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PubMed This is a summary of 16 peer-reviewed journal articles Updated
Pathology

Decoding Your Pathology Report: The 2021 WHO Grading System

At a Glance

The 2021 WHO grading system for meningiomas combines physical tumor characteristics with genetic markers to determine its grade (1, 2, or 3). Specific genetic mutations, like TERT or CDKN2A/B, automatically classify a meningioma as Grade 3, regardless of how it looks under a microscope.

A pathology report is the definitive “biography” of a tumor. In 2021, the World Health Organization (WHO) fundamentally changed how meningiomas are graded. It moved from a system based solely on what the tumor looks like under a microscope (histology) to an integrated diagnosis that prioritizes the tumor’s genetic “blueprint” (molecular markers) [1][2].

The Three Grades: A Quick Reference

The WHO grade helps predict how likely a tumor is to grow back after treatment.

  • Grade 1 (Benign): These are the most common and typically slow-growing. They have low “mitotic activity” (fewer than 4 dividing cells) and no aggressive features [3].
  • Grade 2 (Atypical): These tumors are more likely to recur. A Grade 1 tumor is automatically upgraded to Grade 2 if it shows brain invasion—meaning it has started to push into the surrounding brain tissue—even if it looks benign otherwise [4][5].
  • Grade 3 (Anaplastic/Malignant): These are the most aggressive. They have very high cell division rates and specific genetic mutations that make them prone to rapid growth [1].

The “Molecular Overrule”

The most significant change in the 2021 guidelines is that certain genetic markers now “overrule” the microscope. If a tumor has either of the following markers, it is automatically classified as Grade 3, regardless of how slow-growing it looks [1][6]:

  1. TERT Promoter Mutation: This mutation acts like a “fountain of youth” for tumor cells, allowing them to divide indefinitely [7].
  2. CDKN2A/B Deletion: A homozygous (complete) loss of this gene removes a critical “brake” on cell growth [1][8].

These markers are powerful predictors of a more aggressive clinical course and an increased risk of recurrence [1][8].

What to Look for on Your Report

When reviewing your report, keep a checklist of these key terms:

  • Mitotic Count (Mitoses): This measures how many cells are actively dividing. A count of 4 or more per 10 “high-power fields” (often written on modern reports as 2.5 mm²) typically moves a tumor to Grade 2 [3].
  • Ki-67 (MIB-1) Index: This is a percentage that tells you how fast the tumor is proliferating. A higher Ki-67 percentage is often associated with a higher risk of the tumor returning [9][10].
  • Brain Invasion: Even if the cells look benign, the presence of brain invasion makes the tumor a WHO Grade 2 [4].
  • Necrosis: The presence of “spontaneous necrosis” (areas of dead tumor cells) is a sign of aggressive growth and is an atypical feature [11][12].
  • NF2 Status: Mutations in the NF2 gene are common in meningiomas and may be linked to more aggressive behavior [13].

Ruling Out the “Mimic”: SFT/HPC

Occasionally, a tumor that looks like a meningioma is actually a Solitary Fibrous Tumor (SFT) (formerly called Hemangiopericytoma). To tell them apart, pathologists use a specific test called STAT6 immunohistochemistry (IHC). If the test is positive (meaning the cell nuclei “light up” for the STAT6 protein), it confirms the tumor is an SFT, not a meningioma [14][15]. This distinction is vital because SFTs require different long-term follow-up and treatment strategies [16].

Return to Home | Previous: Symptoms & Decision to Treat | Next: Surgery & Radiation

Common questions in this guide

What does brain invasion mean on a meningioma pathology report?
Brain invasion means the tumor has started to push into the surrounding brain tissue. Under the 2021 WHO guidelines, this automatically makes the tumor a Grade 2 (Atypical), even if it otherwise looks benign under a microscope.
How do TERT or CDKN2A/B mutations affect my meningioma grade?
The presence of a TERT promoter mutation or a complete CDKN2A/B deletion automatically classifies a meningioma as a Grade 3 malignant tumor. These molecular markers overrule the tumor's physical appearance because they indicate a high risk of rapid growth.
What is a mitotic count in a pathology report?
The mitotic count measures how many tumor cells are actively dividing. In meningiomas, a count of 4 or more dividing cells per high-power field typically moves the tumor to a Grade 2 classification, which carries a higher risk of recurrence.
What does the Ki-67 or MIB-1 index mean?
The Ki-67 (or MIB-1) index is a percentage that shows how fast the tumor cells are proliferating. A higher percentage generally indicates a faster-growing tumor and a higher risk of the meningioma returning after treatment.
Why does my report mention STAT6 testing?
Pathologists use the STAT6 test to ensure the tumor is a meningioma and not a Solitary Fibrous Tumor (SFT), which can look very similar. Distinguishing between the two is highly important because they require completely different long-term treatments and follow-up care.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.My pathology report mentions [specific feature, e.g., brain invasion]—how does this change my WHO Grade from 1 to 2?
  2. 2.Was molecular testing performed for TERT promoter mutations or CDKN2A/B deletions, and if so, what were the results?
  3. 3.What was my mitotic count per 10 high-power fields?
  4. 4.How does my Ki-67 labeling index (proliferation rate) influence the likelihood of the tumor returning?
  5. 5.Was STAT6 testing done to confirm this is a meningioma and not a mimic like a Solitary Fibrous Tumor?

Questions For You

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References

References (16)
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    Meningioma: Molecular Updates from the 2021 World Health Organization Classification of CNS Tumors and Imaging Correlates.

    Soni N, Ora M, Bathla G, et al.

    AJNR. American journal of neuroradiology 2025; (46(2)):240-250 doi:10.3174/ajnr.A8368.

    PMID: 38844366
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    Integrated Molecular-Morphologic Meningioma Classification: A Multicenter Retrospective Analysis, Retrospectively and Prospectively Validated.

    Maas SLN, Stichel D, Hielscher T, et al.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2021; (39(34)):3839-3852 doi:10.1200/JCO.21.00784.

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    Atypical Histopathological Features and the Risk of Treatment Failure in Nonmalignant Meningiomas: A Multi-Institutional Analysis.

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    World neurosurgery 2020; (133()):e804-e812 doi:10.1016/j.wneu.2019.10.002.

    PMID: 31605839
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    cIMPACT-NOW update 8: Clarifications on molecular risk parameters and recommendations for WHO grading of meningiomas.

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    Neuro-oncology 2025; (27(2)):319-330 doi:10.1093/neuonc/noae170.

    PMID: 39212325
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    Base MRI Imaging Characteristics of Meningioma Patients to Discuss the WHO Classification of Brain Invasion Otherwise Benign Meningiomas.

    Luo X, Jiang H, Liu XJ, et al.

    Technology in cancer research & treatment 2023; (22()):15330338231171470 doi:10.1177/15330338231171470.

    PMID: 37264676
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    Poor prognosis associated with TERT gene alterations in meningioma is independent of the WHO classification: an individual patient data meta-analysis.

    Mirian C, Duun-Henriksen AK, Juratli T, et al.

    Journal of neurology, neurosurgery, and psychiatry 2020; (91(4)):378-387 doi:10.1136/jnnp-2019-322257.

    PMID: 32041819
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    TERT promoter mutations are associated with poor prognosis and cell immortalization in meningioma.

    Spiegl-Kreinecker S, Lötsch D, Neumayer K, et al.

    Neuro-oncology 2018; (20(12)):1584-1593 doi:10.1093/neuonc/noy104.

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    Prognostic impact of genetic alterations and methylation classes in meningioma.

    Berghoff AS, Hielscher T, Ricken G, et al.

    Brain pathology (Zurich, Switzerland) 2022; (32(2)):e12970 doi:10.1111/bpa.12970.

    PMID: 35213082
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    Degree of Resection and Ki-67 Labeling Index for Recurring Meningiomas.

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    Cureus 2017; (9(11)):e1820 doi:10.7759/cureus.1820.

    PMID: 29312841
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    High risk of recurrence for grade II meningioma: a 10-year multicenter analysis of prognosis factors.

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    Chinese clinical oncology 2021; (10(3)):26 doi:10.21037/cco-20-226.

    PMID: 33752411
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    Recurrence of Atypical Meningioma: A Case Report.

    Paul A, Johnson S, Patel SM

    Cureus 2025; (17(10)):e94686 doi:10.7759/cureus.94686.

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    Histopathological predictors of progression-free survival in atypical meningioma: a single-center retrospective cohort and meta-analysis.

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    Brain tumor pathology 2022; (39(2)):99-110 doi:10.1007/s10014-021-00419-w.

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    Neurofibromatosis type 2 gene mutation and progesterone receptor messenger RNA expression in the pathogenesis of sporadic orbitocranial meningioma.

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    Are bone erosion and peripheral feeding vessels hallmarks of intracranial solitary fibrous tumor/hemangiopericytoma?

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This page explains meningioma pathology terminology for educational purposes only. Always consult your neurosurgeon or neuro-oncologist for interpretation of your specific pathology report and WHO grade.

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