Case Report: Molecular diagnostics and clinical courses of two adult spinal pilocytic astrocytoma long-term survivors with GTF2I::BRAF fusion.

INTRODUCTION

Pilocytic astrocytomas are driven by BRAF and mitogen-activated protein kinase (MAPK) alterations, typically KIAA1549::BRAF fusions. A rare GTF2I::BRAF fusion has been described, but little is known about these cases.

CASE REPORT: Here, we report two cases with GTF2I::BRAF fusions. Case 1 is a 36-year-old man initially diagnosed with myxopapillary ependymoma at the conus medullaris with three recurrences over 23 years requiring two surgeries, three rounds of radiation therapy, and one round of lapatinib/temozolomide. A distant disease focus in T3/T4 was sampled and tested with modern diagnostic techniques revealing a pilocytic astrocytoma on histology and methylation profiling. The patient has subsequently had stable clinical and radiographic findings. Case 2 is another 36-year-old man initially diagnosed with meningitis and later neurosarcoid who underwent biopsy after 12 years when his spinal leptomeningeal disease continued to progress and an intraventricular non-enhancing nodule emerged as a separate focus. Sampling of the leptomeningeal disease led to a diagnosis of pilocytic astrocytoma by histology and a divergent methylation profile. The patient has remained neurologically stable under radiographic surveillance without any intervention.

RESULTS

Radiographic, histological, and molecular data are presented for both cases and compared against the only other reported GTF2I::BRAF CNS case, as well as canonical versions of pilocytic astrocytoma.

CONCLUSION

To our knowledge, this is only the second case series highlighting a unique GTF2I::BRAF fusion and the first to describe it in adults in a spinal location. The manuscript contributes documentation of a rare fusion and tumor presentation to guide clinicians and potential research avenues.