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. 2025 Mar;172(1):195-218.
doi: 10.1007/s11060-024-04898-7. Epub 2025 Jan 2.

Congress of Neurological Surgeons systematic review and evidence based guideline on neuropathology for WHO grade II diffuse glioma: update

Nataniel Mandelberg  1   2 , Tiffany R Hodges  3 , Tony J C Wang  4 , Tresa McGranahan  5 , Jeffrey J Olson  6 , Daniel A Orringer  7   8
Affiliations

Congress of Neurological Surgeons systematic review and evidence based guideline on neuropathology for WHO grade II diffuse glioma: update

Nataniel Mandelberg et al. J Neurooncol. 2025 Mar.

Abstract

QUESTIONS AND RECOMMENDATIONS FROM THE PRIOR VERSION OF THESE GUIDELINES WITHOUT CHANGE: TARGET POPULATION: Adult patients (age ≥ 18 years) who have suspected low-grade diffuse glioma.

Question: What are the optimal neuropathological techniques to diagnose low-grade diffuse glioma in the adult?

Recommendation: Level I Histopathological analysis of a representative surgical sample of the lesion should be used to provide the diagnosis of low-grade diffuse glioma. Level III Both frozen section and cytopathologic/smear evaluation should be used to aid the intra-operative assessment of low-grade diffuse glioma diagnosis. A resection specimen is preferred over a biopsy specimen, to minimize the potential for sampling error issues.

Target population: Patients with histologically-proven WHO grade II diffuse glioma.

Question: In adult patients (age ≥ 18 years) with histologically-proven WHO grade II diffuse glioma, is testing for IDH1 mutation (R132H and/or others) warranted? If so, is there a preferred method?

Recommendation: Level II IDH gene mutation assessment, via IDH1 R132H antibody and/or IDH1/2 mutation hotspot sequencing, is highly-specific for low-grade diffuse glioma, and is recommended as an additional test for classification and prognosis.

Target population: Patients with histologically-proven WHO grade II diffuse glioma.

Question: In adult patients (age ≥ 18 years) with histologically-proven WHO grade II diffuse glioma, is testing for 1p/19q loss warranted? If so, is there a preferred method?

Recommendation: Level III 1p/19q loss-of-heterozygosity testing, by FISH, array-CGH or PCR, is recommended as an additional test in oligodendroglial cases for prognosis and potential treatment planning.

Target population: Patients with histologically proven WHO grade II diffuse glioma.

Question: In adult patients (age > 18 years) with histologically-proven WHO grade II diffuse glioma, is methyl-guanine methyl-transferase (MGMT) promoter methylation testing warranted? If so, is there a preferred method?

Recommendation: There is insufficient evidence to recommend MGMT promoter methylation testing as a routine for low-grade diffuse gliomas. It is recommended that patients be enrolled in properly designed clinical trials to assess the value of this and related markers for this target population.

Target population: Patients with histologically-proven WHO grade II diffuse glioma.

Question: In adult patients (age ≥ 18 years) with histologically proven WHO grade II diffuse glioma, is Ki-67/MIB1 immunohistochemistry warranted? If so, is there a preferred method to quantitate results?

Recommendation: Level III Ki67/MIB1 immunohistochemistry is recommended as an option for prognostic assessment.

New recommendation: TARGET POPULATION: Adult patients (age ≥ 18 years) who have suspected WHO grade II diffuse glioma.

Question: Is testing for ATRX mutations helpful for predicting survival and making treatment recommendations?

Recommendation: There is insufficient evidence to recommend ATRX mutation testing as a means of predicting survival or making treatment recommendations.

Target population: Adult patients (age ≥ 18 years) who have suspected WHO grade II diffuse glioma.

Question: Does the addition of intraoperative optical histologic methods provide accuracy beyond the use of conventional histologic methods in diagnosis and management?

Recommendation: There is insufficient evidence at this time to suggest that intraoperative optical histologic methods offer increased diagnostic accuracy when compared to conventional techniques.

Keywords: Histopathology; Low-grade glioma; Molecular Markers.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests. Disclaimer of liability: This clinical systematic review and evidence-based guideline was developed by a physician volunteer task force as an educational tool that reflects the current state of knowledge at the time of completion. Each chapter is designed to provide an accurate review of the subject matter covered. This guideline is disseminated with the understanding that the recommendations by the authors and consultants who have collaborated in their development are not meant to replace the individualized care and treatment advice from a patient’s physician(s). If medical advice or assistance is required, the services of a competent physician should be sought. The proposals contained in these guidelines may not be suitable for use in all circumstances. The choice to implement any particular recommendation contained in these guidelines must be made by a managing physician in light of the situation in each particular patient and on the basis of existing resources.

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