Spectrum of pediatric central nervous system tumors in North India: a histopathological and immunohistochemical study applying the WHO CNS 2021 classification.
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INTRODUCTION: Pediatric central nervous system (CNS) tumors are the second most common childhood malignancies after leukemia and remain the leading cause of cancer-related mortality in children. Recent advances in molecular pathology have significantly refined their classification and prognostic stratification. AIM: To evaluate the histopathological spectrum of pediatric brain tumors at a tertiary care cancer center in North India and classify them according to the 2021 World Health Organization (WHO) Classification of Central Nervous System Tumors. MATERIALS AND METHODS: A retrospective observational study was conducted using the electronic medical records of the Department of Oncopathology, from a tertiary care cancer center in North India. Pediatric CNS tumors diagnosed between January 2019 and December 2024 were included. Demographic characteristics, tumor location, histopathological diagnosis, immunohistochemical findings, and WHO grade were analyzed. RESULTS: A total of 92 pediatric brain/CNS tumors were diagnosed during the study period, with a male-to-female ratio of 2.5:1. Embryonal tumors constituted the largest group (38.02%), followed by astrocytic tumors (31.52%) and ependymal tumors (23.91%). Among embryonal tumors, medulloblastoma predominated (88.57%), followed by two atypical teratoid/rhabdoid tumors, one pineoblastoma, and one embryonal tumor, NOS with BCOR immunopositivity. Molecular subgrouping using immunohistochemical surrogate markers was performed in seven medulloblastomas, identifying five non-WNT/non-SHH tumors, one SHH-activated TP53-wild-type tumor, and one SHH-activated TP53-mutant tumor. Classification according to WHO CNS 2021 was feasible in ten ependymomas, with all eight supratentorial tumors demonstrating L1CAM positivity consistent with ZFTA fusion-positive ependymoma, while two posterior fossa tumors were classified as posterior fossa group A (PFA) ependymomas. Other tumors included two germinomas and one case each of rhabdoid meningioma, atypical choroid plexus papilloma, adamantinomatous craniopharyngioma, and hemangioblastoma. Grade 4 tumors were the most frequent (48%), followed by grade 3 (27%), grade 1 (17%), and grade 2 (8%) tumors. The posterior fossa was the most common site (51%), followed by the cerebral hemispheres (37%), spinal region (5%), sellar region (2%), pineal region (2%), and hypothalamus (1%). CONCLUSION: Embryonal tumors, particularly medulloblastoma, constituted the predominant pediatric CNS neoplasms in this cohort. Incorporation of immunohistochemistry enabled integrated classification of several tumors according to WHO CNS 2021 recommendations, including molecular subgrouping of medulloblastomas and classification of molecularly defined ependymomas. The tumor spectrum observed is comparable to contemporary Indian and Western series and highlights the increasing importance of integrated histomolecular diagnosis in pediatric neuro-oncology, particularly in resource-limited settings.