Your pathology report for astrocytoma (IDH mutant)

Jason Wasserman MD PhD FRCPC
December 3, 2025

Astrocytoma (IDH-mutant) is a type of brain tumor that arises from astrocytes. Astrocytes are a kind of glial cell that support and protect nerve cells in the brain and spinal cord. The term IDH-mutant refers to tumors with a mutation in one of the IDH genes. These genes are called IDH1 and IDH2.

An IDH-mutant astrocytoma is a diffuse tumor. Diffuse means the tumor cells spread into the surrounding brain tissue rather than forming a distinct border. This type of tumor can be given a WHO grade of 2, 3, or 4 based on microscopic and molecular features.

Where in the brain are these tumors found?

Astrocytoma can develop in many parts of the central nervous system. Most tumors arise in the cerebral hemispheres, especially in the frontal lobes. Less commonly, they can occur in the temporal, parietal, or occipital lobes, the brainstem, or the spinal cord. Their location often explains the symptoms patients experience.

What are the symptoms?

The symptoms of an astrocytoma depend on the tumor’s size and location, as well as its rate of growth. Many people with IDH-mutant astrocytoma notice gradual changes rather than sudden problems. Common symptoms include

  • Seizures.

  • Headaches.

  • Weakness or numbness in an arm or leg.

  • Changes in speech or language.

  • Vision changes.

  • Problems with concentration, memory, or behavior, especially with frontal lobe tumors.

Some tumors are found incidentally when brain imaging is performed for other reasons, such as after head trauma or for long-standing headaches.

What causes IDH mutant astrocytoma?

For most people, an IDH-mutant astrocytoma develops sporadically, meaning there is no clear inherited cause. Researchers have identified specific genetic risk factors in large population studies, but these do not explain most cases.

In a small number of patients, IDH-mutant astrocytoma is associated with inherited conditions that increase the risk of cancer. Examples include Li-Fraumeni syndrome, caused by germline TP53 mutations, and Ollier disease, which is associated with enchondromas and chondrosarcoma. In these rare situations, the tumor is part of a broader cancer predisposition syndrome.

IDH mutations are uncommon in childhood brain tumors but can be seen in adolescents and young adults. Astrocytomas with IDH mutations are much less common in older adults, especially those over 55.

How is this diagnosis made?

Imaging

The diagnosis of IDH-mutant astrocytoma usually begins with brain imaging, most often an MRI. The tumor frequently appears as an area of abnormal signal in the frontal lobes, although it can develop in many parts of the brain and spinal cord. On MRI, these tumors typically look darker on T1 and brighter on T2 images, and they may cause swelling and distortion of nearby structures. A pattern called the T2–FLAIR mismatch sign, where the tumor is very bright on T2 and relatively dark on FLAIR, is highly suggestive of an IDH-mutant astrocytoma, especially in grade 2 and 3 tumors.

Lower-grade (grade 2) tumors usually show little or no contrast enhancement, meaning they do not “light up” much after contrast dye is given. As the tumor becomes higher grade (grade 3 or 4), contrast enhancement, swelling, and sometimes areas of necrosis (dead tissue) become more common. Imaging can strongly suggest a diffuse glioma, such as IDH-mutant astrocytoma, but a tissue sample is needed to make a definite diagnosis.

Biopsy and microscopic features

The diagnosis of IDH-mutant astrocytoma is confirmed by biopsy or surgical removal of tumor tissue. The tissue is examined by a pathologist, who looks at thin sections under a microscope.

Under the microscope, astrocytoma, IDH-mutant is a diffusely infiltrating tumor, meaning tumor cells spread into the surrounding brain tissue rather than forming a sharp border. In WHO grade 2 tumors, the cells are moderately increased in number and have enlarged, irregular nuclei, but usually show only mild atypia (abnormal appearance). Mitotic figures (dividing cells) are rare or absent. Grade 3 tumors show higher cellularity, more variation in nuclear size and shape, and more frequent mitoses. WHO grade 4 astrocytomas show features of high-grade malignancy, such as necrosis and microvascular proliferation (abnormal growth of small blood vessels), similar to what is seen in glioblastoma.

These microscopic features help determine the WHO grade, but by themselves, they do not distinguish IDH-mutant astrocytoma from other types of diffuse glioma. For that, additional tests are needed.

Immunohistochemistry

Immunohistochemistry (IHC) uses antibodies linked to dyes to detect specific proteins in tumor cells. In IDH-mutant astrocytoma, several IHC markers are especially helpful:

  • IDH1 R132H: This stain detects the most common IDH1 mutation (R132H). If positive, it confirms that the tumor is IDH-mutant.

  • ATRX: Many IDH-mutant astrocytomas lose ATRX protein in tumor cell nuclei, while normal cells such as neurons and blood vessel cells remain positive. Loss of ATRX supports an astrocytic tumor rather than an oligodendroglioma.

  • p53: Strong and diffuse nuclear staining for p53 is common and correlates with TP53 gene mutations, which frequently occur in these tumors.

  • GFAP and OLIG2: These markers show that the tumor arises from glial cells and support the diagnosis of an astrocytic glioma.

The combination of positive IDH1 R132H staining, loss of ATRX, and p53 positivity strongly supports the diagnosis of astrocytoma, IDH-mutant.

Molecular tests

Molecular tests analyze the tumor’s DNA and are now a critical part of the diagnostic process. Important molecular studies for IDH-mutant astrocytoma:

  • IDH1 and IDH2 sequencing to confirm IDH mutations, especially when IDH1 R132H immunostaining is negative, even if the tumor still appears IDH-mutant under the microscope.

  • 1p/19q codeletion testing to distinguish IDH-mutant astrocytoma from oligodendroglioma. Chromosomes are long strands of DNA that carry genes, and each has a short arm (p) and a long arm (q). In oligodendroglioma, both the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q) are missing, a change called a 1p/19q codeletion. This combined loss is a defining feature of oligodendroglioma. In astrocytoma, IDH-mutant, this codeletion is absent. So, if the tumor has an IDH mutation but does not show 1p/19q codeletion, it supports the diagnosis of IDH-mutant astrocytoma rather than oligodendroglioma.

  • ATRX and TP53 gene analysis to confirm mutations that are characteristic of IDH-mutant astrocytomas and support the diagnosis when combined with histology and immunohistochemistry.

  • CDKN2A/CDKN2B deletion testing, because loss of both copies of CDKN2A and/or CDKN2B (homozygous deletion) indicates more aggressive behavior and automatically upgrades the tumor to WHO grade 4, even if the microscopic features look lower grade.

  • Additional panels that may include genes such as PDGFRA, MET, MYCN, PIK3R1, and PIK3CA, which are associated with higher-grade disease and shorter survival in some patients.

In some centers, DNA methylation profiling is also used. This test looks at epigenetic patterns—chemical marks on DNA that affect gene expression—and can confirm the diagnosis of IDH-mutant astrocytoma and help distinguish among subgroups and grades.

Integrated diagnosis

The final diagnosis of IDH-mutant astrocytoma is made using an integrated approach that combines all of the information:

  • Clinical and imaging findings.

  • Microscopic appearance (diffuse astrocytic tumor).

  • Immunohistochemistry (IDH1 R132H, ATRX, p53, GFAP, OLIG2).

  • Molecular tests (IDH mutations, absence of 1p/19q codeletion, CDKN2A/CDKN2B status, and other markers).

A diffuse astrocytic tumor is diagnosed as IDH-mutant astrocytoma:

  • It has a confirmed IDH1 or IDH2 mutation.

  • It shows typical astrocytic histology.

  • It lacks 1p/19q codeletion.

  • It often has ATRX loss and TP53 mutation.

The WHO grade (2, 3, or 4) is then assigned based on microscopic features such as mitotic activity, necrosis, and microvascular proliferation, and on key molecular findings such as CDKN2A/CDKN2B homozygous deletion. This integrated diagnosis helps guide treatment and provides the most accurate information about prognosis.

WHO grade

WHO grade is a system used to describe how aggressive a brain tumor is expected to be. For IDH-mutant astrocytoma, the World Health Organization assigns grades 2, 3, or 4. The grade is based on how the tumor looks under the microscope and, in some cases, on specific molecular findings.

  • WHO grade 2: WHO grade 2 IDH-mutant astrocytoma is considered a lower-grade tumor. Under the microscope, these tumors show increased numbers of tumor cells compared to normal brain tissue, with enlarged, irregular nuclei. Still, they usually have very few, if any, mitotic figures (dividing cells). There is no microvascular proliferation (abnormal new blood vessel growth) and no necrosis (areas of dead tumor). These tumors tend to grow slowly, and many patients live for ten years or more, mainly when treatment includes surgery and, when appropriate, radiation or chemotherapy.

  • WHO grade 3: WHO grade 3 IDH-mutant astrocytoma shows more aggressive features. The tumor cells are more densely packed, the nuclei are more atypical and variable in size and shape, and mitotic figures are more frequent. However, grade 3 tumors still lack microvascular proliferation and necrosis. Patients with grade 3 astrocytomas usually have a shorter survival than those with grade 2 tumors, often in the range of five to ten years, depending on treatment and other factors.

  • WHO grade 4: WHO grade 4 IDH-mutant astrocytoma is the highest grade in this group. It is diagnosed when the tumor shows necrosis and/or microvascular proliferation, the classic features of a high-grade glioma. Importantly, even if these microscopic features are absent, homozygous deletion of CDKN2A and/or CDKN2B (loss of both copies of these genes) is enough to classify the tumor as WHO grade 4. Grade 4 astrocytomas, IDH-mutant, behave more aggressively and have a poorer prognosis, with a median survival of around three years in many studies.

The WHO grade is one of the most important predictors of prognosis. It reflects how quickly the tumor is likely to grow and how likely it is to recur after treatment. For IDH-mutant astrocytoma, combining WHO grade with molecular information—such as IDH status, CDKN2A/CDKN2B deletion, and other biomarkers—provides the most accurate picture of expected behavior and helps your care team tailor treatment and follow-up plans.

Biomarkers for IDH-mutant astrocytoma

Biomarkers are specific genetic or protein changes in tumor cells that provide information about how the tumor behaves and how it may respond to treatment. In IDH-mutant astrocytomas, biomarkers help identify tumors at higher risk of progression, refine WHO grade, and identify targets for new therapies. They also help distinguish IDH-mutant astrocytoma from other diffuse glioma types.

What types of biomarkers are tested

Biomarker testing in IDH-mutant astrocytoma focuses on genetic changes in tumor DNA, including mutations, deletions, amplifications, and gene fusions. These are usually assessed with next-generation sequencing or other molecular methods on tissue obtained at biopsy or surgery. Some of these biomarkers, such as CDKN2A and CDKN2B, directly affect grading and prognosis. Others, such as PDGFRA or MET amplification, are associated with more aggressive behavior and may become targets for future therapies.

CDKN2A and CDKN2B

CDKN2A and CDKN2B encode proteins that slow cell division and act as tumor suppressors. When both copies of CDKN2A and/or CDKN2B are lost (homozygous deletion), tumor cells grow more easily and behave more aggressively. In astrocytoma, IDH-mutant, homozygous deletion of CDKN2A and/or CDKN2B is so vital that it automatically upgrades the tumor to WHO grade 4, even if the microscopic features appear lower grade.

These genes are evaluated using molecular tests, such as next-generation sequencing or copy-number analysis, to determine whether one or both copies of the gene have been lost.

Your report will describe whether CDKN2A and CDKN2B are intact or show homozygous deletion. If a homozygous deletion is present, the tumor is classified as WHO grade 4.

RB1

RB1 is a tumor suppressor gene that helps control the cell cycle and prevents cells from dividing too quickly. Loss or mutation of RB1 can lead to faster tumor growth and may be associated with more aggressive behavior in astrocytoma, IDH-mutant.

RB1 status is assessed using next-generation sequencing or other DNA-based tests that detect mutations or deletions in the RB1 gene.

The report will state whether RB1 is mutated, deleted, or intact. Alterations in RB1 may be noted in the tumor’s molecular profile and may be associated with higher-grade or more rapid progression.

CDK4

CDK4 is a gene that encodes a protein that promotes cell cycle progression. When CDK4 is amplified, meaning extra copies of the gene are present, the cell cycle can speed up, leading to accelerated tumor growth. In astrocytoma, IDH-mutant tumors with CDK4 amplification have been associated with more aggressive behavior in some studies.

CDK4 is evaluated using molecular tests, such as next-generation sequencing with copy-number analysis, to determine whether the gene is amplified.

Your report may describe CDK4 as amplified or not amplified. Amplification is often considered a high-risk molecular feature.

PDGFRA

PDGFRA is a gene that encodes a receptor involved in cell growth and survival. When PDGFRA is amplified or mutated, the receptor can become overactive, driving tumor progression. In astrocytoma, IDH-mutant, PDGFRA amplification has been linked to shorter survival and may indicate a more aggressive tumor.

PDGFRA is typically assessed by next-generation sequencing and copy-number analysis, which can detect mutations and gene amplifications.

The tumor will be described as having PDGFRA amplification or not, and specific mutations may also be listed.

MET

MET is a gene that encodes a receptor involved in cell growth and movement. Abnormal MET signaling, including amplification or activating mutations, can promote invasion and progression. In astrocytoma, IDH-mutant, MET alterations have been associated with more aggressive disease.

MET status is evaluated using next-generation sequencing to detect mutations and copy number analysis to identify gene amplification.

Your report will indicate whether MET mutations or MET amplification are present. These changes are usually listed among high-risk molecular features.

PIK3R1

PIK3R1 is a gene that helps regulate the PI3K pathway, which controls cell growth and survival. Mutations in PIK3R1 can activate this pathway and have been linked to shorter survival in some studies of astrocytoma, IDH-mutant.

PIK3R1 is tested for mutations by next-generation sequencing.

The report will state whether the tumor is PIK3R1-mutated or wildtype (no mutation detected). Mutations may be described as part of a high-risk molecular profile.

MYCN

MYCN is an oncogene that promotes cell proliferation when amplified. MYCN amplification has been associated with more aggressive behavior in several brain tumor types, including astrocytoma, IDH-mutant.

MYCN amplification is detected by copy number analysis, often as part of a broader next-generation sequencing panel or DNA methylation profiling with copy-number readout.

Your report will state whether MYCN amplification is present or absent and may describe it as an adverse molecular feature when present.

Prognosis

In general, IDH-mutant astrocytoma has a better prognosis than IDH-wildtype glioblastoma. Still, the outcome varies widely depending on WHO grade, patient age, tumor location, extent of surgical removal, and the molecular changes described above. Many patients with WHO grade 2 tumors live more than ten years after diagnosis, although most tumors eventually progress. WHO grade 3 tumors have an intermediate prognosis, and WHO grade 4 IDH-mutant astrocytomas typically have a median survival of about three years with modern therapy. Molecular features such as homozygous deletion of CDKN2A and CDKN2n, PDGFRA amplification, and other high-risk alterations are associated with shorter survival.

What happens after the diagnosis?

After the diagnosis of IDH-mutant astrocytoma is made, your healthcare team will discuss treatment options with you. Treatment often includes a combination of surgery, radiation therapy, and chemotherapy. The goals are to remove as much tumor as safely possible, control remaining disease, and maintain neurological function and quality of life. Molecular and biomarker testing, including IDH status and the other genes described above, should be performed because the results are important for classification, prognosis, and eligibility for clinical trials and new targeted therapies. You will be followed over time with repeat imaging, neurological assessments, and supportive care tailored to your symptoms and needs.

Questions to ask your doctor

  • What is the WHO grade of my astrocytoma, and what does that mean for my prognosis?

  • Were there any high-risk molecular changes, such as CDKN2A or CDKN2B deletions, PDGFRA amplification, or alterations in MET, PIK3R1, or MYCN?

  • How much of the tumor was removed during surgery?

  • What treatments do you recommend next, and what are the goals of these treatments?

  • Will I be eligible for any clinical trials or targeted therapies based on my tumor’s biomarkers?

  • How will we monitor the tumor over time?

  • What symptoms or changes should I report right away?

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