Pleomorphic xanthoastrocytoma (PXA) is a rare, typically superficial supratentorial astrocytic tumour most frequently seen in paediatric and young adults with BRAF mutations, characterised by marked enhancement and a characteristic dural tail sign.
Description
Pleomorphic xanthoastrocytomas (PXA) are an uncommon circumscribed astrocytic tumour found in young patients, with a World Health Organisation (WHO) grade of 2 or 3. These tumours typically appear as cortical tumours with a cystic component and vivid contrast enhancement. They are most commonly located in the temporal lobe, often presenting with temporal lobe epilepsy. Slow growth characteristics such as a lack of surrounding oedema and scalloping of the overlying bone may be present. Reactive dural involvement, as expressed by a dural tail sign, can be seen, though calcifications are rare.
Pathogenesis
The exact pathogenesis of pleomorphic xanthoastrocytoma is unclear. However, genetic alterations and mutations, particularly in the BRAF gene, play a significant role in the development of this tumour.
Epidemiology, Risk Factors & Associations
- These rare tumours account for only 1% of primary brain tumours.
- They are typically found in young patients, with a peak incidence in the 2nd to 3rd decades of life (10-30 years).
- Slight male predominance.
- Rarely, PXAs have been associated with neurofibromatosis type 1 (NF1).
Clinical Features
PXAs have a predilection for the temporal lobe, most frequently presenting with seizures in approximately 75% of cases.
- Predominantly, patients present with seizures due to cortical involvement.
- Other non-specific symptoms include dizziness, headaches, changes in behaviour and neurological deficits.
Complications
- PXAs can have complications related to their mass effect, such as cerebral oedema and increased intracranial pressure.
- There is a risk of malignant transformation to a higher grade (WHO grade 3) glioblastoma, and recurrence is common, occurring in up to 20% of cases.
Subtypes
Pleomorphic xanthoastrocytoma can be classified into:
- Classic PXA (WHO grade II): Characterised by pleomorphic giant cells and lipid-laden xanthomatous cells.
- Anaplastic PXA (WHO grade III): Displays increased mitotic activity, necrosis, and vascular proliferation. They can be difficult to distinguish from epithelioid glioblastomas.
Pathological Features
Histopathology
Macroscopic appearance
These tumours appear well-circumscribed, often with a cystic component and involvement of the overlying leptomeninges.
Microscopic appearance
Microscopically the margins are not as well defined. There are variable histological features with spindle cells, polygonal cells, multinucleated cells, and lipid-laden xanthomatous astrocytes all identified. Nuclear inclusions are common and nuclear size is highly variable.
Immunophenotype
Immunohistochemistry demonstrates expected glial marker reactivity. There is also variable reactivity for neuronal markers:
- GFAP: Positive, although often only weakly
- S100: Positive
- Neuronal markers including synaptophysin, MAP2, and neurofilament: Variable
- Ki-67 proliferation index: <1%
Genetics
- Most PXAs carry BRAF V600E mutations, as do pilocytic astrocytomas.
- Rare cases of PXAs with IDH1/2 mutations have been reported.
Radiological Features
General Features
- PXAs are typically located superficially, abutting the leptomeninges, with involvement of the cortex and overlying leptomeninges. Virtually always located in the supratentorium (98%).
- Usually appear as a solid enhancing nodule, frequently with a peripheral eccentric cystic component
- May demonstrate a dural tail sign suggestive of reactive dura involvement rather than true invasion
- Calcification is uncommon
- May cause scalloping of adjacent bone
CT
- Temporal lobe hypodense or isodense lesion with cortical involvement
- May be well or poorly demarcated, usually with little or no surrounding oedema.
- Calcification is uncommon. Smooth bone remodelling may be seen.
MRI
- T1: Solid component is iso to hypointense to grey matter. Cystic component is hypointense and may demonstrate fluid levels of there is haemorrhage.
- T1 C+ (Gd): Vividly enhancing mural nodule.
- T2: Solid component is iso to hyperintense to grey matter, and the cystic component is hyperintense.
- T2/FLAIR: Cystic areas show hyperintensity relative to CSF due to higher protein contents. There is little surrounding vasogenic oedema. May display a peripheral rim of decreased signal intensity due to hemosiderin.
- DWI/ADC: No restriction of diffusion.
Grading and Staging
- PXAs are considered either WHO grade 2 or 3 tumours based on histological features.
- Grade 3 tumours have an increased mitotic rate of >5 mitoses per 10 high-power fields but are otherwise histologically very similar with grade 2 tumours.
- Necrosis and vascular proliferation are more common in grade 3 tumours.
Differential Diagnosis
- Ganglioglioma: can look very similar to PXAs, but the contrast enhancement is often less prominent and calcification is present in about 50% of cases. There is no dural tail sign.
- Dysembryoplastic Neuroepithelial Tumours (DNET): Contrast enhancement is uncommon and a “bubbly appearance” is common.
- Oligodendroglioma: Calcifications are very common and it typically presents in an older age group (middle-aged adults, most commonly in the 4th and 5th decades of life).
- Desmoplastic Infantile Ganglioglioma: tends to occur in young children, with prominent dural involvement and large, often multiple, lesions.
- Pilocytic astrocytoma: Typically occurs in the cerebellum of children. Features include a cystic component with an enhancing mural nodule and an often eccentrically placed tumour.
- Glioblastoma: Affects older patients, more aggressive behaviour and a radiographic appearance of necrosis and intense contrast enhancement.
Management
- Surgical resection is typically the first-line treatment for PXA.
- Given the complex nature of these tumours, referral to a neurosurgeon or a neuro-oncologist is recommended.
- Following resection, radiation therapy may be required for subtotal resections or anaplastic tumours.
- Targeted therapies (e.g., BRAF inhibitors) can be considered in patients with recurrent or refractory disease.