World Health Organization Grade Research Articles

Vascular invasion predicts the subgroup of lung adenocarcinomas ≤2.0 cm at risk of poor outcome treated by wedge resection compared to lobectomy

BackgroundRecent randomized control trials (JCOG0802 and CALGB140503) have shown sublobar resection to be noninferior to lobectomy for non–small cell lung cancer (NSCLC) ≤2.0 cm. We have previously proposed histologic criteria stratifying lung adenocarcinoma into indolent low malignant potential (LMP) and aggressive angioinvasive adenocarcinomas, resulting in better prognostication than provided by World Health Organization grade. Here we determine whether pathologic classification is reproducible and whether subsets of adenocarcinomas predict worse outcomes when treated by wedge resection compared to lobectomy. MethodsA retrospective cohort of 108 recipients of wedge resection and 187 recipients of lobectomy for stage I/0 lung adenocarcinomas ≤2.0 cm was assembled from 2 institutions. All tumors were classified by a single pathologist, and interobserver reproducibility was assessed in a subset (n = 92) by 5 pathologists. ResultsAngioinvasive adenocarcinoma (21%-27% of cases) was associated with worse outcomes when treated with wedge resection compared to lobectomy (5-year recurrence-free survival, 57% vs 85% [P = .007]; 5-year disease-free survival [DSS], 70% vs 90% [P = .043]; 7-year overall survival, 37% vs 58% [P = .143]). Adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and LMP exhibited 100% 5-year DSS regardless of the surgical approach. Multivariable analysis showed that angioinvasion, tumor size, margin status, and extent of nodal sampling were significantly associated with recurrence but not with surgical procedure. There was substantial interobserver reproducibility among the pathologists for the diagnosis of angioinvasive adenocarcinoma (κ = 0.71) and the combined indolent AIS/MIA/LMP group (κ = 0.74). ConclusionsThe majority (∼75%) of lung adenocarcinomas ≤2 cm are adequately managed with wedge resection; however, angioinvasive adenocarcinomas (∼25%) treated by wedge resection with suboptimal nodal sampling exhibit poor outcomes, with a 40% to 45% rate of recurrence within 5 years and 60% to 65% overall mortality at 7 years.

NIMG-82. FET PET SENSITIVITY IN PRIMARY BRAIN TUMORS ACCORDING TO CNS WHO 2021: VALUE AND PITFALLS IN PRESURGICAL IMPLEMENTATION

Abstract BACKGROUND FET-PET imaging has emerged as a valuable tool in the characterization of unclear brain lesions that cannot be clearly diagnosed with conventional diagnostic methods. In 2021, the Central Nervous System (CNS) World Health Organization (WHO) introduced significant changes in the classification of CNS tumors. Notably, under the new classification, certain cases of WHO grade II glioma may be reclassified as glioblastoma. Unfortunately, a subset of grade II gliomas, as defined by the 2016 WHO classification, may exhibit no detectable FET uptake and lack contrast enhancement on MRI, which can lead to underestimation of such tumors and potentially result in inappropriate treatment decisions, including avoiding surgery. Question: In how many cases did the diagnostics consisting of MRI and FET PET underestimate the malignancy in unclear brain lesions? METHODS In this study, we conducted a retrospective analysis of all patients who underwent FET PET imaging of the brain between 2017 and June 2021, prior to their first surgical brain intervention. We obtained the results from presurgical MRI-scans and categorized the lesions based on whether they exhibited contrast media enhancement or not, in addition to the postsurgical molecular-histopathologic diagnosis. Our analysis focused on identifying the number of cases in which the diagnosis of malignancy was underestimated in the context of the WHO 2016 classification. To further investigate these cases, we conducted NGS and 850k-analysis to reclassify the results in accordance with the new CNS WHO 2021 classification. RESULTS After enrolling 85 patients, our study found that according to the 2016 classification, preoperative imaging underestimated malignancy in 14 cases (16%) where histopathological analysis revealed high-grade malignant brain tumors. In 32 cases (27%), the preoperative imaging correctly suggested a malignant tumor, which was later confirmed by histopathological analysis after surgery. The final results of this reclassification after the CNS-WHO-2021 will be presented at SNO-meeting.

IMMU-19. MUTANT ISOCITRATE DEHYDROGENASE 1 IN GLIOMA CAUSES A REDUCTION IN ADENOSINERGIC PATHWAY SIGNALING WITHIN THE TUMOR MICROENVIRONMENT

Abstract Glioma is one of the most aggressive cancers and represents approximately 80% of malignant brain tumors. The majority of CNS World Health Organization (WHO) grades 2-3 gliomas and a subset of high-grade gliomas (CNS WHO grade 4) harbor mutated isocitrate dehydrogenase 1 (IDH1R132H; mIDH1). Mutant IDH1 results in the accumulation of 2-hydroxyglutarate (2HG) which elicits profound changes in the glioma transcriptome/biology. Consequently, mIDH1 glioma patients have a significantly increased median survival compared to wildtype IDH1 patients. Recent data from our lab showed that mIDH1 gliomas exhibit increased immune-reactivity of tumor-infiltrating immune cells. A critical pathway that mediates reduction of anti-tumor immune cell reactivity is the adenosinergic pathway (AP), which converts ATP into adenosine via the enzymes CD39 and CD73. Adenosine binds to adenosine receptors, A2AR and A2BR, on immune cells resulting in a decreased immunoreactivity. Although mIDH1 has been implicated in altering the AP, the extent to which the AP is affected by mIDH1 in gliomas is largely unknown. Here we used human and mouse mIDH1 glioma cells in vitro along with in vivo mIDH1 glioma mouse models to examine changes in the AP. Our results show reduced levels of the enzyme, CD73, on the surface of mIDH1 glioma cells, and the ATP concentration in the mIDH1 glioma cell growth media is lower than from wildtype IDH1 glioma cells. Additionally, we discovered that mIDH1 glioma-infiltrating macrophages have decreased expression of CD39 and A2AR compared to their wildtype IDH1 glioma counterparts. Taken together, these data suggest a reduction of the AP mediated-immune suppression in mIDH1 gliomas. Uncovering these differences in the AP provides novel insights on the use of AP inhibitors for glioma treatment, revealing whether the AP is a preferred target in specific glioma types based on the IDH1 mutation status.

QOL-09. QUALITY OF LIFE AFTER SURGERY FOR LOWER GRADE GLIOMAS

Abstract BACKGROUND Limited data exist on long-term quality of life (QOL) for adults diagnosed with lower grade glioma (LGG). METHODS QOL was assessed for 320 adults with LGG (World Health Organization grade 2/3) enrolled in the International Low Grade Glioma Registry using the Medical Outcomes Study 36-Item Short Form (SF-36) health survey. Data on symptoms were also collected. QOL outcomes were examined by treatment group and also compared to those from a population-based case/control study of meningioma (the Meningioma Consortium), in which 1722 meningioma cases diagnosed among residents of Connecticut, Massachusetts, California, Texas, and North Carolina from May 1, 2006 through March 14, 2013 were enrolled and frequency matched to 1622 controls by age, sex and geography. RESULTS The LGG sample average age is 45 years at time of interview and 53.1% male. Almost 55% of patients had received radiation and chemotherapy (primarily temozolomide); 32.4% had received neither treatment. Almost 2/3 LGG subjects report difficulty with speaking, memory, or thinking and over 1/3 report personality change or difficulty driving. After controlling for age and other co-morbidities, individuals diagnosed with LGG report levels of physical, emotional, and mental health functioning below those reported in a meningioma as well as a general healthy population. CONCLUSIONS Despite being relatively young, persons with LGG report significantly reduced QOL compared to persons with non-malignant brain tumors and to a control population, highlighting the need to better acknowledge and manage these symptoms for this group of patients diagnosed in the prime of life.

5-aminolevulinic acid-guided endoscopic biopsy with violet light-emitting diode flashlight in malignant glioma: Technical note.

5-aminolevulinic acid (5-ALA) photodynamic diagnosis (PDD) has enabled better identification of malignant tumor cells and real-time intraoperative guidance. Here, we report a reasonable procedure for 5-ALA-guided endoscopic biopsy with a violet light-emitting diode (LED) flashlight for deep-seated malignant gliomas. A 63-year-old man presented with a headache and left upper homonymous quadrantanopia. Imaging studies showed atypical lesions with non-significant and partial contrast enhancement in the right deep temporo-occipital lobe. An endoscopic biopsy was performed under the guidance of 5-ALA PDD with a violet LED flashlight. The tumor tissues, which were difficult to distinguish from normal brain parenchyma under white light, were positive for 5-ALA fluorescence. The histopathological diagnosis was astrocytoma (the World Health Organization grade 3). The patient underwent adjuvant chemoradiation therapy. Headache and anopia improved, and no recurrence was observed at 12 months follow-up. This technique of neuroendoscopic biopsy guided by 5-ALA PDD fluorescence with a violet LED flashlight may allow a safe and accurate diagnosis of deep-seated malignant gliomas.

Unveiling a Biomarker Signature of Meningioma: The Need for a Panel of Genomic, Epigenetic, Proteomic, and RNA Biomarkers to Advance Diagnosis and Prognosis.

Meningiomas are the most prevalent primary intracranial tumors. The majority are benign but can undergo dedifferentiation into advanced grades classified by World Health Organization (WHO) into Grades 1 to 3. Meningiomas' tremendous variability in tumor behavior and slow growth rates complicate their diagnosis and treatment. A deeper comprehension of the molecular pathways and cellular microenvironment factors implicated in meningioma survival and pathology is needed. This review summarizes the known genetic and epigenetic aberrations involved in meningiomas, with a focus on neurofibromatosis type 2 (NF2) and non-NF2 mutations. Novel potential biomarkers for meningioma diagnosis and prognosis are also discussed, including epigenetic-, RNA-, metabolomics-, and protein-based markers. Finally, the landscape of available meningioma-specific animal models is overviewed. Use of these animal models can enable planning of adjuvant treatment, potentially assisting in pre-operative and post-operative decision making. Discovery of novel biomarkers will allow, in combination with WHO grading, more precise meningioma grading, including meningioma identification, subtype determination, and prediction of metastasis, recurrence, and response to therapy. Moreover, these biomarkers may be exploited in the development of personalized targeted therapies that can distinguish between the 15 diverse meningioma subtypes.

ROLE OF DIFFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING FOR BRAIN TUMOR CHARACTERIZATION

Objectives: This study was conducted with the objective to link the results of diffusion-weighted magnetic resonance imaging (MRI) with the tumor’s histopathological grade. The current study aims to evaluate this and determine the accuracy of diffusion-weighted MRI to determine grade of glioma. Methods: The present study was a hospital-based cross-sectional purposive study. A total of 50 patients undergoing the MR evaluation of the brain with evidence of clinically suspected cerebral mass were enrolled in study based on inclusion and exclusion criteria. Statistical analysis was performed. Results: In our study, the minimum apparent diffusion coefficient (ADC) was significantly lower for high-grade than for low-grade gliomas (1119.68±138.33 vs. 717.18±154.38, p<0.001). Conclusions: By examining diffusion-weighted images and comparing the ADC of gliomas with the World Health Organization grade, we analyze the potential of ADC in predicting tumor grade through this study.

Clinical characteristics and prognostic factors of surgical treatment in children with brainstem tumor.

Brainstem tumors present a significant challenge in surgical treatment, and the prognostic factors in children are lacking. This study aimed to investigate clinical characteristics and prognostic factors of surgical treatment in children with brainstem tumors. 50 children with brainstem tumors who underwent surgical treatment, including frameless- or frame-based stereotactic biopsy and resection, were included and followed up for clinical and biological analysis. Factors of outcomes were assessed by univariate and multivariate analysis. 27 cases (54.0%) underwent resection in all children with brainstem tumors. The rate of resection reached as high as 81.8% in children with non-diffuse intrinsic pontine glioma (DIPG), while in children with DIPG, biopsy was performed in the majority, and resection was obtained in the minority with focal necrosis. A rare complication was found following the surgery. Multivariate analysis considered World Health Organization (WHO) grade 3-4, with hazard ratio (HR)=4.48, 95% confidence interval (CI) of 2.84-8.69, p=0.001, H3K27M mutation (HR=2.50, 95% CI 1.73-5.69, p=0.015), and hydrocephalus (HR=2.17, 95% CI 1.08-5.32, p=0.014) as independent adverse prognostic factors. For Kaplan-Meier analysis, children with WHO grade 3-4, Ki-67 LI ≥ 20%, TP53 mutation, H3K27M mutation, DIPG, and hydrocephalus had significantly decreased overall survival (OS). A high rate of resection has been obtained in non-DIPG, and surgical intervention is remarkably safe and efficient for children with brainstem tumors. WHO grade 3-4, H3K27M mutation, and hydrocephalus indicate poor prognosis in children with brainstem tumors.

Neuroendocrine Tumor of The Appendix: Retrospective 7266 analysis of Appendectomy Patients in a single center

Objective: We aim to identify appendiceal neuroendocrine tumors (NETs) seen after acute appendicitis and investigate their incidence in patients with laparoscopic or open appendectomy surgery. Here we have shaped the characteristic features of the tumor according to the 2010 classification rating of The World Health Organization (WHO) (surgical margin, invasion, grading, TNM stages) and also explored the disease-free survival in these patients. Material and Methods: This is the medical record of the patient with 7266 appendectomy retrospectively evaluated, and with these examples in histopathological analysis, a total of 43 patients were diagnosed with appendicitis NETs and included in the study. Age, gender, prediction of the surgical team during the operation, location of the tumor, WHO grade, depth of invasion, positive surgical margin, tumor size, TNM stage, and postoperative survival of these patients were analyzed retrospectively. Results: In this study, the incidence of appendiceal (NETs) was found to be 0.59% among 7,266 patients. Out of the 42 patients with appendiceal NETs, 27 were female and 16 were male. The mean age of the patients was 33.65 years (range: 11–78). The diagnosis was aided by clinical examination, ultrasound, and abdominal computerized tomography (CT) imaging. Most patients were initially diagnosed with appendicitis, and surgical interventions, including laparoscopic and conventional appendectomy, were performed. The pathological analysis confirmed appendicitis with NETs, classified according to the WHO 2010 recommendation. The majority of patients had well-differentiated NETs (G1 or G2). Surgical resection achieved negative radial margins, and no pathological signs were detected during follow-up colonoscopies. At a median follow-up of 70.2 months, all patients remained disease-free and alive. Conclusion: Appendiceal neuroendocrine tumors are rare but distinct entities that require a multidisciplinary approach for diagnosis and management. Surgical resection is the primary treatment, with systemic therapies reserved for advanced cases. The prognosis is generally favorable, with better outcomes seen in well-differentiated tumors. Long-term follow-up is crucial. Further research is needed to improve understanding and optimize treatment strategies for these tumors.

Cytologic features of meningioma: An analysis of common and uncommon subtypes and diagnostic difficulties during intraoperative procedures.

Despite common histogenesis meningiomas have a wide morphologic spectrum, and the World Health Organization (WHO) recognizes 15 subtypes. They are the most common brain tumour in adults and typically have an extra-axial location. Although there have been important advances in the molecular biology of meningiomas its diagnosis is based on histopathologic features. The great majority are benign WHO grade 1 tumours. There are specific criteria for assigning WHO grade 2 and 3 that can be applied to all meningioma subtypes. Regardless of these criteria, chordoid and clear cell morphologic subtypes are considered grade 2. WHO grade 3 tumours exhibit a very high mitotic index, frank anaplasia or specific molecular abnormalities. The impressive morphologic diversity shown by meningiomas makes them a diagnostic challenge, which can be even greater in intraoperative studies. The focus of this article is to describe and illustrate their main cytologic features, with emphasis on the most infrequent subtypes.

Significant perioperative parameters affecting postoperative complications within 30 days following craniotomy for primary malignant brain tumors

BackgroundThe occurrence of postoperative complications within 30 days (PC1M) of a craniotomy for the removal of a primary malignant brain tumor has been associated with a poor prognosis. However, it is still unclear to early predict the occurrence of PC1M. This study aimed to identify the potential perioperative predictors of PC1M from its preoperative, intraoperative, and 24-h postoperative parameters.MethodsPatients who had undergone craniotomy for primary malignant brain tumor (World Health Organization grades III and IV) from January 2011 to December 2020 were enrolled from a databank of Kaohsiung Veterans General Hospital, Taiwan. The patients were classified into PC1M and nonPC1M groups. PC1M was defined according to the classification by Landriel et al. as any deviation from an uneventful 30-day postoperative course. In both groups, data regarding the baseline characteristics and perioperative parameters of the patients, including a new marker-kinetic estimated glomerular filtration rate, were collected. Logistic regression was used to analyze the predictability of the perioperative parameters.ResultsThe PC1M group included 41 of 95 patients. An American Society of Anesthesiologists score of > 2 (aOR, 3.17; 95% confidence interval [CI], 1.19–8.45; p = 0.021), longer anesthesia duration (aOR, 1.16; 95% CI, 0.69–0.88; p < 0.001), 24-h postoperative change in hematocrit by > − 4.8% (aOR, 3.45; 95% CI, 1.22–9.73; p = 0.0019), and 24-h postoperative change in kinetic estimated glomerular filtration rate of < 0 mL/min (aOR, 3.99; 95% CI, 1.52–10.53; p = 0.005) were identified as independent risk factors for PC1M via stepwise logistic regression analysis. When stratified according to the age of ≥ 65 years (OR, 11.55; 95% CI, 1.30–102.79; p = 0.028), the reduction of kinetic estimated glomerular filtration rate was more robustly associated with a higher risk of PC1M.ConclusionsFour parameters were demonstrated to significantly influence the risk of PC1M in patients undergoing primary malignant brain tumor removal. Measuring and verifying these markers, especially kinetic estimated glomerular filtration rate, would help early recognition of PC1M risk in clinical care.

Predictor factors for recurrence in atypical meningiomas.

Atypical meningiomas (AMs), World Health Organization (WHO) grade 2, are a group of tumors with uneven and unpredictable clinical behavior. Our aim was to analyze possible tumor recurrence predictors, and to identify factors that improve progression-free survival (PFS). Our retrospective study included 81 patients followed up in the Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iaşi, Romania, between 1 January 2010 and 31 December 2020. The histopathological specimens were reviewed according to the WHO 2021 criteria. Analyses included clinical, imaging, pathological and surgical factors. The tumor recurred in 53.1% of the 81 cases within 60 months of surgery. Tumor location (p<0.000), tumor volume (p<0.010), extent of surgical resection (p<0.000) and dural sinus invasion (p<0.001) were predictive factors of recurrence. Gross total resection (Simpson grade I and II) was achieved in 59.2% of patients. Patients with the tumors located in the brain convexity and volume <26.4 cm³ had better survival rates up to recurrence. PFS showed a significant relationship between Simpson grade I-III and biopsy (p<0.000) and was statistically influenced by tumor volume and location, and dural sinus invasion. AMs are a heterogeneous group of tumors, and we identified posterior fossa location, volume ≥26.4 cm³, Simpson grade III and IV resection and dural sinus invasion as predictive factors for relapse and a shorter PFS. Whereas certain characteristics provide some prognostic value, future molecular characterizations of AMs are necessary, which will support the clinical decision-making process.

γδ T cells as a potential therapeutic agent for glioblastoma.

Although γδ T cells comprise a small population of T cells, they perform important roles in protecting against infection and suppressing tumors. With their distinct tissue-localizing properties, combined with their various target recognition mechanisms, γδ T cells have the potential to become an effective solution for tumors that do not respond to current therapeutic procedures. One such tumor, glioblastoma (GBM), is a malignant brain tumor with the highest World Health Organization grade and therefore the worst prognosis. The immune-suppressive tumor microenvironment (TME) and immune-evasive glioma stem cells are major factors in GBM immunotherapy failure. Currently, encouraged by the strong anti-tumoral function of γδ T cells revealed at the preclinical and clinical levels, several research groups have shown progression of γδ T cell-based GBM treatment. However, several limitations still exist that block effective GBM treatment using γδ T cells. Therefore, understanding the distinct roles of γδ T cells in anti-tumor immune responses and the suppression mechanism of the GBM TME are critical for successful γδ T cell-mediated GBM therapy. In this review, we summarize the effector functions of γδ T cells in tumor immunity and discuss current advances and limitations of γδ T cell-based GBM immunotherapy. Additionally, we suggest future directions to overcome the limitations of γδ T cell-based GBM immunotherapy to achieve successful treatment of GBM.

Morphogenetic characteristics of glial tumors in adults per the WHO classifications of 2007, 2016, 2021. Changes in the classifications and their significance for clinical practice

The presented lecture is dedicated to analysis of morphogenetic characteristics of glial tumors in adults in the framework of the World Health Organization (WHO) classifications of 2007, 2016, 2021, changes in the classifications and their significance for clinical practice. This topic is important because the most difficult changes for neurosurgeons to understand in comparison of the WHO classifications of 2007, 2016 and 2021 involved sections on glial tumors and children’s tumors.The authors focus on increasing practical significance of genetic component in tumor characterization. The classification of 2007 was the last purely morphological classification of central nervous system tumors, it did not include genetic principles of tumor division in different groups. In the following years, knowledge on the significance of various mutations for prognosis of glial tumor progression and selection of optimal treatment based in genetic characteristics of the neoplasm has been actively accumulated. In the 2016 edition, morphological and genetic tumor characteristics were consolidated for the first time which was unquestionably a necessary step. Complex integrative analysis of glioma genomes has shown that genetic characteristics have higher prognostic value compared to the WHO Grade. In the classification of 2021, names of the tumors proposed in 2016 were changed, and practical significance of the genetic component in tumor characterization was increased. However, this can further complicate interpretation of histological diagnosis by practicing neurosurgeons.Implementation of the 2021 WHO classification in clinical practice assumes expansion of the spectrum of genetic diagnostic methods. The neurosurgical community should be ready to interpret morphogenetic results and select treatment tactics in tandem with oncologists based on genetic characteristics of the tumor.

A repository of grade 1 and 2 meningioma MRIs in a public dataset for radiomics reproducibility tests.

Meningiomas are the most common primary brain tumors in adults with management varying widely based on World Health Organization (WHO) grade. However, there are limited datasets available for researchers to develop and validate radiomic models. The purpose of our manuscript is to report on the first dataset of meningiomas in The Cancer Imaging Archive (TCIA). The dataset consists of pre-operative MRIs from 96 patients with meningiomas who underwent resection from 2010-2019 and include axial T1post and T2-FLAIR sequences-55 grade 1 and 41 grade 2. Meningioma grade was confirmed based on the 2016 WHO Bluebook classification guideline by two neuropathologists and one neuropathology fellow. The hyperintense T1post tumor and hyperintense T2-FLAIR regions were manually contoured on both sequences and resampled to an isotropic resolution of 1×1×1 mm3 . The entire dataset was reviewed by a certified medical physicist. The data was imported into TCIA for storage and can be accessed at https://doi.org/10.7937/0TKV-1A36. The total size of the dataset is 8.8GB, with 47519 individual Digital Imaging and Communications in Medicine (DICOM) files consisting of 384 image series, and 192 structures. Grade 1 and 2 meningiomas have different treatment paradigms and are often treated based on radiologic diagnosis alone. Therefore, predicting grade prior to treatment is essential in clinical decision-making. This dataset will allow researchers to create models to auto-differentiate grade 1 and 2 meningiomas as well as evaluate for other pathologic features including mitotic index, brain invasion, and atypical features. Limitations of this study are the small sample size and inclusion of only two MRI sequences. However, there are no meningioma datasets on TCIA and limited datasets elsewhere although meningiomas are the most common intracranial tumor in adults.

Clinical profile, histopathological, immunohistochemical, and molecular analyses and treatment of pilocytic astrocytoma: an eight year study from a tertiary health care centre in North East India

BackgroundPilocytic astrocytoma (PA) is a central nervous system (CNS) World Health Organization (WHO) grade 1 glial tumor that is highly prevalent in children and young adults. The main aim of the study was to assess the frequency, clinicopathological features, and treatment of PAs along with their immunohistochemical and molecular analyses in patients from Northeast India. About 144 glial tumors were diagnosed in patients from 3 to 75 yrs of age from January 2015 to March 2022. Nine pediatric PA patients were identified and their clinical data were analyzed. Immunohistochemistry (IHC), fluorescence in-situ hybridization (FISH), and molecular analysis using the real-time polymerase chain reaction (RT-PCR) were performed. Data analysis was performed using the SPSS software.ResultsThe mean age of the glioma patients was 41.7 yrs ± 18.2 with a male/female ratio of 1.3:1. The most common form of the glial tumor was found to be astrocytoma CNS WHO grade 2 (31.9%). The frequency of PA CNS WHO grade 1 was 6.9%. The pediatric PA cohort had a mean age of 9.2 yrs ± 4.9 with a male/female ratio of 2:1. Glial fibrillary acidic protein (GFAP) positive immunostaining and retention of transcriptional regulator alpha-thalassemia mental retardation X-linked protein (ATRX) expression was seen in all the tested PAs. The KIAA1459-BRAF fusion was detected in four PAs. Surgical intervention with total or radical tumor excision was performed for the PA patients. Eight PA patients exhibited improved condition post-surgery.ConclusionWith the advent of healthcare and newer diagnostic facilities there is an increased incidence of glial tumors in developing countries. A combination of histological, immunohistochemical, and molecular analysis is very important for the diagnosis, accurate treatment, and prognosis of PA patients.

Systematic Review of WHO Grade 4 Astrocytoma in the Cerebellopontine Angle: The Impact of Anatomic Corridor on Treatment Options and Outcomes.

Background Despite advances in multimodal oncologic therapies and molecular genetics, overall survival (OS) in patients with high-grade astrocytomas remains poor. We present an illustrative case and systematic review of rare, predominantly extra-axial World Health Organization (WHO) grade 4 astrocytomas located within the cerebellopontine angle (CPA) and explore the impact of anatomic location on diagnosis, management, and outcomes. Methods A systematic review of adult patients with predominantly extra-axial WHO grade 4 CPA astrocytomas was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines through December 2022. Results Eighteen articles were included comprising 21 astrocytomas: 13 exophytic tumors arising from the cerebellopontine parenchyma and 8 tumors originating from a cranial nerve root entry zone. The median OS was 15 months with one-third of cases demonstrating delayed diagnosis. Gross total resection, molecular genetic profiling, and use of ancillary treatment were low. We report the only patient with an integrated isocitrate dehydrogenase 1 (IDH-1) mutant diagnosis, who, after subtotal resection and chemoradiation, remains alive at 40 months without progression. Conclusion The deep conical-shaped corridor and abundance of eloquent tissue of the CPA significantly limits both surgical resection and utility of device-based therapies in this region. Prompt diagnosis, molecular characterization, and systemic therapeutic advances serve as the predominant means to optimize survival for patients with rare skull base astrocytomas.

Multi-Institutional Study of Stereotactic Radiosurgery for Recurrent WHO Grade 2/3 Meningiomas: An Interim Analysis

Meningiomas are the most common tumors of the central nervous system (CNS). Approximately 80% are classified as World Health Organization (WHO) grade 1, while 20% correspond to grade 2 or grade 3. In those with grade 2/3 disease, local recurrence is not uncommon. Salvage treatment options vary widely and include resection, external beam radiation therapy (EBRT), stereotactic radiosurgery (SRS), and/or clinical trials. Although retrospective studies have reported on the use of upfront SRS in grade 2/3 meningiomas, large-scale outcomes with SRS in the recurrent setting are lacking. The objective of this study was to report on oncologic outcomes for patients with recurrent grade 2/3 meningioma treated with SRS. This is an ongoing multi-institutional retrospective cohort study. Eligibility criteria include patients >18 years old with pathologically confirmed WHO grade 2 or 3 meningioma treated with SRS monotherapy at the time of first recurrence. Patients require pathologic confirmation only at time of diagnosis; those with upfront grade 1 disease must have pathologic confirmation of grade 2/3 disease at time of first recurrence. Patients with multifocal disease upfront were excluded from this study. A total of 60 patients met eligibility criteria. Baseline demographics at time of initial diagnosis are shown in table 1. At the time of first recurrence, 57 (95%) were WHO grade 2, and 3 (5%) were grade 3. Median follow up time from first recurrence was 5.02 years. Median marginal SRS dose was 16 Gy (IQR 14-17) to a 2.67cc planning treatment volume (IQR 1.4-5.1). 92% of patients received single fraction SRS. Median time to second recurrence was 5.92 years. 1, 3, and 5-year progression-free survival (PFS) was 95%, 68%, and 51%, respectively. 1, 3, and 5-year overall survival (OS) was 100%, 98%, and 96%, respectively. On multivariate analysis, grade 3 disease was independently associated with worse PFS (HR 15.7, p = 0.03). Median SRS dose and treatment volume did not correlate with PFS. 1 patient (1.7%) experienced symptomatic radiation necrosis requiring steroids, 3 (5.0%) experienced new seizure activity, and 2 (3.3%) additional patients showed clinical evidence of post-treatment neurocognitive decline. Based on this interim analysis, primary SRS for recurrent grade 2/3 meningioma appears safe and feasible, with outcomes comparable to prospective data on high-risk grade 2/3 patients treated with post-operative fractionated EBRT. We look forward to further analysis with a larger cohort which may help guide further prospective studies.

Increased expression of leucine-rich α-2 glycoprotein 1 as a predictive biomarker of favorable progression-free survival in meningioma.

Most meningiomas, which are frequent central nervous system tumors, are classified as World Health Organization (WHO) grade 1 because of their slow-growing nature. However, the recurrence rate varies and is difficult to predict using conventional histopathological diagnoses. Leucine-rich α-2 glycoprotein 1 (LRG1) is involved in cell signal transduction, cell adhesion, and DNA repair and is a predictive biomarker in different malignant tumors; however, such a relationship has not been reported in meningiomas. We examined tissue microarrays of histological samples from 117 patients with grade 1 and 2 meningiomas and assessed their clinical and pathological features, including expression of LRG1 protein. LRG1-high meningiomas showed an increased number of vessels with CD3-positive cell infiltration (P = 0.0328) as well as higher CD105-positive vessels (P = 0.0084), as compared to LRG1-low cases. They also demonstrated better progression-free survival (hazard ratio [HR] 0.11, 95% confidence interval [CI] 0.016-0.841) compared to LRG1-low patients (P = 0.033). Moreover, multivariate analysis indicated that high LRG1 expression was an independent prognostic factor (HR, 0.13; 95% CI, 0.018-0.991; P = 0.049). LRG1 immunohistochemistry may be a convenient tool for estimating the prognosis of meningiomas in routine practice. Further studies are required to elucidate the key role of LRG1 in meningioma progression.

Proton MR spectroscopy shows improved performance to segregate high-grade astrocytoma subgroups when defined with the new 2021 World Health Organization classification of central nervous system tumors.

The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors prioritizes isocitrate dehydrogenase (IDH) mutation to define tumor types in diffuse gliomas, in contrast to the 2016 classification, which prioritized histological features. Our objective was to investigate the influence of this change in the performance of proton MR spectroscopy (1H-MRS) in segregating high-grade diffuse astrocytoma subgroups. Patients with CNS WHO grade 3 and 4 diffuse astrocytoma, known IDH mutation status, and available 1H-MRS were retrospectively retrieved and divided into 4 groups based on IDH mutation status and histological grade. Differences in 1H-MRS between groups were analyzed with the Kruskal-Wallis test. The points on the spectrum that showed the greatest differences were chosen to evaluate the performance of 1H-MRS in discriminating between grades 3 and 4 tumors (WHO 2016 defined), and between IDH-mutant and IDH-wildtype tumors (WHO 2021). ROC curves were constructed with these points, and AUC values were calculated and compared. The study included 223 patients with high-grade diffuse astrocytoma. Discrimination between IDH-mutant and IDH-wildtype tumors showed higher AUC values (highest AUC short TE, 0.943; long TE, 0.864) and more noticeable visual differences than the discrimination between grade 3 and 4 tumors (short TE, 0.885; long TE, 0.838). Our findings suggest that 1H-MRS is more applicable to classify high-grade astrocytomas defined with the 2021 criteria. Improved metabolomic robustness and more homogeneous groups yielded better tumor type discrimination by 1H-MRS with the new criteria. The 2021 World Health Organization classification of brain tumors empowers molecular criteria to improve tumor characterization. This derives in greater segregation of high-grade diffuse astrocytoma subgroups by MR spectroscopy and warrants further development of brain tumor classification tools with spectroscopy. • The new 2021 updated World Health Organization classification of central nervous system tumors maximizes the role of molecular diagnosis in the classification of brain tumors. • Proton MR spectroscopy performs better to segregate high-grade astrocytoma subgroups when defined with the new criteria. • The study provides additional evidence of improved metabolic characterization of brain tumor subgroups with the new criteria.