Pleomorphic xanthoastrocytoma (PXA) is a rare type of brain tumor that originates from astrocytes, which are star-shaped support cells in the brain and spinal cord. “Pleomorphic” indicates that the cells within the tumor vary significantly in shape and size. “Xantho” refers to a yellowish appearance, often due to lipid droplets within the tumor cells. PXA is generally considered a low-grade tumor, meaning it tends to grow slowly. It is an uncommon central nervous system tumor, representing less than 1% of all astrocytomas.
Symptoms and Patient Profile
Symptoms of pleomorphic xanthoastrocytoma often relate to increased pressure within the brain as the tumor grows and displaces healthy tissue. Seizures are the most frequent presenting symptom, occurring in approximately 64% to 75% of patients. These seizures can be focal, affecting specific parts of the body, or more generalized. Other potential symptoms include headaches, nausea, and vomiting. Neurological deficits, such as weakness or changes in vision, may also develop depending on the tumor’s specific location within the brain.
PXA is primarily diagnosed in children and young adults, with a peak incidence typically occurring between 10 and 30 years of age. The average age at diagnosis is around 12 years. These tumors most commonly arise in the supratentorial region, which is the upper part of the brain, particularly in the temporal lobe. A notable genetic characteristic of PXA is the BRAF V600E mutation, found in 50% to 78% of cases. This mutation plays a role in promoting tumor cell growth and survival.
The Diagnostic Process
Diagnosis of pleomorphic xanthoastrocytoma begins with imaging studies, primarily magnetic resonance imaging (MRI) brain scans. These scans can reveal the tumor’s presence, size, and location, which is often superficial in the cerebral hemispheres and may involve the leptomeninges, the membranes covering the brain. PXAs frequently appear on MRI as a solid nodule accompanied by a fluid-filled cyst, and they often show enhancement with contrast dye. While imaging provides valuable information, it alone cannot definitively diagnose PXA, as its appearance can sometimes mimic other brain tumors, including higher-grade gliomas.
A definitive diagnosis of PXA requires a tissue biopsy for microscopic examination. A specialized neuropathologist then analyzes the tissue, looking for characteristic features of PXA. These include the varied cell shapes and sizes (pleomorphism), the presence of lipid-laden or “xanthomatous” cells, and eosinophilic granular bodies. The pathologist also assesses the tumor’s proliferative activity and mitotic rate to determine its grade. Most PXAs are classified as World Health Organization (WHO) grade 2 tumors, indicating a relatively slow-growing nature. However, some may show features of anaplasia and be classified as WHO grade 3.
Standard Treatment Protocols
Primary treatment for pleomorphic xanthoastrocytoma is surgical removal of the tumor. The goal is “gross total resection,” meaning the complete removal of all visible tumor tissue. Complete surgical removal offers the best chance for a long-term cure and a more favorable outcome. Surgeons work to remove as much of the tumor as safely possible while preserving healthy brain tissue and neurological function.
If the tumor cannot be completely removed, or if it recurs after initial surgery, additional treatments may be considered. Radiation therapy can play a role in managing residual tumor or recurrent disease. Chemotherapy may also be used in certain situations, particularly for recurrent tumors or those with more aggressive features. However, conventional chemotherapy has historically shown limited benefit in treating PXA.
Targeted therapy is a significant advance in PXA treatment, especially for tumors harboring the BRAF V600E mutation. Given the high percentage of PXAs with this genetic alteration, drugs known as BRAF inhibitors can be a treatment option. These medications, like vemurafenib or dabrafenib, specifically target the mutated BRAF protein, disrupting the signaling pathway that promotes tumor growth. BRAF inhibitors are considered for recurrent or inoperable tumors, and sometimes in combination with MEK inhibitors to counteract potential drug resistance.
Prognosis and Recurrence
For typical WHO grade 2 pleomorphic xanthoastrocytoma, the prognosis is generally favorable, especially with complete surgical resection. Studies indicate a long-term survival rate of approximately 90% following complete surgical removal. Even with incomplete resection, the long-term survival rate remains higher than 50%. The overall 5-year survival rate for PXA is reported to be around 70% to 80%.
Despite the generally good prognosis, tumor recurrence is a possibility even after successful initial surgery. Approximately 15% to 30% of patients may experience recurrence after 5 years. A significant concern with recurrence is the potential for “anaplastic transformation.” This involves the recurring tumor becoming more aggressive and transforming into a higher-grade tumor, specifically an anaplastic PXA, which is classified as WHO grade 3.
Anaplastic transformation is characterized by increased cellularity, more pronounced pleomorphism, a higher mitotic rate, and sometimes the presence of necrosis. This transformation alters the prognosis, as anaplastic PXAs have a less favorable outlook, with 5-year survival rates ranging from 40% to 57%. Tumors that undergo anaplastic transformation typically require more aggressive treatment approaches, which may include radiation and chemotherapy, reflecting their changed biological behavior.