Diffuse Midline Glioma With Osseous Metastases at Diagnosis: A Case Report

Abstract

Extraneural metastasis is extremely rare in pediatric patients with high-grade glioma and carries a grim prognosis. Detection of metastases at initial presentation is even rarer. A 15-year-old adolescent girl presented with paraplegia, urinary retention, and a constellation of systemic symptoms. Imaging showed a fourth ventricular lesion, innumerable intradural lesions, leptomeningeal seeding throughout the neuraxis, and numerous osteoblastic lesions involving the spine, ribs, sternum, pelvis, humerus, and femurs. Pathology confirmed metastatic diffuse midline glioma, H3K27M-mutant. Our patient died 2 weeks after initial presentation. Further work is needed to develop effective treatment strategies for these high-risk patients.

Extraneural Metastases of Diffuse Midline Glioma, H3 K27M-Mutant at Diagnosis: Case Report, Review of the Literature, and Identifying Targetable Alterations

“…A summary of pediatric HGG cases with extraneural metastases reported in the literature to date is provided in Table 1. To our knowledge, systemic metastases have been described in three other pediatric patients with histologically confirmed H3 K27M-mutant diffuse midline gliomas, at diagnosis in 1 patient 3 and at recurrence in the other 2. 9 H3F3A (K27M) mutations were identified in 2 of these cases, 9 identical to our patient; sequencing data were not available for the last patient, but H3 K27M-mutant status was confirmed by IHC.…”

“…The presence of metastases outside of the CNS is incredibly rare in pediatric HGGs, especially at initial diagnosis, 3,4 and little has been reported in the literature to date about the underlying genomic landscape and potential therapeutic targets in patients with extraneural disease. The patient described above represents a unique case of diffuse midline glioma, H3 K27M-mutant, with extensive biopsyproven axial and appendicular bony metastatic disease identified at diagnosis, as well as possible pulmonary metastases.…”

“…9 H3F3A (K27M) mutations were identified in 2 of these cases, 9 identical to our patient; sequencing data were not available for the last patient, but H3 K27M-mutant status was confirmed by IHC. 3 Metastatic disease outside of the neural axis has been reported in 7 additional pediatric patients with HGGs (or presumed HGGs based on histopathologic descriptions), also often at progression (Table 1). 4,7,8,[10][11][12] Shared characteristics encompass osseous spread, adolescence (median age at diagnosis: 12 y [all but 2 were > 10]), and poor prognosis (median overall survival: 9 mo [range: 2 wk to 22 mo]).…”

“…Extraneural metastases are extremely rare in pediatric HGGs, especially at initial diagnosis 3,4. Osseous, lymph node, pulmonary, or hepatic metastases of glioblastoma have been described in adult patients, though with a very low estimated prevalence (0.5% to 2%), and often presenting at progression and/or following surgical interventions that likely contribute to breakdown of the blood-brain barrier 5,6.…”

“…3,4 Osseous, lymph node, pulmonary, or hepatic metastases of glioblastoma have been described in adult patients, though with a very low estimated prevalence (0.5% to 2%), and often presenting at progression and/or following surgical interventions that likely contribute to breakdown of the blood-brain barrier. 5,6 There are rare case reports documenting bone metastases in the context of pediatric HGGs, 3,4,[7][8][9][10][11][12] including in H3 K27M-mutant diffuse midline gliomas, with most similarly occurring at recurrence. Corresponding tumor sequencing was often not available, precluding further molecular profiling and use of targeted therapy.…”