Unusual glioma tumor case shows need for molecular testing
Initial imaging and genetic analysis made reaching diagnosis challenging
A young girl with an unusual form of low-grade glioma, a type of brain tumor, responded well to standard chemotherapy, emphasizing the value of combining imaging, genetic, and tissue-based testing to guide treatment decisions, a case study shows.
In the girl’s case, initial imaging and genetic analysis made a diagnosis challenging. The tumor lacked common mutations typical in pediatric low-grade gliomas — specifically, alterations in the MAP kinase pathway, a key driver of cell growth in many cancers. By integrating these results with a detailed exam of a biopsy sample, the care team identified the tumor type and could proceed with treatment using standard chemotherapy.
“Our case expands the genetic diversity of non-MAP kinase activated paediatric low-grade glioma and highlights the potential effectiveness of standard chemotherapy,” the researchers wrote. The study, “Unusual paediatric-type diffuse low-grade glioma, non-MAP kinase pathway-activated with aggressive features on neuroimaging and complete response to chemotherapy,” was published in BMJ Case Reports.
Gliomas are brain tumors that arise when support cells in the nervous system, called glial cells, begin to grow uncontrollably. Tumors can range from low grade, which tend to grow slowly, to high grade, which are more aggressive. Treatment options vary based on the tumor’s grade and location, and may include surgery, radiation therapy, and/or chemotherapy.
Several clinical, cellular, and genetic markers may help clinicians determine the gliooma’s grade and type. For example, fast development and worsening of symptoms may suggest a high-grade tumor. MAP kinase pathway mutations and the presence of certain proteins in cells may indicate a lower grade. However, individual features are not always required criteria for a diagnosis, “emphasizing the importance of establishing an integrated molecular diagnosis,” the researchers wrote.
Steps toward a diagnosis
In this case, the girl experienced weakness on her right side that affected her gait and face, with the symptoms beginning two weeks before she sought care.
As a first diagnostic step, the clinicians completed an MRI scan and found a brain tumor. A high-grade glioma was suspected, based on its location and features of the scan, along with the rapid symptom onset.
A biopsy was performed, but histological testing, which looks at microscopic structures and processes from a sample, complicated initial suspicions. Staining for certain proteins yielded results consistent with a low-grade pediatric glioma. However, some cellular structures often seen in these cases were absent.
Genetic testing didn’t find either of two mutations — BRAF V600E and BRAF-KIAA1549 fusion — affecting the MAP kinase pathway that are common in pediatric low-grade glioma. A mutation associated with a higher-grade tumor type (H3K27M) also wasn’t present.
“Together, the histological and molecular findings supported a diagnosis of pediatric-type diffuse low-grade glioma,” wrote the researchers.
The girl began a chemotherapy regimen with carboplatin and vincristine, standard medications for pediatric low-grade gliomas, particularly when a tumor can’t be surgically removed. After treatment, a follow-up MRI scan indicated a complete response.
“Five years post-chemotherapy, the patient remains disease-free,” the researchers wrote. The girl still had mild residual weakness on the right side of her body, however.
These unusual diagnostic findings underscore the importance of a multifaceted approach to tumor assessment, said the researchers. In a MRI, low-grade gliomas may be similar to some more malignant tumors, and typical molecular and genetic markers might not all be present. A combination of methodologies helped the clinical team properly diagnose the tumor and design a treatment plan.
Despite the unusual genetic features of her glioma, the girl responded well to chemotherapy, indicating the treatment was appropriate. Further investigating other unusual or rare cases could help establish protocols and better map the genetic parameters of this type of tumor, the researchers said.
The case also highlights “the need for pre-treatment probability predictors of treatment responsiveness based on clinical, radiographic and genetic variables,” wrote the researchers, who said using a multimodal approach to predict how different types of tumors respond to treatment could help clinicians design individualized therapeutic plans.
About the Author
