Rapidly progressive scalp and lung metastases with fatal pneumothorax in glioblastoma, IDH-wildtype, with MET and CDK6 amplifications: a case report of clinical course and postmortem autopsy, including genetic analysis.

Abstract

We report a rare case of extracranial metastases of a glioblastoma, IDH-wildtype, in a 77-year-old man who initially presented with a right frontal tumor, and gross total resection and adjuvant chemoradiotherapy were performed. The tumor was histologically comprised of two cellular components: astrocytic and poorly differentiated astrocytic tumor cells, with each strongly and infrequently positive for glial markers. Importantly, both components were positive for Nestin and CD44, indicating stemness and migratory characteristics. Three-and-a-half months after surgery, the patient presented with a subcutaneous tumor of the scalp at the surgical site and dyspnea. Imaging studies revealed tumors in the scalp, multiple intracranial locations, and the lungs, complicating a pneumothorax. He died of respiratory failure approximately 4.5 months after tumor resection. An autopsy revealed extra-axial tumors involving the sub/epidural, scalp, and intrathoracic regions, each consisting of tumor cells resembling those of the poorly differentiated astrocytic component observed in the original right frontal tumor. Genetic and copy number analysis proved that the extra-axial tumors were metastatic lesions originating from the right frontal glioblastoma, as MET and CDK6 amplification and TERT promoter mutation were shared in all tumors. These genomic alterations and stemness might contribute to the rapid development of extracranial glioblastoma metastasis and a worse prognosis.