World Health Organization Grade Research Articles

Drug-resistant BRAF V600E-mutant recurrent pleomorphic xanthoastrocytoma, CNS WHO Grade 3 successfully resolved with incidental discontinuation of combined BRAF and MEK inhibitor therapy

Background: Combination therapy with BRAF and MEK inhibitor holds promise for treating gliomas harboring the BRAF V600E mutation; however, the development of acquired resistance remains a challenge. Case Description: We describe a case of repeated recurrent BRAF-mutant pleomorphic xanthoastrocytoma (central nervous system World Health Organization grade 3) treated with combination therapy with BRAF and MEK inhibitor. The patient received dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor); however, she developed resistance to the combination therapy. Remarkably, incidental drug discontinuation contributed to the disappearance of the resistant tumor. The same phenomenon was repeatedly observed after that. Genetic analysis demonstrated that the resistant tumor had BRAF V600E amplification; the resistant tumor remained BRAF→MEK→ERK pathway dependent, and drug resistance might be due to elevated BRAF V600E expression. We speculated that ERK1/2 signal extremes caused by the discontinuation of the combination therapy affected the resistant tumor survival. Conclusion: This case study provides important insights into novel treatment strategies and their underlying mechanisms for gliomas with BRAF mutations.

Outcomes of adjuvant radiation treatment following subtotal resection of world health organization grade II meningiomas.

Existing literature on adjuvant radiation after subtotal resection (STR) of WHO II meningiomas is limited by heterogenous patient cohorts, combining adjuvant and salvage radiation, gross total resection (GTR) and STR, primary radiation treatment vs. re-treatment, or grade II and III meningiomas, all of which have different expected outcomes. Tumor control estimates in a large homogenous patient cohort are needed to accurately counsel patients. A retrospective review of patients that had immediate post-operative imaging-confirmed residual WHO grade II meningioma followed by either adjuvant intensity-modulated radiation therapy (IMRT) or stereotactic radiosurgery (SRS) between 1996 and 2020 was conducted. Kaplan-Meier survival analysis and log-rank test was used to assess progression-free survival (PFS). Thirty-nine patients met inclusion criteria (IMRT = 32; SRS = 7). Overall, the 3-, 5-, and 10-year PFS was 81.1%, 61.2%, and 44.6%, respectively. Median follow-up time was 37 months. When comparing IMRT and SRS cohorts, baseline characteristics did not differ significantly between groups, but significantly larger residual tumor volumes were treated with IMRT (22.2 cm3 vs. 6.3 cm3, p = 0.004). PFS was not significantly different between IMRT and SRS at 3 years (81.1% vs. 80.0%) or 5 years (65.5% vs. 40%) (p = 0.19). There was no significant difference in radiation necrosis between groups (IMRT = 3/32 patients vs. SRS = 0/7 patients, p = 0.32). Our homogenous patient cohort displayed acceptable control rates at 3 years using SRS or IMRT as adjuvant therapy. No significant difference in PFS or radiation necrosis was noted between patients treated with adjuvant IMRT versus SRS.

SURG-03. GENE EXPRESSION CHANGES ASSOCIATED WITH RECURRENCE AFTER GROSS TOTAL RESECTION OF NEWLY DIAGNOSED WHO GRADE 1 MENINGIOMA

Abstract Patients who undergo gross total resection (GTR) of Central Nervous System World Health Organization (WHO) grade 1 meningioma constitute a “low risk” group, but some low risk meningiomas can recur despite reassuring clinical and histological features. In this study, gene expression in newly diagnosed WHO grade 1 meningiomas that had undergone GTR were evaluated for their association with recurrence. This was a retrospective, international, multi-center cohort study that included WHO grade 1 meningiomas that underwent GTR as first treatment. Normalized gene expression values from a previously validated 34-gene panel were evaluated for their association with recurrence. Kaplan-Meier, multivariable Cox proportional hazard analyses, and K-means clustering were performed to assess the association of genes of interest with recurrence and identify molecular subgroups among clinically and histologically low risk meningiomas. 442 patients with WHO grade 1 meningiomas that underwent GTR and had available gene expression profiling data were included in the study. Median follow-up was 5.0 years (interquartile range 2.6-7.7 years), local recurrence occurred in 36 patients (8.1%), 5-year local freedom from recurrence (LFFR) was 90.5%, and median time to recurrence of 2.9 years (range 0.5-10.7 years). Eleven genes were associated with local recurrence, including lower expression of ARID1B, ESR1, LINC02593, PGR, and TMEM30B and higher expression of CDK6, CDKN2C, CKS2, KIF20A, PGK1, and TAGLN. K-means clustering based on these 11 genes distinguished 2 molecular groups of clinically and histologically low risk meningiomas with significant differences in LFFR (HR 2.5, 95% CI 1.2-5.1, p=0.016). In conclusion, gene expression profiling may help to identify newly diagnosed WHO grade 1 meningiomas that have an elevated risk of recurrence despite GTR.

Outcomes of Radiosurgery for WHO Grade 2 Meningiomas: The Role of Ki-67 Index in Guiding the Tumor Margin Dose.

The management of World Health Organization (WHO) grade 2 meningiomas is complicated by their diverse clinical behaviors. Stereotactic radiosurgery (SRS) can be an effective management option. Literature on SRS dose selection is limited but suggests that a higher dose is better for tumor control. We characterize the predictors of post-SRS outcomes that can help guide planning and management. We reviewed a cohort of consecutive patients with pathologically-proven WHO grade 2 meningiomas who underwent SRS at a single institution between 2011 and 2023. Ninety-nine patients (median age 62 years) underwent SRS, 11 of whom received hypofractionated SRS in 5 fractions. Twenty-two patients had received previous irradiation. The median follow-up was 49 months. The median overall survival was 119 months (95% CI 92-NA) with estimated 5- and 10-year survival of 83% and 27%, respectively. The median progression-free survival (PFS) was 40 months (95% CI 32-62), with 3- and 5-year rates at 54% and 35%, respectively. The median locomarginal PFS was 63 months (95% CI 51.8-NA) with 3- and 5-year rates at 65% and 52%. Nine (9%) patients experienced adverse events, 2 Common Terminology Criteria for Adverse Events grade 3 and 7 grade 2, consisting of worsening neurologic deficit from edema. In the single-session cohort, Ki-67 significantly predicted both overall survival and intracranial PFS. Tumors with Ki-67 >10% had 2.17 times the risk of locomarginal progression compared with Ki-67 ≤10% (P = .018) adjusting for covariates. Sex, prescription dose, tumor volume, and location also predicted tumor control. In tumors with Ki-67 >10%, margin dose ≥14 Gy was associated with significantly better tumor control but not for tumors with Ki-67 ≤10%. The management of WHO grade 2 meningiomas requires a multimodality approach. This study demonstrates the value of a targeted SRS approach in patients with limited disease and further establishes predictive biomarkers that can guide planning through a personalized approach.

SURG-02. ANAPLASTIC PLEOMORPHIC XANTHOASTROCYTOMA WITH LEPTOMENINGEAL DISSEMINATION PRESENTING WITH CRANIAL NEUROPATHY IN AN ADULT PATIENT: ILLUSTRATIVE CASE AND REVIEW OF THE LITERATURE

Abstract INTRODUCTION Anaplastic pleomorphic xanthoastrocytomas (APXA) are very rare, grade III malignant astrocytic glial neoplasms first described as a distinct entity in the 2016 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS). They are generally seen in pediatric and young adult patients as supratentorial lesions with both solid and cystic components and have a high propensity for recurrence despite local treatment. APXAs occasionally demonstrate leptomeningeal dissemination (LMD) but extremely seldom at the time of diagnosis. They are typically treated via surgical resection with adjuvant chemoradiation, although there is no standard of care for adjuvant therapy. Case Presentation: The authors describe the case of a 37-year-old male with a history of seizures since age 11 who presented with four months of worsening headache, increasingly frequent seizures, and diplopia with right cranial nerve III palsy. Imaging at the time of diagnosis of his seizure disorder as a child demonstrated a small left temporal lesion, which remained stable on imaging for over 20 years and was never biopsied, however MRI at current presentation showed significant interval enlargement with intralesional hemorrhage and leptomeningeal enhancement involving the left temporal and parietal lobes, left internal auditory canal, and right oculomotor nerve. He underwent surgical resection with gross total resection achieved and pathology revealed WHO Grade III pleomorphic xanthoastrocytoma with ATG7::RAF1 fusion, 9p21 deletion, and TERT promoter mutation on next generation sequencing. This was followed by adjuvant whole brain radiation with boost and treatment with MEK inhibitor cobimetinib. His postoperative course was remarkable for intermittent speech difficulty and improving right third nerve palsy. CONCLUSION We describe the unusual presentation of an already exceedingly rare primary CNS tumor, namely APXA in an adult patient with LMD and cranial neuropathy at the time of diagnosis, and detail tailored adjuvant therapy based on genomic profiling.

EXTH-18. ADAPTER CHIMERIC ANTIGEN RECEPTOR T CELL THERAPY TARGETING SSTR2 IN MENINGIOMA

Abstract Effective treatment options for meningioma patients beyond surgical resection and radiotherapy are limited. This study presents preclinical and translational evidence supporting the efficacy of an adaptor CAR-T cell system targeting Somatostatin Receptor (SSTR) 2 in otherwise untreatable meningiomas. Tissue microarray analysis revealed that SSTR2 expression was generally heterogeneous but high or intermediate in most World Health Organization (WHO) grade 2 (87.8%) and grade 3 (87.5%) meningiomas. The fluorescein-linked, SSTR2 antagonist peptide octofluo was used in conjunction with adaptor FITC (AdFITC) CAR-T cells to treat experimental meningiomas. In vitro, 10 nM octofluo induced tumor cell killing within 72 hours at effector-target cell ratios (E:T) as low as 1:100. This was observed in two human meningioma cell lines, Ben-Men-1 (CAR-T cells vs. untransduced T-cells [UTT]: 47.9% vs. 4.7%, P < 0.001) and IOMM-Lee (CAR-T cells vs. UTT: 40.2% vs. 4.9%, P < 0.001). In vivo, the AdFITC CAR-T cell system inhibited meningioma growth (P = 0.002) and prolonged survival (P = 0.003) in the IOMM-Lee orthotopic model compared to PBS. In a genetically engineered murine meningioma model, the AdFITC CAR-T cell system not only restricted tumor growth (P = 0.0018) and improved survival (P < 0.0001), but cured a substantial proportion of meningioma bearing mice. This treatment also induced the expansion of both CD8+ CAR-T cells (P = 0.0041) and a host T-cell response. Preliminary ex vivo killing assays, involving co-culture of the AdFITC CAR-T cell system with patient-derived meningioma tissue, showed specific lysis rates of 15-20% (ET 1:1) within 12 hours. Targeting SSTR2 with the AdFITC CAR-T cell system emerges as a promising therapeutic approach for meningioma, an early phase clinical trial is warranted.

Study of Molecular Markers in Glioma and Their Association with Clinicopathological Features.

Central nervous system tumors are a major cause of morbidity and mortality worldwide. The most prevalent type of primary brain tumor is glioma. The exploration of significant genetic, epigenetic, and transcriptional abnormalities has not only improved our understanding of glioma pathogenesis but has also revealed that these molecular alterations can serve as useful diagnostic markers for more precise classification and are linked to better treatment response and prognosis. Hence, incorporating molecular markers into routine tumor classification is a major priority in modern glioma diagnostics. The aim is to assess the mutation status of isocitrate dehydrogenase (IDH)-1, alpha-thalassemia/mental retardation syndrome X-linked (ATRX), and tumor protein 53 in glioma, and look for their association with various clinicopathological features. A single-center prospective cohort study, where all biopsies of glioma (January 2019 to July 2020) were evaluated, and immunohistochemistry was performed to assess the expression of IDH-1, ATRX, p53, and Ki-67 index. The data were analyzed using IBM SPSS-24 software. Immunohistochemistry was performed in 123 consecutive cases of glioma. IDH-1 mutation was noted in 54 (43.9%) cases and these patients frequently presented with "seizures" (P = 0.006). The expression was maximum in World Health Organization (WHO) grade 2 tumors (65.4%) (P < 0.001), with the highest frequency in oligodendrogliomas (100% in WHO grade 2 and 3). Furthermore, these tumors showed lower proliferative indices (P = 0.001). ATRX mutation was noted in 59 (48%) and p53 overexpression was noted in 76 (61.8%) cases. These mutations were significantly associated with astrocytic phenotype (P = 0.03). Molecular characterization of glioma is an important step in modern glioma diagnostics and immunohistochemistry can play an important role. IDH-1 mutation is commonly observed in adults, frontal lobe location, patients presenting with seizures, and WHO grade 2 tumors with the highest frequencies in oligodendrogliomas. ATRX and p53 can be used as surrogate markers for tumors of astrocytic lineage.

Spermine Synthase : A Potential Prognostic Marker for Lower-Grade Gliomas.

The objective of this study was to assess the relationship between spermine synthase (SMS) expression, tumor occurrence, and prognosis in lower-grade gliomas (LGGs). A total of 523 LGG patients and 1152 normal brain tissues were included as controls. Mann-Whitney U test was performed to evaluate SMS expression in the LGG group. Functional annotation analysis was conducted to explore the biological processes associated with high SMS expression. Immune cell infiltration analysis was performed to examine the correlation between SMS expression and immune cell types. The association between SMS expression and clinical and pathological features was assessed using Spearman correlation analysis. In vitro experiments were conducted to investigate the effects of overexpressing or downregulating SMS on cell proliferation, apoptosis, migration, invasion, and key proteins in the protein kinase B (AKT)/epithelialmesenchymal transition signaling pathway. The study revealed a significant upregulation of SMS expression in LGGs compared to normal brain tissues. High SMS expression was associated with certain clinical and pathological features, including older age, astrocytoma, higher World Health Organization grade, poor disease-specific survival, disease progression, non-1p/19q codeletion, and wild-type isocitrate dehydrogenase. Cox regression analysis identified SMS as a risk factor for overall survival. Bioinformatics analysis showed enrichment of eosinophils, T cells, and macrophages in LGG samples, while proportions of dendritic (DC) cells, plasmacytoid DC (pDC) cells, and CD8+ T cells were decreased. High SMS expression in LGGs may promote tumor occurrence through cellular proliferation and modulation of immune cell infiltration. These findings suggest the prognostic value of SMS in predicting clinical outcomes for LGG patients.

Temporal muscle thickness is not a prognostic predictor in patients with high-grade glioma, an experience at two centers in China.

Temporal muscle thickness (TMT) serves as an indicator of sarcopenia and holds predictive value for various cancers. This study aims to evaluate the prognostic significance of TMT for high-grade glioma patients. A retrospective review of 172 high-grade glioma patients from January 2015 to December 2022 was conducted. TMT value was measured based on contrast-enhanced T1-weighted magnetic resonance images before surgery. Pearson analysis was used to evaluate potential correlations. Cox regression analysis was performed to evaluate overall survival for high-grade glioma patients. In our study, the cutoff value of TMT was determined as 7.4 mm. TMT value was not a significant prognostic predictor for high-grade glioma patients (hazard ratio [HR]: 1.151, 95% confidence interval [CI]: 0.9299-1.424, p = 0.196). World Health Organization (WHO) VI and high body mass index (BMI) value were significantly associated with poorer survival outcomes (HR: 2.6689, 95% CI: 1.5729-4.528, p < 0.001; HR: 1.120, 95% CI: 1.0356-1.211, p = 0.005). TMT did not show a significant association with other factors (p > 0.05). Notably, age demonstrated a significant difference between the thicker and thinner groups (p = 0.019). Our study revealed that WHO grade and BMI demonstrated significant prognostic value for survival outcomes. Consequently, TMT does not appear to be a significant or applicable predictor in patients with high WHO grades.

A Case of Single Surgical Removal of Two Distinct Meningiomas with Different World Health Organization Grades and Subtypes in an Elderly Patient

Meningioma is one of the most common types of benign primary brain tumors in older adults, and multiple meningiomas are reported in fewer than 1% to 10% of cases. However, there is no definitive treatment guideline for patients with multiple meningiomas. An 80-year-old man presented with abruptly impaired cognition and was found to have two distinct meningiomas located in the temporal and frontal lobes. A single frontotemporal craniotomy was performed to remove both tumors. Pathological analysis revealed different subtypes and World Health Organization grades for each mass. The patient showed symptomatic improvement, experienced no postoperative complications, and exhibited no signs of recurrence during a 1-year follow-up period with evaluations at 3-month intervals. Despite the absence of a standard treatment for multiple meningiomas, surgical resection in a single procedure is feasible in selected patients.

In Reply: A Data-Driven Approach to Predicting 5-Aminolevulinic Acid-Induced Fluorescence and World Health Organization Grade in Newly Diagnosed Diffuse Gliomas.

In Reply: A Data-Driven Approach to Predicting 5-Aminolevulinic Acid-Induced Fluorescence and World Health Organization Grade in Newly Diagnosed Diffuse Gliomas.

Letter: A Data-Driven Approach to Predicting 5-Aminolevulinic Acid-Induced Fluorescence and World Health Organization Grade in Newly Diagnosed Diffuse Gliomas.

Letter: A Data-Driven Approach to Predicting 5-Aminolevulinic Acid-Induced Fluorescence and World Health Organization Grade in Newly Diagnosed Diffuse Gliomas.

Parasagittal and parafalcine cystic meningiomas, as well as other cystic meningiomas case series and systematic literature review

Background and Importance: Cystic components in meningiomas are an infrequent finding and pose diagnostic and therapeutic challenges to neurosurgeons. This study aims to conduct a comprehensive assessment of the clinical characteristics and management approaches for cystic meningiomas (CMs). Case Presentation: The current research investigated rare cases of CM. In the first case (case 1), benign parasagittal CM showed malignant features, including brain swelling and midline shifting. In the second case (case 2), parafalcine CMs demonstrate rare histopathological analysis and have not been documented in previous studies. The third case involved a pregnant woman, while the fourth case showed improvement in an older patient after surgery and indicated that the removal of a CM can result in a good prognosis. All tumors were surgically removed at stage 1 (Simpson stage), and histopathology confirmed World Health Organization (WHO) grade 1 syncytial meningioma in cases 1, 3, and 4. Only case 2 showed grade 3 rhabdoid meningioma. Conclusion:We found that benign CM may cause more brain edema than high-grade meningiomas, especially when they invade the sinus. Parasagittal and parafalcine CM invade the superior sagittal sinus (SSS), making complete excision more challenging and riskier. The presence of the cyst facilitates the removal of the tumor and reduces the risks.

Factors influencing outcome in patients with intramedullary spinal cord tumors undergoing resective surgery.

We evaluated whether preoperative functional status influenced surgical outcomes for patients with intramedullary spinal cord tumors (IMSCT). We analyzed whether lower preoperative McCormick scores impacted primary outcomes for 78 consecutive patients with IMSCT of World Health Organization (WHO) grades I and II undergoing tumor resection between 2010 and 2018. Patients averaged 33.6 years of age, 57.5% were male, and lesions predominantly involved the cervical 23 (29.5%) followed by the thoracic spine 19 (24.3%). Over the average follow-up interval of 69.83 months, IMSCTs recurred in 11.5% of patients, with 6.4% showing functional deterioration. At follow-up, 73.5% of patients with a preoperative modified McCormick score of two or one showed better functional improvement. The WHO pathological grades I and II did not significantly influence outcomes for patients with intramedullary spinal cord lesions. However, patients with low preoperative McCormick scores (two or one) demonstrated better functional outcomes.

Analysis of bleeding outcomes in patients with hypoproliferative thrombocytopenia in the A-TREAT clinical trial.

Despite prophylactic platelet transfusions, hypoproliferative thrombocytopenia is associated with bleeding; historical risk factors include hematocrit (HCT) 25%, activated partial thromboplastin time 30 s, international normalized ratio 1.2, and platelets 5000/μL. We performed a post hoc analysis of bleeding outcomes and risk factors in participants with hematologic malignancy and hypoproliferative thrombocytopenia enrolled in the American Trial to Evaluate Tranexamic Acid Therapy in Thrombocytopenia (A-TREAT) and randomized to receive either tranexamic acid (TXA) or placebo. World Health Organization (WHO) grade 2+ bleeding occurred in 46% of 330 participants, with no difference between the TXA (44%) and placebo (47%) groups (p = 0.66). Overall, the most common sites of bleeding were oronasal (18%), skin (17%), gastrointestinal (11%), and genitourinary (11%). Among participants of childbearing potential, 28% experienced vaginal bleeding. Platelets ≤5000/μL and HCT < 21% (after adjusting for severe thrombocytopenia) were independently associated with increased bleeding risk (HR 3.78, 95% CI 2.16-6.61; HR 2.67, 95% CI 1.35-5.27, respectively). Allogeneic stem cell transplant was associated with nonsignificant increased risk of bleeding versus chemotherapy alone (HR 1.34, 95% CI 0.94-1.91). The overall rate of WHO grade 2+ bleeding was similar to previous reports, albeit with lower rates of gastrointestinal bleeding. Vaginal bleeding was common in participants of childbearing potential. Platelets ≤5000/μL remained a risk factor for bleeding. Regardless of platelet count, bleeding risk increased with HCT < 21%, suggesting a red blood cell transfusion threshold above 21% should be considered to mitigate bleeding. More investigation is needed on strategies to reduce bleeding in this population.

Benign extracranial meningioma with pulmonary metastasis: a case report and review of literature

BackgroundMeningiomas are common central nervous system tumors, predominantly intracranial, they rarely develop extracranially. Moreover, benign meningiomas seldom metastasize.Case presentationThis article presents a case report of a 55-year-old Chinese male patient with a primary World Health Organization grade 1 meningioma originating from the petrous apex of the temporal bone, accompanied by pulmonary metastasis. Following two incomplete resections of the primary tumor, the patient underwent radiotherapy and has since maintained a stable condition.ConclusionThe case report highlights the rare occurrence of pulmonary metastasis in a benign World Health Organization grade 1 meningioma originating from an extracranial site. It also illustrates the important role of radiotherapy in treating patients with meningioma. Additionally, a review of related literature is provided to gain insights for the diagnosis and treatment of the disease.

A targeted gene expression biomarker predicts clinic low-risk meningioma recurrence.

Despite reassuring clinical and histological features, low grade meningiomas can recur after surgery. Targeted gene expression profiling improves risk stratification of meningiomas, but the utility of this approach for clinical low-risk meningiomas is incompletely understood. This was a multicenter retrospective cohort study of meningiomas from patients who were treated at 4 institutions from 1992 to 2023. Adult patients with newly diagnosed or recurrent World Health Organization (WHO) grade 1 meningiomas that were treated with gross total resection (GTR) or subtotal resection (STR), or newly diagnosed WHO grade 2 meningiomas that were treated with GTR, were included. A 34-gene expression biomarker and gene expression risk score (continuous from 0 to 1) was evaluated in all samples. The study cohort was comprised of 723 patients, none of which were used for discovery or training of the gene expression biomarker and 265 of which were previously unreported. There were 626 WHO grade 1 meningiomas, 490 with GTR and 126 with STR, and 97 WHO grade 2 meningiomas with GTR. Targeted gene expression profiling classified 51.3% of clinical low-risk meningiomas as molecular intermediate-risk and 9.5% as molecular high-risk. Combining the gene expression biomarker with extent of resection revealed 19.8% of clinical low-risk meningiomas had unfavorable local freedom from recurrence (LFFR) and overall survival (OS), including 7.1% of newly diagnosed WHO grade 1 meningiomas with GTR. The risk score was prognostic for LFFR (HR per 0.1 increase in risk score 1.89, 95% CI 1.58-2.25) across all WHO grades, extents of resection, and newly diagnosed or recurrent presentations. Targeted gene expression profiling can identify clinical low-risk meningiomas that are likely to recur after surgery.

Multiple Meningiomas with Different Histological Patterns in the Same Patient: Do They Exist? A Case Report and Literature Review

AbstractMeningiomas are the most common form of primary intracranial tumors, accounting for 13 to 26% of total neoplasms arising from arachnoid cap cells of the meningeal layer covering the central nervous system. Multiple intracranial meningiomas, which often have a syndromic association, account for less than 10% of total meningiomas. Multiple meningiomas with different histological patterns or grades in the same patient are very rare. Here we report such a rare case of meningioma with different histological patterns in the same patient. A 56-year-old lady presented to us with complaints of progressive right-sided weakness and speech disturbances, and her magnetic resonance imaging (MRI) showed two distinct extra-axial lesions over left frontal convexity and left fronto-temporo-parietal convexity. She underwent left fronto-temporo-parietal craniectomy and Simpson grade 1 excision of the lesions. Her histopathological examination revealed two different histological patterns: lesion 1 (left fronto-temporo-parietal convexity) was reported as a transitional World Health Organization (WHO) grade 1 meningioma and lesion 2 (left frontal convexity) was reported as angiomatous WHO grade 1 meningioma. She recovered well and was discharged in a stable condition after 3 weeks. Multiple meningiomas are defined as at least two spatially separated meningiomas occurring at the same time or more than two meningiomas arising sequentially from two clearly distinct regions. The exact mechanism of multicentricity is unknown. The treatment protocol for different histological types in the same patient is not clear. The extent of surgical resection remains the mainstay of the treatment and these patients should be followed up closely to watch for recurrence or malignant transformation. The role of radiotherapy in multiple meningiomas is yet to be established.

Utility of Early Postoperative DWI to Assess the Extent of Resection of Adult-Type World Health Organization Grade 2 and 3 Diffuse Gliomas.

World Health Organization (WHO) grade 2 and 3 diffuse gliomas account for approximately 5% of primary brain tumors. They are invasive and infiltrative tumors and have considerable morbidity, causing progressive neurologic deterioration. The mean survival time is <10 years from diagnosis. Surgical debulking represents first-line management. The extent of resection is associated with progression-free and overall survival. Radiologic assessment of the extent of resection is challenging. This can be underestimated on early postoperative MRI, meaning that accurate assessment may be achieved only on delayed follow-up imaging. We hypothesized that DWI may help facilitate more reliable estimates of the extent of resection on early postoperative MRI. This study aimed to assess the utility of DWI in early postoperative MRI to evaluate the extent of resection. A single-center observational cohort study was performed. All patients with histologically confirmed WHO grade 2 and 3 gliomas managed with surgical debulking between January 2015 and December 2020 were identified. Preoperative, early postoperative, and follow-up imaging were reviewed independently by 2 consultant neuroradiologists. The extent of resection was estimated with and without DWI sequences for each case. Two hundred twenty-four patients with WHO grade 2 and 3 gliomas were managed with surgical debulking between 2015 and 2020. DWI was not performed on early postoperative MRI in 2 patients. With the use of DWI, the extent of resection was upgraded in 30% of cases (n = 66/222) and classified as "complete" or "supramaximal" in 58% of these patients (n = 38/66). In cases in which the extent of resection was upgraded with the use of DWI, signal abnormality was stable or reduced at follow-up in 78% (n = 49/63). In cases with worsening signal abnormality, 64% were deemed to be secondary to adjuvant radiation therapy (n = 9/14). Eight percent (n = 5/63) of patients with an increased estimated extent of resection using DWI demonstrated signal progression attributed to true disease progression at follow-up. DWI is a helpful and reliable adjunct in differentiating residual tumor from marginal ischemia in early postoperative MRI in WHO grade 2 and 3 diffuse gliomas and increases the accuracy in assessing the extent of resection. It should be used routinely in these cases.

TGF-β signaling-related signature for predicting prognosis and therapeutic response in lower-grade glioma.

Low-grade glioma (LGG) is a tumor that includes World Health Organization (WHO) grade II and III glioma, the treatment of which consistently results in relapse and drug resistance. Transforming growth factor-beta (TGF-β) is a multifunctional cytokine that regulates various cellular processes, which is found to be abnormal in tumors and promotes glioma development and progression. In this study, we aimed to systematically evaluate the importance of the genes associated with TGF-β in LGG and discover the role of these genes in the prognosis and treatment response of LGG. We used the "Bioconductor Limma" and "consensusClusterplus" R packages to screen differential and prognostic TGF-β-related genes. The R package "GSVA" was used to estimate the infiltration of immune cells and metabolism signature. The drug sensitivity for each TGF-β subtype was assessed by the R package "pRRophetic". The Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm was used to assess the copy number variation (CNV). The onco-print tool of the "complexheatmap package" was employed to visualize the somatic mutation and copy number alteration (CNA) among TGF clusters. We reported three subtypes (A, B, and C) of LGG according to the classification of TGF-β-related genes, where subtype A showed the best prognosis. Subtype B was highly enriched in immune cells. Somatic variations were observed to be diverse in all of the three TGF-β subtypes. Furthermore, another three genes (SHA, AC062021.1, and SNCG) related to TGF-β were identified, which can be a superior predictor of prognosis with a risk score. LGG can be divided into three subtypes based on TGF-β signaling-related genes with distinct immune infiltration, metabolism, somatic variations, and prognosis.