Anaplastic Astrocytoma (WHO Grade III)

Definition

Pathogenesis

• Often evolves from a well-differentiated astrocytoma (WHO Grade II) with a sequence involving:
  • losses of heterozygosity involving chromosomes 19q and 22q
  • retinoblastoma gene alterations
  • deletions of genes that encode p16 and other cell cycle regulators1

Gross Pathology

• Morphologic evidence of tumor progression:
  • may be a focal finding in what would otherwise qualify as a histologically favorable lesion

Histopathology

• Infiltrate is more cellular and cytologically atypical than low-grade astrocytoma (Fig. 1
  

  Fig. 1: Anaplastic astrocytoma. Compared with its low-grade counterpart (well-differentiated astrocytoma (WHO Grade II), this lesion exhibits increased cellularity, the cytologic features of a fully malignant neoplasm, and, at center, mitotic figures.

  )
• Biopsies derived from the tumor–CNS interface may contain only scattered neoplastic elements
• Common nuclear alterations:
  • angulation
  • dense hyperchromasia
  • considerable variation in contour and dimension
  • mitotic figures (firmly establish diagnosis)

Diagnosis

• Not based on a solitary mitotic figure found on close scrutiny of a generous biopsy or resection specimen
• Made when any mitoses in a limited (e.g. stereotactic) neurosurgical sample demonstrating a fibrillary astrocytic neoplasm with pronounced nuclear abnormalities
• Regional blood vessels:
  • an increase is permissible, as is hypertrophy of the lining endothelium
  • complex and disorderly proliferation or zones of coagulative tumor necrosis in the setting of a cytologically malignant fibrillary astrocytic neoplasm mandate classification as a glioblastoma

Differential Diagnosis