- NF1, BRAF. Hair-like Rosenthal fibres.
- Cystic cerebella mass with enhancing nodule. Enlarged optic nerve/chiasm/tract with variable enhancement
Description
Pilocytic astrocytomas, also known as juvenile pilocytic astrocytomas, are circumscribed astrocytic gliomas that typically occur in young patients. They arise from astrocytes, which are star-shaped cells in the central nervous system (CNS). These tumours are a low-grade glioma, classified as a Grade I tumour in the World Health Organisation (WHO) classification of CNS tumours. The term ‘pilocytic’ comes from the Greek word ‘pilos’, which means hair, referencing the thin, elongated, hair-like astrocytes seen in this tumour type.
Pathogenesis
Pilocytic astrocytomas occur due to the uncontrolled proliferation of astrocytes. Along with pleomorphic xanthoastrocytomas, they frequently have BRAF alterations, present in approximately 70% of cases.
Epidemiology, Risk Factors & Associations
- Pilocytic astrocytomas represent approximately 5% of all primary brain and CNS tumours
- Most common in children and adolescents, with a peak incidence between 5 and 14 years of age, typically late in the first decade (9-10 years). However, they can occasionally arise in adults.
- They are the most common primary brain tumour of childhood (15%) and the second most common paediatric posterior fossa tumour (25-35%) after medulloblastomas.
- There is no significant sex or ethnic predilection.
- Strong association with neurofibromatosis type 1 (NF1). Up to 20% of all patients with NF1 will develop these tumours, typically in early childhood. Conversely, approximately one-third of pilocytic astrocytomas involving the optic nerves have associated NF1.
Clinical Features
The clinical presentation of pilocytic astrocytomas is highly variable and depends on the location of the tumour. Common symptoms include headache, nausea, vomiting, and balance disturbances. Specific location-related symptoms might include visual impairment (if the tumour is near the optic pathway) or hydrocephalus (if the tumour blocks the normal cerebrospinal fluid flow).
Complications
- Persistent neurological deficits
- Hydrocephalus
- Malignant transformation is rare but can occur
- Spread via the CSF and presentation as a multifocal mass is rare
Subtypes
There are no recognised subtypes of pilocytic astrocytoma.
Pathological Features
Histopathology
- The term pilocytic refers to the elongated hair-like projections (Rosenthal fibres) from the neoplastic cells.1
- Pilocytic astrocytomas are characterised by a biphasic pattern with compacted bipolar cells (piloid areas) and multipolar cells in a loose myxoid background.
- Microvascular proliferation and necrosis are typically absent.
Immunophenotype
Immunohistochemistry reflects astrocytic differentiation:
- GFAP: Positive
- S100: Positive
- OLIG2: Positive
- IDH R132H mutation: Negative
- p53 protein: Negative or weak
Genetics
- Approximately 60% of pilocytic astrocytomas harbour a BRAF gene alteration, most commonly a BRAF-KIAA1549 fusion gene.
- In addition to BRAF alterations, these tumours, along with other pediatric low-grade gliomas, lack IDH mutations and TP53 mutations.
Radiological Features
General Features
- Classically a well-defined, cystic mass in the cerebellum with a intensely enhancing solid mural nodule (50% of cases). Lack of perilesional oedema is characteristic.
- Other appearances: Solid with necrotic centre (40%), homogeneously solid (10%).
- Cystic degeneration within the solid component may be seen
- Pilocytic astrocytomas can occur anywhere in the CNS but are most frequently found in the cerebellum (60%), followed by hypothalamus, brainstem, cerebral hemispheres and finally optic pathway.
- In patients with NF1, the optic pathway is most commonly involved. Optic nerve lesions are typically smaller.
CT
- Typically presents as a well-circumscribed, cystic mass with a mural nodule.
- The cystic component is usually hypodense, solid component hypo- to isodense to grey matter and may enhance post-contrast.
- Usually no surrounding oedema.
- Haemorrhage is rare
- Calcification is uncommon (20%)
- May demonstrate obstructive hydrocephalus depending on location
- Post-contrast: Usually doesn’t demonstrate angiographic blush.
MRI
- The cystic component usually follows CSF signal, though may vary with protein content
- The solid component enhances intensely and homogenously (does not correlate with aggressive behaviour)
- T1: The cystic component is usually hypo- to isointense and the mural nodule iso- to hypointense.
- T2:
- Posterior fossa: Both the cystic component and the mural nodule are hyperintense. Typically no perilesional oedema.
- Optic pathway: Fusiform optic nerve enlargement and tortuosity. May cause buckling of the optic nerve.
- Flow voids not usually seen.
- Gd+: The mural nodule typically enhances vividly, and the cyst wall enhances in about 50% of cases.
- T2*/GRE/SWI: May show signal loss if calcification or haemorrhage is present.
- DWI/ADC: No restricted diffusion. Solid tumour has similar diffusivity to grey matter. Classically bright on ADC.
Grading and Staging
Pilocytic astrocytomas are classified as WHO Grade I tumours, indicating they are slow-growing and less aggressive than higher-grade gliomas. No formal staging system is used for these tumours as they rarely metastasise outside the CNS.
Differential Diagnosis
- Medulloblastoma: Typically seen in a slightly older age group, medulloblastomas characteristically originate in the cerebellar vermis (midline) rather than the cerebellar hemisphere as seen in pilocytic astrocytomas. Medulloblastomas are more aggressive, WHO grade IV tumours, with a more homogeneous appearance, and they often drop metastasis along the spinal canal.
- Diffuse astrocytoma: A WHO grade II tumour that can occur in various regions of the brain, not just the cerebellum. It typically demonstrates less well-defined borders and a less frequent cystic component on imaging compared to pilocytic astrocytomas. Pathologically, diffuse astrocytomas show infiltrative growth, which is not seen in pilocytic astrocytomas.
- Ependymoma: Although it may present similarly on imaging, ependymomas often fill the fourth ventricle and protrude out of the foramen of Luschka and foramina of Magendie, unlike pilocytic astrocytomas which usually arise from the cerebellar hemisphere. The age group is also typically different, with ependymomas being more common in adults.
- High-grade astrocytoma with piloid features: This condition is seen particularly in adults and in patients with neurofibromatosis type 1, differing from the pediatric predilection of pilocytic astrocytoma. These tumours are aggressive and often present with necrosis and vascular proliferation.
- Haemangioblastoma: Usually seen in adults, and associated with Von Hippel-Lindau disease when found in the cerebellum. Compared to pilocytic astrocytomas; the lesion tends to be smaller with a smaller mural nodule which shows angiographic contrast blush; the cyst wall is usually thinner, does not enhance and doesn’t show calcifications. May be associated
- Atypical teratoid/rhabdoid tumour (AT/RT): Usually seen in younger children, typically under the age of 3 years. It presents as a large, heterogeneously enhancing mass, often with a supratentorial location.
- Ganglioglioma: These are often seen in the temporal lobes and present with chronic seizures. They are often associated with a cortical-based location and calcifications.
- Pleomorphic xanthoastrocytoma (PXA): These tumours have a predilection for the cerebral hemispheres and superficial location, rather than the cerebellum. On imaging, they are often lobulated with a significant amount of calcification and show intense, but often heterogeneous enhancement.
- Cerebellar haemorrhage: This acute condition is usually associated with high blood pressure, trauma, or vascular malformations. It may present with a hyperdense cerebellar lesion on non-contrast CT, but lacks the solid and cystic components, enhancement, and often the clinical history associated with pilocytic astrocytomas.
Prognosis
- Prognosis of pilocytic astrocytomas is generally favourable
- 5-year and 10-year survival rates are typically greater than 95%, adults have a poorer prognosis, with only a 53% 5-year survival rate.
- Cystic tumors have an even better prognosis while fibrillary variants tend to do worse.
- The overall survival rate is high, especially when the tumour can be completely resected. However, despite the benign nature of these tumours, complications such as residual neurological deficits can occur.
- The risk of recurrence or progression is highest in the first few years after diagnosis, but long-term follow-up is necessary as late recurrences can occur.
- Some patients with neurofibromatosis type 1 and high-grade cerebellar tumours diagnosed as pilocytic astrocytomas may actually represent high-grade astrocytoma with piloid features.
Management
Surgical resection is the treatment of choice for pilocytic astrocytomas, with complete resection often being curative. If total resection is not possible, partial resection followed by close observation or chemotherapy can be considered. Radiotherapy is generally reserved for progressive or recurrent disease. Regular follow-up with neuroimaging is crucial for early detection of recurrence. The referral subspecialty is typically neurosurgery or paediatric oncology.
References