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Diagnostic Testing for Diffuse Gliomas


According to the Central Brain Tumor Registry of the United States, diffuse gliomas are the most common primary brain tumors, affecting approximately 15,000 people in the US each year. These tumors are uniformly fatal, but have widely variable clinical courses and treatment approaches that are often predicted by their molecular profile. While diagnostic molecular characterization of these tumors is now possible in modern molecular pathology labs, there is wide variability in the genetic alterations that are tested as well as the methods for detection. The World Health Organization (WHO) provides standardization for diagnostic classes of diffuse gliomas, including their molecular definitions, but there are currently no clinical practice guidelines that address molecular testing more broadly for diffuse gliomas.

To address this gap and develop recommendations for the optimal diagnostic testing for pediatric and adults with diffusely infiltrative gliomas, the College of American Pathologists (CAP) in collaboration with the American Association of Neuropathologists (AANP), the American Society of Clinical Oncology (ASCO), the Association for Molecular Pathology (AMP), and the Society for Neuro-Oncology (SNO) convened an expert panel and reviewed current literature.

Adhering to the National Academy of Medicine guideline standards and using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach1, the panel’s recommendations will help provide evidence-based guidance for improved diagnosis, prognosis, and therapy management for patients with diffuse gliomas. Thirteen draft recommendations were available for public review and comments. The expert panel will assess feedback garnered during that period to help ensure final recommendations are clinically sound and practical.


To assess evidence related to the optimal diagnostic testing for pediatric and adult patients with diffusely infiltrative gliomas in order to provide guidance for improved diagnosis, prognosis, and prediction.

Key Questions

Overarching Question: What ancillary tests are needed to classify diffuse gliomas and sufficiently inform the clinical management of patients?

1a. What genetic and molecular alterations should be included for optimal classification of:

  • Diffuse astrocytoma
  • Oligodendroglioma
  • Oligoastrocytoma
  • Glioblastoma
  • Anaplastic astrocytoma
  • Anaplastic oligodendroglioma
  • Anaplastic oligoastrocytoma
  • Diffuse midline glioma

1b. What are the acceptable techniques/methods for mutation testing of diffuse glioma? What are the expected turn-around-times for individual assays?

1c. What are the acceptable techniques/methods for assessing whole genome copy number alterations?

2. What are the core molecular tests/findings that provide sufficient classifying information in the setting of discreet clinicopathologic entities?

3. What are the acceptable techniques/methods/criteria for determining MGMT promoter methylation status?


American Association of Neuropathologists

American Society of Clinical Oncology

Association of Molecular Pathology

Society for Neuro-Oncology

Panel Members

Daniel J. Brat, MD, PhD, FCAP, Chair

Kenneth Aldape, MD

Peter Canoll, MD, PhD

Meera R. Hameed, MD, FCAP

Brent Harris, MD, PhD, FCAP

Eyas M. Hattab, MBA, MD, FCAP

Michelle Hawks Yount, MS

Jason T. Huse, MD, PhD

Dolores Lopez-Terrada, MD, PhD, FCAP

Robert B. Jenkins, MD, PhD, FCAP

Julia Bridge, MD, FCAP

Howard Colman, MD, PhD

William McDonald, MD, FCAP

Arie Perry, MD, FCAP

Fausto Rodriguez, MD

Martin J. van den Bent, MD, PhD

Lesley Souter, PhD

Carol Colasacco, MLIS, AHIP, SCT(ASCP)

Kearin Reid, MLIS, AHIP, MLS (ASCP)

Nicole E. Thomas, MPH, CT(ASCP)cm

Guideline Information

  • Status: Complete Recommendations
  • Open Comment Period: September 9-October 31, 2019

Additional Information

The CAP Pathology and Laboratory Quality Center for Evidence-based Guidelines develops recommendations related to the practice of pathology and laboratory medicine. Through this work, we and our members continually improve the quality of diagnostic medicine and patient outcomes. For questions, please contact CENTER@CAP.ORG.

  1. Schunemann H, Brozek J, Guyatt G, Oxman A, eds. GRADE Handbook. GRADEpro website. https://gdt.gradepro.org/app/handbook/handbook.html#h.9rdbelsnu4iy. Update October 2013. Accessed August 9, 2019.

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