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  • Updated 03.05.2023
  • Released 03.06.2022
  • Expires For CME 03.05.2026

IDH-mutated diffuse astrocytomas



This article discusses isocitrate dehydrogenase (IDH)-mutated diffuse astrocytoma, their classification, natural history, and management options.

Key points

• IDH-mutated diffuse astrocytoma presents with a wide spectrum of neurologic manifestations.

• Median age at presentation is 45 years, with a slightly higher incidence in males.

• Magnetic resonance imaging with and without contrast is the standard approach for evaluating brain lesions.

• Tissue diagnosis by biopsy or surgery is essential.

• Radiation and chemotherapy prolong survival, but the exact timing is not well delineated.

• Progression-free survival, but not overall survival, is improved by early radiation.

• Procarbazine, CCNU (lomustine), and vincristine combination chemotherapy improves survival; temozolomide likely does as well.

• Observation may be a reasonable option for select cases, keeping in mind that regular imaging is needed in this setting.

Historical note and terminology

Brain tumors were managed historically with surgical resection and radiotherapy starting in the era of Harvey Cushing. In 1976, adjuvant chemotherapy began to be utilized when cyclohexyl chloroethyl nitrosourea (CCNU) was found to increase survival—albeit by only a few months (14). During this era, our understanding and classification of gliomas was based entirely on histology and anatomical location of the tumors. This approach continued until 2016 when a new classification system was developed, guided by a new molecular understanding of gliomas. In particular, mutations in the genes encoding isocitrate dehydrogenase (IDH1 and IDH2), as well as chromosomal 1p19q co-deletion were found to be strongly associated with improved prognosis (35; 53; 40). The 2016 World Health Organization (WHO) classification system defined the following subtypes of grade 2 and grade 3 gliomas:

• Grade 2 diffuse astrocytoma, IDH-wildtype

• Grade 2 diffuse astrocytoma, IDH-mutated

• Grade 2 oligodendroglioma, IDH-mutated and 1p19q co-deleted

• Grade 3 anaplastic astrocytoma, IDH-wildtype

• Grade 3 anaplastic astrocytoma, IDH-mutated

• Grade 3 anaplastic oligodendroglioma IDH-mutated and 1p19q co-deleted


The focus of this article is on astrocytoma, IDH-mutated (IDH1 or IDH2), WHO grade 2, although WHO grade 3 will also be discussed. It is important to recognize that the revised 2021 WHO classification makes use of a simplified system, only denoting the following subtypes:

• Astrocytoma, IDH-mutated

• Oligodendroglioma, IDH-mutated and 1p/19q-codeleted

• Glioblastoma, IDH-wildtype


Notably, the 2021 WHO classification removes the term “anaplastic” and relies on the specific grade within each category type. Glioblastoma IDH-wildtype is a WHO grade 4 tumor. Oligodendrogliomas can be WHO grade 2 or 3. Astrocytoma, IDH-mutated, can be WHO grade 2, 3, or 4 (formerly classified as glioblastoma along with the tumors currently called glioblastoma IDH-wildtype). In addition, the 2021 WHO classification discontinued the use of Roman numerals and replaced them with Arabic numerals.

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