PTHP-20. Unique case of both leptomeningeal and extra-cranial widespread bony metastatic disease early in disease course in H3K27-altered diffuse midline glioma (DMG) with BCOR alteration

Abstract Diffuse intrinsic pontine glioma (DIPG), an aggressive brainstem tumor which predominates in childhood, is usually localized at diagnosis, with potential for leptomeningeal progression in a portion of patients, though extracranial metastases are incredibly rare. Herein we describe a unique case of DIPG with early disseminated disease both within and outside of the central nervous system (CNS). An 8 year-old male presented with three weeks of rightward head deviation and nausea. MRI brain revealed an intrapontine tumor with extension into the prepontine cistern and encasement of the basilar artery, consistent radiographically with DIPG. Numerous small non-enhancing satellite lesions were also demonstrated intracranially, concerning for leptomeningeal metastases, though spinal MRI was negative for disease involvement. The patient underwent pontine biopsy, with pathology consistent with H3p.K28M mutant subtype DMG. Molecular profiling identified somatic mutations in ACVR1, PIK3R1, HC32, and BCOR. The patient received whole brain radiation (36 Gy) with posterior fossa boost (54 Gy). Post-radiation MRI demonstrated favorable response of intracranial disease, but concern for new spinal drop metastases as well as several vertebral bony lesions. FDG PET-CT revealed numerous sclerotic, mildly FDG avid bony lesions throughout the vertebral column, pelvis, and bilateral extremities, worrisome for extracranial bony dissemination. IR-guided biopsy was attempted but non-diagnostic (crushed bone particulates, did not capture lesional tissue). He subsequently received proton spinal radiation including whole vertebral canal and sacrum (36 Gy) followed by SBRT to extremity and pelvic bony lesions (35 Gy). Leptomeningeal disease is rarely present at time of diagnosis in DIPG, though develops in about 30% of patients at progression. One prior study reported a patient with DIPG with similarly early leptomeningeal dissemination at diagnosis, also with somatic BCOR mutation. Extracranial bony metastases have been described in rare cases of DIPG, though lacking comprehensive molecular data. Future research is needed to explore molecular and biological drivers in DMG that contribute to more aggressive behavior and early metastatic spread both intra- and extra-cranially.