Extracranial Metastasis Pathways in Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumour in adults, characterised by rapid local invasion and almost exclusive recurrence within the central nervous system. Extracranial metastases are exceptionally rare, occurring in under 1 % of cases, yet they carry a particularly poor prognosis. Multiple routes have been proposed: iatrogenic seeding during surgical resection or cerebrospinal fluid shunting; direct extension through the dura into venous sinuses; perineural spread along cranial nerves; and true haematogenous dissemination following intratumoural vascular invasion. Evidence of circulating tumour cells in peripheral blood suggests that GBM cells can traverse the blood–brain barrier, adopt a mesenchymal phenotype through epithelial-to-mesenchymal transition and establish secondary growths in bone, lung, lymph nodes and soft tissues. The rarity of extracranial spread likely reflects the unique brain microenvironment and robust immune surveillance, but when it does occur the molecular profiles of metastatic foci often reveal additional genetic drift, divergent mutational signatures and overexpression of invasiveness-associated genes such as MET. Recognition of these pathways is essential for timely diagnosis and may inform the development of targeted therapies to prevent or treat systemic dissemination.

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Extracranial Metastasis Pathways in Glioblastoma Multiforme publication trend

The graph below shows the total number of articles in extracranial metastasis pathways in glioblastoma multiforme across all publications each year (not limited to Nature Index journals).

Technical terms

Glioblastoma multiforme (GBM): The most common and aggressive primary brain tumour in adults, classified as grade IV by the World Health Organization.

Extracranial metastasis: Spread of tumour cells from the central nervous system to organs or tissues outside the skull or spinal canal.

Epithelial-to-mesenchymal transition (EMT): A biological process by which cancer cells gain migratory and invasive properties by adopting a more mesenchymal phenotype.

Circulating tumour cells (CTCs): Cancer cells that have detached from the primary tumour and entered the bloodstream, potentially initiating secondary growths.

Next-generation sequencing (NGS): A high-throughput method that allows rapid sequencing of large stretches of DNA, used to profile genetic alterations in tumours.

References

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2. Metastatic extraneural glioblastoma diagnosed with molecular testing. The Oncologist (2024).
3. Spinal Metastasis in a Patient with Supratentorial Glioblastoma with Primitive Neuronal Component: A Case Report with Clinical and Molecular Evaluation. Diagnostics (2023).