Progressive adult primary glioblastoma in the medulla oblongata with an unmethylated MGMT promoter and without an IDH mutation

Abstract

A 63-year-old woman presented with dizziness followed by gait disturbance and loss of appetite. Magnetic resonance image (MRI) showed that a lesion located in the medulla oblongata, appearing as hyperintense on T2-weighted image and with slight enhancement area, appeared in the ventral aspect of the mass on T1-weighted MR imaging with gadolinium. It was diagnosed as high-grade brain-stem glioma and the patient underwent chemoradiotherapy. However, she died 18 days after treatment, and autopsy was performed. The pathological diagnosis was glioblastoma (GBM) with unmethylated O-6-methylguanine-DNA methyltransferase promoter and wild isocitrate dehydrogenase 1 gene. We report an extremely short clinical course of adult GBM in medulla oblongata with genetic analysis and present a review of the literature.

Adult Diffuse Astrocytoma in the Medulla Oblongata: Molecular Biological Analyses Including H3F3A Mutation of Histone H3.3

“…15) Yoshikawa et al also reported an extremely short clinical course of adult GBM in the medulla oblongata, in which the case had no IDH-1 mutation. 4) In our case, immunohistochemical analyses showed positive staining for IDH-1, which indicated the presence of IDH-1 mutation, and negative staining for mutated p53 was shown as the wild-type pattern, and ATRX mutations (loss of ATRX expression) were not detected. Taken together, these findings indicated that the patient exhibited similar features to cerebral low-grade gliomas and the potential to progress to secondary GBM.…”

“…15) Yoshikawa et al reported the case of adult GBM in the medulla oblongata with an unmethylated MGMT promoter, and the patient had an extremely short clinical course. 4) In our case, MS-PCR showed the methylation of the MGMT promoter, which indicated that TMZ chemotherapy and radiotherapy would be effective. …”

“…1) Adult brain stem gliomas are mostly histologically low grade, 1–3) and result predominantly in the pons and less often in the medulla oblongata and midbrain. 4) Ueoka et al examined 86 patients with brain stem gliomas, including 24 (27.9%) adult patients. Lesions were located in the pons in 75.6% of patients, the midbrain in 15.1% of patients and the medulla in 9.3% of patients.…”

“…Moreover, adult patients occasionally present a rapidly growing tumor similar to pediatric cases. 2,4,5) Recently, recurrent H3F3A mutations of histone H3.3 have been identified as a frequent event in pediatric diffuse intrinsic brainstem gliomas (DIPGs) and thalamic glioblastomas (GBMs), associated with prognosis and survival. 6–9) However, due to its rarity, the relationship between the clinical course and molecular biological features in adult brain stem gliomas have still been poorly understood.…”

Microsurgical resection of a glioblastoma multiforme of the medulla oblongata with intraoperative subcortical stimulation and mapping

“…Although primary GBMs of the medulla oblongata are a rarity, and while initial reports documented no survival with or without treatment, recent reports have documented a longer median survival after tumor removal and radiation and chemotherapy. [4][5][6] In the report by Yoshikawa et al, 3 radiation and chemotherapy was performed without biopsy and the patient died from respiratory arrest 18 days after administration of chemoradiotherapy. The autopsy revealed glioblastoma.…”