Molecular Testing in Gliomas: What is Necessary in Routine Clinical Practice?

PURPOSE OF REVIEW: A number of molecular characteristics are essential for accurate diagnosis and prognostication in glioma. RECENT FINDINGS: The 2021 WHO classification of brain tumors and recent Food and Drug Administration (FDA) pathology agnostic drug approvals highlight the importance of molecular testing in the management of glioma. For diffuse gliomas, it is important to identify IDH mutations, given the favorable clinical behavior and potential for using FDA approved IDH inhibitors in the near future. MGMT promoter methylation testing is the most established molecular marker for response to temozolomide in IDH wild-type glioblastoma and in turn impacts overall survival. Moreover, identification of certain mutations and molecular markers, such as BRAF V600E, hypermutation or elevated tumor-mutational burden and NTRK fusions allow for the use of FDA approved agents that are tumor-agnostic. Finally, molecular testing opens options for clinical trials that are essential for diseases with limited treatment options like gliomas.

The 4S of spinal astrocytoma: specific location, syrinx, spasticity and score on Modified Mccormick Scale (MMS) predict long term outcomes in patients undergoing surgical resection of intramedullary spinal astrocytomas.

OBJECTIVES: The aim of this study was to explore the factors that could predict long term clinical outcomes in SA. METHODS: A retrospective study was conducted wherein SA patients undergoing surgical resection with a minimum follow up of 12 months were included in this study. Modified Mccormick Scale (MMS) was utilized to record the neurological status of the patients both preoperatively and at last follow up. Outcomes were assessed as: long term neurological status, that is final MMS grade and neurological deterioration, defined as increase in MMS score as compared to preoperative MMS score. Survival analysis was performed using the kaplan meier curves. RESULTS: 71 patients were included in this study with mean age of 33.07years. At a mean follow up of 57 months, preoperative MMS was the single independent predictor for moderate-severe neurological deficit (MMS III to V) on multivariate analysis (OR: 30.2, p < 0.001) and had an outstanding AUC of 0.91. Six patients had neurological deterioration at long term follow up. Absence of spasticity (p = 0.028), thoracic-thoracolumbar tumors (p = 0.006), low MMS score (p = 0.01) and hypointense T1 weighted MRI (p = 0.009) were significant predictors of long term neurological deterioration. The median overall survival was 48 months and was significantly higher in low grade tumors (p < 0.001). CONCLUSION: The study highlights the efficacy of clinical features as a predictor of long term functional outcomes in SA patients. Role of spasticity as a prognostic factor was explored for the first time in this study.

Molecular markers for pediatric low-grade glioma.

Over the past decade, our understanding of the molecular drivers of pediatric low-grade glioma (PLGG) has expanded dramatically. These tumors are predominantly driven by RAS/MAPK pathway activating alterations (fusions and point mutations), most frequently in BRAF, FGFR1, and NF1. Furthermore, additional second hits in tumor suppressor genes (TP53, ATRX, CDKN2A) can portend more aggressive behaviour. Accordingly, comprehensive molecular profiling-specifically genetic sequencing, often plus copy number profiling-has become critical for guiding the diagnosis and management of PLGG. In this review, we discuss the most important genetic alterations that inform on classification and prognosis of PLGG, highlighting their diagnostic and therapeutic relevance.

High-grade astrocytoma with piloid features: MRI findings associated with a novel entity.

High-grade astrocytoma with piloid features is a newly defined brain tumor that requires DNA methylation profiling for diagnosis. Imaging features specific to this tumor have only recently been described in the radiological literature. We highlight the case of a 34-year-old man who presented with a 4-week history of headaches and light-headedness. Postresection, pathological analysis identified the tumor based on DNA methylation profiling, and the patient was started on adjuvant chemotherapy with Temozolomide. T2-weighted imaging showed a well-circumscribed cerebellar mass, which correlated with the pathology-reported glial tumor cells being elongated and piloid. T1-postgadolinium imaging showed heterogeneous enhancement of linear serpiginous areas, which correlated with regions of high microvascular density and vessels that showed thickening and hyalinization. Diffusion-weighted imaging and apparent diffusion coefficient mapping did not show significant diffusion restriction. Rosenthal fibres were absent. Given the specific imaging-pathology correlation, this report contributes imaging features associated with this novel diagnostic entity.

Recurrent symptomatic intracranial hemorrhage in high-grade astrocytoma with piloid features: illustrative case.

BACKGROUND: High-grade astrocytoma with piloid features (HGAP) is a novel condition introduced in the 2021 World Health Organization classification. Given that it has been recently classified, reports clarifying its clinical features or diagnostic criteria are lacking, especially in cases of atypical presentation. Herein, the authors present a rare case of HGAP with repeated symptomatic hemorrhages. OBSERVATIONS: A woman in her 20s presented with an acute headache and vertigo. Computed tomography and magnetic resonance imaging revealed a 2.5 × 2.8 × 2.3-cm hemorrhagic cerebellar mass with calcifications. After moderate improvement of her symptoms, she developed recurrent hemorrhage, and the tumor size increased (3.0 × 3.6 × 4.0 cm) 18 days later, necessitating resection. Pathological and molecular analyses confirmed the diagnosis of HGAP with an FGFR1-TACC1 fusion, MTAP/CDKN2A/B deletion, and SETD2 rearrangement. Radiologically, the presence of calcification and cystic components and the absence of perilesional edema were atypical features of previously reported HGAP. LESSONS: Although recurrent symptomatic intracranial hemorrhages are rare in HGAP, enhancing lesions on magnetic resonance imaging suggest the need for resection to obtain tissue for molecular diagnosis and guide adjuvant treatment strategies. https://thejns.org/doi/10.3171/CASE24395.

Epigenetic landscape reorganisation and reactivation of embryonic development genes are associated with malignancy in IDH-mutant astrocytoma.

Accurate grading of IDH-mutant gliomas defines patient prognosis and guides the treatment path. Histological grading is challenging, and aside from CDKN2A/B homozygous deletions in IDH-mutant astrocytomas, there are no other objective molecular markers used for grading. RNA-sequencing was conducted on primary IDH-mutant astrocytomas (n = 138) included in the prospective CATNON trial, which was performed to assess the prognostic effect of adjuvant and concurrent temozolomide. We integrated the RNA-sequencing data with matched DNA-methylation and NGS data. We also used multi-omics data from IDH-mutant astrocytomas included in the TCGA dataset and validated results on matched primary and recurrent samples from the GLASS-NL study. Since discrete classes do not adequately capture grading of these tumours, we utilised DNA-methylation profiles to generate a Continuous Grading Coefficient (CGC) based on classification scores from a CNS-tumour classifier. CGC was an independent predictor of survival outperforming current WHO-CNS5 and methylation-based classification. Our RNA-sequencing analysis revealed four distinct transcription clusters that were associated with (i) upregulation of cell cycling genes; (ii) downregulation of glial differentiation genes; (iii) upregulation of embryonic development genes (e.g. HOX, PAX, and TBX) and (iv) upregulation of extracellular matrix genes. The upregulation of embryonic development genes was associated with a specific increase of CpG island methylation near these genes. Higher grade IDH-mutant astrocytomas have DNA-methylation signatures that, on the RNA level, are associated with increased cell cycling, tumour cell de-differentiation and extracellular matrix remodelling. These combined molecular signatures can serve as an objective marker for grading of IDH-mutant astrocytomas.

Congress of Neurological Surgeons systematic review and evidence­based guidelines on the management of recurrent diffuse low-grade glioma: update.

Target population These recommendations apply to adult patients with recurrent WHO grade 2 infiltrative diffuse glioma (oligodendroglioma, astrocytoma).Questions and Recommendations:Imaging Q1: In adult patients with suspected recurrence of histologically proven WHO grade 2 diffuse glioma, do advanced imaging techniques using magnetic resonance spectroscopy, perfusion weighted imaging, diffusion weighted imaging or PET provide superior assessment of tumor recurrence and histologic progression compared to standard MRI neuroimaging?Recommendation Level III: In adult patients with suspected recurrence of histologically proven WHO grade 2 diffuse glioma, advanced imaging techniques using magnetic resonance spectroscopy, perfusion weighted imaging, diffusion weighted imaging or PET are suggested for identification of tumor recurrence or histologic progression.Pathology Q1: In adult patients with suspected recurrence of histologically proven WHO grade 2 diffuse glioma, is molecular testing for IDH-1, IDH-2, and TP53 Mutations and MGMT promotor methylation mutation warranted for predicting survival and formulating treatment recommendations?Recommendation Level III: It is suggested that IDH mutation status be determined for diagnostic purposes. TP53 mutations occur early in WHO grade 2 diffuse glioma pathogenesis, remain stable, and are not suggested as a marker of predisposition to malignant transformation at recurrence or other measures of prognosis. Assessment of MGMT status is suggested as an adjunct to assessing prognosis. Assessment of CDK2NA status is suggested since this is associated with malignant progression of WHO grade 2 diffuse gliomas.Q2: In adult patients with suspected recurrence of histologically proven WHO Grade 2 diffuse glioma, is testing of proliferation indices (MIB-1 and/or BUdR) warranted for predicting survival and formulating treatment recommendations?Recommendation Level III: It is suggested that proliferative indices (MIB-1 or BUdR) be measured in WHO grade 2 diffuse glioma as higher proliferation indices are associated with increased likelihood of recurrence and shorter progression free and overall survival.Chemotherapy Q1: In adult patients with suspected recurrence of histologically proven WHO grade 2 diffuse glioma, does addition of temozolomide (TMZ), other cytotoxic agents or targeted agents to their treatment regimen improve PFS and/or OS?Recommendation Level III: Temozolomide is suggested in the therapy of recurrent WHO grade 2 diffuse glioma as it may improve clinical symptoms. PCV is suggested in the therapy of WHO grade 2 diffuse glioma at recurrence as it may improve clinical symptoms with the strongest evidence being for oligodendrogliomas. TMZ is suggested as the initial choice for recurrent WHO grade 2 diffuse glioma. Carboplatin is not suggested as there is no significant benefit from carboplatin as single agent therapy for recurrent WHO grade 2 diffuse gliomas. There is insufficient evidence to make any recommendations regarding other agents in the management of recurrent WHO grade 2 diffuse glioma.Radiotherapy Q1: In adult patients with suspected recurrence of histologically proven WHO grade 2 diffuse glioma, does addition of radiotherapy to treatment regimen improve PFS and/or OS?Recommendation Level III: Radiation is suggested at recurrence if there was no previous radiation treatment. Q2: In adult patients with suspected recurrence of histologically proven WHO grade 2 diffuse glioma after previous radiotherapy, does addition of re-irradiation or proton therapy to the treatment regimen improve PFS and/or OS?Recommendation Level III: It is suggested that re-irradiation be considered in the setting of WHO grade 2 diffuse glioma recurrence as it may provide benefit in PFS and OS.Surgery Q1: In adult patients with suspected recurrence of histologically proven WHO grade 2 diffuse glioma, does surgical resection improve PFS and/or OS?. There is insufficient evidence to make any new specific recommendations regarding the value of surgery or extent of resection in relationship to survival for recurrent WHO grade 2 diffuse glioma.

Intracranial tumor in a patient with mucopolysaccharidosis type 1 (Scheie syndrome): An extremely rare combination.

Scheie syndrome is a mild variant of mucopolysaccharidosis type I (MPS I), a rare group of lysosomal storage diseases that affect multiple organ systems. It is rarely associated with neoplasia. To the best of our knowledge, only a single case of mucopolysaccharidosis associated with a brain tumor has been reported, and it was nearly three decades ago. We present the case of a 10-year-old female with Scheie syndrome associated with a brain tumor. Physical and laboratory findings were suggestive of Scheie syndrome. A skeletal survey also revealed a spectrum of dysostosis multiplex supporting MPS. Children with MPS can have rapidly enlarging head sizes due to hydrocephalus, but our patient had several red flags that demanded further evaluation. A brain MRI revealed a mass in the fourth ventricle and a biopsy of the mass revealed pilocytic astrocytoma grade 1. Intraventricular pilocytic astrocytoma itself is a rare occurrence, accounting for only 4%-15.6 % of all pilocytic astrocytomas. Altered mucopolysaccharide metabolism can be involved in tumor pathogenesis, but the exact mechanism is unknown. Mucopolysaccharidoses, being a group of complicated disorders, are difficult to manage, and many symptoms can be missed in children due to intellectual disability. This case highlights the importance of suspecting brain tumors in children with mucopolysaccharidoses who present with signs and symptoms of increased intracranial pressure. Prompt diagnosis and management can save the child from dire neurological consequences.

IGFBP7+ subpopulation and IGFBP7 risk score in astrocytoma: insights from scRNA-Seq and bulk RNA-Seq.

Background: Glioma is the predominant malignant brain tumor that lacks effective treatment options due to its shielding by the blood-brain barrier (BBB). Astrocytes play a role in the development of glioma, yet the diverse cellular composition of astrocytoma has not been thoroughly researched. Methods: We examined the internal diversity of seven distinct astrocytoma subgroups through single-cell RNA sequencing (scRNA-seq), pinpointed crucial subgroups using CytoTRACE, monocle2 pseudotime analysis, and slingshot pseudotime analysis, employed various techniques to identify critical subgroups, and delved into cellular communication analysis. Then, we combined the clinical information of GBM patients and used bulk RNA sequencing (bulk RNA-seq) to analyze the prognostic impact of the relevant molecules on GBM patients, and we performed in vitro experiments for validation. Results: The analysis of the current study revealed that C0 IGFBP7+ Glioma cells were a noteworthy subpopulation of astrocytoma, influencing the differentiation and progression of astrocytoma. A predictive model was developed to categorize patients into high- and low-scoring groups based on the IGFBP7 Risk Score (IGRS), with survival analysis revealing a poorer prognosis for the high-IGRS group. Analysis of immune cell infiltration, identification of genes with differential expression, various enrichment analyses, assessment of copy number variations, and evaluation of drug susceptibility were conducted, all of which highlighted their significant influence on the prognosis of astrocytoma. Conclusion: This research enhances comprehension of the diverse cell composition of astrocytoma, delves into the various factors impacting the prognosis of astrocytoma, and offers fresh perspectives on treating glioma.

Analysis of Spinal Pilocytic Astrocytoma in 12 Case Reports and Literature Review.

Spinal pilocytic astrocytoma (PA) is a rare disorder with atypical, clinical and imaging characteristics, and generally limited to case reports. We analysed the clinical manifestations, imaging findings, treatment and prognostic follow-up of 12 patients with spinal PA admitted from January 2010 to July 2021, and reviewed the relevant literature. Radiological assessment, especially magnetic resonance imaging, can help to provide effective diagnostic information. The diagnosis and differentiation of this disease is discussed in an attempt to contribute to a more comprehensive preoperative assessment.

Determinants of long-term survival in patients with IDH-mutant gliomas.

BACKGROUND: Survival times of patients with IDH-mutant gliomas are variable and can extend to decades. Many studies provide progression-free rather than overall survival times and prognostic factors remain ill-defined. Here we explored characteristics of short- and long-term survivors within a cohort of patients with extended follow-up. METHODS: This single-center, case-control study included 86 patients diagnosed between 1998 and 2023 who either died within 6 years after diagnosis or survived at least 15 years. Patient characteristics and prognostic factors were stratified by short- (< 6 years) versus long-term (≥ 15 years) survival. RESULTS: Forty-seven patients (55%) diagnosed with astrocytoma and 39 patients (45%) with oligodendroglioma were included retrospectively. Median follow-up of the survivors was 16.6 years (range 15-28.9). Thirty-four deaths (40%) had been reported at database closure. Long-term survival was associated with CNS WHO grade 2 (p < 0.01), smaller tumor volumes (p = 0.01), lack of contrast enhancement (p < 0.01), wait-and-scan strategies (p < 0.01) and female sex (p = 0.04). In multivariate analyses for oligodendroglioma, larger T2 tumor volumes were associated with shorter survival (HR 1.02; 95% CI 1.01-1.05; p = 0.04). In patients with astrocytoma, lack of contrast enhancement (HR 0.38; 95% CI 0.15-0.94; p = 0.04) and wait-and-scan strategies (HR 5.75; 95% CI 1.66-26.61; p = 0.01) were associated with longer survival. CONCLUSION: Large T2 tumor volume and contrast enhancement may be important risk factors for shorter survival, while age might be of lesser importance. Wait-and-scan strategies may yield excellent long-term survival in some patients with astrocytoma.

Central nervous system dissemination in spinal cord astrocytomas: association with H3 K27M mutation.

OBJECTIVE: Patients with spinal cord astrocytomas (SCAs) are at high risk for CNS dissemination, yet comprehensive data on characteristics of dissemination are lacking. This study depicts the exact incidence and patterns of dissemination by analyzing data from a large-scale dataset of SCA. METHODS: The authors included 94 patients with SCA based on the 2021 WHO classification from 2011 to 2022, retrospectively collected their clinical and pathological characteristics, and analyzed factors influencing SCA dissemination. RESULTS: CNS dissemination, encompassing leptomeningeal spreading and/or subarachnoid seeding, was evaluated in 94 patients with and without H3 K27 alterations, with an overall dissemination rate reaching 85.0% at 5-year follow-up. Patients with altered H3 K27 had a significantly higher 5-year CNS dissemination rate than patients with H3 K27 wildtype status (95.2% vs 68.0%, p = 0.002). The median dissemination-free survival in H3 K27-altered patients was 14.37 (95% CI 2.84-25.89) months, significantly shorter than those with H3 K27 wildtype (statistics not calculated; p < 0.001). Based on univariate Cox regression analysis, H3 K27M alteration, higher histopathological grade, Ki-67 index (≥ 10%), and tumor length (≥ 4 segments) were identified as potential factors associated with CNS dissemination in SCAs. Multivariate Cox regression analysis revealed that H3 K27M alteration appeared to be a risk factor for this phenomenon (HR 2.089, 95% CI 0.940-4.642, p = 0.070). Following dissemination, H3 K27-altered patients had a median postdissemination survival of 8.83 (95% CI 7.13-10.54) months, which was significantly shorter than the 13.40 (95% CI 3.98-34.26) months in those with H3 K27 wildtype (p = 0.008). CONCLUSIONS: Factors indicative of higher SCA malignancy, such as H3 K27M alteration, higher histopathological grade, Ki-67 index (≥ 10%), and tumor length (≥ 4 segments), were similarly suggestive of higher rates of dissemination. The occurrence of dissemination is closely associated with the outcome events in patients with SCA.

Optimal treatment strategy for low-grade spinal cord astrocytoma: a retrospective, multicenter analysis by the Neurospinal Society of Japan.

OBJECTIVE: Primary spinal cord gliomas are rare, and among these astrocytomas (WHO grade II) are much rarer. The optimal treatment strategy thus remains unclear. The authors conducted a multicenter study led by the Neurospinal Society of Japan (NSJ) to analyze treatment policies and outcomes. The aim was to present optimal treatment methods for spinal cord astrocytoma and to identify predictors of better outcomes. METHODS: Among 1033 consecutive cases of spinal cord intramedullary tumors treated surgically at 58 centers affiliated with the NSJ, 57 patients were diagnosed with diffuse astrocytoma (WHO grade II) and were enrolled in the present study. Among these 57 patients, treatment methods, outcomes, and tumor proliferation rate as evaluated by the MIB-1 staining index (SI) were analyzed, and the optimal treatment method for spinal cord astrocytomas (grade II) was determined. In addition, the authors searched for factors predicting better treatment outcomes. RESULTS: Treatment for spinal cord astrocytoma comprised three methods: surgery alone in 30 patients, adjuvant radiation therapy in 13 patients, and adjuvant chemoradiotherapy in 13 patients. One patient who did not undergo surgery was excluded from survival analysis. Treatment with surgery alone or surgery with radiotherapy was associated with significantly longer overall and progression-free survivals than that with adjuvant chemoradiotherapy. Patients treated with radiation therapy had a higher MIB-1 SI than those treated with surgery alone. The extent of tumor resection tended to correlate with longer survival. In contrast, postoperative neurological worsening showed the inverse order. Adjuvant chemoradiotherapy was associated with the shortest survival in both total cases and recurrent cases. The optimal cutoff value of MIB-1 SI for predicting longer survival by surgery alone was less than 4.0%. CONCLUSIONS: The optimal treatment for spinal cord astrocytoma is maximal tumor resection without neurological impairment. When some tumor remains in patients with an MIB-1 SI less than 4.0%, a wait-and-see approach is optimal. If the MIB-1 SI is higher than 4.0%, local radiation therapy is recommended. Adjuvant chemotherapy is not recommended for the treatment of grade II spinal cord astrocytoma.

Consensus guidelines for the management of posterior fossa tumour for low- and middle-income countries.

The posterior fossa is a limited compartment therefore lesions compressing its structures can result in devastating outcomes. It can cause significant neurological deficit due to mass effect on critical structures and hydrocephalus. Due to the nature of the infratentorial region, urgent surgical intervention is often the first-line option. Surgical neuro-oncologists guide patients and caregivers through the course of this disease and to inform them about the various options for management and long-term outcome optimisation. There is currently conflicting data; however, institutional experiences can guide us towards achieving improvements in surgical outcomes and quality of life. Advances in molecular classifications coupled with highdose radiation treatment improve our capacity for improving overall survival in these patients. Common childhood tumours are ependymomas, medulloblastomas, and juvenile pilocytic astrocytomas, while adults often present with metastases, and less commonly, cerebellar haemangioblastomas and gliomas. This paper outlines management strategies with consideration for multidisciplinary care and resourcelimited settings.

Diencephalic syndrome in a child with chronic malnutrition. / Síndrome diencefálico en un niño con desnutrición crónica.

Russell's diencephalic syndrome is a set of signs and symptoms characterized by extreme weight loss, with no impairment of height or head circumference, without changes in intake or appetite. It is due to hypothalamic dysfunction associated with space-occupying lesions in this region. It is a rare cause of malnutrition in pediatrics, so its diagnosis is often delayed. Here we describe the case of a 17-month-old male patient with weight loss for 3 months who was admitted to the pediatric inpatient ward due to suspected intestinal malabsorption syndrome. After ruling out the most common causes of malnutrition, the patient was diagnosed with pilomyxoid astrocytoma of the brainstem.

El síndrome diencefálico de Russel es un conjunto de signos y síntomas que se caracteriza por una pérdida de peso marcada, sin afección de la talla ni el perímetro cefálico, sin modificaciones en la ingesta ni el apetito. Se debe a una disfunción hipotalámica asociada a lesiones ocupantes de espacio en dicha región. Es una causa poco frecuente de desnutrición en pediatría, por lo que el diagnóstico suele retrasarse. Se presenta el caso de un paciente de 17 meses de edad, con pérdida de peso de 3 meses de evolución que ingresó al internado pediátrico por sospecha de síndrome de malabsorción intestinal. Tras descartar las causas más frecuentes de desnutrición, se realizó diagnóstico de astrocitoma pilomixoide cerebral.

Integrated assessment of malignancy in IDH-mutant astrocytoma with p16 and methylthioadenosine phosphorylase immunohistochemistry.

In the fifth edition of the World Health Organization's (WHO) classification of tumors of the central nervous system (CNS), molecular analysis is required for not only determining each tumor type but assessing its prognosis based on malignancy (CNS WHO grade). A notable example is the loss of tumor suppressor gene cyclin-dependent kinase inhibitor 2A (CDKN2A), and CDKN2A homozygous deletion (HD) is a novel CNS WHO grade 4 marker in isocitrate dehydrogenase gene (IDH)-mutant astrocytoma. However, incorporating molecular workup into the "routine diagnostics" of each brain tumor type remains a major challenge, especially in resource-limited settings, including low- and middle-income countries. We herein validated the usefulness of p16 and methylthioadenosine phosphorylase (MTAP) immunohistochemistry (IHC) as potential surrogates for the assessment of CDKN2A status in 20 IDH-mutant astrocytoma cases. Of note, loss or retention of p16 and MTAP could accurately predict CDKN2A HD (p16: 87.5%, MTAP: 88.9%) or non-HD (p16: 100%, MTAP: 100%) with a single marker alone. Importantly, we revealed contributing factors to gray-zone IHC results (p16: 5-20%, MTAP: mosaic), including (1) hemizygous deletion of CDKN2A, (2) degenerative findings, and (3) intratumoral CDKN2A HD heterogeneity, the detailed histologic and molecular assessment of which would be a key to achieving integrated assessment of malignancy in IDH-mutant astrocytoma. We characterized the pitfalls of each method and provided for the first time a practical flowchart of astrocytoma grading, contributing to a normalization of WHO2021-based molecular diagnostics in resource-limited settings.

AB010. Analyzing Response Assessment in Neuro-Oncology (RANO) response criteria in WHO grade III anaplastic astrocytomas in comparison to clinician evaluation: a case report.

BACKGROUND: Anaplastic astrocytoma [AA; World Health Organization (WHO) grade III] is a diffusely infiltrative astrocytic brain tumor with anaplasia and represents 3.3% of primary brain tumors. Overall, 5-year median survival can range from 22% to 50%, depending on various prognostic features, including the patient's age, tumor location and genetics, resection, etc. Given the higher grade and increased likelihood of transformation to WHO-grade IV tumors (glioblastomas), these tumors are generally treated aggressively upfront. Headache and seizures are the most common symptoms, occurring in about 50% of the cases. Other symptoms, including memory loss, motor weakness, language deficit, and cognitive and personality changes, occur in 20% of cases. Standard treatment involves surgical resection, radiotherapy, and chemotherapy, but treatment options are greatly limited for progression and recurrence. This paper highlights the case of a 48-year-old male who presents with chronic progressive cephalgia and a new-onset seizure. We review the diagnostic and therapeutic challenges associated with the treatment of AA. CASE DESCRIPTION: We describe a patient who presented with chronic progressive cephalgia, gradual right-sided weakness, an asymmetrical face, slurred speech, and a new-onset focal-to-bilateral seizure. A cranial magnetic resonance imaging revealed a mass in the left frontoparietal region, causing herniation of the cerebri to the right. The patient had a maximal tumor resection, and the histopathology showed tissue sections containing tumors that were infiltrative in the stroma, forming a diffuse pattern consisting of proliferation of oval, round, polygonal, spindle, pleomorphic oval nucleated cells, hyperchromatic, some nucleoli appearing prominent, and cytoplasmaeosinophilic. There were areas of stromal necrosis and mitosis [3/10 high power field (HPF)]. The pathology result was reported with AA. The patient underwent concomitant chemoradiation and followed oral chemotherapy with temozolomid. Subsequent imaging revealed a significant decrease in the tumor's size and a resolution of the compression of the brain parenchyma underneath. The Response Assessment in Neuro-Oncology (RANO) evaluation showed partial responses with good clinical improvement. CONCLUSIONS: The case presented an AA that was responsive to radiotherapy and temozolomid chemotherapy. Despite being rare, knowledge of this malignant tumor type and a multidisciplinary approach to case management are essential to optimizing treatment results.

AB027. Distinguishing oligodendroglioma from astrocytoma: a radiological case report.

BACKGROUND: Oligodendroglioma, the third most common glioma, accounts for 5% of primary brain tumors and around 20% of all glial neoplasms. It is a rare brain tumor that develops from glial cells called oligodendrocytes, which cover nerve cells. Oligodendroglioma is classified as an adult diffuse glioma in the fifth edition of the World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS). Patients may present with cognitive impairment, aphasia, behavioral changes, and seizures. The symptoms at presentation are often related to the anatomic location of the tumor. CASE DESCRIPTION: A 55-year-old female presented with episodes of facial seizure with drooping on the right side of her face 4 months before coming to our hospital. Her seizures lasted around one minute, causing her to be unable to speak during the seizure. She also complained of chronic headaches in the last 1 year. She initially underwent a non-contrast computed tomography (CT) scan of the brain. The scans showed an isodense calcified mass on the perifalcine anterior left lobe with surrounding peritumoral edema. Magnetic resonance imaging (MRI) brain confirmed the presence of an intraaxial white matter mass involving the left frontal lobe. This tumor did not demonstrate any contrast enhancement. MRI findings were suggestive of a low-grade astrocytoma. Histopathological examination following craniotomy and tumor removal surgery confirmed the diagnosis of oligodendroglioma not otherwise specified (NOS) CNS WHO grade II. Molecular analysis revealed to be isocitrate dehydrogenase (IDH) wildtype, inconsistent with the classic molecular profile of oligodendroglioma. The patient underwent adjuvant radiotherapy following surgery. Subsequent follow-up assessments demonstrated stable disease with improvement in symptoms. CONCLUSIONS: Differentiating between oligodendroglioma and astrocytoma poses a significant challenge due to their overlapping clinical and radiological features, yet understanding their key differences is crucial for accurate diagnosis. On MRI, calcification strongly favors oligodendrogliomas, while T2/fluid-attenuated inversion recovery (FLAIR) mismatch sign favors astrocytoma. Only 50% of oligodendrogliomas appear to be contrast-enhanced. While oligodendrogliomas and astrocytomas share some similarities, careful consideration is essential for accurate differentiation, even though histopathological and molecular findings are the final determinants of diagnosis.

AB084. T2-fluid-attenuated inversion recovery (T2-FLAIR) mismatch as predictive MRI findings of diffuse astrocytoma: a case report.

BACKGROUND: Diffuse astrocytomas are a subtype of astrocytic tumors classified as World Health Organization (WHO) grade II tumors. Magnetic resonance imaging is a useful diagnostic tool for assessing diffuse astrocytomas. However, their growth pattern resembles other low-grade gliomas, such as oligodendroglioma. The potential magnetic resonance imaging (MRI) feature, T2-fluid-attenuated inversion recovery (T2-FLAIR) mismatch, may be predictive in identifying diffuse astrocytomas. This involves a hyperintense signal in T2-weighted and a hypointense signal in T2-FLAIR, which oligodendroglioma does not exhibit. CASE DESCRIPTION: A 30-year-old female seeks medical advice regarding her complaint of persistent headaches. The clinical findings suggested an anaplastic oligodendroglioma, and an MRI examination was requested to confirm. At first glance, MRI findings showed multiple cystic intratumoral and calcification, which is prone to oligodendroglioma diagnosis. However, a T2-FLAIR mismatch was observed upon closer examination, with a hyperintense signal in T2-weighted imaging and a hypointense signal in T2-FLAIR, potentially leading to diffuse astrocytoma diagnosis. Moreover, the histopathological analysis revealed isocitrate dehydrogenase (IDH)-mutant findings consistent with the characteristics of diffuse astrocytoma. Our findings of the observed T2-FLAIR mismatch were consistent with other reported cases and studies that have indicated the potential predictive value of T2-FLAIR mismatch in identifying diffuse astrocytomas. This case highlights the importance of careful observation and close examination of MRI findings, especially in differentiating between similar low-grade gliomas. The presence of a T2-FLAIR mismatch can aid clinicians in making informed decisions regarding the diagnosis and subsequent treatment plan for patients presenting with symptoms suggestive of astrocytic tumors. CONCLUSIONS: In conclusion, the T2-FLAIR mismatch sign is consistent with being the radiogenomic signature of IDH-mutant diffuse astrocytomas, as seen in our case report.

A pilocytic astrocytoma with novel ATG16L1::NTRK2 fusion responsive to larotrectinib: a case report with genomic and functional analysis.

The outcome of pilocytic astrocytoma (PA) depends heavily on the success of surgery. In cases where surgery alone is not curative, genetic analysis can be used to identify treatment targets for precision medicine. Here, we report a pediatric PA case that underwent incomplete surgical resection due to the tumor location. Clinical routine analyses demonstrated that the tumor did not carry any BRAF alteration. After postoperative surveillance, according to the low-grade glioma (LGG) protocol, recurrent tumor progressions resulted in multiple chemotherapy regimens. Screening formalin-fixed paraffin-embedded tumor material using an open-ended RNA sequencing panel revealed a novel in-frame autophagy related 16 like 1-neurotrophic receptor tyrosine kinase 2 (ATG16L1::NTRK2) fusion gene. The NTRK2 rearrangement was subsequently confirmed by fluorescent in situ hybridization on tumor tissue sections. Functional validation was performed by in vitro transient transfection of HEK293 cells and showed the ATG16L1::TRKB fusion protein to activate both the mitogen-activated protein kinase pathway and the phosphoinositide 3-kinase oncogenic pathways through increased phosphorylation of extracellular signal-regulated kinase, AKT, and S6. As a result of the identification of the NTRK fusion, the patient was enrolled in a phase I/II clinical trial of the highly selective TRK inhibitor larotrectinib. The patient responded well without significant side effects, and 8 months after the start of treatment, the contrast-enhancing tumor lesions were no longer detectable, consistent with a complete response as per Response Assessment in Neuro-Oncology (RANO) criteria. Presently, after 22 months of treatment, the patient's complete remission is sustained. Our findings highlight the importance of screening for other oncogenic drivers in BRAF-negative LGGs since rare fusion genes may serve as targets for precision oncology therapy.