A rare case of H3K27-altered diffuse midline glioma with multiple osseous and spinal metastases at the time of diagnosis

Abstract

Background: H3K27-altered diffuse midline gliomas are uncommon central nervous system tumors with extremely poor prognoses.

Case presentation: We report the case of a 24-year-old man patient with multiple, inter alia osseous metastases who presented with back pain, hemi-hypoesthesia, and hemi-hyperhidrosis. The patient underwent combined radio-chemotherapy and demonstrated temporary improvement before deteriorating.

Conclusions: H3K27-altered diffuse midline glioma presents an infrequent but crucial differential diagnosis and should be considered in cases with rapid neurological deterioration and multiple intracranial and intramedullary tumor lesions in children and young adults. Combined radio-chemotherapy delayed the neurological deterioration, but unfortunately, progression occurred three months after the diagnosis.

Keywords: Diffuse midline Glioma; Extraneural metastases; H3K27M; Neuro-oncology.

Fig. 1

The initial MR spine image presents intra- and extra-medullary metastatic tumor lesions. A Sagittal T2-weighted MRI demonstrates diffuse long-distance bulky disease in the spinal cord, as well as diffuse intraosseous lesions. B Contrast-enhanced sagittal T1-weighted MRI of the spinal cord shows a contrast-enhanced metastatic lesion at the craniocervical junction

Fig. 2

Cerebral contrast-enhanced T1-weighted MR scans present multiple metastatic tumor lesions. A contrast-enhanced axial T1-weighted MRI demonstrates lesions at the left lateral ventricle and the right caudate nucleus. B, C Contrast-enhanced sagittal (B) and coronary (C) T1-weighted MRI shows a large metastatic lesion at the right craniocervical transition

Fig. 3

MRI of the thoracic and the lumbar spine. A: sagittal T2-weighted MR-image of the lumbar spine demonstrates diffuse metastatic lesions in the conus medullaris and along the cauda equina. B: sagittal T2-weighted MRI shows diffuse intradural, extramedullar bulky disease along the thoracic spinal cord. Both images of the thoracic and the lumbar spine present intraosseous tumor lesions. C, D Contrast-enhanced T1-weighted sagittal (C) and axial (D) MRI demonstrates diffuse infiltrating bulky tumor-lesions intradural along the spinal cord, the conus medullaris, and the cauda equina

Fig. 4

CT images sagittal (A) and axial (B) of the vertebral column demonstrate diffuse intraosseous lesions along the entire spine (cervical to sacral) and the sternum

Fig. 5

Histological and immunohistochemical analysis. A H&E of the cranial stereotactic biopsy shows a tumor with small, round cells. B H&E of the lumbar biopsy reveals a partial rhythmic tumor with vascular proliferates (arrows). C H3K27M immunohistochemistry shows a strong nuclear positivity of the tumor cells. Endothelial cells of vascular proliferates are negative (arrows). D The tumor cells show a loss of the trimethylated lysine (H3K27-m3). E The tumor cells are ATRX-positive. F H3K27M immunohistochemistry reveals tumor cells in the retrieved bone sample

Fig. 6

The first follow-up MR after initiation of radio-chemo-therapy shows a partial response of both intracranial (A) and intraspinal (B, C) tumor manifestations. The osseous lesions remained stable