Secondary Logo

Institutional members access full text with Ovid®

Share this article on:

Incorporating Advances in Molecular Pathology Into Brain Tumor Diagnostics

Velázquez Vega, José, E., MD*; Brat, Daniel, J., MD, PhD

Advances In Anatomic Pathology: May 2018 - Volume 25 - Issue 3 - p 143–171
doi: 10.1097/PAP.0000000000000186
Review Articles

Recent advances in molecular pathology have reshaped the practice of brain tumor diagnostics. The classification of gliomas has been restructured with the discovery of isocitrate dehydrogenase (IDH) 1/2 mutations in the vast majority of lower grade infiltrating gliomas and secondary glioblastomas (GBM), with IDH-mutant astrocytomas further characterized by TP53 and ATRX mutations. Whole-arm 1p/19q codeletion in conjunction with IDH mutations now define oligodendrogliomas, which are also enriched for CIC, FUBP1, PI3K, NOTCH1, and TERT-p mutations. IDH-wild-type (wt) infiltrating astrocytomas are mostly primary GBMs and are characterized by EGFR, PTEN, TP53, NF1, RB1, PDGFRA, and CDKN2A/B alterations, TERT-p mutations, and characteristic copy number alterations including gains of chromosome 7 and losses of 10. Other clinically and genetically distinct infiltrating astrocytomas include the aggressive H3K27M-mutant midline gliomas, and smaller subsets that occur in the setting of NF1 or have BRAF V600E mutations. Low-grade pediatric gliomas are both genetically and biologically distinct from their adult counterparts and often harbor a single driver event often involving BRAF, FGFR1, or MYB/MYBL1 genes. Large scale genomic and epigenomic analyses have identified distinct subgroups of ependymomas tightly linked to tumor location and clinical behavior. The diagnosis of embryonal neoplasms also integrates molecular testing: (I) 4 molecularly defined, biologically distinct subtypes of medulloblastomas are now recognized; (II) 3 histologic entities have now been reclassified under a diagnosis of “embryonal tumor with multilayered rosettes (ETMR), C19MC-altered”; and (III) atypical teratoid/rhabdoid tumors (AT/RT) now require SMARCB1 (INI1) or SMARCA4 (BRG1) alterations for their diagnosis. We discuss the practical use of contemporary biomarkers for an integrative diagnosis of central nervous system neoplasia.

*Department of Pathology and Laboratory Medicine, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, GA

Department of Pathology, Feinberg School of Medicine and Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL

The authors have no funding or conflicts of interest to disclose.

Reprints: Daniel J. Brat, MD, PhD, Department of Pathology, Northwestern University Feinberg School of Medicine, Ward 3-140, 303 East Chicago Avenue, Chicago, IL 60611 (e-mail: daniel.brat@northwestern.edu).

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.