Diffuse Astrocytoma WHO Grade II

Abstract

Diffuse astrocytoma is a diffusely infiltrating astrocytoma with a mutation in either the IDH1 or IDH2 gene. Gemistocytic astrocytoma is a variant of IDH-mutant diffuse astrocytoma characterized by the presence of a conspicuous (though variable) proportion of gemistocytic neoplastic astrocytes (gemistocytes).

It affects young adults aged 30–40 years and is located in any part of the brain, preferentially in the frontal and temporal lobes.

It presents as a homogeneous, primary white matter mass with no contrast enhancement. Well-differentiated neoplastic astrocytes are seen microscopically in a loosely structured tumor matrix. The neoplastic astrocytes have round to oval nuclei, vesicular with intermediate-sized masses of chromatin, distinct nucleolus, and no stainable cytoplasm.

Genes affected in astrocytomas WHO grade II include: IDH1/2 (isocitrate dehydrogenase 1, isocitrate dehydrogenase 2) with an IDH1 point mutation, resulting in a transition of arginine to histidine in the enzyme’s catalytic site at amino acid position 132 (R132H); TP53 (tumor suppressor gene, on chromosome 17p13.1, encoding tumor protein 53); PDGFRA (oncogenic; encoding platelet-derived growth factor receptor, α-peptide). Diffuse astrocytomas lack 1p/19q co-deletion. Epigenetic changes include promoter hypermethylation of two tumor suppressor genes, ARF and MGMT. Genes differentially expressed in astrocytomas WHO grade II show upregulation (CD9, CSPG2, NTF3, EGFR, PDGFRA, TIMP3) and downregulation (TYRO3).

Treatment consists of surgery with an attempt of total removal followed by chemotherapy in individual cases after incomplete tumor resection. Median survival time ranges between 6 and 8 years. Tumor progression might occur after 4–5 years. Changes in various genes, e.g., mutation, deletion, amplification, might influence overall outcome.