10230-CS-22 Intracranial recurrence patterns and mechanisms of progression in an autopsy case of primary thoracic spinal malignant glioma

Abstract We report a case of a patient who died due to intracranial recurrence one year after treatment for a spinal glioma. In this report, we present the clinical course and pathological findings, and we discuss the intramedullary progression and mechanisms of intracranial recurrence. The patient was a 43-year-old woman who initially presented with bilateral lower limb paralysis and urinary dysfunction. Eight months after onset, a spinal lesion biopsy was performed, and the diagnosis of malignant glioma was made. According to the Stupp regimen, she underwent focal spinal radiotherapy (50. 4 Gy in 28 fractions) combined with temozolomide, followed by maintenance therapy. Following initial treatment, her clinical course remained stable except for gradual ventricular enlargement. However, 10 months after treatment initiation, brain MRI revealed faint enhancement extending from the splenium to the body of the corpus callosum. Progressive ventricular enlargement and worsening consciousness followed, leading to hydrocephalus. A ventriculoperitoneal shunt was placed, and cerebrospinal fluid cytology at that time was negative. Bevacizumab was administered in response to disease progression, but the patient’s respiratory status deteriorated, and she died one year after the start of treatment. Autopsy revealed a diagnosis of diffuse midline glioma, H3K27-altered, originating in the thoracic spinal cord. Immunohistochemistry showed GFAP positivity, ATRX loss, IDH R132H negativity, p53 wild-type pattern (<10%), and H3K27me3 loss. DNA sequencing demonstrated wild-type IDH1/2 and the presence of an H3F3A K28M mutation. Tumor cells were found to have recurred and progressed continuously from the primary thoracic spinal cord lesion to the cerebrum. While cerebrospinal fluid dissemination may have been present, the main route of recurrence and progression appeared to be via spread along central nervous system fibers, either through intraparenchymal white matter tracts or subependymal pathways.