Dipg-51. abdominal metastases of diffuse midline glioma, h3k27-altered with a ventriculoperitoneal shunt

Abstract Extraneural metastases are extremely rare in diffuse midline glioma (DMG), H3K27-altered, despite a tendency toward aggressive local growth and potential neuroaxis dissemination at progression. Ventriculoperitoneal shunt (VPS) placement for cerebrospinal fluid diversion is commonly performed in patients with thalamic tumors and increasingly considered in brainstem disease with developing hydrocephalus. Herein, we present a case of DMG seeding the abdomen presumably via the VPS. This patient was diagnosed at 22 years of age with a bithalamic tumor with extension into the brainstem and cerebellum as well as non-contiguous periventricular spread to the bilateral frontal lobes, with associated hydrocephalus. The patient underwent VPS insertion and biopsy, with pathology consistent with DMG, H3K27-altered. Whole exome sequencing revealed H3-3A and TP53 alterations as well as PDGFRA amplification. Treatment consisted of upfront craniospinal photon irradiation, with subsequent reduction in thalamic disease burden. Adjuvant therapy with an oral PDGFRA inhibitor (avapritinib) was initiated, though discontinued after two weeks due to worsening neurocognitive deficits. The patient presented three months post-completion of radiation, five months from diagnosis, and six weeks following VPS revision with rapidly progressive abdominal distension and altered mental status, with imaging demonstrating omental caking and significant malignant ascites, resulting in shunt malfunction and increased intracranial pressure. With limited therapeutic options, the family decided not to pursue further intervention and the patient died five days later. Autopsy confirmed metastatic disease throughout omentum, in addition to diffuse leptomeningeal dissemination. Comprehensive molecular profiling of diagnostic and post-mortem thalamic and omental tissue is in process to assess temporal as well as spatial genomic heterogeneity, including of metastasis-mediated pathways. In summary, abdominal dissemination of DMG, H3K27-altered is uncommon, but possible, especially in the presence of a VPS. Further research is necessary to determine biologic mechanisms and predictors of extraneural metastases in this disease.