Diagnosis Of Central Nervous System Tumors Research Articles

EPID-06. PEDIATRIC BRAIN TUMOUR DIAGNOSTIC DELAY DURING COVID-19 PANDEMIC IN A REGIONAL NEURONCOLOGY CENTRE

Abstract BACKGROUND The Pediatric Central Nervous System (CNS) tumors incidence has increased in the last decades. A diagnostic delay could be related to adverse effects involving neurosurgical approach. Moreover, many studies report that Coronavirus-19 pandemic has even increased the diagnostic delay of solid tumors, in particular CNS types. METHODS We conducted a retrospective study including all pediatric patients who received a diagnosis of CNS tumor at Udine Hospital between January 2020 and December 2021. Our first aim was to assess if there has been a variation in the incidence rate and a possible diagnostic delay of CNS pediatric tumors during 2020-2021. As a secondary objective we evaluated if the Coronavirus-19 pandemic has affected our ability to identify tumor relapses caused by delays in planning follow-up exams and imaging. Data of every patient were recorded and compared with data from a historical cohort recruited between 2000 and 2011. RESULTS 25 patients were enrolled in the study: 19 (11 males) were diagnosed with a primitive CNS tumor, 7 (3 males) with a secondary lesion. Incidence rate during 2020-2021 was 5.17 per 100.000 inhabitants (age 0-18 years) and median diagnostic interval was 6.7 weeks, both higher than in the historical cohort (but not statistically significant). Median age was 10 +/- 4,7 age (IQR 25°-75°5,9-13,7). No substantial variation of clinical presentation was detected, although some symptoms were found to be more frequent than in the past. A significant rise in the number of high histological grade tumors was recorded (63% vs 12%, p value < 0.001), but there was no difference in tumor relapses diagnostic delay (median 6,7 weeks compared with 5 weeks in historical cohort). CONCLUSIONS Coronavirus-19 pandemic had no impact in diagnostic delay, planning and execution of follow-up exams in children with CNS tumors.

Pediatric neuropathology practice in a low- and middle-income country: capacity building through institutional twinning.

Accurate and precise diagnosis is central to treating central nervous system (CNS) tumors, yet tissue diagnosis is often a neglected focus in low- and middle-income countries (LMICs). Since 2016, the WHO classification of CNS tumors has increasingly incorporated molecular biomarkers into the diagnosis of CNS tumors. While this shift to precision diagnostics promises a high degree of diagnostic accuracy and prognostic precision, it has also resulted in increasing divergence in diagnostic and management practices between LMICs and high-income countries (HICs). Pathologists and laboratory professionals in LMICs lack the proper training and tools to join the molecular diagnostic revolution. We describe the impact of a 7-year long twinning program between Canada and Pakistan on pathology services. During the study period, 141 challenging cases of pediatric CNS tumors initially diagnosed at Aga Khan University Hospital (AKUH), Karachi, were sent to the Hospital for Sick Children in Toronto, Canada (SickKids), for a second opinion. Each case received histologic review and often immunohistochemical staining and relevant molecular testing. A monthly multidisciplinary online tumor board (MDTB) was conducted to discuss the results with pathologists from both institutions in attendance. Diagnostic discordance was seen in 30 cases. Expert review provided subclassification for 53 cases most notably for diffuse gliomas and medulloblastoma. Poorly differentiated tumors benefited the most from second review, mainly because of the resolving power of specialized immunohistochemical stains, NanoString, and targeted gene panel next-generation sequencing. Collaboration with expert neuropathologists led to validation of over half a dozen immunostains at AKUH facilitating diagnosis of CNS tumors. LMIC-HIC Institutional twinning provides much-needed training and mentorship to pathologists and can help in infrastructure development by adopting and validating new immunohistochemical stains. Persistent unresolved cases indicate that molecular techniques are indispensable in for diagnosis in a minority of cases. The development of affordable alternative molecular techniques may help with these histologically unresolved cases.

Availability and utilization of molecular testing for primary central nervous system tumors among US hospitals.

Advanced molecular testing has increasingly become an integral component for accurate diagnosis of central nervous system (CNS) tumors. We sought to establish the current state of molecular testing availability and approaches for the diagnosis of CNS tumors in US hospitals that conduct high volumes of CNS tumor resections. We distributed a 16-item survey inquiring about molecular testing approaches for CNS tumors to 115 neuropathologists at US hospitals with neurosurgery residency programs. Thirty-five neuropathologists (30.4%) responded to the survey, all of whom indicated their institutions perform molecular testing on CNS tumor tissue. The most commonly offered tests were MGMT methylation profiling and next-generation sequencing. Fourteen respondents (40%) indicated that their institution is able to test for and report all of the molecular alterations included in our survey. Nine (25.7%) respondents indicated that molecular testing is performed as standard of care for all patients with resected CNS tumors. Our results suggest that even in academic hospitals with a high volume of CNS tumor resections, molecular testing for these tumors is limited. Continued initiatives are necessary to expand the availability of molecular testing for CNS tumors to ensure diagnostic accuracy and guide targeted therapy.

Abstract 5137: BRAF mutations in primary central nervous system tumors

Abstract Background: BRAF alterations are present in a variety of primary central nervous system (CNS) tumors from 3% in glioblastomas to 60% in pleomorphic xanthoastrocytomas. BRAF V600E mutation is the most common BRAF alteration found in tumors and has been successfully targeted by combining BRAF/MEK inhibitors in different tumor types, including gliomas. We aimed to describe the clinical and genomic features of primary CNS tumors harboring BRAF alterations and real-world data on BRAF-targeted therapy including our experience sequencing BRAF-directed therapies (BDI) in gliomas. Methods: Single-center retrospective analysis of patients with diagnosis of primary CNS tumors with NGS testing. Clinical, histological and molecular characteristics were analyzed. Results: 44 patients with BRAF mutant primary CNS tumors were included, 28 (64%) were male. 24 (55%) had histology consistent with high-grade glioma (HGG), 14 (32%) low grade glioma (LGG), 4 (9%) low grade neuroepithelial tumors and 2 (4%) others. Missense mutations were found in 77%, followed by amplifications (9%), fusions (9%) and in/del alterations (5%). V600E was the most common mutation (63%), followed by class 2 (16%) and 3 (7%) mutations and amplifications (9%). Co-occurring mutations were found in CDKN2A/B (22), TERT (20) and MTAP (12), median TMB was 2 mut/mb and only 2 patients had high TMB. 4 patients had commuted IDH1 (3 R132H), non-concurring with a V600E mutation. For patients with HGG, median age at diagnosis was 47 years and 16 (66%) were male. Lesions were more frequent in left hemisphere (70%) and temporal lobe (54%). V600E was found in 50% of cases, KIAA1549-BRAF fusion was found in 1 case. Median follow-up was 40 months (95% CI 11-68) and median overall survival (OS) was 22 months (3.4-40) for the whole population, and 56 (4-109) months for patients treated with BDI (n=4). All 4 patients had an OS >30 months. In the LGG cohort, median age at diagnosis was 34 years (IQR 24-46), 8 (57%) were male. 50% of the lesions were in the left side and 21% of the tumors were in the posterior fossa. 78% had a V600E mutation, with no statistical difference with HGG cohort (p=.082). Median follow up was 11 months, median OS was not reached. For 5 patients treated at recurrence with BDI, median PFS was 15 months (3-27).5 patients were treated with plixorafenib (PLX8394) on clinical trial achieving disease control (PR +SD) in 4 cases. Upon progression, 4 were rechallenged with dabrafenib + trametinib and 1 with another BDI. 4 patients had a partial response with duration of response >6 months in 3 cases. Conclusion: BRAF mutant CNS tumors are a heterogeneous disease. Longer survival was observed in the small group of HGG patients treated with BDI compared to SoC (56 months vs 22months). BDI rechallenge showed durable responses in heavily pretreated patients. Further molecular characterization of these patients is ongoing. The best therapeutical sequencing strategy for BDI remains uncertain. Citation Format: Juan B. Blaquier, Fulvio D'Angelo, Dalissa Tejera, Ruham A. Nasany, Gaurav Saigal, Antonio Iavarone, Macarena I. de la Fuente. BRAF mutations in primary central nervous system tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5137.

Identifying brain tumor patients' subtypes based on pre-diagnostic history and clinical characteristics: a pilot hierarchical clustering and association analysis.

Central nervous system (CNS) tumors are severe health conditions with increasing incidence in the last years. Different biological, environmental and clinical factors are thought to have an important role in their epidemiology, which however remains unclear. The aim of this pilot study was to identify CNS tumor patients' subtypes based on this information and to test associations with tumor malignancy. 90 patients with suspected diagnosis of CNS tumor were recruited by the Neurosurgery Unit of IRCCS Neuromed. Patients underwent anamnestic and clinical assessment, to ascertain known or suspected risk factors including lifestyle, socioeconomic, clinical and psychometric characteristics. We applied a hierarchical clustering analysis to these exposures to identify potential groups of patients with a similar risk pattern and tested whether these clusters associated with brain tumor malignancy. Out of 67 patients with a confirmed CNS tumor diagnosis, we identified 28 non-malignant and 39 malignant tumor cases. These subtypes showed significant differences in terms of gender (with men more frequently presenting a diagnosis of cancer; p = 6.0 ×10-3) and yearly household income (with non-malignant tumor patients more frequently earning ≥25k Euros/year; p = 3.4×10-3). Cluster analysis revealed the presence of two clusters of patients: one (N=41) with more professionally active, educated, wealthier and healthier patients, and the other one with mostly retired and less healthy men, with a higher frequency of smokers, personal history of cardiovascular disease and cancer familiarity, a mostly sedentary lifestyle and generally lower income, education and cognitive performance. The former cluster showed a protective association with the malignancy of the disease, with a 74 (14-93) % reduction in the prevalent risk of CNS malignant tumors, compared to the other cluster (p=0.026). These preliminary data suggest that patients' profiling through unsupervised machine learning approaches may somehow help predicting the risk of being affected by a malignant form. If confirmed by further analyses in larger independent cohorts, these findings may be useful to create potential intelligent ranking systems for treatment priority, overcoming the lack of histopathological information and molecular diagnosis of the tumor, which are typically not available until the time of surgery.

The Iterative Design Process of an Explainable AI Application for Non-Invasive Diagnosis of CNS Tumors: A User-Centered Approach.

Artificial Intelligence (AI) is well-suited to help support complex decision-making tasks within clinical medicine, including clinical imaging applications like radiographic differential diagnosis of central nervous system (CNS) tumors. So far, there have been numerous examples of theoretical AI solutions for this space, for example, large-scale corporate efforts like IBM's Watson AI. However, clinical implementation remains limited due to factors related to the alignment of this technology in the clinical setting. User-Centered Design (UCD) is a design philosophy that focuses on developing tailored solutions for specific users or user groups. In this study, we applied UCD to develop an explainable AI tool to support clinicians in our use case. Through four design iterations, starting from basic functionality and visualizations, we progressed to functional prototypes in a realistic testing environment. We discuss our motivation and approach for each iteration, along with key insights gained. This UCD process has advanced our conceptual idea from feasibility testing to interactive functional AI interfaces designed for specific clinical and cognitive tasks. It has also provided us with directions to develop further an AI system for the non-invasive diagnosis of CNS tumors.

Intraoperative Integrated Diagnostic System for Malignant Central Nervous System Tumors.

The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors uses an integrated approach involving histopathology and molecular profiling. Because majority of adult malignant brain tumors are gliomas and primary CNS lymphomas (PCNSL), rapid differentiation of these diseases is required for therapeutic decisions. In addition, diffuse gliomas require molecular information on single-nucleotide variants (SNV), such as IDH1/2. Here, we report an intraoperative integrated diagnostic (i-ID) system to classify CNS malignant tumors, which updates legacy frozen-section (FS) diagnosis through incorporation of a qPCR-based genotyping assay. FS evaluation, including GFAP and CD20 rapid IHC, was performed on adult malignant CNS tumors. PCNSL was diagnosed through positive CD20 and negative GFAP immunostaining. For suspected glioma, genotyping for IDH1/2, TERT SNV, and CDKN2A copy-number alteration was routinely performed, whereas H3F3A and BRAF SNV were assessed for selected cases. i-ID was determined on the basis of the 2021 WHO classification and compared with the permanent integrated diagnosis (p-ID) to assess its reliability. After retrospectively analyzing 153 cases, 101 cases were prospectively examined using the i-ID system. Assessment of IDH1/2, TERT, H3F3AK27M, BRAFV600E, and CDKN2A alterations with i-ID and permanent genomic analysis was concordant in 100%, 100%, 100%, 100%, and 96.4%, respectively. Combination with FS and intraoperative genotyping assay improved diagnostic accuracy in gliomas. Overall, i-ID matched with p-ID in 80/82 (97.6%) patients with glioma and 18/19 (94.7%) with PCNSL. The i-ID system provides reliable integrated diagnosis of adult malignant CNS tumors.

Correlation of Intraoperative Frozen Section Reporting with Histopathological Diagnosis in Central Nervous System Tumors – A Study of 30 Cases

Abstract Introduction: Central Nervous System (CNS) tumors, though relatively less common (approx 2% of all tumors), display a gamut of clinical and histological presentations. Frozen section analysis in CNS tumors in a known modality which can be a beneficial tool with potential to guide intra-operative management and a likelihood of bettering outcomes. Our study aims to ascertain the correlation and concordance between intra-operative frozen section diagnosis with final histopathological diagnosis in CNS tumors. Methods: We studied a total of 30 cases of CNS tumors for which frozen section was carried out and the same were compared with the diagnosis after final histopathological examination. For statistical analysis SPSS software version 20.0 (IBM, Armonk, New York, USA), Pearsons’s correlation coefficient Test and Chi square test were used. Results: Out of the 30 cases studied, 24 cases (80%) were completely concordant, 05 cases (16.7%) were partially concordant and 01 case (3.3%) was discordant. Considering the concordant and partially concordant cases, the sensitivity was estimated to be 96.7%. Conclusion: Intraoperative frozen section diagnosis encompasses certain limitations in layered diagnosis. Despite the limitations of retrospective studies, this study highlights its diagnostic value as a rapid and reliable method for accurate diagnosis of CNS tumors.

Children's Oncology Group's 2023 blueprint for research: Central nervous system tumors.

Tumors of the central nervous system (CNS) are a leading cause of morbidity and mortality in the pediatric population. Molecular characterization in the last decade has redefined CNS tumor diagnoses and risk stratification; confirmed the unique biology of pediatric tumors as distinct entities from tumors that occur in adulthood; and led to the first novel targeted therapies receiving Food and Drug Administration (FDA) approval for children with CNS tumors. There remain significant challenges to overcome: children with unresectable low-grade glioma may require multiple prolonged courses of therapy affecting quality of life; children with high-grade glioma have a dismal long-term prognosis; children with medulloblastoma may suffer significant short- and long-term morbidity from multimodal cytotoxic therapy, and approaches to improve survival in ependymoma remain elusive. The Children's Oncology Group (COG) is uniquely positioned to conduct the next generation of practice-changing clinical trials through rapid prospective molecular characterization and therapy evaluation in well-defined clinical and molecular groups.

Implementation of DNA Methylation Array Profiling in Pediatric Central Nervous System Tumors: The AIM BRAIN Project: An Australian and New Zealand Children's Haematology/Oncology Group Study

DNA methylation array profiling for classifying pediatric central nervous system (CNS) tumors is a valuable adjunct to histopathology. However, unbiased prospective and interlaboratory validation studies have been lacking. The AIM BRAIN diagnostic trial involving 11 pediatric cancer centers in Australia and New Zealand was designed to test the feasibility of routine clinical testing and ran in parallel with the Molecular Neuropathology 2.0 (MNP2.0) study at Deutsches Krebsforschungszentrum (German Cancer Research Center). CNS tumors from 269 pediatric patients were prospectively tested on Illumina EPIC arrays, including 104 cases co-enrolled on MNP2.0. Using MNP classifier versions 11b4 and 12.5, we report classifications with a probability score ≥0.90 in 176 of 265 (66.4%) and 213 of 269 (79.2%) cases, respectively. Significant diagnostic information was obtained in 130 of 176 (74%) for 11b4, and 12 of 174 (7%) classifications were discordant with histopathology. Cases prospectively co-enrolled on MNP2.0 gave concordant classifications (99%) and score thresholds (93%), demonstrating excellent test reproducibility and sensitivity. Overall, DNA methylation profiling is a robust single workflow technique with an acceptable diagnostic yield that is considerably enhanced by the extensive subgroup and copy number profile information generated by the platform. The platform has excellent test reproducibility and sensitivity and contributes significantly to CNS tumor diagnosis.

Factors affecting administration of palliative care in primary central nervous system tumors: An NCDB analysis.

e24146 Background: Primary central nervous system (CNS) tumors are a diverse group of neoplasms that can vary greatly in terms of their cellular origin, histological features, clinical behavior, and prognosis. Many diagnoses leave patients with a poor prognosis and an impaired quality of life. Palliative care (PC) has long been used as a means to improve quality of life and symptoms associated with debilitating malignancies; however, its use in CNS tumors is not well characterized. Yet, the plethora of life-altering symptoms such as gait impairment, cognitive decline, motor deficits, and seizures provide a need for further multidisciplinary approaches to integrating PC with primary CNS tumor diagnoses. We aim to assess factors that influence the receipt of PC in the current data on central nervous system tumor patients and assess differences in overall survival. Methods: This study retrospectively evaluated the use of PC in patients with single primary malignant central nervous system tumors (gliomas, neuroepitheliomatous neoplasms, and meningiomas) diagnosed and recorded in the National Cancer Database (NCDB) between 2004 and 2020. Patients were identified by ICD-O-3 coding and patients with other malignancies were excluded. Multivariable logistic regression was performed to evaluate associations between patient characteristics and the use of PC, and Kaplan-Meier curves with log-rank analysis were used to determine survival for each group. Results: After excluding patients without information on utilization of PC, a total of 9295 patients with primary CNS tumors were considered in the final analysis. Overall, 1.31% received palliative care. From patients receiving palliative care, 81.1-93.4% received non-curative treatment with surgery, radiation, chemotherapy, or a combination of one or more of these modalities with additional pain management. Odds of receiving palliative care were decreased in black patients, patients who received non-palliative surgical treatment, patients with a primary tumor site at the optic chiasm, patients with unilateral tumors, and patients with private, medicaid, other government, or unknown insurance status. Odds of receiving palliative care were increased with increased Charlson-Deyo Score, in patients receiving non-palliative systemic or radiation treatment, and patients with a primary site at the spinal dura. Utilization of PC was associated with a decreased 1-year and 5-year overall survival. Conclusions: PC use in CNS tumors was influenced by tumor location, treatment type, insurance status, patient race, and comorbidity index. This study demonstrates the areas in which use of PC utilization is still lacking across a diverse set of CNS tumors and patients. Further exploration is needed into the integration of palliative care broadly across these malignancies as it still remains low despite the abundance of quality-of-life altering symptoms.

Parent-reported health-related quality of life in pediatric childhood cancer survivors and factors associated with poor health-related quality of life in aftercare

PurposeDespite advances in cancer treatment, there is a prevalence of pediatric childhood cancer survivors still at risk of developing adverse disease and treatment outcomes, even after the end of treatment. The present study aimed to (1) explore how mothers and fathers assess the health-related quality of life (HRQoL) of their surviving child and (2) evaluate risk factors for poor parent-reported HRQoL in childhood cancer survivors about 2.5 years after diagnosis.MethodsWe assessed parent-reported HRQoL of 305 child and adolescent survivors < 18 years diagnosed with leukemia or tumors of central nervous system (CNS) with the KINDL-R questionnaire in a prospective observational study with a longitudinal mixed-methods design.ResultsIn agreement with our hypotheses, our results show that fathers rate their children’s HRQoL total score as well as the condition-specific domains family (p = .013, d = 0.3), friends (p = .027, d = 0.27), and disease (p = .035, d = 0.26) higher than mothers about 2.5 years after diagnosis. Taking variance of inter-individual differences due to family affiliation into account, the mixed model regression revealed significant associations between the diagnosis of CNS tumors (p = .018, 95% CI [− 7.78, − 0.75]), an older age at diagnosis, (p = .011, 95% CI [− 0.96, − 0.12]), and non-participation in rehabilitation (p = .013, 95% CI [− 10.85, − 1.28]) with poor HRQoL in children more than 2 years after being diagnosed with cancer.ConclusionBased on the results, it is necessary for health care professionals to consider the differences in parental perceptions regarding children’s aftercare after surviving childhood cancer. High risk patients for poor HRQoL should be detected early, and families should be offered support post-cancer diagnosis to protect survivors’ HRQoL during aftercare. Further research should focus on characteristics of pediatric childhood cancer survivors and families with low participation in rehabilitation programs.

Predictors of Delayed Diagnosis of Pediatric CNS Tumors in the Emergency Department.

Central nervous system (CNS) tumor diagnoses are frequently delayed in children, which may lead to adverse outcomes and undue burdens on families. Examination of factors associated with delayed emergency department (ED) diagnosis could identify approaches to reduce delays. We performed a case-control study using data from 2014 to 2017 for 6 states. We included children aged 6 months to 17 years with a first diagnosis of CNS tumor in the ED. Cases had a delayed diagnosis, defined as 1 or more ED visits in the 140 days preceding tumor diagnosis (the mean prediagnostic symptomatic interval for pediatric CNS tumors in the United States). Controls had no such preceding visit. We included 2828 children (2139 controls, 76%; 689 cases, 24%). Among cases, 68% had 1 preceding ED visit, 21% had 2, and 11% had 3 or more. Significant predictors of delayed diagnosis included presence of a complex chronic condition (adjusted odds ratio [aOR], 9.73; 95% confidence interval [CI], 6.67-14.20), rural hospital location (aOR, 6.37; 95% CI, 1.80-22.54), nonteaching hospital status (aOR, 3.05, compared with teaching hospitals; 95% CI, 1.94-4.80), age younger than 5 years (aOR, 1.57; 95% CI, 1.16-2.12), public insurance (aOR, 1.49, compared with private; 95% CI, 1.16-1.92), and Black race (aOR, 1.42, compared with White; 95% CI, 1.01-1.98). Delayed ED diagnosis of pediatric CNS tumors is common and frequently requires multiple ED encounters. Prevention of delays should focus on careful evaluation of young or chronically ill children, mitigating disparities for Black and publicly insured children, and improving pediatric readiness in rural and nonteaching EDs.

Psychosocial outcomes in long-term Dutch adult survivors of childhood cancer: The DCCSS-LATER 2 psycho-oncology study.

This study compares a comprehensive range of psychosocial outcomes of adult childhood cancer survivors (CCS) to general population-based references and identifies sociodemographic and medical risk factors. CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (diagnosed 1963-2001) part 2 (attained age ≥18 years, diagnosed <18 years, ≥5years since diagnosis) completed the Rosenberg Self-Esteem Scale, Hospital Anxiety and Depression Scale, Distress Thermometer, Self-Rating Scale for Post-Traumatic Stress Disorder, and the Short Form-36 (Health Related Quality of Life). CCS' scores were compared with references using analysis of variances and logistic regression analysis, controlling for age and sex (p<.05). Risk factors for worse psychosocial outcomes were assessed with regression analyses (p<.05). CCS, N=1797, mean age 35.4years, 49.0% female, all ≥15years since diagnosis, participated. Three percent reported posttraumatic stress disorder because of childhood cancer and 36.6% experienced clinical distress. CCS did not differ from references on self-esteem and anxiety but were less depressed (d=-.25), and scored poorer on all health-related quality of life scales, except for bodily pain (.01≤d≥-.36). Female sex, lower educational attainment, not being in a relationship, and being unemployed were negatively associated with almost all psychosocial outcomes. Except for a central nervous system tumor diagnosis, few medical characteristics were associated with psychosocial outcomes. CCS appear resilient regarding mental health but have slightly poorer health-related quality of life than references. Sociodemographic characteristics and central nervous system tumors were related to most psychosocial outcomes, but no clear pattern was observed for other medical factors. Future studies should address additional factors in explaining CCS' psychosocial functioning, such as coping, social support, and physical late effects.

Utility of genome-wide DNA methylation profiling for pediatric-type diffuse gliomas

Despite the current progress of treatment, pediatric-type diffuse glioma is one of the most lethal primary malignant tumors in the central nervous system (CNS). Since pediatric-type CNS tumors are rare disease entities and highly heterogeneous, the diagnosis is challenging. An accurate diagnosis is essential for the choice of optimal treatment, which leads to precision oncology and improvement of the patient's outcome. Genome-wide DNA methylation profiling recently emerged as one of the most important tools for the diagnosis of CNS tumors, and the utility of this novel assay has been reported in both pediatric and adult patients. In the current World Health Organization classification published in 2021, several new entities are recognized in pediatric-type diffuse gliomas, some of which require methylation profiling. In this review, we investigated the utility of genome-wide DNA methylation profiling in pediatric-type diffuse glioma, as well as issues in the clinical application of this assay. Furthermore, the combination of genome-wide DNA methylation profiling and other comprehensive genomic assays, which may improve diagnostic accuracy and detection of the actionable target, will be discussed.

HISTOPATHOLOGICAL SPECTRUM AND DESCRIPTIVE EPIDEMIOLOGY OF CENTRAL NERVOUS SYSTEM TUMORS DIAGNOSED AT A TERTIARY CARE CENTER

Central Nervous System (CNS) tumours are rare and account for 1-2% of all malignancies.[1,2] It can present as a primary tumour or a metastatic neoplasm. Primary tumours show a bimodal peak. Objective: To provide an overview of the descriptive epidemiology and histological spectrum of CNS tumours in a tertiary care centre. Methods: This is a retrospective study, which includes all histologically diagnosed cases of CNS tumours from 2017-2020, retrieved from archives of department of Pathology in Saveetha medical college. The frequency and distribution of CNS tumours based on age, gender, histology and grades according to WHO Classication of CNS Tumours 2016 were analysed. Results: In our study, the incidence of CNS tumours was more common in the age group of 41-50 years and had a female preponderance. The most common tumour observed was meningioma followed by astrocytoma. WHO Grade I tumour was found to be most common among the primary CNS tumours. Histological examination remains the gold standard for diagnosis of CNS tumours. This study shows the incidence and distribution of CNS tumours. It helps identifying the burden of the disease in the community and can be further used for comparative studies in the future.

A retrospective epidemiological study of the World Health Organization (WHO)-classified primary brain and other Central Nervous System (CNS) tumors from a tertiary health care center in Northeast India

BackgroundBrain and other central nervous systems (CNS) tumors are a heterogeneous group of neoplasms that are prevalent in all age groups and gender. The study aimed to investigate the pattern of distribution of World Health Organization (WHO) classified primary brain and other CNS tumors among different age groups and gender at a tertiary care center in Northeast India. This is the first study of CNS tumors from this region of the country. The data obtained can be useful for correct diagnosis, timely treatment, and management of CNS tumors in this area. It can also provide relevant information concerning research and funding for this disease. Data collection was done retrospectively from January 1996 to March 2022. Distribution frequency as per age, gender, histopathology type, and tumor location was estimated. Data analysis was performed using the SPSS software.ResultsA total of 1441 primary brain and other CNS tumors were examined in the study. There were 232 pediatric cases (16.1%) and 1209 adult cases (83.9%). The ratio of males to females was 1.4. The majority of the cases in the overall cohort were meningiomas (n = 346; 24%). Among the pediatric cohort, the maximum occurrence of gliomas, glioneuronal, and neuronal tumors (n = 68; 29.3%) was seen while meningiomas (n = 336; 27.8%) showed the highest prevalence in the adult cohort. There were 248 other distinct cases of CNS (17.2%) of which 62 (26.7%) were identified within the pediatric cohort and the remaining 186 (15.4%) were detected among the adult population. Most of the tumor sites was supratentorial areas (n = 759; 52.7%) with the next being spinal cord (n = 258; 18%).ConclusionThis is the first study from Northeast India that highlights the prevalence of WHO-classified CNS tumors. With newer and advanced health care and diagnostic facilities, there is an increased incidence of CNS tumors in developing countries. Our study may help in understanding the epidemiological aspects and highlight the need for research, funding, and maintenance of a hospital-based tumor registry for this particular ailment.

Neuroimaging to diagnose central nervous system tumours in children.

Headache, vomiting, lethargy, and seizures are common symptoms in healthy children with benign viral illnesses, but they are also signs that could represent a central nervous system (CNS) tumour. Primary care providers and guardians are hesitant to expose children to radiation associated with computed tomography scans or take on risks associated with the sedation frequently needed for magnetic resonance imaging. When should primary care providers order radiologic head imaging for children with common symptoms to identify those with a CNS tumour? Central nervous system tumours have no pathognomonic features, which often results in delays in diagnosis. Owing to the high prevalence of infratentorial tumours, children commonly present with symptoms of increased intracranial pressure, making a detailed history and a comprehensive physical examination, including ophthalmoscopy for papilledema, especially important. Magnetic resonance imaging is the criterion standard test but it may take time to access, and young children may need sedation. Hence, computed tomography may be a preferable first option.The HeadSmart initiative in the United Kingdom provides guidance to obtain brain imaging within 4 weeks of onset of persistent symptoms that are associated with CNS tumours. We advocate applying the same criteria in Canada in order to reduce delay in diagnosis of CNS tumours in children.

Events in CNS Tumor Pathology Post-2016 WHO CNS: cIMPACT-NOW Updates and Other Advancements: A Comprehensive Review Plus a Summary of the Salient Features of 2021 WHO CNS 5.

The 2016 World Health Organization Classification (WHO) of Tumors of the Central Nervous System (CNS) represented a major change. It recommended an "integrated diagnosis" comprising histologic and molecular information facilitating a more precise diagnosis of specific CNS tumors. Its goal was to provide greater diagnostic precision and reproducibility resulting in more clinical relevance and predictive value, ultimately leading to better patient care. Advances in molecular classification, mostly resulting from DNA methylation array profiling of CNS tumors, were occurring at a very rapid pace and required more rapid integration into clinical practice. cIMPACT-NOW updates and other recent papers plus salient features of 2021 WHO CNS5 in this comprehensive write-up were reviewed. CNS tumor classification needs to be updated at a rapid pace and mechanisms put into place to guide diagnosticians and clinicians in the interim period if major changes in the classification of tumor types came to light. Recognizing the need to integrate these into clinical practice more rapidly and without inordinate delay, the International Society of Neuropathology (ISN) 2016 sponsored an initiative called cIMPACT-NOW. Goal of cIMPACT-NOW was to provide clarification regarding contentious issues arising in the wake of the 2016 WHO CNS update as well as report new advancements in molecular classification of CNS tumors and new tumor entities emerging as a result of these advancements. cIMPACT-NOW updates: It thus laid the foundation for the 5th edition of the WHO Classification of CNS tumors (2021 WHO CNS 5). We have discussed cIMPACT updates in detail in this review. In addition, molecular diagnostics including DNA methylation-based classification of CNS tumors and the practical use of molecular classification in the prognostication and treatment of CNS tumors is discussed. Finally, the salient features of the new CNS tumor classification are summarized.

Intraoperative cytological diagnosis of brain tumours: Apreliminary study using a deep learning model.

Intraoperative pathological diagnosis of central nervous system (CNS) tumours is essential to planning patient management in neuro-oncology. Frozen section slides and cytological preparations provide architectural and cellular information that is analysed by pathologists to reach an intraoperative diagnosis. Progress in the fields of artificial intelligence and machine learning means that AI systems have significant potential for the provision of highly accurate real-time diagnosis in cytopathology. To investigate the efficiency of machine-learning models in the intraoperative cytological diagnosis of CNS tumours. We trained a deep neural network to classify biopsy material for intraoperative tissue diagnosis of four major brain lesions. Overall, 205 medical images were obtained from squash smear slides of histologically correlated cases, with 18 high-grade and 11 low-grade gliomas, 17 metastatic carcinomas, and 9 non-neoplastic pathological brain tissue samples. The neural network model was trained and evaluated using 5-fold cross-validation. The model achieved 95% and 97% diagnostic accuracy in the patch-level classification and patient-level classification tasks, respectively. We conclude that deep learning-based classification of cytological preparations may be a promising complementary method for the rapid and accurate intraoperative diagnosis of CNS tumours.