Teaching Case

A 37-year old man complaining since the last 3 months of progressive headaches, memory failure, sporadic vomiting and gait disturbances was admitted to the emergency department because of an acute onset of urinary incontinence. A brain CT was performed and showed a homogeneous isodense mass at the level of the third ventricle and left thalamus, with secondary hydrocephalus. No calcifications or hemorrhage were noticed within the lesion. The patient was referred for a brain MRI.

On the initial MRI, an infiltrating, relatively well-defined, mass at the level of the left thalamus extending into the right thalamus and mesencephalon with slightly high signal intensity on the T2-weighted images and very bright signal on the T2-FLAIR-weighted images (Figure 1) ws observed.  The mass showed heterogeneous contrast-enhancement, predominantly in the periphery, with a small necrotic focus. Moreover, there is high signal intensity on DWI with restriction on the ADC map, and a remarkable elevation of cerebral brain volume on the perfusion-weighted images, suggestive of a high-grade tumour. The lesion produced marked mass effect on the third ventricle and the aqueducts of Sylvius with moderate dilatation of the lateral ventricles and signs of transependymal edema (Figure 1). A ventriculostomy and external ventricle drain was inserted to relief symptoms (Figure 2). Eventually, a biopsy of the lesion established the diagnosis of a diffuse midline glioma with H3 K27M mutation, WHO grade IV. The patient was treated with radio-chemotherapy.

One month later, the patient was admitted to the emergency department because of fever and severe headache. An emergency CT showed a marked progressive disease with severe mass effect on the adjacent structures. An MRI was performed the next day, showing a size increase of the infiltrative lesion with multiple necrohemorrhagic components and adjacent edema extending bilaterally into the cerebral peduncles, basal ganglia and thalami (Figure 3). The patient is presently on radio-chemotherapy treatment, which is well tolerated.

Diffuse midline glioma´s with H3 K27M–mutant had been added to the 2016 update of the WHO classification of CNS tumours as a distinct entity (2). These tumours are classified as WHO grade IV tumours regardless of histological features (1). According to Qiu et al. there are three diagnostic criteria 1) a diffuse growth pattern, 2) a midline location (e.g. thalamus, brainstem, spinal cord) and 3) an H3 K27M (H3FQ or HIST1H3B/C) mutation (1). The prognosis is poor with a 2-years survival rate of less than 10% after surgery and adjuvant radiochemotherapy (1). The majority of these tumours are found in the pediatric population, mostly seen as infiltrating lesions in the pons, but they can also be seen elsewhere on the midline, e.g. brainstem, spinal cord and thalamus. In adults, these tumours are most frequently found in the thalamus and can appear as a solid lesion rather than infiltrating lesion (1). An extensive spread is relatively frequent, either craniocaudally to involve the cerebral hemispheres and spinal cord, as well as leptomeningeal spread (1). There is a high variable presentation on MRI, reflective of the different gross pathological changes, as well as the degree of tumour enhancement can vary greatly and is not representative of tumour grade (1).