Diffuse Intrinsic Pontine Glioma

Excerpt

Diffuse intrinsic pontine glioma (DIPG) remains one of the most devastating diagnoses in the field of pediatric neurooncology. Arising within the pons, DIPG is a highly aggressive, infiltrative tumor that primarily affects children between the ages of 5 and 10. Despite decades of research, the prognosis remains poor, with a median survival of less than 1 year from the time of diagnosis. The deep anatomic tumor location, diffuse infiltration into vital brainstem structures, and the resistance to conventional therapies collectively contribute to its formidable clinical challenge. Initially described as a distinct clinicopathologic entity in the mid-twentieth century, DIPG is now recognized as a biologically and molecularly unique tumor subgroup within the spectrum of pediatric high-grade gliomas. In the 2021 World Health Organization (WHO) update on central nervous system tumors, DIPGs are classified as diffuse midline glioma, H3K27M mutant, highlighting their characteristic epigenetic dysregulation rather than their purely anatomic location.

Clinically, DIPGs present insidiously with the triad of rapidly evolving cranial nerve deficits, long tract signs, and ataxia that reflect their intrinsic involvement of pontine nuclei and adjacent fiber tracts. Magnetic resonance imaging (MRI) typically demonstrates an expanded, T2-hyperintense lesion centered in the pons with indistinct margins and minimal contrast enhancement. The mainstay of treatment is fractionated radiotherapy, which offers only transient symptom relief and minimal survival benefit. Emerging research has demonstrated the efficacy of dordaviprone, formerly known as ONC201, a dopamine receptor antagonist, in treating DIPG beyond conventional radiotherapy.