Glioma tumour biology: from histopathology to molecular diagnostics

The human brain is one of the most complex biological structures. Consequently, diseases affecting the central nervous system present some of the greatest challenges in modern medicine. Among these conditions, gliomas remain particularly significant due to their aggressive nature, diagnostic complexity and poor clinical outcomes. Despite advances in surgery, radiotherapy and systemic therapies, gliomas continue to account for substantial morbidity and mortality worldwide.¹ 

Historically, glioma classification relied heavily on microscopic examination of tissue architecture and cellular morphology. Histopathological features such as cellular atypia, mitotic activity, necrosis and microvascular proliferation formed the foundation of tumour grading. While these morphological characteristics remain essential, advances in molecular pathology have demonstrated that tumours with similar microscopical appearance may possess markedly different biological behaviour and clinical outcomes.² 

Publication of the fifth edition of the World Health Organization (WHO) Classification of Tumors of the Central Nervous System (WHO CNS5) is a major milestone in neuropathology. Molecular alterations now form part of the diagnostic criteria, rather than acting as supplementary information.³ Biomarkers including IDH mutation status, ATRX loss, 1p/19q codeletion, TERT promoter mutations and CDKN2A/B deletions have become integral to diagnosis, prognostication and treatment planning. Histopathological assessment is now interpreted alongside immunohistochemistry (IHC) findings and genomic data to produce comprehensive integrated reports. Understanding molecular pathways, genomic alterations and biomarker significance has become an essential component of professional practice.