Tarik Tihan

Background: The Central Brain Tumor Registry of the United States (CBTRUS) uses a histology grouping model based on the World Health Organization (WHO) to classify cancer registry records for clinically relevant statistical reporting. Methods: CBTRUS, together with its consulting neuropathologists, reviewed and aligned its histology groupings with the 2021 WHO Classification update. Obsolete histology nomenclature along with their International Classification of Diseases for Oncology 3 ^rd edition (ICD-O-3) codes were identified, currently included histologies were reclassified as appropriate, and new codes found in 2021 WHO were incorporated. An evaluation was conducted of the frequency of histology codes affected in the reclassification process, as well as incidence and survival pre- and post-reclassification of CBTRUS Tumor Type Groupings. Results: After review of the CBTRUS grouping scheme, 205 codes were reclassified and 2 new codes were incorporated. Tumor type groups most affected were those classified as glioma. Reclassification resulted in 167,038 of 491,804 (34%) cases having a grouping reclassification or reporting change, indicating that the 2021 revision of the WHO Classification has significantly impacted the collection and reporting of primary b CNS tumors. Conclusion: This work demonstrates the need to be responsive to changes in classification and coding for statistics to reflect real-world clinical use. This will require collaboration from all parties to have the ability to reconcile clinical practices and surveillance requirements. KEY POINTS: Classification changes in cancer registration pose challenges to reporting clinically-relevant population-based epidemiologic statistics for central nervous system (CNS) tumors. The Central Brain Tumor Registry of the United States provides an example of aligning ICD-O-3 and 2021 WHO CNS classification with cancer registry reporting. Implementation of ICD-O-4 and the latest WHO (CNS6) will undoubtedly be challenging to cancer registry reporting yet will ultimately improve our understanding of these tumors and their impact on a population. IMPORTANCE OF THE STUDY: We performed this study to report on the Central Brain Tumor Registry of the United States (CBTRUS) tumor classification scheme which was revised to make it consistent with the 2021 WHO classification (CNS5) revision and to provide a roadmap for implementation of the recently published ICD-O 4 ^th edition. While we have previously published descriptive epidemiology for selected entities based on the CNS5 classifications, this is the first CBTRUS grouping scheme to include molecular information coded in the Brain Molecular Marker Site-Specific Data Item. LAY SUMMARY: Central nervous system (CNS) tumor classification systems help doctors, researchers, and cancer registries identify and track specific types of CNS tumors. When the World Health Organization (WHO) updated its CNS tumor classification in 2021, the Central Brain Tumor Registry of the United States (CBTRUS) reviewed and updated its reporting system to match these changes. More than 200 tumor codes were reclassified, affecting nearly one-third of CNS tumor records, and most heavily impacted gliomas. These updates improve the accuracy and clinical relevance of national CNS tumor statistics. Ongoing collaboration among treating physicians, pathologists, cancer registries, and researchers will be essential as future classification updates are implemented.

WHO CNS5 mandates integrated histo‐molecular classification of medulloblastomas (MBs) and other CNS embryonal tumors. However, advanced molecular diagnostics remain inaccessible in many low‐ and lower‐middle‐income countries (LICs/LMICs), limiting implementation of molecularly informed risk stratification and therapy. The ADAPTR group (Adapting Diagnostic Approaches for Practical Taxonomy in Resource‐Restrained Regions) is an initiative of the Asian Oceanian Society of Neuropathology (AOSNP) and aims to provide practical guidelines for CNS tumor diagnostics at various levels of pathology resource restraints. In this manuscript, we propose a practical approach to diagnosis of MBs and other CNS embryonal tumors based on ADAPTR resource levels (RLs). The emphasis is mainly on using histopathological approaches with immunohistochemistry (IHC), while molecular testing recommendations are categorized as “can be considered,” “highly recommended” or “obligatory” to reach the next level diagnosis. In each RL, either a WHO CNS5 diagnosis with an accompanying CNS WHO grade or an ADAPTR descriptive diagnosis with an associated ADAPTR histologic grade and comment is provided, depending on the context. “Histology‐oriented integrated diagnosis format” for each tumor type at different RLs along with diagnostic flow charts has been generated to suit these RLs. For MBs, at RL I–II, diagnosis relies on histopathology and basic IHC with structured ADAPTR descriptive reporting. At RL III, surrogate IHC panels enable assignment to WNT‐activated, SHH‐activated and non‐WNT/non‐SHH groups, facilitating clinically actionable risk stratification. RL IV incorporates targeted molecular tests (e.g., MYC/MYCN amplification, CTNNB1 and TP53 mutations) for prognostic refinement. RL V supports comprehensive molecular classification through next‐generation sequencing and DNA methylation profiling. Parallel RL‐based algorithms are proposed for other CNS embryonal tumors, incorporating essential surrogate and confirmatory markers. These AOSNP‐ADAPTR recommendations provide a practical adaptation of WHO CNS5 guidelines suited to routine diagnosis in resource‐restrained regions. This model promotes equitable, risk‐adapted care while supporting progressive strengthening of global neuropathology capacity.

Background: The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention (CDC) and National Cancer Institute (NCI), is the largest aggregation of histopathology-specific population-based data for primary brain and other central nervous system tumors (BTs) in the United States. Summarized are the key findings from the 2025 CBTRUS annual statistical report and additional clinically relevant statistics for neuro-oncology healthcare providers. Methods: CBTRUS incidence data are an aggregation of 48 central cancer registries (CCRs) from the CDC’s National Program of Cancer Registries (NPCR) and four CCRs from the NCI’s Surveillance, Epidemiology, and End Results Program covering the entire US population. Puerto Rico was excluded. Survival data were obtained from 43 NPCR CCRs. Mortality data were obtained from the National Vital Statistics System. All incidence and mortality rates were age-adjusted using the 2000 US standard population. Relative survival was estimated using the life table method. Overall survival was estimated using Kaplan–Meier models. Results: The average annual age-adjusted incidence rate (AAAIR) of all BTs was 26.05 per 100,000 population. Incidence was higher among females and non-Hispanic Black individuals. The most common malignant tumors were gliomas. The most common non-malignant tumors were low-grade meningiomas. Mortality rates and median survival varied by age, sex, and tumor type. Conclusions: This summary describes the most up-to-date population-based incidence, mortality, and survival of primary BT types in the United States with an age-focused analysis and aims to serve as a concise resource for neuro-oncology healthcare providers.

This single-center retrospective cohort study sought to characterize the clinical spectrum of small vessel predominant primary CNS vasculitis (sv-PCNSV) and to investigate the impact of early intensive immunosuppressive therapy on remission. We analyzed data of patients diagnosed with biopsy-proven sv-PCNSV at our institution between 2009 and 2023. "Early intensive treatment" (EIT) was defined by cyclophosphamide therapy within 3 months of immunosuppressive treatment initiation. Patients in the "escalation treatment" (ESC) group initially received glucocorticoids, either as monotherapy or in conjunction with azathioprine, mycophenolate mofetil, or methotrexate. Twenty-six patients (50% female) met the study criteria, including 7 with amyloid-beta-related angiitis (ABRA). The median age at onset was 55.5 years (range 20-82), and headache (76.9%) and altered mental status (61.5%) were common presenting symptoms. Neuroimaging commonly showed bihemispheric T2/FLAIR lesions (77%) and abnormal gadolinium enhancement (88.5%), but intracranial vascular irregularities indicating large or medium vessel involvement were rare (11.5%). Among patients with non-ABRA sv-PCNSV (n = 19), some demonstrated spinal cord involvement (15.8%) and others exhibited isolated unihemispheric disease (21.1%). Although CSF testing (n = 23) often demonstrated mild pleocytosis, a notable minority of patients (17.4%) had a normal CSF analysis. Six patients (23.1%) underwent repeat brain biopsy because of initial nondiagnostic findings. Remission was achieved in all patients in the EIT group (n = 12/12), in contrast to 78.6% of patients in the ESC group (n = 11/14). Time to remission was significantly shorter among patients in the EIT group compared with the ESC group (median 5 vs 19 months, hazard ratio = 0.24, 95% CI [0.10-0.63], p < 0.005). Most patients achieving remission continued maintenance therapy, with an overall relapse rate of 19%. This study highlights the considerable clinical heterogeneity in sv-PCNSV, a rare but serious condition. Early, aggressive treatment with cyclophosphamide is associated with a shorter time to remission, and further validation in prospective studies is warranted.

Health Professionals Education symposium, organized by the Koç Academy of Medical Education Research (KAMER), convened in October 2024 to discuss the evolving role of technology and social accountability in health professions education. The symposium adopted the concept of “healthcare professionals’ education” as a unifying framework for synchronizing the training of medical and nursing students within a continuum of holistic healthcare education in low-and-middle income countries. The rationale for the symposium was to call on the dire need to improve healthcare professionals’ education to reduce the increasing gap between the global north and global south. The discussion topics involved critical and current issues such as social accountability, health advocacy, and professionalism. Study groups explored aligning education with societal needs, addressing healthcare disparities, and integrating professional values into medical and nursing curricula. Presentations also focused on the integration of technology into healthcare education. Participants examined big data, artificial intelligence, simulation technologies, and digital learning platforms, identifying challenges and opportunities for their implementation. The symposium highlighted the transformative impact of interprofessional education, health advocacy, and technology in shaping socially accountable, patient-centered healthcare systems. Key recommendations included integrating community-oriented curricula, leveraging data-driven strategies for program enhancement, and expanding access to advanced educational technologies. This manuscript summarizes the symposium’s conclusions and emphasizes the need to transform healthcare professionals’ education in low-and-middle income countries to align with contemporary societal demands and to reduce the disparity gap.

Mosaic gain of chromosome 1q (chr1q) has been associated with malformation of cortical development (MCD) and epilepsy. Hyaline protoplasmic astrocytopathy (HPA) is a rare neuropathologic finding seen in cases of epilepsy with MCD. The cell-type specificity of mosaic chr1q gain in the brain and the molecular signatures of HPA are unknown. We present the case of a child with pharmacoresistant epilepsy who underwent epileptic focus resections at age 3 and 5 years and was found to have mosaic chr1q gain and HPA. We performed single-nuclei RNA sequencing (snRNA-seq) of brain tissue from the second resection. snRNA-seq showed increased expression of chr1q genes specifically in subsets of neurons and astrocytes. Differentially expressed genes associated with inferred chr1q gain included AKT3 and genes associated with cell adhesion or migration. A subpopulation of astrocytes demonstrated marked enrichment for synapse-associated transcripts, possibly linked to the astrocytic inclusions observed in HPA. snRNA-seq may be used to infer the cell-type specificity of mosaic chromosomal copy number changes and identify associated gene expression alterations, which in the case of chr1q gain may involve aberrations in cell migration. Future studies using spatial profiling could yield further insights on the molecular signatures of HPA.

Introduction: Pilocytic astrocytoma (PA) is one of the most common primary intracranial neoplasms in childhood with an overall favorable prognosis. Despite decades of experience, there are still diagnostic and treatment challenges and unresolved issues regarding risk factors associated with recurrence, most often due to conclusions of publications with limited data. We analyzed 499 patients with PA diagnosed in a single institution over 30 years in order to provide answers to some of the unresolved issues. Materials and Methods: We identified pilocytic astrocytomas diagnosed at the University of California, San Francisco, between 1989 and 2019, confirmed the diagnoses using the WHO 2021 essential and desirable criteria, and performed a retrospective review of the demographic and clinical features of the patients and the radiological, pathologic and molecular features of the tumors. Results: Among the patients identified from pathology archives, 499 cases fulfilled the inclusion criteria. Median age at presentation was 12 years (range 3.5 months - 73 years) and the median follow-up was 78.5 months. Tumors were predominantly located in the posterior fossa (52.6%). There were six deaths, but there were confounding factors that prevented a clear association of death to tumor progression. Extent of resection was the only significant factor for recurrence-free survival. Recurrence-free survival time was 321.0 months for gross total resection, compared to 160.9 months for subtotal resection (log rank, p NF1 status, tumor location, molecular alterations, and outcome. Smaller series with apparently significant results may have suffered from limited sample size, limited variables, acceptance of univariate analysis findings as well as a larger p value for biological significance. PA still remains a predominantly surgical disease and every attempt should be made to achieve gross total resection since this appears to be the most reliable predictor of recurrence-free survival.