Increasing evidence indicates that the differences between the clinicopathologic entities of astrocytoma (ie,

WHO grades I-IV) reflect the type and sequence of genetic alterations acquired during the process of
transformation.[1, 2]
Pilocytic astrocytomas (ie, WHO grade I) arise throughout the neuraxis, but preferred sites include the optic
nerve, optic chiasm/hypothalamus, thalamus and basal ganglia, cerebral hemispheres, cerebellum, and brain
stem. These tumors show low cellularity, low proliferative and mitotic activity, and rarely metastasize or undergo
malignant transformation. In general, they do not aggressively infiltrate surrounding tissue and regressive
changes in long-standing lesions are common. These tumors are the principle CNS neoplasm
of neurofibromatosis type 1 (NF1). Findings on cytogenetic analysis are typically normal, although gains of
chromosomes 7 and 8 are observed in one third of tumors. Mutational inactivation of the TP53 gene does not
appear to play a role in the evolution of this tumor.
Pilomyxoid astrocytoma (PMA) is a recently defined variant of pediatric low-grade astrocytoma. PMAs have
been classified with pilocytic astrocytomas but have been found to have different histologic features and to
behave more aggressively than pilocytic astrocytomas. PMAs have a tendency to disseminate and, in some
reports, have a worse prognosis compared with pilocytic astrocytomas.
Diffuse astrocytomas (ie, WHO grade II) may arise in any area of the CNS but most commonly develop in the
cerebrum, particularly the frontal and temporal lobes. The brain stem and spinal cord are the next most
frequently affected sites, whereas the cerebellum is a distinctly uncommon site. These tumors are moderately
cellular, infiltrative, and often enlarging, which distorts but does not destroy neighboring anatomical structures.
Mitotic activity is generally absent. TP53mutations and overexpression of the platelet-derived growth factor
receptor are the principal associated genetic alterations, although these findings are more frequently observed
in adults than in children.
Anaplastic astrocytoma (ie, WHO grade III) arises in the same locations as diffuse astrocytomas, with a
preference for the cerebral hemispheres. These tumors show increased cellularity, distinct nuclear atypia,
marked mitotic activity, and a tendency to infiltrate through neighboring tissue. A high frequency
of TP53 and PTENmutations has been recognized in adult tumors, with pediatric tumors showing much less.
Glioblastoma multiforme (ie, WHO grade IV) tumors occur most often in the subcortical white matter of the
cerebral hemispheres. Combined frontotemporal location with infiltration into the adjacent cortex, basal ganglia,
and contralateral hemisphere is typical. Glioblastoma is the most frequent tumor of the brain stem in children,
while the cerebellum and spinal cord are rare sites. These tumors are highly cellular, with high proliferative and
mitotic activity. Although rapid and extensive invasion of surrounding tissue is common, distant metastasis
within or outside the CNS is rare. Refer to the image below.

This section displays a typical field of a

glioblastoma multiforme (grade IV) with pseudopalisading neovascularity, nuclear atypia, numerous mitoses, and areas of
hemorrhage.

Pediatric glioblastomas have a pattern of genetic alterations different from that in adults.
Although TP53 mutations and loss of heterozygosity (LOH) on 17p is observed in pediatric tumors, the
frequency is much less. Overexpression of p53 protein has been associated with worse clinical outcome in

pediatric high-grade astrocytomas. Other studies have shown that overexpression of the epidermal growth
factor receptor (EGFR) is observed in most pediatric high-grade astrocytomas, but this does not appear to be
associated with outcome. EGFR amplification, which is commonly seen in adult high-grade astrocytomas, has
been described in diffuse pontine gliomas of childhood but is otherwise a rare event in the pediatric tumors.
However, LOH on chromosome 10 occurs at a high frequency in both adults and children, supporting the view
that LOH on chromosome 10 is instrumental to the development of glioblastoma.