Diffuse Astrocytomas, IDH Wildtype

Chapter 3 - Histology and Molecular Pathology of Gliomas

Tumour cells in diffuse astrocytomas often resemble non-neoplastic astrocytes with variable eosinophilic cell processes blending into the neuropil.

Like guerrilla warriors, these tumour cells tend to invade extensively the surrounding CNS parenchyma. Visualisation of the invasive front is problematic.

Diffuse astrocytomas lacking “brisk” mitotic activity, necrosis and florid microvascular proliferation (MVP) are diagnosed as low-grade (WHO Grade 2).

Increased mitotic activity leads to a diagnosis of anaplastic astrocytoma (Grade 3); presence of necrosis and/or florid MVP means glioblastoma (Grade 4).

Immunohistochemical staining for glial fibrillary acidic protein (GFAP) is a helpful but non-specific tool for recognising astroglial differentiation of tumour cells.

Glioblastoma is not only the most malignant, but also by far the most frequent diffuse astrocytoma. Furthermore, about 90% of glioblastomas are IDH wildtype.

IDH wildtype diffuse astrocytomas in adults are typically ATRX wildtype and TERT Promoter mutant; TP53 in these tumours may be wildtype or mutant.

Grade 2 or 3 IDH wildtype astrocytomas in adults with gain of chromosome 7, loss of chromosome 10, and/or EGFR Amplification/EGFR variant III may in fact be glioblastomas.

Most diffuse gliomas in children are different at the molecular level; markers like Histone H3 K27M mutation indicate high-grade malignancy irrespective of histology.

Revision Questions

  1. Which histological features are used for grading diffuse astrocytomas?
  2. What is by far the most frequent diffuse glioma?
  3. Which molecular markers in diffuse, IDH wildtype astrocytoma indicate glioblastoma?

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Last update: 18 September 2017