diffuse_astrocytoma_idh_mutant

Diffuse astrocytoma IDH Mutant

A diffuse astrocytoma with a mutation in either the IDH1 or IDH2 gene. Use of the former term “low-grade glioma” is discouraged.

Since most diffuse astrocytomas carry the IDH mutation, historical data (pre-IDH era) regarding what was formerly called low-grade astrocytomas (WHO grade II) is reflective of the current category to a limited extent.

These tumors tend to occur in children and young adults. They are relatively rare, comprising only ≈ 5% of primary brain tumors, and 15% of all gliomas. Pediatric (age < 20 years) diffuse astrocytomas (IDH mutation status not determined) occur at a rate of 0.26 per 100,000, about half that for adult (0.48).

There is a predilection for temporal, posterior frontal and anterior parietal lobes. In the pediatric population, a significant number occur in the thalamus, which is unusual in adults.

Characterized by slow growth. Most present with seizures.

Subtypes of IDH-mutant diffuse astrocytoma.

DNA methylation patterns of metabolic genes successfully distinguished the molecular subtypes of IDHmut and IDHwt gliomas. Promoter methylation of lactate dehydrogenase A negatively correlated with protein expression and was associated with IDHmut gliomas. Mitochondrial DNA copy number was increased in IDHmut tumours and did not change in recurrent tumours.Hierarchical clustering based on metabolism panel IHC revealed distinct subclasses of IDHmut and IDHwt gliomas with an impact on patient outcome. Further quantification of these markers allowed for the prediction of survival under antiangiogenic therapy.

A mitochondrial signature was associated with increased survival in all analyses, which could indicate tumour subgroups with specific metabolic vulnerabilities 1).

Gemistocytic astrocytoma IDH-mutant (WHO grade II).

T2-Fluid-attenuated inversion recovery (FLAIR) mismatch sign is now known to be a specific yet insensitive image feature for IDH-mutant, 1p19q non-codeleted astrocytoma. The current study revealed that lesion presenting T2-FLAIR mismatch exhibited extremely long T1- and T2-relaxation time while T2-FLAIR matched lesions showed low to moderate values. On the other hand, IDH-wildtype tumors presented noticeably short T1- and T2-relaxation time. These different relaxation time characteristics seemed to render T2-FLAIR mismatch sign of becoming such a unique and specific image feature for IDH-mutant, 1p19q non-codeleted astrocytoma 2).

see Pediatric diffuse astrocytoma

Low degrees of cellularity with highly differentiated cells and preservation of normal brain elements within the tumor. Calcifications are rare. Anaplasia and mitoses are absent (single mitosis is allowed). Blood vessels may be slightly increased in number. These tumors stain positive for GFAP. In the absence of 1p/19q codeletion, areas of cells resembling oligodendrogliomas are compatible with the diagnosis.

IDH mutation present by definition. ATRX & TP53 mutations support the diagnosis. Prognostically distinct subgroups based on a number of genetic markers have been tentatively identified5 but will not be covered here.

Usually hypodense on CT. Most are hypointense on T1WI MRI, and show high-intensity changes on T2WI that extend beyond the tumor volume.

Most do not enhance on CT or MRI (although up to 40% do, and these may have a worse prognosis).

Diffuse astrocytoma IDH Mutant outcome.


1)
Braun Y, Filipski K, Bernatz S, Baumgarten P, Roller B, Zinke J, Zeiner PS, Ilina E, Senft C, Ronellenfitsch MW, Plate KH, Bähr O, Hattingen E, Steinbach JP, Mittelbronn M, Harter PN. Linking epigenetic signature and metabolic phenotype in IDH mutant and IDH wildtype diffuse glioma. Neuropathol Appl Neurobiol. 2020 Oct 20. doi: 10.1111/nan.12669. Epub ahead of print. PMID: 33080075.
2)
Kinoshita M, Uchikoshi M, Sakai M, Kanemura Y, Kishima H, Nakanishi K. T(2)-FLAIR Mismatch Sign Is Caused by Long T(1) and T(2) of IDH-mutant, 1p19q Non-codeleted Astrocytoma. Magn Reson Med Sci. 2020 Feb 27. doi: 10.2463/mrms.bc.2019-0196. [Epub ahead of print] PubMed PMID: 32101817.
  • diffuse_astrocytoma_idh_mutant.txt
  • Last modified: 2020/10/21 08:58
  • by administrador