Diffuse Intrinsic Pontine Glioma (DIPG) is a highly aggressive, high-grade brain tumor. It is primarily known for its occurrence in childhood, where it represents one of the most devastating pediatric cancers. The tumor originates in the pons, a critical structure within the brainstem responsible for numerous involuntary and sensory functions. While the vast majority of cases are diagnosed in children, its rare appearance in the adult population presents a distinct clinical and molecular challenge.
Defining Adult DIPG
Diffuse Intrinsic Pontine Glioma in adults is an exceptionally rare cancer typically affecting individuals between 20 and 40 years old. This tumor type develops within the pons, a central part of the brainstem. The term “diffuse intrinsic” refers to the tumor’s pattern of growth, meaning the cancer cells spread and infiltrate the normal brain tissue rather than forming a distinct, removable mass.
The adult presentation is classified as a high-grade glioma, often designated as a Grade IV entity by the World Health Organization (WHO). A significant biological distinction from the pediatric form lies in the frequency of the H3 K27M mutation, a specific alteration in histone proteins that drives tumor growth. This mutation is present in up to 90% of pediatric DIPG cases, but it is found in a range of 15% to 60% of adult cases.
Tumors lacking the H3 K27M mutation often display different molecular signatures and may be categorized based on other genetic markers. This difference suggests that adult DIPG is a more biologically heterogeneous disease than the pediatric form. Adult patients who harbor the H3 K27M mutation often demonstrate a slightly longer overall survival compared to children with the same alteration.
Specific Symptoms of Adult DIPG
The tumor’s location in the pons directly causes symptoms related to the dysfunction of cranial nerves and motor pathways. One of the most common initial signs is a progressive difficulty with balance and coordination, known as ataxia. This often manifests as an unsteady gait or general clumsiness, which steadily worsens over time.
Facial weakness and issues with controlling eye movements are also characteristic symptoms because the pons contains the nuclei for several cranial nerves. Patients frequently experience diplopia, or double vision, due to the misalignment of the eyes caused by weakened eye muscles. They may also exhibit facial drooping or difficulty with facial expressions, indicating nerve impairment on one or both sides of the face.
The tumor’s location can also affect the ability to speak clearly and swallow effectively. Difficulty swallowing (dysphagia) can lead to choking or aspiration risk. Speech changes, such as slurred or slow speech (dysarthria), result from poor muscle control in the mouth and throat. Some adults may also experience headaches or nausea, particularly if the tumor obstructs the flow of cerebrospinal fluid, leading to increased pressure within the skull.
Confirmation of Diagnosis
Diagnosis of Diffuse Intrinsic Pontine Glioma is primarily achieved through characteristic findings on Magnetic Resonance Imaging (MRI). Because of the tumor’s deep location within the brainstem, imaging provides the safest and most reliable initial confirmation. The MRI typically shows a diffuse expansion and infiltration of the pons.
Specific characteristics are visible on the different MRI sequences, which help distinguish the tumor from other brainstem lesions. On T2-weighted images, the tumor mass usually appears abnormally bright, or hyperintense, compared to the surrounding healthy tissue. Conversely, on T1-weighted images, the tumor is generally darker, or hypointense. The tumor often shows little to no contrast enhancement after the injection of a contrast agent, though mild, heterogeneous enhancement can sometimes be observed.
Biopsy is often avoided because of the significant risk of causing severe neurological deficits due to the brainstem’s sensitivity. It is generally reserved for atypical cases where imaging is inconclusive or when tissue is required for molecular analysis to confirm the presence of mutations like H3 K27M. Obtaining this molecular profile is important as it may qualify the patient for specific clinical trials or targeted therapies.
Treatment Strategies
Treatment for adult DIPG is complex due to the tumor’s location and infiltrative nature, which prevents surgical removal without causing severe harm. Surgical intervention is generally limited to procedures that manage complications, such as the placement of a shunt to relieve pressure caused by the buildup of cerebrospinal fluid (hydrocephalus). The focus of treatment is therefore on symptom management and disease control.
Radiation therapy is the established standard of care and the primary initial treatment for adult DIPG. The goal of radiation is to temporarily shrink the tumor, slow its progression, and alleviate neurological symptoms such as double vision or difficulty walking. A typical course involves delivering a total dose, often between 54 and 60 Gray, administered in small daily fractions over several weeks.
Systemic chemotherapy has shown limited effectiveness against DIPG, mainly because the blood-brain barrier restricts the passage of most drugs into the tumor site. Standard chemotherapy agents like Temozolomide are sometimes administered concurrently with radiation therapy, but their impact on long-term survival remains modest. This challenge has driven research toward therapies that can bypass or cross the blood-brain barrier more effectively.
Given the poor prognosis associated with standard treatments, participation in clinical trials is a valuable option for many adults with DIPG. These trials investigate novel approaches, including targeted agents designed to block specific molecular pathways, such as those related to the H3 K27M mutation. Immunotherapy approaches, which harness the body’s own immune system to fight the cancer, are also being explored.