Pleomorphic xanthoastrocytoma (PXA) is a rare type of brain tumor that arises from astrocytes, which are star-shaped glial cells in the brain and spinal cord. The exact cause of PXA is not fully understood, but it is known to be linked to specific genetic and molecular changes that affect how cells grow and divide.
At the core, PXA develops due to mutations in genes that regulate cell growth pathways, particularly those involved in the MAPK (mitogen-activated protein kinase) signaling pathway. This pathway is crucial for controlling cell proliferation, differentiation, and survival. When mutations occur in components of this pathway, such as the BRAF gene (commonly the BRAF V600E mutation), it can lead to uncontrolled cell growth, contributing to tumor formation. These mutations cause the astrocytes to become abnormal and multiply excessively, forming the tumor mass.
In addition to MAPK pathway alterations, other genetic changes have been observed in PXA tumors. For example, deletions or mutations in tumor suppressor genes like CDKN2A/B, which normally help regulate the cell cycle and prevent unchecked growth, are frequently found. Loss of function in these genes removes important brakes on cell division, further promoting tumor development.
PXA is classified as a circumscribed astrocytic glioma, meaning it tends to be well-defined and localized rather than diffusely infiltrating the brain tissue. It most often affects children and young adults but can occur at any age. The tumor typically arises in the cerebral hemispheres, especially in the temporal lobe, and sometimes involves the superficial cortex and leptomeninges.
There is also a noted association between PXA and certain genetic conditions, such as neurofibromatosis type 1 (NF1). NF1 is a hereditary disorder caused by mutations in the NF1 gene, which encodes neurofibromin, a protein that negatively regulates the RAS/MAPK pathway. Individuals with NF1 have an increased risk of developing various tumors, including gliomas like PXA, due to the dysregulation of this pathway.
Histologically, PXA tumors show a mixture of cell types with pleomorphic (variable) shapes and sizes, including lipid-laden (xantho) astrocytes, which give the tumor its name. Despite this variability, the tumor cells often retain some features of astrocytes and show relatively low-grade behavior compared to more aggressive gliomas.
Environmental or external causes of PXA have not been clearly identified. Unlike some cancers linked to radiation or chemical exposure, PXA appears primarily driven by intrinsic genetic mutations rather than external carcinogens.
In summary, pleomorphic xanthoastrocytoma arises mainly due to genetic mutations that disrupt normal cell growth regulation, especially involving the MAPK signaling pathway and tumor suppressor genes. These molecular changes cause astrocytes to grow abnormally, forming the tumor. Associations with genetic syndromes like neurofibromatosis type 1 further highlight the role of inherited genetic factors in its development.
