prótons 1H e perfusão), observando-se aspecto necrótico e irregular da lesão, edema/infiltração peritumoral, isointensidade do componente sólido em T2, associada a realce irregular e periférico pelo meio de contraste, pico de lípides e de lactato e aumento dos níveis de colina e creatina na espectroscopia de prótons, aumento do volume sanguíneo cerebral relativo (rCBV) na perfusão, multifocalidade e “drop” mestástase em um dos casos. Conclusão: O presente estudo descreve características do GSM, discutindo as informações na literatura científica, ilustrando algumas particularidades desses tumores.

Glioblastoma is the most frequent and aggressive primary brain tumor, characterized by extensive brain invasion and rarely, systemic metastases. The pathogenesis of metastatic glioblastoma is largely unknown. We present the first integrated clinical/histologic/genetic analysis of 5 distinct brain and lung foci from a unique case of recurrent, multifocal, multicentric and metastatic glioblastoma. The initial right frontotemporal gliosarcoma received standard surgical/chemoradiation therapy and recurred 1.5 years later, co-occurring with three additional masses localized to the ipsilateral temporal lobe, cerebellum and lung. Synchronous metastatic lung carcinoma was suspected in this long-term smoker patient with family history of cancer. However, glioblastoma was confirmed in all tumors, although with different morphologic patterns, including ependymomatous and epithelioid. Genomic profiling revealed a germline FANCD2 variant of unknown significance, and a 4-gene somatic mutation signature shared by all tumors, consisting of TERT promoter and PTEN, RB1 and TP53 tumor suppressor mutations. Additional GRIN2A and ATM heterozygous mutations were selected in the cerebellar and lung foci, but were variably present in the supratentorial foci, indicating reduced post-therapeutic genetic evolution in brain foci despite morphologic variability. Significant genetic drift characterized the lung metastasis, likely explaining the known resistance of circulating glioblastoma cells to systemic seeding. MET overexpression was detected in the initial gliosarcoma and lung metastasis, possibly contributing to invasiveness. This comprehensive analysis sheds light on the temporospatial evolution of glioblastoma and underscores the importance of genetic testing for diagnosis and personalized therapy.

Background Prognostic factors for single primary gliosarcoma (PGS) remain unknown. Objective The purpose of our study was to examine patient, tumor, and treatment characteristics as potential predictors of survival using Surveillance, Epidemiology, and End Results (SEER) program data (1973‐2013). Methods The patients of single PGS were selected based on the exclusion criteria from SEER. Kaplan‐Meier survival analysis, log‐rank test and Cox proportional hazards models were used to analyze all the data. Results Single PGS has an apparent popularity for the temporal lobe (35.2%, hazard ratio [HR] = 0.440, 95%CI = 0.251‐0.770) and frontal lobe (20.9%, HR = 0.408, 95%CI = 0.231‐0.720) which could achieve a better survival rate than cerebrum (P = .034). The mean age at diagnosis was 60.07 ± 14.161. The overall 6‐month, 1‐year, 2‐year, and 5‐year survival was 55.40%, 29.58%, 10.01%, and 2.73%. Age at diagnosis was proved to be a significant predictor of overall survival (OS) (P 60 mm (P= .003, HR = 1.899, 95%CI = 1.244‐2.901) showed a higher risk of death. Surgery played a critical role in OS (P 40 mm). Surgery intervention and radiation therapy were beneficial factors., This is the first large sample study of single primary gliosarcoma to examine patient, tumor, and treatment characteristics as potential predictors of survival using Surveillance, Epidemiology, and End Results (SEER) program data (1973‐2013). This study indicated that outcome of single PGS would become poorer along with patients' age getting older. Surgery intervention and radiation therapy were beneficial factors.

The authors present the case of a patient who after undergoing craniotomy for glioblastoma resection was found to have gliosarcoma recurrence in the subdural space without intraparenchymal recurrence. A 74-year old man originally presented with the first seizure of his life and was found to have a right temporal glioblastoma multiforme. He underwent craniotomy and adjuvant chemotherapy and radiation therapy. Five months later, he presented with what was to be presumed to be a right subdural hematoma found on surveillance imaging. After expanding on repeat imaging, the patient was electively taken for burr hole evacuation, however intraoperatively thickened membranes were encountered leading to craniotomy and resection of lesion with pathology consistent with gliosarcoma. What we describe is novel because not only was there rare subdural spread of previously resected glioblastoma observed, but also transformation to the more aggressive tumor of gliosarcoma. Thus, we add to the body of literature and evidence to the clinical consideration of glioma as a rare cause of non-traumatic subdural collection. Specifically in a population of patients who have already undergone glioma resections, work up of subdural collections should include contrasted MRI beyond CT. The treatment paradigm does not change in this presentation of glioma recurrence. Surgical decompression and resection to alleviate brain compression, followed by adjuvant chemotherapy and radiation. Keywords: Glioma, Gliosarcoma, Glioblastoma, Extra-axial, Subdural, Collection, Recurrence, Hematoma

Meningeal dissemination (MDS) of glioblastoma is rare, although its incidence might have been underestimated. MDS of glioblastoma has a fatal course. Thus, rapid and precise diagnosis of MDS is important for further palliative treatment. Unfortunately, MDS of glioblastoma could be diagnosed at a delayed time, causing failure to treat patient optimally. Herein, we present a case of a 56-year-old male with MDS of glioblastoma mimicking chronic subdural hemorrhage (CSDH) after head trauma due to slip down. During treatment for CSDH, MDS of glioblastoma was not controlled appropriately. The patient succumbed to MDS of glioblastoma at 9 weeks after the date of diagnosis of CSDH which could be an MDS.

Background Gliosarcoma (GS) refers to the presence of mesenchymal differentiation (as seen using light microscopy) in the setting of glioblastoma (GB, an astrocytoma, WHO Grade 4). Although the same approach to treatment is typically adopted for GS and GB, there remains some debate as to whether GS should be considered a discrete pathological entity. Differences between these tumors have not been clearly established at the molecular level. Methods Patients with GS (n=48) or GB (n=1229) underwent molecular profiling (MP) with a pan-cancer panel of tests as part of their clinical care. The methods employed included next-generation sequencing (NGS) of DNA and RNA, copy number variation (CNV) of DNA and immunohistochemistry (IHC). The MP comprised 1153 tests in total, although results for each test were not available for every tumor profiled. We analyzed this data retrospectively in order to determine if our results were in keeping with what is known about the pathogenesis of GS by contrast with GB. We also sought novel associations between the MP and GS vs. GB which might improve our understanding of pathogenesis of GS. Results Potentially meaningful associations (pAll of the differences we observed have been associated with epithelial-to-mesenchymal transition (EMT) in other tumor types. Many of the changes we saw in GS are novel in the setting of glial tumors, including copy number amplification in LYL1 and mutations in PTPN11. Conclusions GS shows certain characteristics of EMT, by contrast with GB. Treatments targeting immuno-evasion may be of greater therapeutic value in GS relative to GB.

Aim: To evaluate the Apparent diffusion co-efficient in grading of Glial tumors with histo-pathological gradingMethod: Cross sectional hospital based observational study conducted over a time period of 2 years. All the cases registered with Acharya Vinoba Bhave Rural Hospital Sawangi, Wardha, diagnosed on histo-pathological findings as Glial tumours were included in this present study. All patients were examined on GE Brivo MRI machine with 1.5 Tesla magnetic field strength in the Department of Radiodiagnosis. Using b value of 1000 s/sq. mm, slice thickness 5mm, interslice gap 2mm applied in the x, y and z axes, central as well as peripheral portions of the tumor were manually sampled, preferably getting rid of any cystic or necrotic areas within them. Histo-pathological diagnostic acumen was augmented with radiological features of the brain tumors upon routine MRI SEQUENCES coupled with ADC values.Result: In the present study, out of the total of 142 patients included, the glial tumour cases were 54 in number. Amongst this group of glial tumours, the tumours diagnosed were pleomorphic xanthoastrocytoma, pontine glioma, and thalamic glioma, low grade glioma at other sites, high grade gliomas, grade 3 astrocytomas, glioblastoma multiformae, gliomatosis cerebri and gliosarcoma. The mean ADC for Pleomorphic xanthoastrocytoma, pontine glioma, thalamic glioma and Low grade gliomas were 0.98, 0.82, 0.95 and 0.89 respectively. While, the mean normalized ADC for Pleomorphic xanthoastrocytoma, pontine glioma, thalamic glioma and Low grade gliomas were 1.23, 1.03, 1.19 and 1.12 respectively.Conclusion: The research gap analysis towards which research question was framed stands filled up by the generated new knowledge in terms of ‘Apparent Diffusion Coefficient’ and ‘Normalised Apparent Diffusion Coefficient’ values with identified cut off / demarcating values for gradation of Glial Tumors into Low Grade / High Grade tumors

Aim – To evaluate the metabolic ratios for grading of Glial tumors with histo-pathological grading.Method: Cross sectional hospital based observational study conducted over time period of 2 years. All cases registered with Acharya Vinoba Bhave Rural Hospital Sawangi, Wardha, diagnosed on histo-pathological findings as Glial tumours were included in present study. All patients were examined on GE Brivo MRI machine with 1.5Tesla magnetic field strength in the Department of Radiodiagnosis. Using b value of 1000 s/sq. mm, slice thickness 5mm, interslice gap 2mm applied in the x, y and z axes, central as well as peripheral portions of the tumor were manually sampled, preferably getting rid of any cystic or necrotic areas within them. Histo-pathological diagnostic acumen was augmented with radiological features of brain tumors upon routine MRI SEQUENCES coupled with ADC values.Result: In the present study, out of the total of 142 patients included, the glial tumour cases were 54 in number. Amongst this group of glial tumours, the tumours diagnosed were pleomorphic xanthoastrocytoma, pontine glioma, and thalamic glioma, low grade glioma at other sites, high grade gliomas, grade 3 astrocytomas, glioblastoma multiformae, gliomatosis cerebri and gliosarcoma. Upon application of logistic regression analysis, ‘cut off values’ for different metabolite ratios were calculated towards facilitation of grading of brain tumours. The observed ‘cut off values’ were 0.96 for Mi:Cr, 1.03 for Naa:Cr, Cho:LL showed it to be 1.452, 2.15 for Cho:Cr, 2.06 for Cho:Naa, 2.04 for LL:Cr and 2.48 for Cho:Mi respectively.Conclusion: The research gap analysis towards which research question was framed stands filled up by the generated new knowledge in terms of ‘’metabolic ratios’ with identified cut off / demarcating values for gradation of Glial Tumors into Low Grade / High Grade tumors

Enzastaurin (ENZA, DB102) is an oral serine/threonine kinase inhibitor targeting the protein kinase C (PKC) and phosphoinositide 3-kinase (PI3K)/AKT pathways to inhibit tumor cell proliferation, induce tumor cell apoptosis, and suppress tumor-induced angiogenesis. We report the long-term clinical response of a GBM patient treated with ENZA who has survived for 15 years from initial diagnosis, despite tumor recurrence 5 years ago. In 2006, the 44-year-old man was diagnosed with GBM and underwent surgical resection of the tumor. He subsequently enrolled in a Phase I/II trial evaluating ENZA in newly diagnosed GBM and gliosarcoma (NCT00402116), in September 2006. He was treated with radiation and concurrent temozolomide (TMZ) + ENZA, followed by adjuvant TMZ + ENZA, which he tolerated well. He stopped treatment electively in November 2010, after 51 adjuvant cycles, in the setting of stable imaging without evidence of tumor activity. The patient did well until January 2016, when a serial MRI scan showed tumor progression; he underwent a second surgical resection (pathology: recurrent GBM, IDH1 R132H neg, ATRX retained, EGFR amplified, MGMT methylated) followed by re-irradiation with concurrent TMZ. Given the patient’s prior prolonged disease control, he started a compassionate treatment of ENZA in combination with adjuvant TMZ in April 2016. TMZ was stopped in June 2018 after 28 cycles; he continues single agent ENZA to date, with no evidence of tumor progression as of May 2021. Consistent with DGM1 (Denovo Genomic Marker 1) being an ENZA efficacy predicting biomarker, the patient is DGM1 positive. This case provides clinical evidence that the addition of ENZA to standard of care may provide substantial long-term benefit in DGM1 positive patients with GBM. A Phase 3 study of ENZA in DGM1 positive newly diagnosed GBM patients is currently ongoing (ENGAGE study, NCT03776071).

BACKGROUND To improve the long-term results of complex treatment of patients with malignant gliomas MATERIAL AND METHODS The long-term results of treatment of 220 patients with malignant gliomas of supratentorial localization (anaplastic astrocytomas, glioblastomas, giant cell glioblastomas, gliosarcomas) were evaluated. Of these patients, in addition to standard treatment methods (surgery, radiation therapy and chemotherapy), 110 patients underwent specific antitumor immunotherapy. In 110 patients, only standard methods were used in the complex treatment structure. Follow-up results were considered follow-up data, and a relapse-free period was also evaluated. RESULTS The implementation of specific antitumor immunotherapy in patients with malignant gliomas was safe and did not lead to an increase in the number of complications compared with the control group. It was revealed that the use of immunotherapy based on autologous dendritic cells, in addition to standard methods of treating patients, increases the average life expectancy (in patients with anaplastic astrocytomas up to 40.5 months (p = 0.001), in patients with glioblastomas up to 21.8 months (p = 0.002)) and the value of the relapse-free period (in patients with anaplastic astrocytomas up to 17.4 months (p = 0.002), in patients with glioblastomas up to 14.3 months (p = 0.003)), provided that three or more courses are carried out. Conducting 1 or 2 courses of immunotherapy does not significantly affect the average life expectancy and median survival of patients. CONCLUSION The development and use in clinical practice of specific antitumor immunotherapy based on autologous dendritic cells seems to be a very promising direction for further research, the development of which will improve the long-term results of treatment of patients.

Background Captopril is a well-characterized, FDA-approved drug that has demonstrated promise as a repurposed oncology therapeutic. Captopril’s known anti-cancer effects include inhibition of Matrix Metalloproteinase-2 (MMP-2), an endopeptidase which selectively breaks down the extracellular matrix to promote cell migration. MMP-2 is a known therapeutic target in gliomas, tumors with significant clinical need. Using an aggressive gliosarcoma model, we assessed captopril’s effects on MMP-2 expression in vitro and in vivo as well as its efficacy as an adjuvant in combination therapy regimens in vivo. Methods Following captopril treatment, MMP-2 protein expression and migratory capabilities of 9 L gliosarcoma cells were assessed in vitro via western blots and scratch wound assays, respectively. Rats were intracranially implanted with 9 L gliosarcoma tumors, and survival was assessed in the following groups: control; captopril (30 mg/kg/day); temozolomide (TMZ) (50 mg/kg/day), and captopril+TMZ. In vivo experiments were accompanied by immunohistochemistry for MMP-2 from brain tissue. Results In vitro, captopril decreased MMP-2 protein expression and reduced migratory capacity in 9 L gliosarcoma cells. In a gliosarcoma animal model, captopril decreased MMP-2 protein expression and extended survival as a TMZ adjuvant relative to untreated controls, captopril monotherapy, and TMZ monotherapy groups (27.5 versus 14 (p Conclusions Captopril decreases gliosarcoma cell migration, which may be mediated by reduction in MMP-2 protein expression. Captopril provided a survival advantage as a TMZ adjuvant in a rat intracranial gliosarcoma model. Captopril may represent a promising potential adjuvant to TMZ therapy in gliosarcoma as a modulator of the MMP-2 pathway.

PurposeThe aim of this study was the development and external validation of a logistic regression model to differentiate gliosarcoma (GSC) and glioblastoma multiforme (GBM) on standard MR imaging.MethodsA univariate and multivariate analysis was carried out of a logistic regression model to discriminate patients histologically diagnosed with primary GSC and an age and sex-matched group of patients with primary GBM on presurgical MRI with external validation.ResultsIn total, 56 patients with GSC and 56 patients with GBM were included. Evidence of haemorrhage suggested the diagnosis of GSC, whereas cystic components and pial as well as ependymal invasion were more commonly observed in GBM patients. The logistic regression model yielded a mean area under the curve (AUC) of 0.919 on the training dataset and of 0.746 on the validation dataset. The accuracy in the validation dataset was 0.67 with a sensitivity of 0.85 and a specificity of 0.5.ConclusionsAlthough some imaging criteria suggest the diagnosis of GSC or GBM, differentiation between these two tumour entities on standard MRI alone is not feasible.

Background Gliosarcoma is a rare variant of IDH- wild type glioblastoma with both glial and mesenchymal differentiation. It accounts for approximately 2% of glioblastomas and has a poor prognosis similar to that of classic glioblastoma. It is seen mostly between 40 and 60 years of age with a mean age over 50 years. Pediatric gliosarcoma is even rarer than gliosarcoma in adults. We describe the clinicopathological features of gliosarcoma in patients under 20 years of age and determine whether there are significant differences from gliosarcoma in adults. We also present detailed review of published literature on pediatric gliosarcoma. Methods Slides of gliosarcomas in patients under 20 years of age were reviewed. Clinicopathological features were noted in detail and follow up was obtained. Results Eleven cases of gliosarcoma were reported in patients under 20 years of age. Ages ranged from three to 19 years (mean age 13 years). Frontal, parietal and temporal lobes were the commonest locations. Mean and median tumor size was six and five cm respectively. All 11 cases demonstrated the classic biphasic pattern. In 10 cases, glial component was astrocytic and was highlighted on GFAP. Sarcomatous component in most cases resembled fibrosarcoma and was high grade in 72.7%. Glial areas were reticulin poor while sarcomatous areas were reticulin rich. In over 45% cases, bizarre tumor giant cells were seen in the sarcomatous areas. In 1 case, sarcomatous areas showed extensive bone and cartilage formation. Other histologic features included hyalinized blood vessels, hemorrhage, infarction, gemistocytic cells, rhabdoid cells etc. Follow up was available in nine patients, five received chemoradiation post resection while three received radiotherapy only. Prognosis was dismal and eight patients died within one to 14 months following resection. Conclusions Gliosarcomas in patients under 20 comprised 13% of all gliosarcomas reported during the study period. Frequency and mean age were higher compared to other published reports. Pathological features were similar to those described in literature. Clinicopathological features and prognosis of pediatric gliosarcomas were similar to adult gliosarcomas.

Many neurological diseases present with substantial genetic and phenotypic heterogeneity, making assessment of these diseases challenging. This has led to ineffective treatments, significant morbidity, and high mortality rates for patients with neurological diseases, including brain cancers and neurodegenerative disorders. Improved understanding of this heterogeneity is necessary if more effective treatments are to be developed. We describe a new method to measure phenotypic heterogeneity across the whole rodent brain at multiple spatial scales. The method involves co-registration and localized comparison of in vivo radiologic images (e.g. MRI, PET) with ex vivo optical reporter images (e.g. labeled cells, molecular targets, microvasculature) of optically cleared tissue slices. Ex vivo fluorescent images of optically cleared pathology slices are acquired with a preclinical in vivo optical imaging system across the entire rodent brain in under five minutes, making this methodology practical and feasible for most preclinical imaging labs. The methodology is applied in various examples demonstrating how it might be used to cross-validate and compare in vivo radiologic imaging with ex vivo optical imaging techniques for assessing hypoxia, microvasculature, and tumor growth.

Congenital gliosarcoma are a very rare entity and only 9 congenital gliosarcoma cases have been reported in the literature. It’s a variant of glioblastoma multiforme. Prognosis, however, sometimes is in contradiction with the pathological appearance and seems to be more closely related to the grade of surgical resection. This report documents the presentation of a 5-month-old boy with voluminous congenital gliosarcoma of the right frontal lobe. We describe clinical diagnosis, histological aspects, radiological features and current management of this very aggressive tumor. International consensus is yet to be envisaged for the management of this very aggressive tumor, with a special emphasis on antenatal detection of these cases.

Gliosarcoma is rare among pediatric patients and among individuals with Neurofibromatosis Type 1 (NF1). Here we compare 2 pediatric gliosarcoma patients, one of whom has NF1. We performed whole-exome sequencing, methylation, and copy number analysis on tumor and blood for both patients. Whole-exome sequencing showed higher mutational burden in the tumor of the patient without NF1. Copy number analysis showed differences in chromosomal losses/gains between the tumors. Neither tumor showed O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. The NF1 patient survived without progression while the other expired. This is the first reported case of gliosarcoma in a child with NF1.

Glioblastoma multiforme (GBM) is the most common malignant glial cell tumor of the brain. GBM typically occurs in the cerebral hemispheres and is characterized as a grade IV neoplasm due to its highly invasive nature. GBM can be subdivided into two subtypes, gliosarcoma and giant cell (GC) glioblastoma. While there are similarities between the subtypes, the biggest differences are the rate of occurrence with GC accounting for only 1% of cases, and the tendency of GC to occur more commonly in younger aged patients. In this case study, a GC neoplasm is documented in a 68-year-old male cadaver.

Gliosarcoma (GSC) is a rare histological variant of glioblastoma (GBM). Due to limited evidence regarding clinical, genetic and radiographic characteristics of GSC, this study aimed to analyze independent outcome predictors of GSC, and to address the differences between GSC and GBM concerning the baseline characteristics and patients' survival.Patients treated between 2001 and 2018 for the diagnosis of GBM and GSC were included in this study. Patients' records were reviewed for demographic, clinical, genetic and radiographic characteristics. Univariate, multivariate and propensity score matched analyses were performed.In the GSC sub-cohort (N = 56), patients' age, preoperative clinical status, midline tumor location and tumor size were found to be independently associated with overall survival. As compared to GBM individuals (N = 1249), a temporal location (p = 0.002), presence of eccentric tumor cysts (p 0.001), a higher ratio of TP53 staining (p = 0.002) and a lower ratio of GFAP staining (p = 0.005) were characteristic for GSC. The diagnosis of GSC was associated with a poorer survival (p = 0.002) independently of the patients' age, sex, clinical status and extent of resection, However, this association was no more significant, when enhancing the multivariate analysis with molecular-genetic characteristics (IDH1 mutation and MGMT promotor methylation status).Certain radiographic and molecular-genetic patterns present the distinct characteristics of GSC. There is an association between the diagnosis of GSC and a poorer outcome. This difference might be linked to different genetic alterations in GBM and GSC. Prospective studies are needed to further elucidate the characteristics of GSC and develop targeted treatment approaches for this rare variant.

Gliosarcoma (GS) is a variant of IDH wild type of glioblastoma (WHO grade IV). It is characterized by biphasic tissue pattern showing glial and mesenchymal components. The glial component is usually similar to glioblastoma and the sarcomatous component is usually spindle cell type. Rarely the sarcomatous component can show additional lines of mesenchymal differentiation like cartilage, bone, smooth muscle, skeletal muscles etc. These tumours are more firm and discrete because of the high content of reticulin and collagen in the sarcomatous component. Originally these tumours were thought to arise from sarcomatous transformation of proliferating blood vessels or dedifferentiation of an advanced glioma. The recent studies show that both glial and sarcomatous component show identical mutations in p53, PTEN and TERT genes and suggest a monoclonal origin from a common stem cell. There is no significant difference in prognosis between glioblastoma and gliosarcoma. Here we report a case of gliosarcoma with chondrosarcomatous differentiation in a 52 year old gentleman. The case is presented here for its rarity.

Glioblastoma multiforme (GBM) has few clinically approved therapeutic regimens. One of these therapeutic options includes placing biodegradable wafers releasing BCNU (Gliadel®) into the tumor bed at the time of surgical removal of the tumor. Due to the significant benefit this polymer technology has had clinically, we have prepared wafers releasing Temozolomide (TMZ), an anticancer drug used systemically for treating GBM. TMZ delivered via polymer wafer could be used as a complementary treatment with or as an alternative to Gliadel®. TMZ is an alkylating agent which is water soluble. To remain comparable with the preclinical studies that led to Gliadel® the same size of wafers were formulated with TMZ. Wafers were loaded with 50% w/w TMZ in poly(lactic acid-glycolic acid) (PLGA) and showed reliable release of high dose TMZ for a period of 4 weeks. To achieve this 30-day release of the highly water soluble drug, we developed an encapsulation method, where the drug powder was first coated with the polymer to form core-shell particles in which the coating shell served as a rate controlling membrane for the drug particles. Wafers were also made with a co-loading of TMZ and BCNU. All wafers were tested in vivo by treating an intracranial 9 L gliosarcoma model in F344 rats. Rats that were either untreated or treated with blank wafer died within 11 days while the median survival for rats treated with systemic TMZ was 18 days. The group that received the BCNU alone wafer had a median survival of 15 days, the group that received the TMZ wafer alone had a median survival of 19 days, and the group treated with the BCNU-TMZ wafer had a median survival of 28 days with 25% of the animals living long term (p .0038 vs. Control; p .001 vs. Blank Polymer). These findings demonstrate the potential of this newly designed wafer for treating GBM. Moreover, this concept, can pave the way for other drug combinations that may improve the clinical application of numerous agents to treat solid tumors.

Gliosarcoma (GSM) is a rare primary neoplasm of the brain, characterized by a biphasic tissue pattern with alternating areas displaying glial and mesenchymal differentiation. GSM is usually treated as glioblastoma multiforme (GBM) and the prognosis is poor. Here, we discuss a 50-year-old male presenting with sudden decreased consciousness and a history of recent headache. A noncontrasted computed tomography of the brain revealed a well-circumscribed, hyperdense lesion in the left frontal lobe with significant perilesional edema, suggestive of an intracranial hemorrhage. The patient underwent emergency craniotomy to evacuate the hematoma. Intraoperatively, a mass was present, and fluid around the mass was collected and analyzed. Cytology revealed the presence of malignant cells. A 1-week postmagnetic resonance imaging (MRI) revealed a heterogenously enhancing mass in the left frontal lobe, suggestive of a high-grade glioma. The patient was then treated with radiation followed by adjuvant treatment with temozolomide plus bevacizumab. One year after the surgery, the patient was readmitted with headache, right-sided hemiparesis, and seizure. A follow-up MRI found a residual mass in the same region. A second surgery was performed. Histopathology examination showed GSM, and this was confirmed with an immunohistochemistry panel including glial fibrillary acid protein and vimentin. GSM is a rare variant of GBM. Intracranial hemorrhage is an uncommon clinical presentation of GSM. Diagnosis is established by histopathology. Treatment is surgery, followed by radiotherapy and chemotherapy. The study was approved by the Health Research Review Committee of Mohammad Hoesin Central General Hospital and Faculty of Medicine Sriwijaya University (No. 089/kepkrsmhunsri/2019) on March 1, 2019.