Case of the Week

•Background:

• Diffuse midline gliomas (DMGs) are rapidly fatal tumors of childhood, with a median survival of 9–11 months. Median survival is approximately 4 months without radiation therapy.
• These are WHO grade 4 tumors and represent about one-half of childhood high-grade gliomas.
• Most of these tumors demonstrate H3 K27 genetic alteration, though there is a subset of histone-wild-type tumors.
• DMGs classically occur in the pons, where they have been historically called diffuse intrinsic pontine gliomas. However, these tumors may also occur at extrapontine sites, particularly in the thalami and spinal cord.

•Clinical Presentation:

• Median patient age at diagnosis is between 6 and 7 years old.
• Patient presentation depends on tumor location. Pontine DMGs typically present with pyramidal tract signs, and cranial nerve palsies that are of short onset and demonstrate rapid progression.
• Symptoms associated with elevated intracranial pressure may also be seen at presentation.

•Key Diagnostic Features:

• The typical MR imaging finding is an expansile, T2-FLAIR hyperintense lesion in the brainstem (especially the pons), thalamus, or spinal cord.
• Although there may be areas of postcontrast enhancement within the lesion, most of the tumor is usually nonenhancing.
• Areas of internal restricted diffusion may be seen.
• There is typically little to no surrounding parenchymal edema.
• Imaging findings have historically clinched the diagnosis, though with improvement in understanding of tumor genetics, stereotactic biopsies are becoming more common in these patients to help direct treatment and determine patient eligibility for clinical trials.

•Differential Diagnosis:

• Diffuse astrocytoma, low-grade: Similar to DMGs, these tumors are typically T2-FLAIR hyperintense and nonenhancing. Their behavior is usually much less aggressive, and, as a result, patients present with more indolent symptoms and have longer survival. The typical location, expansile quality, and infiltrative appearance of this tumor favor DMG over a low-grade glioma.
• Diffuse pediatric high-grade glioma (IDH wild-type): Although commonly also T2-FLAIR hyperintense and expansile, these tumors typically demonstrate larger enhancing components, internal heterogeneity with areas of necrosis, and surrounding parenchymal edema.

•Treatment:

• Tumor location typically precludes safe surgical resection.
• Conventional fractionated external beam radiation therapy is the principal therapeutic option, which only modestly extends survival and temporarily relieves symptoms.