Chordoid Glioma Pathology and Treatment Approaches

Chordoid glioma is a rare, slow-growing neuroepithelial tumour most often encountered in the anterior wall of the third ventricle. Histologically classified as World Health Organization grade II, it is distinguished by cords of epithelioid glial cells set in a mucinous stroma. Clinical presentation frequently includes headaches, visual disturbances and endocrine dysfunction arising from hypothalamic or pituitary compression. Radiologically, these lesions exhibit homogeneous contrast enhancement on MRI and often induce obstructive hydrocephalus. Immunohistochemical staining uniformly shows positivity for glial fibrillary acidic protein, while proliferative indices remain low. Molecular profiling has revealed a near-universal PRKCA D463H mutation, implicating aberrant Protein Kinase C alpha activity in oncogenesis. This mutation promotes activation of downstream translation initiation and MAPK signalling, creating potential vulnerabilities to targeted inhibitors. Surgical gross total resection remains the principal curative approach, yet the deep and delicate location of these tumours complicates complete removal and carries a high risk of hypothalamic injury. Subtotal resection followed by stereotactic radiosurgery has emerged as a viable alternative, balancing tumour control against neurological morbidity. Ongoing investigation into MEK inhibitors and other pathway-directed agents seeks to expand the therapeutic armamentarium. Collectively, advances in molecular characterisation and multimodal management strategies have begun to improve outcomes for this challenging neoplasm.

Research from Nature Portfolio

Seminal studies have defined the genetic hallmark of chordoid glioma as a recurrent D463H missense mutation in the PRKCA gene. Comprehensive exome and transcriptome analyses of multiple chordoid glioma specimens demonstrated that this mutation is present in the vast majority of cases and is associated with up-regulation of eukaryotic translation initiation pathways. Functional assays revealed that mutant PKCα enhances proliferative capacity of astrocytic and tanycytic cells, the presumed cells of origin. In parallel, genomic profiling of independent cohorts confirmed consistent kinase-domain alteration of PRKCA and showed that mutant tumour cells exhibit elevated phospho-ERK levels and anchorage-independent growth. Crucially, these transformed cells are sensitive to MEK inhibition, pointing to a rational targeted therapy for residual or unresectable disease.

Chordoid Glioma Pathology and Treatment Approaches publication trend

The graph below shows the total number of articles in chordoid glioma pathology and treatment approaches across all publications each year (not limited to Nature Index journals).

Technical terms

Chordoid glioma: Rare low-grade neuroepithelial tumour arising in the anterior third ventricle.

PRKCA D463H: Recurrent missense mutation in the protein kinase C alpha gene characteristic of chordoid glioma.

Gross total resection (GTR): Surgical removal of all visible tumour tissue.

Gamma Knife radiosurgery (GKRS): Stereotactic radiotherapy delivering focused high-dose radiation beams.

Glial fibrillary acidic protein (GFAP): Intermediate filament protein marker expressed in astrocytic cells.

References

1. A recurrent point mutation in PRKCA is a hallmark of chordoid gliomas. Nature Communications (2018).
2. A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle. Nature Communications (2018).
3. Chordoid glioma: a rare radiologically, histologically, and clinically mystifying lesion. World Journal of Surgical Oncology (2015).
4. Chordoid Glioma of the Third Ventricle: A Case Report and a Treatment Strategy to This Rare Tumor. Frontiers in Oncology (2020).
5. Occurrence of Chordoid Glioma With Sodium Ion Metabolism Disorder 5 Years After Meningioma Surgery and Whole-Exome Sequencing: A Case Report and Literature Review. Frontiers in Genetics (2021).
6. Chordoid Glioma as a Differential Diagnosis of Anterior Third Ventricle Tumours: A Rare Case Report and Five‐Year Follow‐Up. Case Reports in Radiology (2019).