Recent updates in pediatric diffuse glioma classification: insights and conclusions from the WHO 5th edition.

Abstract

The World Health Organization (WHO) Central Nervous System (CNS) Tumors Classification 5^th edition (2021) integrates both molecular and histopathological criteria for diagnosing glial tumors. This updated classification highlights significant differences between pediatric and adult gliomas in terms of molecular characteristics and prognostic implications. The 5^th edition comprises a new category of pediatric-type diffuse low-grade glioma (PDLGG) and pediatric-type diffuse high-grade glioma (PDHGG), classified mainly based on genetic alterations and histopathological features. We reviewed the microscopy, diagnostic molecular pathology, and prognosis of various tumors under the categories PDLGG and PDHGG. The review also addresses the need for clarification concerning overlapping diagnostic features. PDLGG are characterized by diffuse growth, low-grade morphology, and MYB/MYBL1(MYB Proto-Oncogene Like 1) gene fusion or mitogen-activated protein kinase (MAPK) pathway alterations. In contrast, PDHGG is described by diffuse growth, high-grade morphology, and increased mitosis and often shows alterations of histone gene resulting in epigenetic alterations, which contrasts with common isocitrate dehydrogenase (IDH) mutation and epidermal growth factor receptor (EGFR) amplification seen in adult-type high-grade glioma.