Extra-CNS and dural metastases in fusion+ adult glioblastoma, IDH-wildtype.

BACKGROUND

Adult glioblastomas (GBMs), IDH-wildtype, WHO grade 4 with fusion have a better prognosis than standard GBMs. Whether this extended survival leads to late biological consequences is unknown. Although constituting only 4% of all GBMs, fusion-positive GBMs manifest recurrent morphological features that allow prediction of this subtype, possibly affecting trial eligibility and/or targeted therapies. However, we have previously shown that an identical histological pattern can be present in wildtype examples, and conversely, occasional fusion-positive tumors lack this stereotypic morphology; thus, ultimately molecular characterization is required. We now report for the first time an adult with fusion-positive GBM showing archetypal histological features who developed extracranial metastases to provide further insight into potential behavior of the GBM type.

METHODS

Report of a 70-year-old man with left parietal GBM who developed 2 subsequent metastases, all 3 of which were assessed by next-generation sequencing (NGS) and DNA methylation.

RESULTS

Biopsy-proven dural metastases occurred at 8 months and cervical lymph node metastasis at 12-month post-diagnosis before the patient succumbed at 23 months. By NGS, all 3 tumors showed fusion as well as an additional fusion of uncertain significance. DNA methylation profiling demonstrated mesenchymal subtype in the initial biopsy and RTKII subtype in subsequent dural and lymph node metastases, indicating intratumor spatial heterogeneity or temporal evolution.

CONCLUSION

Rarely, fusion-positive GBM patients may develop dural and extracranial metastatic spread, the latter with subclass switching on epigenomic analysis.