Diffuse Astrocytomas, IDH Mutant & 1p/19q Non-codeleted

Chapter 3 - Histology and Molecular Pathology of Gliomas

The vast majority of Grade 2 and 3 diffuse gliomas are IDH1 or IDH2 mutant; around 90% of these tumours are IDH1 R132H mutant.

The approximately 10% of glioblastomas that are IDH mutant are nowadays considered “secondary glioblastomas” (i.e. derived from a lower grade precursor tumour).

Diffuse IDH wildtype and IDH mutant astrocytomas cannot be delineated with routine histology. Currently, grading of these tumours is performed in the same way.

However, patients with IDH mutant astrocytomas are on average younger, have a better prognosis and may need different management than those with IDH wildtype tumours.

Histological criteria for grading within molecularly defined glioma categories will need modification: e.g. the impact of mitotic activity may differ between these groups.

Sequencing analysis of the IDH1 and IDH2 hotspot regions (IDH1 R132, IDH2 R172) is the gold standard to demonstrate the IDH mutant status of diffuse gliomas.

Molecular features supporting the diagnosis of IDH mutant astrocytoma are: presence of TP53 and ATRX mutation, absence of TERT Promoter mutation.

An Antibody specifically targeting mutant IDH1 R132H protein nowadays allows for easy recognition of the most frequent IDH mutant form of diffuse glioma.

Lack of nuclear ATRX expression correlates well with ATRX mutation. Immunohistochemical stainings may be of great help when molecular testing is not possible.

Revision Questions

  1. Which subgroups of diffuse astrocytomas are frequently IDH mutant?
  2. What is the most frequent IDH mutation found in diffuse gliomas?
  3. Which molecular markers support the diagnosis of IDH mutant astrocytoma?

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Last update: 18 September 2017