Spindle Cell Predominant Anaplastic Pleomorphic Xanthoastrocytoma (WHO Grade 3) With Focal Piloid Features: A Rare Case Study With Comprehensive Molecular Profiling

Abstract

Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic tumor of the central nervous system. The typical form demonstrates relatively low-grade histologic features, whereas an anaplastic variant shows more aggressive behavior, including increased mitotic activity and necrotic changes. These tumors are often associated with alterations involving key growth signaling pathways and cell cycle regulatory genes, with molecular features that may resemble those seen in other high-grade astrocytic neoplasms. We describe an unusual example of an anaplastic pleomorphic xanthoastrocytoma showing focal piloid differentiation. The patient presented with acute neurologic symptoms, and imaging demonstrated a large, enhancing, well-circumscribed cerebral lesion with limited surrounding edema. Histologic evaluation revealed a highly cellular astrocytic neoplasm composed of spindle-shaped cells with marked pleomorphism, including scattered multinucleated forms, brisk mitotic activity, and necrotic areas. At the periphery, regions with elongated bipolar glial cells and occasional cytoplasmic inclusions suggestive of piloid morphology were identified. Molecular analysis demonstrated an activating alteration in the mitogen-activated protein kinase (MAPK) pathway along with additional genomic abnormalities, while mutations commonly associated with diffuse gliomas were not detected. The presence of piloid features within an otherwise anaplastic tumor is rare and may be relevant to the relatively favorable outcome observed during extended follow-up.