Epidemiology of central nervous system germ cell tumors: global patterns, geographic variation, and methodological challenges

Central nervous system germ cell tumors (CNS GCTs) are rare neoplasms that predominantly affect children and adolescents and exhibit striking geographic and demographic variation. Although they account for only a small proportion of primary brain tumors worldwide, their incidence is consistently higher in East Asian populations than in Western countries; CNS GCTs represent only 2-5% of pediatric brain tumors in Western populations, whereas they account for approximately 8-20% in East Asia. CNS GCTs also demonstrate a marked male predominance and a characteristic age distribution with peak incidence during adolescence, with a high male-to-female ratio. In this review, we summarize current knowledge on the epidemiology of CNS GCTs, focusing on global incidence patterns, regional and demographic differences, and temporal trends reported in population-based studies. Comparative studies across Asian and Western cohorts have suggested geographic variation not only in disease frequency but also in clinical presentation, including differences in tumor location distribution. Potential risk factors are also discussed; recent genomic studies have identified susceptibility loci at the BAK1 enhancer region, whose higher allele frequency in East Asian populations may partially contribute to the observed geographic disparity. In addition, we highlight the methodological challenges associated with studying this rare tumor, including limitations of cancer registry data, differences in diagnostic criteria and reporting across countries, especially the difficulty of distinguishing germinoma from non-germinomatous GCTs in large datasets. By integrating findings from international registries and recent epidemiological studies, this review aims to provide a comprehensive overview of the current landscape of CNS GCT epidemiology and to identify key gaps that should be addressed through future multinational collaborative research.