Can Grade 1 Meningioma Progress to Grade 2 or 3?
Yes, grade 1 meningiomas can harbor molecular features that indicate higher-risk biology and may behave more aggressively than their histologic grade suggests, though true histologic progression over time is a distinct concept from initial molecular misclassification. 1
Understanding Meningioma Grading Evolution
The current WHO CNS5 classification system recognizes that histologic grade alone does not fully capture tumor biology. The 2025 cIMPACT-NOW update specifically identifies scenarios where grade 1 meningiomas demonstrate unexpectedly aggressive behavior, warranting molecular testing. 1
Key Molecular Markers That Override Histologic Grade
Certain molecular alterations automatically upgrade a tumor to grade 3, regardless of histologic appearance: 1
- TERT promoter oncogenic variants = automatic CNS WHO grade 3
- Homozygous deletion of CDKN2A/CDKN2B = automatic CNS WHO grade 3
These markers can be present even in morphologically benign-appearing (grade 1) meningiomas, meaning the tumor was always biologically higher grade despite its histologic appearance.
Molecular Upgrading from Grade 1 to Grade 2
The cIMPACT-NOW consortium now recommends assigning CNS WHO grade 2 to tumors with grade 1 morphology when they demonstrate: 1
- Chromosomal arm 1p deletion combined with 22q deletion and/or NF2 oncogenic variants
This represents a formal recognition that molecular features can and should override purely histologic grading.
Clinical Scenarios Requiring Molecular Testing
Molecular testing should be pursued in grade 1 meningiomas when: 1
- Unexpectedly rapid growth on serial imaging
- Early recurrence after resection
- Brain invasion with otherwise benign histology (BIOB meningioma)
- Borderline features between grade 1 and 2 (e.g., 3 mitoses per 1.6 mm² or 2 of 5 "soft" criteria)
- Specific histologic subtypes: chordoid, clear cell, rhabdoid, or papillary
- Young patients (children and adolescents)
Evidence of Molecular-Histologic Discordance
Real-world data demonstrates significant discordance between histologic and molecular grades: 2
- 29% of WHO grade 1 meningiomas harbor copy number profiles consistent with higher-grade biology
- 8% of all meningiomas harbor TERT, CDKN2A/B, or BAP1 mutations, with 6% occurring in histologic grade 1 tumors
- 32% of meningiomas reclassify to either higher-risk or lower-risk when molecular data is integrated 3
Additional High-Risk Molecular Features
Loss of H3K27me3 expression increases in frequency with higher grade and at recurrence, though it currently provides prognostic information within grade 2 meningiomas rather than changing grade assignment. 1
BAP1 and PBRM1 inactivation are associated with rhabdoid/papillary features and may indicate innately higher-grade biology, with over 80% of BAP1-mutant meningiomas initially classified as grades 2-3. 1
Clinical Implications
The practical answer is nuanced: A grade 1 meningioma may not "progress" in the traditional sense of acquiring new mutations over time, but rather may have been molecularly higher-grade from the outset, only revealed through:
- Molecular testing showing high-risk alterations
- Clinical behavior (rapid growth, early recurrence) prompting re-evaluation
- Recurrence specimens showing histologic progression
For brain-invasive otherwise benign (BIOB) meningiomas specifically, molecular markers should determine the final grade assignment, with low-risk molecular profiles confirming grade 1 and higher-risk profiles upgrading to grade 2. 1
Common Pitfalls to Avoid
- Do not rely solely on histologic grade for grade 1 meningiomas showing aggressive clinical behavior 1
- Do not dismiss rapid growth or early recurrence in a histologic grade 1 tumor—pursue molecular testing 1
- Do not assume all grade 1 meningiomas have favorable prognosis—molecular profiling identifies a subset with higher-risk biology 3, 2
- Recognize that H3K27me3 loss provides prognostic information but does not currently change grade assignment 1