Astrocytomas

Related Subjects: |Brain tumours |Astrocytomas |Brain Metastases |Tuberous sclerosis |Turcot's syndrome |Lhermitte Duclos Disease |Oligodendroglioma |Acute Hydrocephalus |Intracranial Hypertension |Primary CNS Lymphoma (PCNSL) |Astrocytomas |Glioblastoma

🌟 Astrocytomas are primary brain tumours arising from astrocytes – the star-shaped support cells that quietly keep neurons functioning. Clinically, they’re best thought of as a spectrum rather than a single disease, ranging from slow, almost sneaky tumours to relentlessly aggressive ones. 🧬 Modern classification now blends histology with molecular genetics, shifting us toward biology-driven diagnosis, prognosis, and treatment decisions.

Classification (WHO 2021) 🧠

Astrocytomas are classified using both grade and molecular status. The key divider is IDH mutation status – because IDH-mutant and IDH-wildtype tumours behave so differently that they are effectively separate diseases.

• Astrocytoma, IDH-mutant (Grade 2) 🟢 – low-grade, slow-growing, often seizure-presenting.
• Astrocytoma, IDH-mutant (Grade 3) 🟠 – increased mitoses, more aggressive behaviour.
• Astrocytoma, IDH-mutant (Grade 4) 🔴 – necrosis and/or microvascular proliferation.
• Glioblastoma, IDH-wildtype (Grade 4) ⚠️ – biologically distinct and highly aggressive.

Epidemiology 📊

Astrocytomas can occur at any age, but age gives important clues about tumour biology. IDH-mutant tumours tend to affect younger adults, while IDH-wildtype tumours dominate later life. In the UK, astrocytomas account for a large proportion of adult primary brain tumours seen in neuro-oncology practice.

• IDH-mutant astrocytomas: typically present at 30–50 years 👨‍🦱👩‍🦱.
• IDH-wildtype tumours: peak incidence in older adults 👴.
• Slight male predominance overall ⚖️.

Pathophysiology 🧬

Astrocytomas develop through the gradual accumulation of genetic changes that disrupt cell cycle control, DNA repair, and metabolism. A pivotal early event is mutation in the IDH gene, producing the oncometabolite 2-hydroxyglutarate. This molecule interferes with epigenetic regulation, locking cells in an abnormal, poorly differentiated state and paving the way for malignant progression.

• IDH1 or IDH2 mutations – early driver events 🔑.
• TP53 mutations – impaired apoptosis and DNA damage response.
• ATRX loss – telomere dysfunction and genomic instability.
• Hypoxia and angiogenesis – fuel progression to higher grades 🚀.

Clinical Presentation 🚑

Presentation depends on where the tumour sits and how fast it grows. Lower-grade tumours often smoulder for years, while higher-grade disease causes rapid neurological decline. Seizures are a classic and important red flag, especially in younger adults.

• New-onset seizures ⚡.
• Progressive headache 🤕.
• Focal neurological deficits.
• Cognitive, behavioural, or personality change 🧠.

Neuroimaging 🖥️

MRI is the imaging modality of choice. As astrocytomas become more aggressive, enhancement, necrosis, and surrounding oedema become more prominent. Remember: imaging often underestimates tumour extent due to diffuse infiltration.

• Grade 2: T2/FLAIR hyperintensity, minimal or no enhancement.
• Grade 3: Variable enhancement, increasing mass effect.
• Grade 4: Ring enhancement, necrosis, and extensive oedema.

Diagnosis 🔬

Definitive diagnosis requires tissue. Histology alone is no longer sufficient – molecular testing is essential to guide management and prognosis.

• Maximal safe surgical resection where possible 🧑‍⚕️.
• Stereotactic biopsy for deep or eloquent lesions.
• Routine molecular profiling (IDH, ATRX, TP53).

Management 🧑‍⚕️

Management is individualised, balancing tumour control against preservation of neurological function. Lower-grade tumours focus on long-term disease control, while higher-grade astrocytomas require aggressive multimodal therapy. In the UK, care is coordinated through specialist neuro-oncology MDTs.

• Surgery as first-line treatment.
• Radiotherapy for higher-grade or progressive disease.
• Chemotherapy (e.g. temozolomide) in selected patients 💊.
• Active surveillance for carefully selected low-grade tumours 👀.

Prognosis ⏳

Prognosis varies widely across the astrocytoma spectrum. IDH-mutant tumours generally carry a far better outlook than IDH-wildtype disease. Grade, molecular profile, and baseline functional status are the strongest predictors of outcome.

• Grade 2 IDH-mutant: survival often exceeds 10 years 🌱.
• Grade 3 IDH-mutant: intermediate prognosis.
• Grade 4 astrocytoma: poor prognosis despite treatment ⚠️.

Clinical Cases 🩺

Case 1 – The Seizure Presentation ⚡
A 34-year-old man presents with a first-ever focal seizure. MRI shows a non-enhancing T2/FLAIR hyperintense lesion in the frontal lobe. Biopsy confirms an IDH-mutant Grade 2 astrocytoma. This case highlights the classic low-grade presentation and the importance of long-term disease control strategies.

Case 2 – Gradual Decline 🧠
A 48-year-old woman develops progressive headaches and subtle personality change over 6 months. MRI demonstrates a partially enhancing lesion with mass effect. Histology reveals an IDH-mutant Grade 3 astrocytoma, illustrating malignant progression within the astrocytoma spectrum.

Case 3 – Rapid Deterioration 🚨
A 72-year-old man presents with weeks of worsening confusion and hemiparesis. MRI shows a ring-enhancing mass with necrosis and oedema. Molecular testing confirms IDH-wildtype glioblastoma, emphasising the aggressive biology and poor prognosis of this entity.

Key Learning Points 📌

• Astrocytomas are best understood as a molecular spectrum.
• IDH mutation status is central to modern diagnosis and prognosis.
• Diffuse infiltration explains inevitable recurrence.
• Management relies on specialist multidisciplinary care.