Prolonged survival in a patient with a cervical spine H3K27M-mutant diffuse midline glioma

Abstract

We report a case of prolonged survival in a patient with known cervical intramedullary H3K27M-mutant diffuse midline glioma. A 39-year-old man presented for evaluation with several months of progressive upper extremity pain and weakness. MRI of the cervical spine revealed an intramedullary ring-enhancing lesion centred at C3-C4. Following subtotal surgical resection, a diagnosis of glioblastoma (GBM) was confirmed. Subsequent testing at a later date revealed an H3K27M mutation. He was initially treated with radiation and concomitant and adjuvant temozolomide. He had multiply recurrent disease and was treated with various regimens, including the histone deacetylase inhibitor valproic acid. The patient passed away 31 months (~2.5 years) after diagnosis. Our case is one of few reported adult spinal cord GBMs possessing the H3K27M mutation, and one with the longest reported overall survival in the literature to date.

Valproic Acid Enhanced Apoptosis by Promoting Autophagy Via Akt/mTOR Signaling in Glioma

“…While Chen et al reported that amphiregulin (AR) secretion induced by VPA conferred resistance to TMZ 35 . Clinically, only a few phase I trials have unfolded that VPA was probably correlated with improved survival, histological progression, and decrease in progression-free survival in glioma patients 38,55 . Hence, our study may forecast the potential application of VPA for phase I clinical trial.…”

Spinal Cord Diffuse Midline Glioma, H3K27M- mutant Effectively Treated with Bevacizumab: A Report of Two Cases

“…The overall median survival time of spinal cord DMG, H3K27M-mutant has been reported to range from 6 to 16 months, 14 – 16) with the longest survival time reported to be 31 months. 3) In general, DMG, H3K27M-mutant is associated with shorter survival time than DMG without H3K27M mutation, regardless of tissue histological features. 17) When cases in the thalamus, pons, and spinal cord are considered together, DMG with H3K27M mutation has a reported median overall survival of 13.1 months, compared to 23.1 months for DMG without mutation.…”

“…1) Diffuse midline glioma (DMG) with histone H3K27M mutation (DMG, H3K27M-mutant) is a newly described entity in the revised World Health Organization classification (WHO, 2016) that corresponds to a grade IV diagnosis regardless of tissue histological features. 2) The intersection of these two categories is extremely uncommon: fewer than 100 adult cases of spinal cord DMG, H3K27M-mutant have been reported in the literature, 3) and only 4.3% of all DMG, H3K27M-mutant cases are located in the spinal cord. 4) In general, DMG, H3K27M-mutant often results in rapid neurological deterioration and has a poor prognosis, 5) with a 2-year survival rate under 10%.…”

Diffuse midline glioma, H3K27-altered, of the conus medullaris presenting as acute urinary retention: illustrative case

“…Currently, there have been fewer than 20 reported cases of spinal cord DMG, H3K27-altered, in adults and only 1 other case localized to the level of the conus medullaris. [5][6][7][8][9] The radiographic features of DMG, H3K27-altered, are highly variable among the few reported cases. Nevertheless, identifying relevant features at presentation can improve prognostication and the choice of treatment.…”