Pathology of Supratentorial Pleomorphic Xanthoastrocytomas in Children

Pathophysiology

• Nomenclature: PXA is classified as a Grade II astrocytic tumor (W.H.O.). However, a subclass of PXAs with anaplastic features also has been described.
• Site of origin: The tumor arises most frequently in the temporal lobe (45%) (13,19), and 22% are present in two lobes at the same time. 98% are supratentorial (27). Although a cerebellar location is extremely rare, it has been described (14).
• Pattern and other characteristics of growth: PXAs usually appear well circumscribed macroscopically and involve the leptomeninges. Microscopically, PXAs are less well defined and infiltrate the parenchyma.
• Gross appearance: The macroscopic appearance is often cystic (50–60%) with a yellowish nodular component that appears well circumscribed.

Molecular/Genetic Pathology

• Distinct genetic profile: Several studies have focused on the genetic abnormalities found in PXA (9, 10). The genetic background for PXA seems to be distinct from that underlying diffuse astrocytic tumors (11). 

Histopathology

• Marked cellular atypia: Cellular pleomorphism (also giving name to the tumor) with multinucleated giant cells and spindle cells marks this tumor. There is extreme cellular atypia and nuclear pleomorphism, with xanthomatous astrocytic cells and multinucleated giant cell formation. Granular eosinophilic bodies are present.

PXA: H&E stain, 100x

PXA: H&E stain, 400X

• Low mitotic activity: PXA is considered a grade II tumor in the latest W.H.O. classification due to its low mitotic activity (2). However, there is an anaplastic variant that has increased mitotic activity (>5 mitosis per 10 HPF), necrosis, and microvascular proliferation (12). Necrosis is present only in the anaplastic variant.
• Yellow vacuoles: Vacuolated tumor cells containing lipid droplets (giving the name “xantho,” meaning “yellow,” to the tumor).
• Immunohistochemical astrocytic features: GFAP reactivity is a rule (98%). The tumor is also positive for S100, reticulin, class III betatubulin, and sometimes synaptophysin. It is negative for p53 and chromogranin.