World Health Organization Grade Research Articles

68Ga-Fibroblast Activation Protein Inhibitor PET/CT Improves Detection of Intermediate and Low-Grade Sarcomas and Identifies Candidates for Radiopharmaceutical Therapy.

Fibroblast activation protein-α (FAP) is often highly expressed by sarcoma cells and by sarcoma-associated fibroblasts in the tumor microenvironment. This makes it a promising target for imaging and therapy. The level of FAP expression and the diagnostic value of 68Ga-FAP inhibitor (FAPI) PET for sarcoma subtypes are unknown. We assessed the diagnostic performance and accuracy of 68Ga-FAPI PET in various bone and soft-tissue sarcomas. Potential eligibility for FAP-targeted radiopharmaceutical therapy (FAP-RPT) was evaluated. Methods: This prospective observational trial enrolled 200 patients with bone and soft-tissue sarcoma who underwent 68Ga-FAPI PET/CT and 18F-FDG PET/CT (186/200, or 93%) for staging or restaging. The number of lesions detected and the uptake (SUVmax) of the primary tumor, lymph nodes, and visceral and bone metastases were analyzed. The Wilcoxon test was used for semiquantitative assessment. The association of 68Ga-FAPI uptake intensity, histopathologic grade, and FAP expression in sarcoma biopsy samples was analyzed using Spearman r correlation. The impact of 68Ga-FAPI PET on clinical management was investigated using questionnaires before and after PET/CT. Eligibility for FAP-RPT was defined by an SUVmax greater than 10 for all tumor regions. Results: 68Ga-FAPI uptake was heterogeneous among sarcoma subtypes. The 3 sarcoma entities with the highest uptake (mean SUVmax ± SD) were solitary fibrous tumor (24.7 ± 11.9), undifferentiated pleomorphic sarcoma (18.8 ± 13.1), and leiomyosarcoma (15.2 ± 10.2). Uptake of 68Ga-FAPI versus 18F-FDG was significantly higher in low-grade sarcomas (10.4 ± 8.5 vs. 7.0 ± 4.5, P = 0.01) and in potentially malignant intermediate or unpredictable sarcomas without a World Health Organization grade (not applicable [NA]; 22.3 ± 12.5 vs. 8.5 ± 10.0, P = 0.0004), including solitary fibrous tumor. The accuracy, as well as the detection rates, of 68Ga-FAPI was higher than that of 18F-FDG in low-grade sarcomas (accuracy, 92.2 vs. 80.0) and NA sarcomas (accuracy, 96.9 vs. 81.9). 68Ga-FAPI uptake and the histopathologic FAP expression score (n = 89) were moderately correlated (Spearman r = 0.43, P < 0.0002). Of 138 patients, 62 (45%) with metastatic sarcoma were eligible for FAP-RPT. Conclusion: In patients with low-grade and NA sarcomas, 68Ga-FAPI PET demonstrates uptake, detection rates, and accuracy superior to those of 18F-FDG PET. 68Ga-FAPI PET criteria identified eligibility for FAP-RPT in about half of sarcoma patients.

Lateral Transorbital Endoscope-Assisted Resection of Anterior Temporal Lobe Neoplasm: 2-Dimensional Operative Video.

Transorbital neuroendoscopic surgery (TONES) is a minimally invasive approach, providing excellent access to extradural pathology of the sphenoid wing, orbital apex, Meckel's cave, and lateral cavernous sinus.1-10 Few cases of intradural pathology, such as gliomas or epileptic foci of the temporal lobe, have been described, apart from cadaveric anatomic studies.11-13 In this video, we present the case of a 63-year-old man with first time seizure. MRI demonstrated a fluid-attenuated inversion recovery hyperintense, noncontrast enhancing medial temporal lobe lesion consistent with low grade glioma. While frontotemporal craniotomy is the standard approach for this lesion, the TONES approach detailed in the video (the patient consented to the procedure and to the publication of his image) provided excellent access to the lesion, which minimized unnecessary trauma or removal of the lateral temporal lobe during the approach.4,14,15 The dura was closed primarily, overlayed with abdominal fat and fibrin glue, and a lumbar drain was left in place for 24 hours. The TONES approach avoided not only temporal lobe violation but also temporalis muscle disruption and any sort of external bone manipulation, which expedited the patient's recovery.16 The patient's eyelid incision was barely visible as early as postoperative day 7 with minimal ecchymosis. Postoperative MRI demonstrated a gross total resection. Pathology was consistent with a central nervous system World Health Organization grade 1 dysembryoplastic neuroepithelial tumor, a low-grade lesion with low risk of recurrence.17,18.

The Association Between Task Complexity and Cortical Language Mapping Accuracy.

Direct cortical stimulation (DCS) mapping enables the identification of functional language regions within and around gliomas before tumor resection. Intraoperative mapping is required because glioma-infiltrated cortex engages in synchronous activity during task performance in a manner similar to normal-appearing cortex but has decreased ability to encode information for complex tasks. It is unknown whether task complexity influenced DCS mapping results. We aim to understand correlations between audiovisual picture naming (PN) task complexity and DCS error rate. We also asked what functional and oncological factors might be associated with higher rates of erroneous responses. We retrospectively reviewed intraoperative PN and word reading (WR) task performance during awake DCS language mapping for resection of dominant hemisphere World Health Organization grade 2 to 4 gliomas. The complexity of word tested in PN/WR tasks, patient characteristics, and tumor characteristics were compared between correct and incorrect trials. Between 2017 and 2021, 74 patients met inclusion criteria. At median 18.6 months of follow-up, 73.0% were alive and 52.7% remained recurrence-free. A total of 2643 PN and 978 WR trials were analyzed. A greater number of syllables in PN was associated with a higher DCS error rate (P = .001). Multivariate logistic regression found that each additional syllable in PN tasks independently increased odds of error by 2.40 (P < .001). Older age was also an independent correlate of higher error rate (P < .043). World Health Organization grade did not correlate with error rate (P = .866). More severe language impairment before surgery correlated with worse performance on more complex intraoperative tasks (P < .001). A higher error rate on PN testing did not correlate with lower extent of glioma resection (P = .949). Word complexity, quantified by the number of syllables, is associated with higher error rates for intraoperative PN tasks but does not affect extent of resection.

A case of a pineal parenchymal tumor of intermediate differentiation with bifocal lesions differentiated by negative placental alkaline phosphatase in the spinal fluid.

Placental alkaline phosphatase (PLAP) in the spinal fluid is helpful for the diagnosis of intracranial germinomas. Bifocal lesions involving the pineal and pituitary regions have also been reported as characteristic findings of intracranial germinomas. We present a rare case of a 15-year-old boy with a pineal parenchymal tumor of intermediate differentiation (PPTID) with bifocal lesions negative for PLAP. Magnetic resonance imaging of the brain revealed bifocal mass lesions in the pineal and suprasellar regions and non-communicating hydrocephalus. We initially suspected a germinoma based on imaging findings, but all tumor markers, including PLAP, in the spinal fluid were negative. Based on these results, germinoma was considered less likely, and an endoscopic third ventriculostomy and endoscopic tumor biopsy were performed for diagnosis. The histopathological diagnosis was PPTID, corresponding to World Health Organization grade 3, in both pineal and suprasellar specimens. A craniotomy for tumor removal was performed, resulting in total resection. PLAP is known to have high sensitivity and extremely high negative predictive value for germinomas. Although bifocal lesions highly suggest germ cell tumors, there are exceptions, as in the present case. This case suggests that PLAP measurements are useful for differentiation, leading to appropriate treatment strategies.

Structural- and DTI- MRI enable automated prediction of IDH Mutation Status in CNS WHO Grade 2–4 glioma patients: a deep Radiomics Approach

BackgroundThe role of isocitrate dehydrogenase (IDH) mutation status for glioma stratification and prognosis is established. While structural magnetic resonance image (MRI) is a promising biomarker, it may not be sufficient for non-invasive characterisation of IDH mutation status. We investigated the diagnostic value of combined diffusion tensor imaging (DTI) and structural MRI enhanced by a deep radiomics approach based on convolutional neural networks (CNNs) and support vector machine (SVM), to determine the IDH mutation status in Central Nervous System World Health Organization (CNS WHO) grade 2–4 gliomas.MethodsThis retrospective study analyzed the DTI-derived fractional anisotropy (FA) and mean diffusivity (MD) images and structural images including fluid attenuated inversion recovery (FLAIR), non-enhanced T1-, and T2-weighted images of 206 treatment-naïve gliomas, including 146 IDH mutant and 60 IDH-wildtype ones. The lesions were manually segmented by experienced neuroradiologists and the masks were applied to the FA and MD maps. Deep radiomics features were extracted from each subject by applying a pre-trained CNN and statistical description. An SVM classifier was applied to predict IDH status using imaging features in combination with demographic data.ResultsWe comparatively assessed the CNN-SVM classifier performance in predicting IDH mutation status using standalone and combined structural and DTI-based imaging features. Combined imaging features surpassed stand-alone modalities for the prediction of IDH mutation status [area under the curve (AUC) = 0.846; sensitivity = 0.925; and specificity = 0.567]. Importantly, optimal model performance was noted following the addition of demographic data (patients’ age) to structural and DTI imaging features [area under the curve (AUC) = 0.847; sensitivity = 0.911; and specificity = 0.617].ConclusionsImaging features derived from DTI-based FA and MD maps combined with structural MRI, have superior diagnostic value to that provided by standalone structural or DTI sequences. In combination with demographic information, this CNN-SVM model offers a further enhanced non-invasive prediction of IDH mutation status in gliomas.

Clinical and radiologic features in patients with the WHO grade I and II meningiomas

Introduction: Meningiomas are the most common benign tumor of the central nervous system, accounting for 53.3% and 37.6% of all central nervous system tumors (1). The World Health Organization (WHO) Grade I meningiomas account for 80.5% of all meningiomas and are considered benign meningiomas; the WHO Grade II meningiomas account for 17.7% of all meningiomas and exhibit more aggressive behavior. Methods: In the period 2015-2022, a retrospective single-center study at the clinic of neurosurgery at the Clinical Center University of Sarajevo was conducted, which included patients with a pathohistological finding of WHO Grade I or II meningioma. Depending on the pathohistological grade of the tumor, patients were divided into two groups: Grade I and Grade II patients. Patients were examined clinically and radiologically. Clinical data collected included in the study: Gender, age, number of symptoms before surgery, whether patients were symptomatic or asymptomatic, pre-operative Eastern Cooperative Oncology Group,and Karnopsky performance scale. Pre-operative contrast magnetic resonance imaging of the head measured tumor volume, temporal muscle thickness (TMT), sagittal midline shift, and surrounding cerebral edema. Results: A total of 80 patients were enrolled in the study, 68 with WHO Grade I and 12 with WHO Grade II meningiomas. We found that patients with Grade I meningioma were younger and that the mean thickness of the temporal muscle was statistically thicker than in patients with Grade II. Increasing TMT was significantly and positively associated with Grade I tumors and negatively associated with Grade II tumors (p = 0.032). Conclusion: This study demonstrates that TMT can serve as a radiologic pre-operative indicator of meningioma grade and provide valuable guidance to neurosurgeons in surgical planning. Further studies are needed to validate these results.

Recurrence of Resected Skull Base Meningiomas during Long-term Follow-up: Incidence and Predisposing Factors

Abstract Introduction Skull base meningiomas (SBMs) are often subtotally resected and there is a paucity of evidence regarding the long-term rates of postoperative tumor progression. We aimed to investigate the factors that influence tumor recurrence in patients with an extended period of follow-up. Methods Surgically resected tumors with long-term radiological follow-up were included for analysis. Data were collected on patient demographics, anatomical location, Simpson grade, World Health Organization (WHO) grade, modality of reintervention, and functional status. Recurrence was defined as tumor progression requiring intervention. Kaplan–Meier method and log-rank test were used to calculate recurrence-free probability. Cox regression analysis was used to determine factors associated with tumor progression. Results Sixty-one patients were identified. Median radiological follow-up was 11.25 (IQR 4.3) years. Median age at first surgery was 50 (IQR 17) years. A total of 55/61(90%) tumors were WHO grade I and 6/61(10%) were grade II. Gross total resection (GTR) was achieved in 37/61 (60.7%) patients with subtotal resection (STR) in 24/61 (39.3%). In total, 28/61(45.9%) demonstrated recurrence/regrowth with a median time to recurrence of 2.8 (IQR 5) years. Also, 15/37 (40.5%) and 13/24 (54.2%) patients with GTR and STR, respectively, had tumor recurrence. Of the 28 recurrences, 4/28 (14.3%) underwent reresection, 9/28 (32.1%) were managed with radiotherapy, and 15/28 (53.6%) received both reresection and radiotherapy. Tumor grade was the only significant predictor of tumor recurrence (p = 0.033). Neurological function at last follow-up was significantly worse (modified Rankin scale &gt;2) in patients with recurrence (p = 0.035). Conclusion Surgically resected SBMs are associated with a significant recurrence rate during prolonged follow-up, irrespective of the extent of resection achieved. We recommend a prolonged period of radiological surveillance for SBM following surgical resection.

The Evolving Classification of Meningiomas: Integration of Molecular Discoveries to Inform Patient Care.

Meningioma classification and treatment have evolved over the past eight decades. Since Bailey, Cushing, and Eisenhart's description of meningiomas in the 1920s and 1930s, there have been continual advances in clinical stratification by histopathology, radiography and, most recently, molecular profiling, to improve prognostication and predict response to therapy. Precise and accurate classification is essential to optimizing management for patients with meningioma, which involves surveillance imaging, surgery, primary or adjuvant radiotherapy, and consideration for clinical trials. Currently, the World Health Organization (WHO) grade, extent of resection (EOR), and patient characteristics are used to guide management. While these have demonstrated reliability, a substantial number of seemingly benign lesions recur, suggesting opportunities for improvement of risk stratification. Furthermore, the role of adjuvant radiotherapy for grade 1 and 2 meningioma remains controversial. Over the last decade, numerous studies investigating the molecular drivers of clinical aggressiveness have been reported, with the identification of molecular markers that carry clinical implications as well as biomarkers of radiotherapy response. Here, we review the historical context of current practices, highlight recent molecular discoveries, and discuss the challenges of translating these findings into clinical practice.

DOTATATE PET/MR Imaging Differentiates Secondary-Progressive from de Novo World Health Organization Grade 3 Meningiomas.

WHO grade 3 meningiomas are rare and poorly understood and have a higher propensity for recurrence, metastasis, and worsened clinical outcomes compared with lower-grade meningiomas. The purpose of our study was to prospectively evaluate the molecular profile, PET characteristics, and outcomes of patients with World Health Organization grade 3 meningiomas who were imaged with gallium 68 (68Ga) DOTATATE PET/MR imaging. Patients with World Health Organization grade 3 meningiomas enrolled in our prospective observational cohort evaluating the utility of (68Ga) DOTATATE PET/MR imaging in somatostatin receptor positive brain tumors were included. We stratified patients by de novo-versus-secondary-progressive status and evaluated the differences in the PET standard uptake value, molecular profiles, and clinical outcomes. Patients met the inclusion criteria (secondary-progressive: 7/14; de novo: 7/14). The secondary-progressive cohort had a significantly higher per-patient number of surgeries (4.1 versus 1.6; P = .011) and trended toward a higher number of radiation therapy courses (2.4 versus 1.6; P = .23) and cumulative radiation therapy doses (106Gy versus 68.3Gy; P = .31). The secondary-progressive cohort had a significantly lower progression-free survival compared with the de novo cohort (4.8 versus 37.7 months; P = .004). Secondary-progressive tumors had distinct molecular pathology profiles with higher numbers of mutations (3.5 versus 1.2; P = .024). Secondary-progressive tumors demonstrated higher PET standard uptake values (17.1 versus 12.4; P = .0021). Our study confirms prior work illustrating distinct clinical outcomes in secondary-progressive and de novo World Health Organization grade 3 meningiomas. Furthermore, our findings support (68Ga) DOTATATE PET/MR imaging as a useful management strategy in World Health Organization grade 3 meningiomas and provide insight into meningioma biology, as well as clinical management implications.

Amide proton transfer weighted and diffusion weighted imaging based radiomics classification algorithm for predicting 1p/19q co-deletion status in low grade gliomas

Background1p/19q co-deletion in low-grade gliomas (LGG, World Health Organization grade II and III) is of great significance in clinical decision making. We aim to use radiomics analysis to predict 1p/19q co-deletion in LGG based on amide proton transfer weighted (APTw), diffusion weighted imaging (DWI), and conventional MRI.MethodsThis retrospective study included 90 patients histopathologically diagnosed with LGG. We performed a radiomics analysis by extracting 8454 MRI-based features form APTw, DWI and conventional MR images and applied a least absolute shrinkage and selection operator (LASSO) algorithm to select radiomics signature. A radiomics score (Rad-score) was generated using a linear combination of the values of the selected features weighted for each of the patients. Three neuroradiologists, including one experienced neuroradiologist and two resident physicians, independently evaluated the MR features of LGG and provided predictions on whether the tumor had 1p/19q co-deletion or 1p/19q intact status. A clinical model was then constructed based on the significant variables identified in this analysis. A combined model incorporating both the Rad-score and clinical factors was also constructed. The predictive performance was validated by receiver operating characteristic curve analysis, DeLong analysis and decision curve analysis. P < 0.05 was statistically significant.ResultsThe radiomics model and the combined model both exhibited excellent performance on both the training and test sets, achieving areas under the curve (AUCs) of 0.948 and 0.966, as well as 0.909 and 0.896, respectively. These results surpassed the performance of the clinical model, which achieved AUCs of 0.760 and 0.766 on the training and test sets, respectively. After performing Delong analysis, the clinical model did not significantly differ in predictive performance from three neuroradiologists. In the training set, both the radiomic and combined models performed better than all neuroradiologists. In the test set, the models exhibited higher AUCs than the neuroradiologists, with the radiomics model significantly outperforming resident physicians B and C, but not differing significantly from experienced neuroradiologist.ConclusionsOur results suggest that our algorithm can noninvasively predict the 1p/19q co-deletion status of LGG. The predictive performance of radiomics model was comparable to that of experienced neuroradiologist, significantly outperforming the diagnostic accuracy of resident physicians, thereby offering the potential to facilitate non-invasive 1p/19q co-deletion prediction of LGG.

UBA2 as a Prognostic Biomarker and Potential Therapeutic Target in Glioma.

Gliomas are characterized by aggressive behavior, leading to severe disability and high mortality. Ubiquitin-like modifier activating enzyme 2 (UBA2) is a subunit of the E1-activating enzyme involved in the SUMOylation (SUMO, small ubiquitin-related modifier) of numerous proteins. Although the abnormality of UBA2 is linked to the progression of various tumor types, the role of UBA2 in glioma is still unknown. A bioinformatic analysis using several public databases was conducted to examine the expression level, clinicopathological correlations, and prognostic significance of UBA2 in glioma. The correlation between UBA2 expression and drug sensitivity in cancers was also explored. Multiple cellular experiments were conducted to validate the role of UBA2 in glioma. Analysis of multiple databases and cellular experiments revealed that UBA2 was overexpressed in glioma tissues and cell lines, respectively. UBA2 expression in gliomas correlated with World Health Organization (WHO) grade, IDH gene status, 1p19q deletion, histological type, and immune cell infiltration in glioma. UBA2 expression in carcinomas also correlated with drug sensitivity. Kaplan-Meier analysis revealed that high expression of UBA2 predicted poorer survival in glioma patients. A nomogram model containing UBA2 expression was constructed for clinical practice. Knockdown of UBA2 was observed to suppress glioma cell progression and sensitize glioma cells to irradiation in vitro. Overall, this research showed that UBA2 might be involved not only in the development of glioma but also in the regulation of immunity, drug sensitivity, and radiosensitivity. Therefore, UBA2 may be a potential target for therapy and a candidate biomarker for glioma diagnosis and prognosis.

Migratory schwannoma of the cauda equina with a change in radicular pattern: illustrative case.

Intradural spinal tumors are an uncommon entity with a variety of pathologies and symptom patterns. Few cases reports in the literature have described tumor migration within the spinal canal. A 38-year-old male presented with bilateral upper lumbar radicular symptoms of anterior thigh pain, with an enhancing tumor of the cauda equina initially located at L1-2. He declined surgery initially, and at a follow-up 3 years later, his symptoms were unchanged but the tumor was now located at T12-L1. He again declined surgery, but 3 months later, he had a significant change in his pain distribution, which was now along his posterolateral right leg to his foot with associated dorsiflexion and extensor hallicus longus weakness. At this time, the tumor had migrated to L2-3. He underwent laminectomy and tumor resection with resolution of his radicular symptoms and improvement in his strength back to baseline by the 1-month follow-up. Pathology was consistent with a World Health Organization grade I schwannoma. Migratory schwannoma is a rare entity but should be considered when radicular symptoms acutely change in the setting of a known intradural tumor. Repeat imaging should be performed to avoid wrong-level surgery. Intraoperative imaging can also be used for tumor localization.

Association Between Pretreatment 11C-Methionine Positron Emission Tomography Metrics, Histology, and Prognosis in 125 Newly Diagnosed Patients with Adult-Type Diffuse Glioma Based on the World Health Organization 2021Classification

To clarify the relationships between 11C-methionine (MET) positron emission tomography (PET) metrics and the histology, genetics, and prognosis of adult-type diffuse glioma (ADG) based on the World Health Organization (WHO) 2021 classification. A total of 125 newly diagnosed ADG patients were enrolled. We compared the maximum standardized uptake value (SUVmax), tumor-to-normal ratio (TNR), metabolic tumor volume (MTV), and total lesion methionine uptake (TLMU) to the histology and genetics of the ADG patients. We also evaluated the prognoses of the 93 surgically treated patients. The isocitrate dehydrogenase (IDH) wild (w) ADG patients showed significantly higher MET-PET metrics (p<0.05 for all parameters), significantly shorter overall survival (OS) and progression-free survival (PFS) (p<0.0001 for both) than those of the IDH mutant (m) ADG patients. In the IDHm ADG group, the SUVmax, MTV, and TLMU values were significantly higher in IDHm grade (G) 4 astrocytoma patients than IDHm G2/3 astrocytoma patients (p<0.05 for all), but not than G2-3 oligodendroglioma patients. The PFS was significantly shorter in the G4 astrocytoma patients versus the G2/3 astrocytoma and G3 oligodendroglioma patients (p<0.05 for both). The SUVmax and TNR values were significantly higher in recurrent patients than non-recurrent patients (p<0.01 for both), but no significant differences were found in MTV or TLMU values. MET-PET metrics well reflect the histological subtype, WHO grade and prognosis of ADG based on the 2021 WHO classification, with the exception of oligodendroglial tumors. Volumetric parameters were not significantly associated with recurrence, unlike the SUVmax and TNR.

Letter to the Editor Regarding “Beyond the Surgical Margin: Patterns of Recurrence in World Health Organization Grade 2 Intracranial Meningiomas”

Letter to the Editor Regarding “Beyond the Surgical Margin: Patterns of Recurrence in World Health Organization Grade 2 Intracranial Meningiomas”

In Reply to Letter to the Editor Regarding “Beyond the Surgical Margin: Patterns of Recurrence in World Health Organization Grade 2 Intracranial Meningiomas”

In Reply to Letter to the Editor Regarding “Beyond the Surgical Margin: Patterns of Recurrence in World Health Organization Grade 2 Intracranial Meningiomas”

Prognostic Factors and Outcomes in World Health Organization Grade 1 and Grade 2 Intracranial Meningiomas—5-Year Institutional Experience

Meningiomas are the most frequent primary intracranial tumour. While histological grade and grade of excision are established predictors of recurrence, nuances such as the role of radical excision of dural attachment and postoperative radiotherapy in intermediate-risk groups remain unanswered. This report presented data from 451 WHO Grade 1 and 248 WHO Grade 2 intracranial meningiomas operated between 2010 and 2015, analysing their clinical and radiological features and surgical details. Outcomes were assessed among 352 WHO Grade 1 and 208 WHO Grade 2 meningiomas, studying the effect of extent of resection and use of radiotherapy. Kaplan Meier analysis was used to determine differences in survival by extent of resection and use of postoperative radiotherapy in the treatment of WHO Grade 1 and 2 meningiomas. The mean age of the cohort was 46.3 years, with a female predominance. On univariate analysis, gender, WHO grade, and Simpson grade were significant predictors of recurrence. On multivariate analysis, WHO grade and Simpsons grade remained significant predictors of recurrence. Recurrence was significantly associated with poor performance status and mortality. Postoperative radiation significantly improved progression-free survival among Grade 2 meningioma that underwent gross total resection (GTR), but not among WHO Grade 1 and 2 meningioma after subtotal resection (STR). WHO Grade and Simpson grade are independent predictors of recurrence among meningiomas. Irrespective of Grade, gross total resection must be effected when possible, and postoperative radiotherapy may be recommended in Grade 2 meningioma.

DNMT3A promotes glioma growth and malignancy via TNF-α/NF-κB signaling pathway.

DNMT3A is the main molecule responsible for DNA methylation in cells. DNMT3A affects the progression of inflammation, degenerative diseases, and malignant tumors, and exhibits significant aberrantly expression in tumor tissues. Transcriptome data and relevant clinical information were downloaded from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO) datasets. Differential expression analysis and prognostic analysis were conducted based on above statistics. We constructed a clinical prognostic model and identified DNMT3A as an independent prognostic factor to accurately predict patient prognosis. Differential gene enrichment analysis revealed that DNMT3A affects the progression of glioma through multiple pathways, among which the tumor necrosis factor-α (TNF-α)/nuclear factor-kappa B (NF-κB) pathway shows a strong correlation. Immunological analysis also revealed a certain correlation between DNMT3A and tumor immunity. We demonstrated through gene editing that DNMT3A can affect the release of TNF-α in cells, thereby affecting the progression of glioma. Functional experiments have also demonstrated that DNMT3A plays a crucial role in tumors. RNA-sequencing and survival analyses of lower-grade glioma (LGG) patients in TCGA, CGGA, and GEO cohorts showed that high DNMT3A expression correlated with poor prognosis of LGG patients. Univariate and multivariate Cox regression analyses showed that DNMT3A expression was an independent prognostic indicator in LGG. The prognosis prediction nomogram with age, World Health Organization (WHO) grading, and DNMT3A expression showed reliable performance in predicting the 1-, 3-, and 5-year overall survival (OS) of LGG patients. Functional enrichment analysis, gene set enrichment analysis (GSEA), and ESTIMATE algorithm analyses showed that DNMT3A expression was associated with the tumor infiltration of immune cells and predicted response to immunotherapy in two immunotherapy cohorts of pan-cancer patients. Furthermore, short hairpin RNA (shRNA)-mediated knockdown of DNMT3A in the LGG cell lines suppressed proliferation, migration, and invasion of LGG cells by downregulating the TNF-α/NF-κB signaling pathway. Our data showed that DNMT3A was a potential prognostic biomarker in glioma. DNMT3A promoted proliferation and malignancy of LGG cells through the TNF-α/NF-κB signaling pathway. DNMT3A is a promising therapeutic target for treating patients with LGG.

Recurrence and Mortality Rate in a 42 Patient Cohort of Giant Meningiomas

BackgroundGiant meningiomas may show special features in terms of biological behavior and management. We aimed to research recurrence and mortality of giant meningiomas. MethodsMedical files of patients with meningioma with at least one dimension of ≥5 cm in any plane in radiological investigations between December 2012 and January 2022 were retrospectively reviewed. Tumor dimensions were measured on magnetic resonance images except one. All patients except two underwent clinical follow-up at a mean of 27.19 ± 29.87 (range, 4–112) months. ResultsThere were 42 patients, 26 (61.9%) women and 16 (38.1%) men who ranged in age from 31 to 85 (mean, 60.31 ± 14.86) years. Headache (57.1%) was the most common symptom. The mean tumor size was 70.14 ± 19.03 (range, 50–152) mm. Tumors were most located at the frontal convexity (40.5%). Simpson grade I resection was achieved in 19% of the cases. The tumors were World Health Organization (WHO) grade 1 in 74% and grade 2 in 26% of the cases. Major complications developed in 26.1% of the patients. Recurrence happened in 5 (11.9%) cases. The number of WHO grade 2 tumors (p = 0.013; p<0.05) and tumor size (p = 0.006; p<0.01) were significantly higher in the recurrent cases. Mortality was % 11.9 and statistically significantly higher in the recurrence group (p = 0.025; p<0.05). ConclusionGiant intracranial meningiomas are challenging because of surgical experience, tumor size, peritumoral edema, blood supply, anatomical changes, and limited visibility. They have a high risk of recurrence and mortality.

The Ribbon Sign as a Radiological Indicator of Intramedullary Spinal Cord Subependymomas

INTRODUCTION: Intramedullary spinal cord (IMSC) subependymomas are rare World Health Organization grade 1 ependymal tumors. The potential presence of functional neural tissue within the tumor and poorly demarcated planes presents a risk to resection. Recognition of an intramedullary subependymoma on preoperative imaging can assist in operative planning and factor into the decision-making for gross- or sub-total resection. However, no definitive pathognomonic features have been reported on magnetic resonance imaging (MRI). METHODS: We retrospectively reviewed preoperative MRIs of patients presenting with IMSC tumors at a large tertiary academic institution between April 2005 and January 2022. The diagnosis was confirmed histologically. The “ribbon sign” was defined as a ribbon-like structure of T2 isointense spinal cord tissue interwoven between regions of T2 hyperintense tumor. The ribbon sign was confirmed by an expert neuroradiologist. RESULTS: MRIs from 151 patients were reviewed, including 42 (28%) astrocytomas, 82 (54%) ependymomas, 8 (5.3%) gangliogliomas, and 19 (13%) hemangioblastomas. Of the 82 ependymomas, ten patients (12%) presented with intramedullary subependymomas. The ribbon sign was demonstrated on nine (90%) patients with histologically proven subependymomas. No other tumor types displayed the ribbon sign. CONCLUSIONS: The ribbon sign is a distinctive imaging feature of IMSC subependymomas and indicates the presence of spinal cord tissue between eccentrically located tumor. Recognition of the sign should prompt clinicians to consider a diagnosis of subependymoma. Unlike their intracranial counterparts, resection of these lesions can be technically difficult, particularly in cases with poor demarcation between cord and tumor. Therefore, the risks and benefits of gross- vs. sub-total resection should be carefully considered and discussed with patients.

The Spectrum of Central Nervous System Tumors at a Tertiary Care Center Primarily Serving a Rural Population.

Background Central nervous system (CNS) tumors cause significant mortality and morbidity in all age groups. There was no data about the histological spectrum of all CNS tumors in the tertiary care center serving primarily the rural population of Uttar Pradesh. Aims and objectives The present study aimed to describe the histopathological spectrum of all CNS tumors reported in a rural tertiary care center at Saifai, Uttar Pradesh. It also aimed to provide an overview of the descriptive epidemiology of CNS tumors. Material and methods This was a retrospective, cross-sectional study. The study duration was three years. A total of 115 cases of CNS tumors were studied during that period. Cases were classified according to their histological types, and results were analyzed. Results The most common histological group was neuroepithelial tumors, with 53 cases (46.08%). This group had 36 cases of astrocytic tumors (31.3%), three cases of oligodendroglial tumors (2.6%), five cases of oligoastrocytic tumors (4.34%), five cases of ependymal tumors (4.34%), and four cases of embryonal tumors (3.47%). The second most common tumor wasmeningeal tumors, with 32 cases (27.82%). The male/female ratio (M/F) ratio was 0.7. Females were found to be more affected by almost all histologic categories. Most meningiomas (89.6%) were of World Health Organization (WHO) grade I (26 cases out of 29). Astrocytic tumors showed WHO grade I, II, III, and IV tumors in two cases (5.5%), twelve cases (33.3%), four cases (11.1%), and eighteen cases (50%), respectively. In the younger age group (0-20 years), ependymoma and medulloblastoma were most common, followed by pilocytic astrocytoma and schwannoma. Conclusion In this region, neuroepithelial tumors were seen more commonly than meningioma. Females were found to be more affected by CNS tumors. This study has provided relevant data, which can be used for research and better patient management. Further studies with the incorporation of advanced radiological investigation and immunohistochemistry have been recommended.