AUTHOR=De Martino Lucia , Picariello Stefania , Russo Carmela , Errico Maria Elena , Spennato Pietro , Papa Maria Rosaria , Normanno Nicola , Scimone Giuseppe , Colafati Giovanna Stefania , Cacchione Antonella , Mastronuzzi Angela , Massimino Maura , Cinalli Giuseppe , Quaglietta Lucia 

TITLE=Extra-neural metastases in pediatric diffuse midline gliomas, H3 K27-altered: presentation of two cases and literature review

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=Volume 16 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2023.1152430

DOI=10.3389/fnmol.2023.1152430

ISSN=1662-5099

ABSTRACT=Pediatric diffuse midline gliomas (DMG), H3 K27-altered, are the most aggressive pediatric central nervous system (CNS) malignancies.Disease outcome is dismal with a median survival of less than one year. Extra-neural metastases are an unusual occurrence in DMG and have been rarely described. Here, we report on two pediatric patients affected by DMG with extra-neural dissemination. Their clinical, imaging, and molecular characteristics are reported here. An 11-year-old male 5 months after the diagnosis of diffuse intrinsic pontine glioma (DIPG) developed metastatic osseous lesions confirmed with computed tomography (CT) guided biopsy of the left iliac bone. The patient died one month after the evidence of metastatic progression. Another 11-year-old female was diagnosed with a cerebellar H3K27altered DMG. After six months she developed diffuse sclerotic osseous lesions. A CT-guided biopsy of the right iliac bone was nondiagnostic. She further developed multifocal chest and abdominal lymphadenopathy and pleural effusions. Next-generation sequencing (NGS) and whole exome sequencing (WES) of the pleural fluid confirmed the presence of H3.3A mutation (c.83A>T, p.K28M). The patient died 24 months after the diagnosis of DMG and 3 months after the evidence of metastatic pleural effusion.