Remarkable response to radiation in a non-enhancing diffuse pediatric-type high-grade glioma with germline ATM mutation: The role of PET imaging and integrated histological and molecular analysis.
Academic Article
Overview
abstract
We report a 19-year-old female with a non-enhancing, diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, harboring a germline ATM alteration. She presented with headaches, diplopia, papilledema, and obstructive hydrocephalus, and had a Karnofsky Performance Status of 70. MRI revealed infiltrative signal abnormality, and amino acid [F18]Fluciclovine PET/MRI identified increased avidity in the right lateral thalamus which guided biopsy sampling. Histopathology showed a hypercellular infiltrative glioma with high mitotic activity. DNA sequencing analysis with matched germline whole-exome sequencing identified a pathogenic ATM mutation, with biallelic ATM deficiency in tumor. Genome-wide DNA methylation confirmed the diagnosis. The patient received craniospinal radiation with a boost and concurrent temozolomide. She achieved rapid and significant neurologic recovery of function with KPS increasing to 90, accompanied by radiographic improvement. This case highlights the utility of PET/MRI in biopsy planning and underscores the importance of integrated histological and molecular diagnosis for management of non-enhancing gliomas.
