Molecular glioblastoma: high-grade malignancy with low-grade histomorphology

Glioblastoma is a highly aggressive primary malignancy of the central nervous system. Classically, the histology is that of a diffusely infiltrative astrocytic glioma with one or more high-grade features, these being microvascular proliferation and necrosis; prominent mitotic activity is also a common feature. However, since the 2021 edition of the WHO Classification of Tumours of the Central Nervous System (CNS WHO 2021), it is recognised that in rare cases these high-grade features may be absent entirely, with specific molecular alterations being sufficient to support the diagnosis. The case presented here is an example of such a lesion, with low-grade histomorphology, but high-grade molecular features. Such cases highlight the importance of molecular testing and integrated diagnosis in neuropathology, as well as careful evaluation of the diagnostic criteria as presented in CNS WHO 2021.