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The World Health Organization's 5th edition classification of Central Nervous System (CNS) tumors differentiates diffuse gliomas into adult and pediatric variants. Pediatric-type diffuse low-grade gliomas (pDLGGs) are distinct from adult gliomas in their molecular characteristics, biological behavior, clinical progression, and prognosis. Various molecular alterations identified in pDLGGs are crucial for treatment. There are four distinct entities of pDLGGs. All four of these tumor subtypes exhibit diffuse growth and share overlapping histopathological and imaging characteristics. Molecular analysis is essential for differentiating these lesions. [ABSTRACT FROM AUTHOR]

Simple Summary: This study presented an artificial intelligence-based classification emphasizing error identification and quantification of cellularity and nuclear morphological features in digital pathological images of common astrocytic tumors. The identification of incorrect predictions was essential for the subsequent development of better techniques. Quantifying cellularity and nuclear morphological features brought deeper insights into neoplastic morphology and paved the way for further development of a scoring system for objective classification and precision diagnosis to improve interobserver variations. Interobserver variations in the pathology of common astrocytic tumors impact diagnosis and subsequent treatment decisions. This study leveraged a residual neural network-50 (ResNet-50) in digital pathological images of diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma to recognize characteristic pathological features and perform classification at the patch and case levels with identification of incorrect predictions. In addition, cellularity and nuclear morphological features, including axis ratio, circularity, entropy, area, irregularity, and perimeter, were quantified via a hybrid task cascade (HTC) framework and compared between different characteristic pathological features with importance weighting. A total of 95 cases, including 15 cases of diffuse astrocytoma, 11 cases of anaplastic astrocytoma, and 69 cases of glioblastoma, were collected in Taiwan Hualien Tzu Chi Hospital from January 2000 to December 2021. The results revealed that an optimized ResNet-50 model could recognize characteristic pathological features at the patch level and assist in diagnosis at the case level with accuracies of 0.916 and 0.846, respectively. Incorrect predictions were mainly due to indistinguishable morphologic overlap between anaplastic astrocytoma and glioblastoma tumor cell area, zones of scant vascular lumen with compact endothelial cells in the glioblastoma microvascular proliferation area mimicking the glioblastoma tumor cell area, and certain regions in diffuse astrocytoma with too low cellularity being misrecognized as the glioblastoma necrosis area. Significant differences were observed in cellularity and each nuclear morphological feature among different characteristic pathological features. Furthermore, using the extreme gradient boosting (XGBoost) algorithm, we found that entropy was the most important feature for classification, followed by cellularity, area, circularity, axis ratio, perimeter, and irregularity. Identifying incorrect predictions provided valuable feedback to machine learning design to further enhance accuracy and reduce errors in classification. Moreover, quantifying cellularity and nuclear morphological features with importance weighting provided the basis for developing an innovative scoring system to achieve objective classification and precision diagnosis among common astrocytic tumors. [ABSTRACT FROM AUTHOR]

Objectives We present the case of a 37-year-old female who underwent partial resection in 2018 for a diffuse fibrillary astrocytoma (WHO II) that invaded almost the entire right cerebral hemisphere. The patient followed conventional radiotherapy and chemotherapy. She presents after 6 years of regularly follow-ups with left hemiparesis, intracranial hypertension syndrome and tumor recurrence on MRI. The patient underwent another surgical intervention and the new histopathological diagnosis was diffuse astrocytoma grade IV. Therapeutic options for these patients are limited considering the fact that a gross total resection or a conventional re-irradiation could impact the quality of life. Therefore, exploring new therapeutic methods, such as targeted molecular therapy like EGFR antagonists or proteasome inhibitors, or proton therapy, should be considered. Material and Methods We conducted extensive research in two public medical databases for information related to the molecular pathways and management of primary and recurrent malignant astrocytoma and relevant articles were selected. Subsequently, we correlated this information with our direct experience in our case and discussed the observed results. Results Treatment modalities for these patients include reintervention, re-irradiation and second line chemotherapeutics. In relapsing cases the goal of reintervention is both to alleviate symptoms and obtain tumoral tissue for immunohistochemical analysis for identification of the new mutations. Conventional re-irradiation for large lesions carries high risks of producing both short-term and long-term side effects, impacting the quality of life. Alternatively, proton therapy minimizes the risk of adverse events due to Bragg peak reducing the irradiation of the surrounding tissue. Conclusions Genetic characterization of these lesions can facilitate targeted molecular therapy and help in establishing the prognosis. Re-irradiation of malignant astrocytomas with proton therapy is an effective treatment measure allowing for comparable tumor control to conventional radiotherapy.

Auditory processing is initiated within the primary auditory cortex, concealed within the sylvian fissure bilaterally on a collection of gyri described as Heschl's Gyrus (HG). Glial neoplasms localized to or involving HG are rare. The main symptoms of these tumours are complex partial seizures characterized by auditory features. Here, we describe an unusual case of bilateral tinnitus and hemi-paraesthesia associated with a HG diffuse astrocytoma. Bilateral tinnitus secondary to intrinsic brain tumours is atypical. Bilateral tinnitus is frequently observed in patients with noise-induced hearing loss, presbycusis, ototoxic medication, and metabolic and psychiatric disease. In the case we present, the synchronous sensory and auditory symptoms are likely due to seizure activity affecting the primary auditory and somatosensory cortex. In a patient presenting with chronic, bilateral tinnitus with no known underlying otologic disease which is associated with hemi-body paraesthesia, we would advocate for consideration of brain imaging to exclude pathology in HG. [ABSTRACT FROM AUTHOR]

Primary glioblastoma develops de novo without clinical or histological evidence of a low-grade precursor lesion, whereas secondary glioblastoma develops from a low-grade glioma. The present report describes an extraordinary case of IDH-wildtype secondary glioblastoma arising in IDH-mutant diffuse astrocytoma. A 31-year-old female had a surgical history of IDH-mutant diffuse astrocytoma on the left frontal lobe six years before. Magnetic resonance imaging revealed new infiltrative lesions in the left frontal lobe adjacent to the previous lesion. The patient underwent tumourectomy, and the new infiltrative lesion was diagnosed as glioblastoma. Interestingly, the IDH-1 (p.Arg132His) mutation was found in diffuse astrocytoma but not in glioblastoma based on next generation sequencing. ATRX (p.Gln1670Ter) and TP53 (p.His193Arg) mutations were found in both lesions. Additionally, the PTEN (p.His296Pro) mutation was identified only in glioblastoma. A well-accepted hypothesis is that the IDH mutation initiates in glial progenitor cells and causes secondary glioblastoma harboring the IDH mutation to develop from low grade glioma with IDH mutation. However, this case showed that the other genetic mutations can be initiated before the IDH mutation in glioma oncogenesis. Contrary to the previous hypothesis, this is the first case of IDH-wildtype secondary glioblastoma arising in IDH-mutant diffuse astrocytoma. [ABSTRACT FROM AUTHOR]

We discuss a case of a paediatric low grade glioma where the integrated diagnosis was a diffuse astrocytoma with MYB or MYBL1 alteration. Surgical excision of the tissue revealed a low grade tumour appearance with small round nuclei and fine fibrillary cytoplasm. MYB or MYBL1-alteration was shown on methylation array analysis. MYB and MYBL1 are transcriptional transactivators that have important roles in cell proliferation, and their overexpression can lead to tumour formation. The diagnosis of novel subtypes of paediatric low-grade gliomas is now possible due to the increasing role of molecular pathology. [ABSTRACT FROM AUTHOR]

Introduction: Gliomas are the most common primary intracranial tumors. The current World Health Organization (WHO) classification of central nervous system tumors recommends integrated histo-molecular diagnosis of gliomas. However, molecular testing is not available in even most of the advanced centers of our country, and histopathology aided with immunohistochemistry (IHC) is still widely used for diagnosis. Immunohistochemical markers such as iso-citrate dehydrogenase1 (IDH1) and Alpha Thalassemia/ Mental Retardation Syndrome X-linked (ATRX) can be reliably used for the correct diagnosis, prognosis, and treatment of gliomas. Aim: We aimed to develop a diagnostic algorithm by integrating morphology, IDH1, and ATRX status of gliomas seen in our institute for 1 year. Settings and Design: Analytical cross-sectional study. Materials and Methods: This study included 60 histopathologically confirmed cases of astrocytic (n = 51) and oligodendroglial tumors (n = 9). Clinical, radiological, and histopathological features were noted and tumor grades assigned according to the WHO recommendations. IDH1 and ATRX mutation status was evaluated using IHC. The tumors were divided into three molecular groups on the basis of their IDH1 and ATRX mutation status: (1) Group 1: IDH1 negative and ATRX positive, (2) Group 2: IDH1 positive and ATRX positive, (3) Group 3: IDH1 positive and ATRX negative. Results: The mean age of presentation was 45.0 ± 15.8 years with a male-to-female ratio of 2:1. Seizures, headache, and hemiparesis were the most common modes of presentation. The tumor subtypes studied were glioblastoma (n = 32), anaplastic astrocytoma (n = 7), diffuse astrocytoma (n = 6), oligodendroglioma (n = 6), pilocytic astrocytoma (n = 6), and anaplastic oligodendroglioma (n = 3). IDH1 mutation was present in 26 cases including anaplastic astrocytoma (n = 7), diffuse astrocytoma (n = 6), oligodendroglioma (n = 5), secondary glioblastoma (n = 5), and anaplastic oligodendroglioma (n = 3). ATRX mutation, i. e., loss of ATRX was observed in 17 cases including diffuse astrocytoma (n = 5), anaplastic astocytoma (n = 5), anaplastic oligodendroglioma (n = 3), oligodendroglioma (n = 3), and secondary glioblastoma (n = 1). All six cases of pilocytic astrocytoma were negative for IDH1 and ATRX mutation. There were 34 patients in Group 1 (IDH1-- and ATRX +), nine cases in Group 2 (IDH1 + and ATRX +), and 17 patients in Group 3 (IDH1 + and ATRX-). Conclusion: Diagnosis of gliomas should be based on a detailed clinicoradiological and histopathological assessment, followed by genotypic characterization. Evaluation for IDH1and ATRX status has both diagnostic and prognostic value as it helps in differentiating gliomas from reactive gliosis, primary glioblastoma from secondary glioblastoma, and pilocytic astrocytoma (WHO grade I) from diffuse astrocytoma (WHO grade II). Tumors with IDH1 mutations have a better outcome than those with wild-type IDH. IHC can serve as a useful surrogate to conventional molecular tests in resource-constrained settings. By devising an algorithm based on morphological and IHC features, we were able to stratify gliomas into three prognostic subgroups. [ABSTRACT FROM AUTHOR]

Malignant progression of diffuse low-grade glioma (LGG) is a critical event affecting patient survival; however, the incidence and related factors have been inconsistent in literature. According to the PRISMA guidelines, we systematically reviewed articles from 2009, meta-analyzed the incidence of malignant progression, and clarified factors related to the transformation. Forty-one articles were included in this study (n = 7,122; n, number of patients). We identified two definitions of malignant progression: histologically proven (Htrans) and clinically defined (Ctrans). The malignant progression rate curves of Htrans and Ctrans were almost in parallel when constructed from the results of meta-regression by the mean follow-up time. The true transformation rate was supposed to lie between the two curves, approximately 40% at the 10-year mean follow-up. Risk of malignant progression was evaluated using hazard ratio (HR). Pooled HRs were significantly higher in tumors with a larger pre- and postoperative tumor volume, lower degree of resection, and notable preoperative contrast enhancement on magnetic resonance imaging than in others. Oligodendroglial histology and IDH mutation (IDHm) with 1p/19q codeletion (Codel) also significantly reduced the HRs. Using Kaplan-Meier curves from eight studies with molecular data, we extracted data and calculated the 10-year malignant progression-free survival (10yMPFS). The 10yMPFS in patients with IDHm without Codel was 30.4% (95% confidence interval [95% CI]: 22.2-39.0) in Htrans and 38.3% (95% CI: 32.3-44.3) in Ctrans, and that with IDHm with Codel was 71.7% (95% CI: 61.7-79.5) in Htrans and 62.5% (95% CI: 55.9-68.5) in Ctrans. The effect of adjuvant radiotherapy or chemotherapy could not be determined.

Background. Despite the fact that cerebral astrocytoma belongs to low-grade tumors (grade II gliomas), it often leads to disability and death of patients. The localization of the tumor determines the severity of the clinical symptoms of the disease, which significantly affects its prognosis. The choice of the optimal treatment strategy for astrocytoma localized in the brain stem poses challenges and enables the vast majority of patients to be classified as inoperable. Therefore, radiation therapy or chemoradiotherapy are the main treatment modalities for patients with low-grade glioma. The location of the tumor in close proximity to vital centers makes radiation therapy planning difficult., because the delivery of high doses of radiation can cause serious treatment complications.Description of the clinical case. We present a clinical case of a successful treatment of a young, 20-year-old male patient with diffuse astrocytoma of the brain stem. As radical surgery was impossible to be performed, the patient was offered radiation therapy. The morphology, size, and location of the primary tumor posed challenges for selecting an optimal treatment strategy due to a high risk of damage to vital centers, which could lead to disability and even death of the patient. The use of proton therapy made it possible to deliver the maximum allowable dose of radiation to the tumor, limiting radiation exposure to surrounding healthy tissues. The patient received the complete course of proton therapy. After 36 months of follow-up, no complications and signs of disease progression were found.Conclusion. Despite the high risk of treatment complications, the use of proton therapy made it possible to complete the planned course of treatment, achieve tumor stabilization and significantly improve the life quality of the patient.

Simple Summary: Current data show that resilience is an important factor in cancer patients' well-being. We explored the resilience of patients with lower grade glioma (LGG) and the potentially influencing factors. Our data indicate that stigmatization and the functional status are significantly associated with the patients' resilience. These factors should be identified and targeted therapeutically in clinical routines. Current data show that resilience is an important factor in cancer patients' well-being. We aim to explore the resilience of patients with lower grade glioma (LGG) and the potentially influencing factors. We performed a cross-sectional assessment of adult patients with LGG who were enrolled in the LoG-Glio registry. By phone interview, we administered the following measures: Resilience Scale (RS-13), distress thermometer, Montreal Cognitive Assessment Test for visually impaired patients (MoCA-Blind), internalized stigmatization by brain tumor (ISBI), Eastern Cooperative Oncological Group performance status (ECOG), patients' perspective questionnaire (PPQ) and typical clinical parameters. We calculated correlations and multivariate regression models. Of 74 patients who were assessed, 38% of those showed a low level of resilience. Our results revealed significant correlations of resilience with distress (p < 0.001, −0.49), MOCA (p = 0.003, 0.342), ECOG (p < 0.001, −0.602), stigmatization (p < 0.001, −0.558), pain (p < 0.001, −0.524), and occupation (p = 0.007, 0.329). In multivariate analyses, resilience was negatively associated with elevated ECOG (p = 0.020, β = −0.383) and stigmatization levels (p = 0.008, β = −0.350). Occupation showed a tendency towards a significant association with resilience (p = 0.088, β = −0.254). Overall, low resilience affected more than one third of our cohort. Low functional status is a specific risk factor for low resilience. The relevant influence of stigmatization on resilience is a novel finding for patients suffering from a glioma and should be routinely identified and targeted in clinical routine. [ABSTRACT FROM AUTHOR]

Background: Malignant transformation (MT) of low-grade astrocytoma (LGA) produces a poor prognosis in benign tumors. Currently, variables linked with MT of LGA have proven equivocal. The present study aims to evaluate the risk variables, indicating that LGA gradually differentiates to malignant astrocytoma.Methods: Retrospective cohort analysis of LGA patients was performed. Both univariate and multivariate studies were used to discover variables connected to MT using the Cox regression method. As a result, the cumulative incidence of MT for each covariate survival curve was built after the final model.Results: In the current study, 115 individuals with LGA were included in the analysis, and MT was found in 16.5% of cases. In the case of MT, 68.4% of patients progressed to glioblastoma, whereas 31.6% progressed to anaplastic astrocytoma. Significant factors included supratentorial tumor (hazard ratio (HR) 3.41, 95% CI 1.18-12.10), midline shift > 5 mm (HR 7.15, 95% CI 2.28-34.33), and non-total resection as follows: subtotal resection (HR 5.09, 95% CI 0.07-24.02), partial resection (HR 1.61, 95% CI 1.09-24.11), and biopsy (HR 2.80, 95% CI 1.18-32.52).Conclusion: In individuals with LGA, MT dramatically altered the disease's natural history to a poor prognosis. The present study's analysis of the clinical features of patients indicated supratentorial LGA, a midline shift greater than 5 mm, and the degree of resection as risk factors for MT. The more extensive the resection, the greater the reduction in tumor load and MT. In addition, more molecular study is necessary to elucidate the pathophysiology of MT. [ABSTRACT FROM AUTHOR]

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.

Abstract Background Hospital-based cancer registries can provide information on the magnitude and distribution of cancers in a given hospital. Hospital-based brain tumor registry data, focusing on glioma, from a tertiary care rural neurological center is lacking in the scientific literature. This data can be useful in understanding the need for research and funding required for these specific brain tumors. Data of patients operated for glioma, at our institute, was collected between January 2004 and December 2015. Patients’ clinical details and histopathological diagnosis were recorded. Data were analyzed and compared with that of previously published literature, and inferences were drawn on patterns of reporting and epidemiology. Results A total of 1450 cases of glioma, with a mean age of 39.3 (± 17.36 SD) years with males (66.6%) comprising more population as compared to females. Majority of patients 70.8% (n = 1027) belong to the economically active age group of country (18–60 years). Majority of cases (41.4%) were glioblastoma with the next common tumor (22.8%) being diffuse astrocytoma (n = 331) followed by pilocytic astrocytoma (6.2%) and oligodendroglioma (4.5%) in that order. While our data followed similar trends with other Indian data the average age of glioma was a decade younger to what is quoted earlier in Indian and international studies. Conclusion This data for glioma gives a glimpse of the prevalence of this tumor in a primarily rural population and highlights the need for a National Brain Tumor Registry with the need for the development of evidence-based policymaking and enhanced research into this particular ailment.

Fang He,1 Yunxia Xia,1 Xiaoling Ling2 1The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, Gansu, People’s Republic of China; 2Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, People’s Republic of ChinaCorrespondence: Xiaoling LingDepartment of Oncology, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, People’s Republic of ChinaTel +86 18693165668Email ldyy_lingxl@Lzu.edu.cnAbstract: Continuous optimization of diagnosis and treatment of malignant tumors has led to significantly prolonged survival in cancer patients. Despite the recent increase in the incidence of multiple primary malignant tumors (MPMT), it remains rare in clinical practice; therefore, normative guidance on its etiology, diagnosis, and treatment is insufficient. Here we describe the case of a patient with three primary malignant tumors, namely breast cancer, diffuse astrocytoma, and hepatic malignant perivascular epithelioid cell tumors (PEComa) and discuss relevant literature.Keywords: multiple primary malignant tumors, breast cancer, diffuse astrocytoma, liver malignant PEComa, etiology, prognosis

Purpose: The presence of necrosis or microvascular proliferation was previously the hallmark for glioblastoma (GBM) diagnosis. The 2021 WHO classification now considers IDH-wildtype diffuse astrocytic tumors without the histological features of glioblastoma (that would have otherwise been classified as grade 2 or 3) as molecular GBM (molGBM) if they harbor any of the following molecular abnormalities: TERT promoter mutation, EGFR amplification, or chromosomal + 7/−10 copy changes. We hypothesize that these tumors are early histological GBM and will eventually develop the classic histological features. Methods: Medical records from 65 consecutive patients diagnosed with molGBM at three tertiary-care centers from our institution were retrospectively reviewed from November 2017-October 2021. Only patients who underwent reoperation for tumor recurrence and whose tissue at initial diagnosis and recurrence was available were included in this study. The detailed clinical, histopathological, and radiographic scenarios are presented. Results: Five patients were included in our final cohort. Three (60%) patients underwent reoperation for recurrence in the primary site and 2 (40%) underwent reoperation for distal recurrence. Microvascular proliferation and pseudopalisading necrosis were absent at initial diagnosis but present at recurrence in 4 (80%) patients. Radiographically, all tumors showed contrast enhancement, however none of them showed the classic radiographic features of GBM at initial diagnosis. Conclusions: In this manuscript we present preliminary data for a hypothesis that molGBMs are early histological GBMs diagnosed early in their natural history of disease and will eventually develop necrosis and microvascular proliferation. Further correlative studies are needed in support of this hypothesis. [ABSTRACT FROM AUTHOR]

Background Malignant transformation (MT) of low-grade gliomas changes dramatically the natural history to poor prognosis. Currently, factors associated with MT of gliomas have been inconclusive, in particular, diffuse astrocytoma (DA). Objective The present study aimed to explore the molecular abnormalities related to MT in the same patients with different MT stages. Methods Twelve specimens from five DA patients with MT were genotyped using next-generation sequencing (NGS) to identify somatic variants in different stages of MT. We used cross-tabulated categorical biological variables and compared the mean of continuous variables to assess for association with MT. Results Ten samples succussed to perform NGS from one male and four females, with ages ranging from 28 to 58 years. The extent of resection was commonly a partial resection following postoperative temozolomide with radiotherapy in 25% of cases. For molecular findings, poly-T-nucleotide insertion in isocitrate dehydrogenase 1 (IDH1) was significantly related to MT as a dose–response relationship (Mann–Whitney's U test, p = 0.02). Also, mutations of KMT2C and GGT1 were frequently found in the present cohort, but those did not significantly differ between the two groups using Fisher's exact test. Conclusion In summary, we identified a novel relationship between poly-T insertion polymorphisms that established the pathogenesis of MT in DA. A further study should be performed to confirm the molecular alteration with more patients.

Familial melanoma-astrocytoma syndrome is a tumor predisposition syndrome caused by inactivating germline alteration of the CDKN2A tumor suppressor gene on chromosome 9p21. While some families with germline CDKN2A mutations are prone to development of just melanomas, other families develop both melanomas, astrocytomas, and occasionally other nervous-system neoplasms including peripheral nerve sheath tumors and meningiomas. The histologic spectrum of the astrocytomas that arise as part of this syndrome is not well described, nor are the additional genetic alterations that drive these astrocytomas apart from the germline CDKN2A inactivation. Herein, we report the case of a young man with synchronous development of a pleomorphic xanthoastrocytoma, diffuse astrocytoma, and paraspinal mass radiographically consistent with a peripheral nerve sheath tumor. His paternal family history is significant for melanoma, glioblastoma, and oral squamous cell carcinoma. Genomic profiling revealed that he harbors a heterozygous deletion in the germline of chromosome 9p21.3 encompassing the CDKN2A and CDKN2B tumor suppressor genes. Both the pleomorphic xanthoastrocytoma and diffuse astrocytoma were found to have homozygous deletion of CDKN2A/B due to somatic loss of the other copy of chromosome 9p containing the remaining intact alleles. Additional somatic alterations included BRAF p.V600E mutation in the pleomorphic xanthoastrocytoma and PTPN11, ATRX, and NF1 mutations in the diffuse astrocytoma. The presence of germline CDKN2A/B inactivation together with the presence of multiple anatomically, histologically, and genetically distinct astrocytic neoplasms, both with accompanying somatic loss of heterozygosity for the CDKN2A/B deletion, led to a diagnosis of familial melanoma-astrocytoma syndrome. This remarkable case illustrates the histologic and genetic diversity that astrocytomas arising as part of this rare glioma predisposition syndrome can demonstrate.
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We report on a case of a 16-year old boy with a contrast-enhancing mass on the left parietal lobe that showed complete remission after biopsy. Histological examination revealed a diffuse glioma. Due to this unusual course, an extended neurological evaluation was carried out. Cerebrospinal fluid (CSF) was analysed and electrophysiological studies were performed. There was no strong evidence for an inflammable disease and no other pathology could be identified with sufficient certainty. In the follow up cranial MRI scan 6, 12, and 18 months after surgery, complete remission of the contrast-enhancing mass and the perifocal edema persisted. Such a case has not yet been reported.

BACKGROUND Structural damage to the brain substance in adults is one of the most common causes of epilepsy. Currently, such patients are prescribed drug therapy and/or surgery. With this approach, epileptic symptoms can persist in a significant proportion of patients (up to 30%, depending on the disease).AIM OF STUDY To clarify the efficacy of stereotactic radiosurgery (STS) as part of the complex treatment of patients suffering from pharmacoresistant symptomatic epilepsy with hippocampal sclerosis, vascular malformations, and some benign tumors of the brain and its membranes.MATERIAl AND METHODS Examination and radiosurgical treatment were carried out in 45 patients with various brain diseases accompanied by symptomatic epilepsy, provided that the previous conservative or surgical treatment was insufficiently effective. During the observation period, the frequency of seizures was assessed and the presence and nature of postoperative complications were recorded.RESUlTS With a median follow-up of 30 months, good outcomes (class I–II according to J. Engel’s scale) were observed in 5 out of 8 patients with hippocampal sclerosis who underwent STS after amygdaloghippocamplobectomy; seizure frequency decreased in all patients. Complications of STS were noted in 2 patients and had a transient nature. In the group of patients with meningiomas, in 4 out of 8 patients, seizures completely stopped, in 3 patients the frequency of seizures decreased by more than 90%, in another 1 the frequency of seizures decreased by 60%. There were no complications of STS during the observation period. Inintracerebral tumors (diffuse astrocytoma), Engel Ia outcome was observed in both patients. In the group of patients with cavernous angiomas, there were good outcomes (class I–II according to J. Engel’s scale) in 17 patients (85%). Deterioration (Engel IVc outcome) was observed in 1 patient (5%), 2 patients (10%) had complications of STS. In the group of patients with arteriovenous malformations, good outcomes (classes I–II according to J. Engel’s scale) were found in all 7 patients. The complication after STS was revealed in 1 patient.CONClUSION The presented results confirm the high efficiency and low risk of side effects when using stereotactic radiosurgery in the complex treatment of patients with epilepsy associated with common structural brain lesions.

Diffuse astrocytoma is the most common glioma, account for 70% of all gliomas. The involvement of various growth factors, growth factor receptor and cell cycle influence the pathogenesis of astrocytoma. EGFRvIII is the most common mutant variant of EGFR involving cell proliferation which is being studied extensively. pRb is a protein encoded by the RB gene that plays an important role in regulating the cell cycle from G1 to S phase, particularly during transcription and protein synthesis. The objectives of this study are to analyze the expression of EGFRvIII and pRb in grades II, III and IV astrocytomas and to analyze the correlation between EGFRvIII and pRb expressions. The research design used was cross sectional. The samples were consisted of 2 grade II astrocytomas, 8 grade III astrocytomas and 15 grade IV astrocytomas that diagnosed at Dr. Soetomo Hospital, Surabaya, in the period of 2014 to 2018. Immunohistochemistry with monoclonal antibodies EGFRvIII and pRB were applied on all samples. The differences in the expression of EGFRvIII and pRb in grade II, III and IV astrocytomas were analyzed using Kruskall Wallis. The correlation between EGFRvIII and pRb expression in astrocytomas was analyzed using Spearman test. There were no significant differences in expression of EGFRvIII in grade II, III and IV astrocytomas (p = 0.717, p>0.05). There was no significant difference in pRb expression in grade II, III and IV astrocytoma (p = 0.631, p>0.05). There was no significant correlation between the expression of EGFRvIII and pRb in diffuse astrocytoma (rs = 0.02 p = 0.923, p>0.05). [ABSTRACT FROM AUTHOR]

Purpose: Histological diagnosis of glioblastoma (GBM) was determined by the presence of necrosis or microvascular proliferation (histGBM). The 2021 WHO classification now considers IDH-wildtype diffuse astrocytic tumors without the histological features of glioblastoma (that would have otherwise been classified as grade 2 or 3) as molecular GBM (molGBM, WHO grade 4) if they harbor any of the following molecular abnormalities: TERT promoter mutation, EGFR amplification, or chromosomal + 7/− 10 copy changes. The objective of this study was to explore and compare the survival outcomes between histGBM and molGBM. Methods: Medical records for patients diagnosed with GBM at the three tertiary care academic centers of our institution from November 2017 to October 2021. Only patients who underwent adjuvant chemoradiation were included. Patients without molecular feature testing or with an IDH mutation were excluded. Univariable and multivariable analyses were performed to evaluate progression-free (PFS) and overall- survival (OS). Results: 708 consecutive patients were included; 643 with histGBM and 65 with molGBM. Median PFS was 8 months (histGBM) and 13 months (molGBM) (p = 0.0237) and median OS was 21 months (histGBM) versus 26 months (molGBM) (p = 0.435). Multivariable analysis on the molGBM sub-group showed a worse PFS if there was contrast enhancement on MRI (HR 6.224 [CI 95% 2.187–17.714], p < 0.001) and a superior PFS on patients with MGMT methylation (HR 0.026 [CI 95% 0.065–0.655], p = 0.007). Conclusions: molGBM has a similar OS but significantly longer PFS when compared to histGBM. The presence of contrast enhancement and MGMT methylation seem to affect the clinical behavior of this subset of tumors. [ABSTRACT FROM AUTHOR]

Diffuse astrocytoma is an infiltrating type of glioma (World Health Organization grade II), which even with histopathology, is difficult to diagnose. Magnetic resonance imaging (MRI) is the cornerstone for diagnoses and follow-up of brain gliomas. This report describes a case of diffuse astrocytoma in a 48-year-old man who presented with sudden right-sided weakness and repeated convulsive attacks. On brain computed tomography, the case was diagnosed and treated as an acute infarction. Ten days later, the patient returned with a total loss of consciousness. Brain MRI images revealed an irregularly outlined lesion involving the splenium of the corpus callosum that extended into the left periventricular parietal lobe of the brain with cystic foci in the septum pellucidum. Contrast-enhanced and new sequences of MRI was helpful in approach to diagnosis because of its superior tissue characterization. The histopathology results ultimately confirmed the diagnosis of diffuse astrocytoma. The patient died postoperatively.

In 2016, the World Health Organization revised its guidelines to retain only gemistocytic astrocytoma (GemA) as a distinct variant of diffuse astrocytoma (DA). In the past, grade II GemAs were linked with a worse prognosis than DA. However, it is unclear how consistently the tumor subtype has been diagnosed over time. We used more recent data to compare outcomes between grade II GemA and DA. Patients with grade II DA and GemA were extracted from the Surveillance, Epidemiology, and End Results database between 1973 and 2016. Kaplan-Meier curves estimated survival differences across different eras, with a focus on patients diagnosed between 2000 and 2016, and propensity score matching was used to balance baseline characteristics between DA and GemA cohorts. Of 2467 patients with grade II astrocytoma diagnosed between 2000 and 2016, 132 (5.35%) had GemA, and 2335 (94.65%) had DA. At baseline, marked demographic and treatment differences were noted between tumor subtypes, including age at diagnosis and female sex. GemA patients did not have worse survival compared with DA patients at baseline (P = 0.349) or after propensity score matching (P = 0.497). Multivariate Cox models found that surgical extent of resection was associated with a survival benefit for DA patients, and both DA and GemA patients >65 years old had dramatically inferior survival. Our data suggest that the impact of GemA versus DA histopathology depends more on the decade of queried data rather than patient-specific demographics. Using more recent longitudinal data, we found that grade II GemA and DA tumors did not have significant differences in survival. These data may prove useful for clinicians counseling patients with grade II GemA. [ABSTRACT FROM AUTHOR]

Background Malignant transformation (MT) of low-grade astrocytoma (LGA) triggers a poor prognosis in benign tumors. Currently, factors associated with MT of LGA have been inconclusive. The present study aims to explore the risk factors predicting LGA progressively differentiated to malignant astrocytoma. Methods The study design was a retrospective cohort study of medical record reviews of patients with LGA. Using the Fire and Gray method, the competing risk regression analysis was performed to identify factors associated with MT, using both univariate and multivariable analyses. Hence, the survival curves of the cumulative incidence of MT of each covariate were constructed following the final model. Results Ninety patients with LGA were included in the analysis, and MT was observed in 14.4% of cases in the present study. For MT, 53.8% of patients with MT transformed to glioblastoma, while 46.2% differentiated to anaplastic astrocytoma. Factors associated with MT included supratentorial tumor (subdistribution hazard ratio [SHR] 4.54, 95% confidence interval [CI] 1.08–19.10), midline shift > 1 cm (SHR 8.25, 95% CI 2.18–31.21), and nontotal resection as follows: subtotal resection (SHR 5.35, 95% CI 1.07–26.82), partial resection (SHR 10.90, 95% CI 3.13–37.90), and biopsy (SHR 11.10, 95% CI 2.88–42.52). Conclusion MT in patients with LGA significantly changed the natural history of the disease to an unfavorable prognosis. Analysis of patients' clinical characteristics from the present study identified supratentorial LGA, a midline shift more than 1 cm, and extent of resection as risk factors associated with MT. The more extent of resection would significantly help to decrease tumor burden and MT. In addition, future molecular research efforts are warranted to explain the pathogenesis of MT. [ABSTRACT FROM AUTHOR]

Introduction. Mutations in the isocytrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) are considered driver genetic events in gliomas. Their frequency reaches 7080 % in low-grade gliomas and in secondary glioblastomas, and their oncogenic effect is realized by accumulation of the metabolite 2-hydroxyglutarate, which disrupts DNA and protein methylation processes. The aim of the study was to analyze the associations between the presence of IDH1/2 mutations and clinical and morphological parameters of glial tumors. Material and Methods. The study included 147 patients with glial brain tumors. Associations between IDH1/2 status and tumor histological type, age of disease onset, tumor localization, and clinical manifestations were investigated. Results. Gliomas containing IDH1/2 mutations were characterized by a younger age at diagnosis (mean: 39.5 years) compared to IDH-negative cases (47.2 years) (p

Neurofibromatosis type 1 (NF1) is one of the most common genetic neurocutaneous disorders, and it is well known to be associated with peripheral or central nervous system malignancies. The most common malignant tumors are malignant peripheral nerve sheath tumors (MPNSTs); MPNSTs are the most common cause of death in patients with NF1. Central nervous system malignancies rarely occur. So far, the occurrence of spinal cord malignancies is exceedingly rare. Herein, we report a rare case of a 69-year-old male with NF1 following tumor resection twice for cutaneous MPNSTs developing intramedullary diffuse astrocytoma in the conus medullaris, which initially presented with traumatic spinal cord injury associated with a compression fracture from fall. Contrast-enhanced magnetic resonance imaging and biopsy of the spinal cord were required to establish the final diagnosis.

The World Health Organization (WHO) Central Nervous System (CNS) Tumors Classification 5 th edition (2021) integrates both molecular and histopathological criteria for diagnosing glial tumors. This updated classification highlights significant differences between pediatric and adult gliomas in terms of molecular characteristics and prognostic implications. The 5 th edition comprises a new category of pediatric-type diffuse low-grade glioma (PDLGG) and pediatric-type diffuse high-grade glioma (PDHGG), classified mainly based on genetic alterations and histopathological features. We reviewed the microscopy, diagnostic molecular pathology, and prognosis of various tumors under the categories PDLGG and PDHGG. The review also addresses the need for clarification concerning overlapping diagnostic features. PDLGG are characterized by diffuse growth, low-grade morphology, and MYB/MYBL1(MYB Proto-Oncogene Like 1) gene fusion or mitogen-activated protein kinase (MAPK) pathway alterations. In contrast, PDHGG is described by diffuse growth, high-grade morphology, and increased mitosis and often shows alterations of histone gene resulting in epigenetic alterations, which contrasts with common isocitrate dehydrogenase (IDH) mutation and epidermal growth factor receptor (EGFR) amplification seen in adult-type high-grade glioma., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s).)

Introduction Astrocytomas are the most common gliomas, classified on the basis of grade and IDH mutation status according to the World Health Organization (WHO) 2016 update. IDH mutations are seen in 70 to 80% of diffuse grade II and III astrocytomas and are associated with better outcome. They serve as predictive biomarker in IDH -targeted therapies such as small-molecule inhibitors or vaccines. Objective The aim of this study was to analyze the clinical, morphological, immunohistochemical, and molecular genetic characteristics of diffuse astrocytoma (DA: grades II and III). The IDH mutant and wild-type tumors are compared and contrasted with survival analysis on follow-up. Materials and Methods This was a retrospective study conducted on surgically resected tumor specimens. The hematoxylin and eosin-stained slides were examined for histologic features. Immunohistochemistry (IHC) was performed using IDH1R132H , ATRX, p53 , and Ki67. All cases of negative immunohistochemical expression of IDH1R132H were subjected to IDH1 mutation analysis by Sanger sequencing. Overall survival was estimated by the Kaplan-Meier method using the log-rank (Mantel–Cox) test. Results The study included 51 cases of DA in the age of 17 to 66 years, mean ± standard deviation was 35.5 ± 9.7 years, and male:female ratio was 2:1.The IDH1R132H cytoplasmic immunopositivity was seen in 36 cases (70.5%), of which 63.6% were of grade II and 72.5% were of grade III. ATRX showed loss of expression in 50 cases (98%), and p53 showed diffuse strong immunohistochemical expression in all the cases of IDH mutant tumors. The difference in the age at presentation for IDH mutant (32.5 years) and wild type tumors (38 years) was statistically significant. Median survival was 55.3 months and 22.2 months in of IDH mutant and wild type cases, respectively. Conclusion IHC and sequencing for IDH mutations is helpful in making an integrated diagnosis and classifying definite molecular subgroups of astrocytic tumors. Mutations in IDH core-elate with survival. IDH mutant tumors showed longer survival duration and are good prognostic indicators. [ABSTRACT FROM AUTHOR]

Background: Hospital-based cancer registries can provide information on the magnitude and distribution of cancers in a given hospital. Hospital-based brain tumor registry data, focusing on glioma, from a tertiary care rural neurological center is lacking in the scientific literature. This data can be useful in understanding the need for research and funding required for these specific brain tumors. Data of patients operated for glioma, at our institute, was collected between January 2004 and December 2015. Patients' clinical details and histopathological diagnosis were recorded. Data were analyzed and compared with that of previously published literature, and inferences were drawn on patterns of reporting and epidemiology. Results: A total of 1450 cases of glioma, with a mean age of 39.3 (± 17.36 SD) years with males (66.6%) comprising more population as compared to females. Majority of patients 70.8% (n = 1027) belong to the economically active age group of country (18–60 years). Majority of cases (41.4%) were glioblastoma with the next common tumor (22.8%) being diffuse astrocytoma (n = 331) followed by pilocytic astrocytoma (6.2%) and oligodendroglioma (4.5%) in that order. While our data followed similar trends with other Indian data the average age of glioma was a decade younger to what is quoted earlier in Indian and international studies. Conclusion: This data for glioma gives a glimpse of the prevalence of this tumor in a primarily rural population and highlights the need for a National Brain Tumor Registry with the need for the development of evidence-based policymaking and enhanced research into this particular ailment. [ABSTRACT FROM AUTHOR]

Background: Malignant transformation (MT) of low-grade astrocytoma (LGA) triggers a poor prognosis in benign tumors. Currently, factors associated with MT of LGA have been inconclusive. The present study aims to explore the risk factors predicting LGA progressively differentiation to malignant astrocytoma. Materials and Methods: The study design was a retrospective cohort study of medical record reviews of patients with LGA. Using the Fire and Grey method, the competing risk regression analysis was performed to identify factors associated with MT, using both univariate and multivariable analyses. Hence, the survival curves of the cumulative incidence of MT of each covariate were constructed following the final model. Results: Ninety patients with LGA were included in the analysis, and MT was observed in 14.4% of cases in the present study. For MT, 53.8% of patients with MT transformed to glioblastoma, while 46.2% differentiated to anaplastic astrocytoma. Factors associated with MT included supratentorial tumor (subdistribution hazard ratio [SHR] 4.54, 95% CI 1.08-19.10), midline shift >1 cm (SHR 8.25, 95% CI 2.18-31.21), nontotal resection as follows: Subtotal resection (SHR 5.35, 95% CI 1.07-26.82), partial resection (SHR 10.90, 95% CI 3.13-37.90), and biopsy (SHR 11.10, 95% CI 2.88-42.52). Conclusion: MT in patients with LGA significantly changed the natural history of the disease to an unfavorable prognosis. Analysis of patients' clinical characteristics from the present study identified supratentorial LGA, a midline shift more than 1 cm, and extent of resection as risk factors associated with MT. The more extent of resection would significantly help to decrease tumor burden and MT. In addition, future molecular research efforts are warranted to explain the pathogenesis of MT. [ABSTRACT FROM AUTHOR]

Background: Diffuse astrocytoma (DA) is a rare disease with inadequately understood epidemiological characteristics and prognosis. Identification of the factors associated with the survival in DA patients is therefore necessary. In this study, we aim to investigate the clinicopathological characteristics of DA to delineate factors influencing the survival of DA.Methods: A population-based cohort study was conducted, utilizing prospectively extracted data from the Surveillance, Epidemiology and End Results (SEER) database. Patients with histological diagnosis of DA in the SEER database from 1973 to 2017 were included.Results: A total of 799 participants with DA were included, consisting of 95.9% fibrillary astrocytoma and 4.1% protoplasmic variants. The average age of participants was 41.9 years, with 57.2% being male. The majority of the population was white (87.5%). More than half (53.9%) of the patients were married. DA arose mostly in the cerebrum (63.8%). Around 71.6% of the population had received surgical treatment. The overall 1-, 3-, 5-, and 10-year survival rate were 73.7, 55.2, 49.4, and 37.6%, respectively. Kaplan–Meier analysis showed that age at diagnosis, marital status, primary tumor site, tumor size, and surgery was possibly associated with cancer-specific survival (CSS) (p < 0.05). Multivariate Cox proportional hazard analysis indicated that surgery was a protective factor whereas older age, larger tumor size, and tumor in the brainstem were harmful factors for patients with DA. Moreover, a nomogram predicting 5- and 10-year survival probability for DA was developed.Conclusions: Age, primary tumor site, tumor size, and surgery were associated with the survival of patients with DA.

Chromosomal 7q34 duplication and BRAF-KIAA1549 fusion is a characteristic genetic alteration in pilocytic astrocytomas. 7q34 gain appears to be common in diffuse astrocytomas, but its significance is unclear. We assessed BRAF gain and BRAF mutations in 123 low-grade diffuse gliomas, including 55 diffuse astrocytomas, 18 oligoastrocytomas and 50 oligodendrogliomas. Quantitative polymerase chain reaction (PCR) revealed BRAF gain in 17/50 (34%) oligodendrogliomas, a significantly higher frequency than in diffuse astrocytomas (7/55; 13%; P = 0.0112). BRAF gain was common in low-grade diffuse gliomas with 1p/19q loss (39%) and those lacking any of the genetic alterations analyzed (31%), but was rare in those with TP53 mutations (2%). Logistic regression analysis showed a significant positive association between 1p/19q loss and BRAF gain (P = 0.0032) and a significant negative association between TP53 mutations and BRAF gain (P = 0.0042). Fluorescence in situ hybridization (FISH) analysis of 26 low-grade diffuse gliomas with BRAF gain additionally revealed BRAF-KIAA1549 fusion in one oligodendroglioma. Sequencing of cDNA in 17 low-grade diffuse gliomas showed BRAF-KIAA1549 fusion in another oligodendroglioma. A BRAF(V600E) mutation was also detected in one oligodendroglioma, and a BRAF(A598V) in one diffuse astrocytoma. These results suggest that low-grade diffuse gliomas with 1p/19q loss have frequent BRAF gains, and a small fraction of oligodendrogliomas may show BRAF-KIAA1549 fusion.

The tumor immune microenvironment (TIME) plays a pivotal role in tumor development, progression, and prognosis. However, the characteristics of the TIME in diffuse astrocytoma (DA) are still unclear. Leveraging mass cytometry with a panel of 33 markers, we analyzed the infiltrating immune cells from 10 DA and 4 oligodendroglioma (OG) tissues and provided a single cell-resolution landscape of the intricate immune microenvironment. Our study profiled the composition of the TIME in DA and confirmed the presence of immune cells, such as glioma-associated microglia/macrophages (GAMs), CD8+ T cells, CD4+ T cells, regulatory T cells (Tregs), and natural killer cells. Increased percentages of PD-1+ CD8+ T cells, TIM-3+ CD4+ T cell subpopulations, Tregs and pro-tumor phenotype GAMs substantially contribute to the local immunosuppressive microenvironment in DA. DAs and OGs share similar compositions in terms of immune cells, while GAMs in DA exhibit more inhibitory characteristics than those in OG.