Pleomorphic Xanthoastrocytoma: Symptoms and Treatment

Pleomorphic Xanthoastrocytoma (PXA) is a rare type of brain tumour that primarily affects children and young adults. Known for its distinctive histological features, PXA has generally considered a low-grade glioma with a relatively favourable prognosis compared to other brain tumours. However, its complexity lies in its potential for recurrence and malignant transformation. 

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What is Pleomorphic Xanthoastrocytoma?

Pleomorphic Xanthoastrocytoma is a rare neoplasm that originates in the brain's glial tissue, specifically affecting the astrocytes. These tumours are usually located in the cerebral hemispheres, particularly the temporal lobe. Although classified as World Health Organization (WHO) Grade II tumours, indicating a relatively low malignancy, PXAs can occasionally exhibit aggressive behaviour, leading to a Grade III classification upon recurrence.

Pathology and Radiological Features

The pathology of PXA is characterized by pleomorphic, or variably shaped, tumour cells with prominent xanthomatous, or lipid-laden, cytoplasm. Despite their atypical appearance, these tumours often possess a relatively circumscribed growth pattern. Radiologically, PXAs typically present as supratentorial, enhancing lesions on MRI scans, often with a cystic component and a mural nodule.

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Symptoms of Pleomorphic Xanthoastrocytoma

The clinical presentation of Pleomorphic Xanthoastrocytoma is primarily influenced by the tumour's location. Common symptoms include:

Symptom Variability

The symptomatology can vary significantly between patients, often delaying diagnosis. The slow-growing nature of low-grade PXAs means that symptoms may develop gradually over time, complicating the clinical picture.

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Diagnosis of Pleomorphic Xanthoastrocytoma

Clinical Evaluation and Imaging

The diagnostic process for PXA begins with a thorough clinical evaluation followed by neuroimaging. Magnetic Resonance Imaging (MRI) is the modality of choice, providing detailed information about the tumour's size, location, and characteristics. A gadolinium-enhanced MRI typically reveals a well-demarcated mass with mixed cystic and solid components.

Histological Examination

Definitive diagnosis requires histopathological examination following surgical resection or biopsy. The presence of pleomorphic, lipid-laden cells with occasional mitotic figures is indicative of PXA. Immunohistochemical staining for glial fibrillary acidic protein (GFAP) supports the astrocytic origin of the tumour cells.

Genetic Insights: BRAF Mutations

Recent advancements in molecular pathology have identified BRAF V600E mutations in a significant subset of PXAs. This genetic aberration is not only crucial for confirming the diagnosis but also provides potential therapeutic targets, given the availability of BRAF inhibitors.

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Treatment Options for Pleomorphic Xanthoastrocytoma

Surgical Resection

The cornerstone of PXA treatment is maximal safe surgical resection. Given the tumour's well-circumscribed nature, complete excision is often achievable and is associated with favourable outcomes. However, the risk of recurrence necessitates careful postoperative monitoring.

Adjuvant Therapies

While surgery remains the primary treatment, adjuvant therapies may be considered in cases of incomplete resection, recurrence, or malignant transformation. Options include:

Emerging Targeted Therapies

The identification of BRAF mutations in PXAs has paved the way for targeted therapies. BRAF inhibitors, such as vemurafenib, have shown promise in treating recurrent or progressive PXAs harboring this mutation. Clinical trials are ongoing to further explore these options and improve patient outcomes.

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Prognosis and Follow-up

Prognostic Factors

The prognosis for patients with Pleomorphic Xanthoastrocytoma is generally favourable, particularly for those with complete surgical resection and absence of malignant features. However, factors such as age, tumour size, and BRAF mutation status can influence outcomes.

Long-term Monitoring

Given the potential for recurrence and malignant transformation, long-term follow-up with regular MRI scans is essential. Early detection of tumour regrowth allows for timely intervention, which may include repeat surgery or adjuvant therapy.