Advanced Magnetic Resonance Imaging in Pediatric Glioblastomas

Abstract

The shortly upcoming 5th edition of the World Health Organization Classification of Tumors of the Central Nervous System is bringing extensive changes in the terminology of diffuse high-grade gliomas (DHGGs). Previously “glioblastoma,” as a descriptive entity, could have been applied to classify some tumors from the family of pediatric or adult DHGGs. However, now the term “glioblastoma” has been divested and is no longer applied to tumors in the family of pediatric types of DHGGs. As an entity, glioblastoma remains, however, in the family of adult types of diffuse gliomas under the insignia of “glioblastoma, IDH-wildtype.” Of note, glioblastomas still can be detected in children when glioblastoma, IDH-wildtype is found in this population, despite being much more common in adults. Despite the separation from the family of pediatric types of DHGGs, what was previously labeled as “pediatric glioblastomas” still remains with novel labels and as new entities. As a result of advances in molecular biology, most of the previously called “pediatric glioblastomas” are now classified in one of the four family members of pediatric types of DHGGs. In this review, the term glioblastoma is still apocryphally employed mainly due to its historical relevance and the paucity of recent literature dealing with the recently described new entities. Therefore, “glioblastoma” is used here as an umbrella term in the attempt to encompass multiple entities such as astrocytoma, IDH-mutant (grade 4); glioblastoma, IDH-wildtype; diffuse hemispheric glioma, H3 G34-mutant; diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype; and high grade infant-type hemispheric glioma. Glioblastomas are highly aggressive neoplasms. They may arise anywhere in the developing central nervous system, including the spinal cord. Signs and symptoms are non-specific, typically of short duration, and usually derived from increased intracranial pressure or seizure. Localized symptoms may also occur. The standard of care of “pediatric glioblastomas” is not well-established, typically composed of surgery with maximal safe tumor resection. Subsequent chemoradiation is recommended if the patient is older than 3 years. If younger than 3 years, surgery is followed by chemotherapy. In general, “pediatric glioblastomas” also have a poor prognosis despite surgery and adjuvant therapy. Magnetic resonance imaging (MRI) is the imaging modality of choice for the evaluation of glioblastomas. In addition to the typical conventional MRI features, i.e., highly heterogeneous invasive masses with indistinct borders, mass effect on surrounding structures, and a variable degree of enhancement, the lesions may show restricted diffusion in the solid components, hemorrhage, and increased perfusion, reflecting increased vascularity and angiogenesis. In addition, magnetic resonance spectroscopy has proven helpful in pre- and postsurgical evaluation. Lastly, we will refer to new MRI techniques, which have already been applied in evaluating adult glioblastomas, with promising results, yet not widely utilized in children.

Pediatric extra-axial glioblastoma with bone invasion leading to a subcutaneous mass: A case report

“…Irrespective of the treatment approach chosen, “pediatric glioblastoma” continues to present as a devastating disease, with median survival durations spanning from 13 to 73 months and a 5-year survival rate of <20%. [ 5 , 8 , 16 ] Nevertheless, several studies have highlighted a relatively more favorable prognosis and the potential for long-term survival among pediatric patients when compared to adults. [ 15 , 16 ]…”

“…However, it remains a rare entity in the pediatric population, constituting only 3–15% of primary central nervous system (CNS) tumors in children. [ 8 ]…”

Adult-type and Pediatric-type Diffuse Gliomas

“…Three molecularly and prognostically distinct subgroups (groups with frequent MYCN amplification, PDGFRA amplification, TERT mutation) with the group showing frequent MYCN amplification being associated with the shortest overall survival (median 14 months). Most tumors are localized within the hemispheres [ 85 – 91 ] Infant-type hemispheric glioma: most prominent difference to the other entities within this group is the patients age limited to infancy. Typical genetic alterations are receptor tyrosine kinase fusions including the genes for the tyrosine kinases ROS1, ALK, MET and the NTRK family.…”

“…Up to now, no specific differences regarding conventional imaging characteristics have been observed when comparing these tumors with other high-grade gliomas. Irrespective of their localization, most tumors show mass effects with T1 hypointensity, contrast enhancement, T2/FLAIR-hyperintensity of varying degree, indistinct margins and a perifocal edema [ 76 , 91 ].…”

Imaging of supratentorial intraventricular masses in children: a pictorial review—part 2

“…Notably, these tumors are primarily found within or may extend into the ventricular system in children. Furthermore, certain types of adult diffuse gliomas can appear in children, notably in older children and adolescents [ 42 ].…”