High-Grade Brain Tumours
What are high-grade brain tumours
High-grade brain tumours, also known as Grade III and Grade IV tumours according to the World Health Organization classification (WHO CNS5, 2021 edition), are characterised by rapid growth and markedly infiltrative behaviour within brain tissue.
In contrast to low-grade tumours, they require prompt diagnosis and coordinated management by a multidisciplinary team of specialists.
The molecular identity of the tumour is now a key factor in both classification and treatment planning.
The status of the IDH gene, methylation of the MGMT promoter and, particularly in paediatric patients, histone H3 mutations, largely determine prognosis and the choice of the most appropriate therapeutic approach.
Types of high-grade tumours
This category includes several different tumour types, the most common and clinically significant of which is glioblastoma.
Grade III: Anaplastic Tumours
Anaplastic astrocytoma, IDH-mutant (Grade III): progresses more rapidly than the corresponding Grade II diffuse astrocytoma, with greater cellular atypia and a higher proliferative index.
Anaplastic oligodendroglioma, IDH-mutant and 1p/19q co-deleted (Grade III): despite its aggressiveness, it tends to respond better to chemotherapy than astrocytic gliomas of the same grade.
Anaplastic ependymoma (Grade III): a rarer type, which may occur in both the brain and the spinal cord.
Grade IV
Glioblastoma, IDH-wildtype (Grade IV): the most common primary malignant brain tumour in adults, with characteristic heterogeneity, areas of necrosis and marked vascular proliferation.
It is the subject of active research interest and published clinical experience by Dr Mazarakis, particularly in the management of older patients.
Diffuse glioma, H3 K27-altered (Grade IV): occurs mainly in children and young adults, with a predilection for the brainstem, thalamus and spinal cord.
Diffuse hemispheric glioma, H3 G34-mutant (Grade IV): a rarer type found in the cerebral hemispheres, mainly in younger patients.
Embryonal Tumours (Mainly Paediatric)
Medulloblastoma: the most common malignant brain tumour in childhood, located in the cerebellum and requiring a specialised, multimodal treatment approach.
Secondary (Metastatic) Tumours
Metastatic brain tumours originate from primary malignant neoplasms elsewhere in the body, most commonly from the lung, breast or skin, in the case of melanoma.
Although they are a different clinical entity from primary brain tumours, they are often managed neurosurgically according to similar principles of maximal safe resection, in combination with radiotherapy and treatment of the primary disease.
Symptoms
High-grade brain tumours usually progress more rapidly than their low-grade counterparts, with symptoms that may worsen over the course of a few weeks.
Progressively worsening headache, particularly in the morning, new epileptic seizures, and rapidly evolving neurological deficits such as limb weakness, speech disturbance or confusion are often the first signs.
In several cases, changes in personality or cognitive function are also observed, which may initially be wrongly attributed to other causes such as stress or fatigue, making early imaging investigation particularly important.
Diagnosis
MRI of the brain with contrast usually demonstrates characteristic high-grade features, such as irregular contrast enhancement, central necrosis and extensive surrounding oedema.
The definitive diagnosis is established by histological examination, combined with molecular testing for IDH status, MGMT promoter methylation and, where clinically indicated, H3 mutations.
These findings play a major role in determining both prognosis and the choice of adjuvant treatment, which is why complete molecular diagnosis is now an integral part of the initial assessment.
Treatment
Regardless of the specific type, the initial treatment of high-grade brain tumours almost always includes maximal safe surgical resection, with the aim of reducing tumour burden, relieving symptoms and obtaining sufficient tissue for accurate histological and molecular diagnosis.
Subsequent treatment varies according to the type and grade of the tumour.
For Grade III anaplastic gliomas, radiotherapy is usually followed by chemotherapy, with anaplastic oligodendroglioma often responding particularly well when 1p/19q co-deletion is present.
For Grade IV glioblastoma, an established international protocol is used, consisting of radiotherapy with concurrent and then adjuvant chemotherapy, tailored according to the patient’s age.
Medulloblastoma, a mainly paediatric tumour, follows a different multimodal pathway, with craniospinal radiotherapy and specific chemotherapy protocols, whereas metastatic tumours are managed surgically according to the same principles of maximal safe resection, but in coordination with treatment of the primary disease.
Treatment decisions are always made within the framework of a multidisciplinary neuro-oncology board, involving neuroradiologists, neuropathologists and radiation oncologists, so that the approach is fully individualised according to each patient’s age, general condition and molecular profile.
Prognosis
The prognosis of high-grade tumours varies considerably depending on the tumour type.
Grade III anaplastic gliomas generally have a better long-term course than Grade IV glioblastoma, while medulloblastoma has its own distinct prognosis, which depends largely on the child’s age and molecular subtype.
In all cases, the molecular identity of the tumour, the patient’s age and general condition are key prognostic factors.
Continuous progress in neuro-oncology research, in which Dr Mazarakis is actively involved, aims to improve both survival and quality of life for these patients.
Book an Appointment
Dr Nektarios Mazarakis sees patients with high-grade brain tumours at his clinics in Athens and Thessaloniki, offering specialist assessment that combines his surgical experience with active participation in international neuro-oncology research.