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Practice Guideline
. 2022 May 1;146(5):547-574.
doi: 10.5858/arpa.2021-0295-CP.

Molecular Biomarker Testing for the Diagnosis of Diffuse Gliomas

Daniel J Brat  1 , Kenneth Aldape  2 , Julia A Bridge  3   4 , Peter Canoll  5 , Howard Colman  6 , Meera R Hameed  7 , Brent T Harris  8 , Eyas M Hattab  9 , Jason T Huse  10 , Robert B Jenkins  11 , Dolores H Lopez-Terrada  12 , William C McDonald  13 , Fausto J Rodriguez  14 , Lesley H Souter  15 , Carol Colasacco  16 , Nicole E Thomas  16 , Michelle Hawks Yount  17 , Martin J van den Bent  18 , Arie Perry  19
Affiliations
Practice Guideline

Molecular Biomarker Testing for the Diagnosis of Diffuse Gliomas

Daniel J Brat et al. Arch Pathol Lab Med. .

Abstract

Context.—: The diagnosis and clinical management of patients with diffuse gliomas (DGs) have evolved rapidly over the past decade with the emergence of molecular biomarkers that are used to classify, stratify risk, and predict treatment response for optimal clinical care.

Objective.—: To develop evidence-based recommendations for informing molecular biomarker testing for pediatric and adult patients with DGs and provide guidance for appropriate laboratory test and biomarker selection for optimal diagnosis, risk stratification, and prediction.

Design.—: The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. A systematic review of literature was conducted to address the overarching question, "What ancillary tests are needed to classify DGs and sufficiently inform the clinical management of patients?" Recommendations were derived from quality of evidence, open comment feedback, and expert panel consensus.

Results.—: Thirteen recommendations and 3 good practice statements were established to guide pathologists and treating physicians on the most appropriate methods and molecular biomarkers to include in laboratory testing to inform clinical management of patients with DGs.

Conclusions.—: Evidence-based incorporation of laboratory results from molecular biomarker testing into integrated diagnoses of DGs provides reproducible and clinically meaningful information for patient management.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found in the Appendix at the end of this article.

Figures

Figure 1.
Figure 1.. Testing Algorithm for Diffuse Gliomas with IDH1/2 Mutations.
A – refer to Figure 2. ATRX, ATRX chromatin remodeler; CDKN2A/B Cyclin Dependent Kinase Inhibitor 2A (CDKN2A)/ Cyclin Dependent Kinase Inhibitor 2B (CDKN2B); Codel, codeletion; IDH, Isocitrate Dehydrogenase (NADP(+)); MVP, microvascular proliferation; Mut, mutation; TERTp, Telomerase Reverse Transcriptase promoter; TP53, Tumor protein p53; WHO, World Health Organization. Blue indicates WHO-defined entities; Green indicates recommended tests; *Some institutions/laboratories may prefer to perform 1p/19q codeletion as the initial step for IDH-mutant gliomas. See recommendations 2-4.**Additional molecular biomarker testing and DNA methylation profiling maybe helpful in establishing a diagnosis for challenging cases.
Figure 2.
Figure 2.. Testing Algorithm for Diffuse Gliomas Without IDH1/2 Mutations.
A – refer to Figure 1. ALK, ALK receptor tyrosine kinase; BRAF, B-Raf proto-oncogene; EGFR, epidermal growth factor receptor; FGFR1, Fibroblast Growth Factor Receptor; H3, histone 3 gene mutation; H3K27me3, H3 K27M trimethylation (H3K27me3) IDH, Isocitrate Dehydrogenase (NADP(+)); IHC, immunohistochemistry; Mut, mutation; TERTp, Telomerase Reverse Transcriptase promoter; CNA, copy number alteration; MAPK, Mitogen-activated protein kinase; MET, mesenchymal epithelial transition factor; MGMTp, O-6-Methylguanine-Deoxiribose Nucleic Acid Methlytransferase promoter; MYB, MYB proto-oncogene (MYB); MYBL1, MYB-like; NTRK, Neurotrophic tyrosine receptor kinase; PDGFRA, platelet derived growth factor receptor alpha; MYCN, N-myc proto-oncogene protein; ROS1, ROS proto-oncogene 1; WHO, World Health Organization. Blue indicates WHO-defined entities; Green indicates recommended tests; Italic indicates good practice statements. **Additional molecular biomarker testing and DNA methylation profiling maybe helpful in establishing a diagnosis for challenging cases.
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