Description
Diffuse astrocytomas represent a category of primary central nervous system (CNS) neoplasms that demonstrate diffuse infiltration of the brain’s normal architecture. They are classified as grade II neoplasms in the WHO classification of CNS tumors, presenting less aggressive characteristics than higher-grade gliomas, but with a potential for malignant transformation.
Pathogenesis & Subtypes
Diffuse astrocytomas arise from glial precursor cells, with an accumulation of genetic mutations leading to uncontrolled cell proliferation and the formation of a neoplasm. Two key subtypes are recognised based on the presence or absence of mutations in the isocitrate dehydrogenase (IDH) gene:
- IDH-mutant diffuse astrocytomas: The IDH mutation is the earliest genetic alteration, and is accompanied by other genetic alterations such as TP53 mutations and ATRX inactivation. This mutation leads to an abnormal production of 2-hydroxyglutarate, an oncometabolite that promotes tumour progression. This subtype carries a more favourable prognosis.
- IDH-wildtype diffuse astrocytomas: These typically harbour genetic alterations seen in higher-grade gliomas, including EGFR amplification, PTEN mutation, and loss of chromosome 10. This subtype is the most common type in adults.
Epidemiology, Risk Factors & Associations
- Diffuse astrocytomas represent approximately 10-15% of all astrocytomas.
- They primarily affect adults in their 30s to 50s, with a slight male preponderance.
- Prior exposure to ionising radiation is a known risk factor.
- No significant associations with inherited syndromes are reported for diffuse astrocytomas.
Clinical Features
Clinically, diffuse astrocytomas often present insidiously over months to years, typically with seizures (the most common presenting symptom), headaches, or focal neurological deficits, such as motor weakness, sensory changes, or cognitive decline, based on the tumour’s location.
Complications
Over time, diffuse astrocytomas may progress to higher-grade gliomas, known as anaplastic astrocytomas or glioblastoma. This malignant transformation is accompanied by a worsening clinical course and decreased survival.
Pathological Features
Histopathology
Histopathology typically reveals a diffusely infiltrating tumour with relatively low cellularity, comprised of neoplastic astrocytes with mild to moderate nuclear atypia. Mitotic activity is usually low. In IDH-mutant astrocytomas, additional features such as microvascular proliferation and necrosis may be present.
Radiological Features
General Features
- Tumours are typically located in the cerebral white matter, often involving the frontal lobes.
- They are poorly circumscribed and infiltrative, often crossing the corpus callosum to involve both cerebral hemispheres (‘butterfly glioma’).
MRI
- T1-weighted: Low signal intensity.
- T2/FLAIR: High signal intensity, representing the increased water content due to tumour infiltration.
- Contrast-enhanced T1: Minimal to no enhancement is typical, distinguishing from higher-grade gliomas.
- DWI: May show increased apparent diffusion coefficient values
- MR spectroscopy: Often shows an increased choline:creatine ratio and decreased N-acetylaspartate, suggestive of tumour infiltration.
Grading and Staging
Diffuse astrocytomas are classified as WHO grade II tumors.
Diagnosis
Diagnosis is based on a combination of radiographic features and histopathologic confirmation. A stereotactic biopsy or surgical resection is often performed to obtain tissue. Molecular profiling to determine IDH mutation status is integral to diagnosis.
Differential Diagnosis
- Oligodendroglioma: Often presents similarly but typically located in the frontal lobes. They are characterised radiographically by calcifications and histologically by the presence of ‘fried egg’ cells and a ‘chicken-wire’ vascular pattern. They are IDH-mutant and 1p/19q-codeleted. Radiologically, they are well-circumscribed, often calcified lesions that are hypointense on T1-weighted and hyperintense on T2-weighted MRI sequences.
- Anaplastic astrocytoma: Like Diffuse Astrocytomas, these tumours are often hyperintense on T2-weighted and FLAIR MRI sequences, with variable contrast enhancement. However, Anaplastic Astrocytomas are more likely to exhibit areas of necrosis and may have a more aggressive growth pattern with pronounced mass effect. Despite these features, distinguishing between Diffuse Astrocytoma and Anaplastic Astrocytoma can be challenging based on imaging alone, and histopathological evaluation is often necessary.
- Glioblastoma: Characterised by a rim-enhancing lesion on MRI, with a necrotic centre and surrounding oedema. Glioblastomas also frequently exhibit more pronounced mass effect and irregular margins.
- Metastasis: Unlike primary brain tumours, metastases are typically located at the grey-white junction and often multiple. They typically have a rim-enhancing appearance on contrast-enhanced MRI, similar to glioblastomas, but their multiplicity and distribution may help in differentiation.
- Primary CNS lymphoma: This entity is usually hyperdense on non-contrast CT, shows homogenous enhancement, and restricts on diffusion-weighted imaging. A key feature that may distinguish primary CNS lymphoma from high-grade glioma is the lack of necrosis and less pronounced mass effect.
- CNS infections (e.g., abscess): Abscesses typically present as rim-enhancing lesions on contrast-enhanced MRI, similar to high-grade gliomas. However, they may exhibit a dual rim sign (an inner hypointense and outer hyperintense rim on T2-weighted images) and markedly restrict diffusion, which can help distinguish them from neoplastic processes.
Management
Management includes maximal safe surgical resection, followed by radiotherapy. Temozolomide chemotherapy may also be used, particularly in IDH-mutant tumours. Neuro-oncology referral is crucial for management planning. Regular follow-up with surveillance imaging is essential due to the potential for malignant transformation.