Gliomas are tumors originating in the brain or spinal cord from glial cells. Accurate diagnosis and classification are essential for understanding their behavior, standardizing diagnoses, and guiding treatment.
Evolution of Glioma Classification
Historically, glioma classification relied primarily on histology, examining tissue samples under a microscope to identify cell types and structural features. This morphology-based approach had limitations, including variability in interpretation among pathologists. Reliance on visual assessment often proved insufficient in predicting tumor behavior or treatment response. Tumors appearing similar microscopically could exhibit vastly different clinical courses. This highlighted the need for a more refined and accurate classification system, leading the World Health Organization (WHO) to establish new classifications.
The Shift to Molecular Markers
The 2021 WHO Classification of Tumors of the Central Nervous System (WHO CNS5) fundamentally changed glioma classification by integrating molecular markers with traditional histology. Molecular markers are specific genetic alterations or protein expression patterns found within tumor cells. This new approach moves beyond appearance alone to understand a tumor’s underlying biological characteristics. These markers offer greater precision for diagnosis, prognosis, and predicting treatment response. Identifying specific genetic changes provides deeper insights into a tumor’s likely aggressiveness and its potential vulnerabilities, allowing for more comprehensive characterization.
Essential Molecular Signatures
One important molecular marker is the Isocitrate Dehydrogenase (IDH) mutation, commonly found in diffuse low-grade gliomas. Tumors with IDH mutations generally exhibit less aggressive behavior and are associated with a more favorable patient outlook. These mutations are frequently present in WHO Grade II and III gliomas, influencing their growth patterns.
Another significant molecular signature is the 1p/19q co-deletion, which involves the simultaneous loss of specific regions on chromosome 1 and chromosome 19. This genetic alteration defines oligodendrogliomas. Its presence indicates a better prognosis and an improved response to chemotherapy and radiation treatments.
The H3 K27M mutation, a change in a histone H3 protein, identifies a distinct and often aggressive type of glioma. This mutation is particularly relevant for diffuse midline gliomas, which frequently occur in children. Tumors with H3 K27M mutations typically have a less favorable prognosis and are assigned a high grade, irrespective of their microscopic appearance.
New Categories of Glioma
The 2021 WHO classification redefines glioma types by integrating histological and molecular findings. Adult-type diffuse gliomas are now consolidated into three main categories: Astrocytoma, IDH-mutant; Oligodendroglioma, IDH-mutant and 1p/19q co-deleted; and Glioblastoma, IDH-wildtype.
All IDH-mutant astrocytomas are now grouped as a single type, graded 2 to 4, regardless of previous histological terms. The term “glioblastoma” is reserved for IDH-wildtype tumors, reflecting their distinct, more aggressive profile. Pediatric-type diffuse gliomas are recognized as a separate group with unique molecular alterations; “glioblastoma” is no longer applied to these childhood tumors.
Impact on Patient Management
This precise glioma classification leads to more accurate prognoses, helping medical teams predict tumor behavior and patient outcomes. Understanding a tumor’s molecular profile enables personalized treatment strategies, including identifying targeted therapies.
For example, an IDH mutation can guide treatment decisions, with new drugs like Vorasidenib showing promise for IDH-mutant glioma patients. The unique molecular landscape of H3 K27M-mutant gliomas also leads to exploration of novel therapeutic options. This detailed classification facilitates more homogeneous clinical trials, accelerating new treatment discovery and testing. These advancements aim to enhance patient outcomes and improve quality of life.