Integrated diagnostics of diffuse gliomas

Czech version

Authors: M. Hendrych ¹; H. Valeková ²; T. Kazda ³; R. Lakomý ⁴; J. Šána ⁵; R. Jančálek ²; O. Slabý ⁵; M. Hermanová ¹
Authors‘ workplace: I. ústav patologie, LF MU a FN u sv. Anny v Brně ¹; Neurochirurgická klinika LF MU a FN U sv. Anny v Brně ²; Klinika radiační onkologie LF MU a MOÚ Brno ³; Klinika komplexní onkologické péče LF MU a MOÚ Brno ⁴; CEITEC – Středoevropský technologický institut, MU Brno ⁵
Published in: Klin Onkol 2020; 33(4): 248-259
Category: Review
doi: https://doi.org/10.14735/amko2020248

Overview

Recently, the World Health Organization (WHO) classification of tumours of the central nervous system (CNS) has brought essential changes. The currently valid revised WHO 2016 classification of CNS tumours introduced the concept of integrated diagnostics, which incorporated not only histopathological morphological finding and immunophenotype but also molecular-genetic characteristics of the tumour. Thus, the final integrated diagnosis comprises the traditional morphological and growth pattern characteristics of a tumour including histopathological grade and also specific molecular biomarkers. The classification of tumour based on a combination of both tumour phenotype and genotype enables more precise prognostic stratification, increases the objectivity of diagnostics and prediction of response to treatment. In 2017, an international platform, The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy – not official WHO (cIMPACT-NOW), was established to create and formulate practical recommendations for integrated diagnostics of CNS tumours and upcoming WHO classification. The incorporation of molecular biomarkers into the integrated diagnostics radically changed the classification of diffuse gliomas, which include entities with different morphological characteristics, genetic alterations and biological behaviour. This review article summarizes essential morphological, immunophenotypical and molecular genetic characteristics of diffuse gliomas within the scope of integrated diagnostics according to the valid WHO classification of tumours of the CNS and subsequent recommendations of diagnostic approaches.

This work was supported by grant of the Ministry of Health of the Czech Republic – Conceptual Development of a Research Organization (MMCI 00209805) and Grant Agency of Masaryk University (MUNI/A/1562/2018).

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers

Keywords:

diffuse gliomas – integrated diagnosis – WHO 2016

Sources

1. Louis DN, Ohgaki H, Wiestler OD et al. WHO Classification of Tumours of the Central Nervous System. World Health Organization classification of tumours. Revised 4th edition. Lyon: International Agency for Research on Cancer 2016.

2. Louis DN, von Deimling A, Cavenee WK. Diffuse astrocytic and oligodendroglia tumours – introduction. In: Louis DN, Ohgaki H, Wiestler OD et al. WHO Classification of Tumours of the Central Nervous System. World Health Organization classification of tumours. Revised 4th edition. Lyon: International Agency for Research on Cancer 2016: 16–17.

3. Louis DN, Ellison DW, Brat DJ et al. cIMPACT-NOW: a practical summary of diagnostic points from Round 1 updates. Brain Pathol 2019; 29 (4): 469–472. doi: 10.1111/bpa.12732.

4. Perry A, Wesseling P. Histologic classification of gliomas. In: Berger MS, Weller M. Handbook of clinical neurology. Vol 134: Gliomas. Cambridge: Elsevier 2016: 71–95. doi: 10.1016/B978-0-12-802997-8.00005-0.

5. Wesseling P, Capper D. WHO 2016 Classification of gliomas. Neuropathol Appl Neurobiol 2018; 44 (2): 139–150. doi: 10.1111/nan.12432.

6. Barresi V, Lionti S, Valori L et al. Dual-genotype diffuse low-grade glioma: is it really time to abandon oligoastrocytoma as a distinct entity? J Neuropathol Exp Neurol2017; 76 (5): 342–346. doi: 10.1093/jnen/nlx024.

7. Louis DN, Giannini C, Capper D et al. cIMPACT-NOW update 2: diagnostic clarifications for diffuse midline glioma, H3 K27M-mutant and diffuse astrocytoma/anaplastic astrocytoma, IDH-mutant. Acta Neuropathol 2018; 135 (3): 481–484. doi: 10.1007/s00401-018-1826-y.

8. Dang L, White DW, Gross S et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2009; 462 (7274): 739–744. doi: 10.1038/nature08
617.

9. Gondim DD, Curless KL, Cheng L et al. Determining IDH-mutational status in gliomas using IDH1-R132H antibody and polymerase chain reaction. Appl Immunohistochem Mol Morphol 2019; 27 (10): 722–725. doi: 10.1097/PAI.0000000000000702.

10. Dewitt JC, Frosch MP, Samore WR et al. Cost-effectiveness of IDH testing in diffuse gliomas according to the 2016 WHO classification of tumors of the central
nervous system recommendations. Neuro Oncol 2017; 19 (12): 1640–1650. doi: 10.1093/neuonc/nox120.

11. Vogazianou AP, Chan R, Pearson DM et al. Distinct patterns of 1p and 19q alterations identify subtypes of human gliomas that have different prognoses. Neuro Oncol 2010; 12 (7): 664–678. doi: 10.1093/neuonc/nop075.

12. Lee J, Solomon DA, Tihan T. The role of histone modifications and telomere alterations in the pathogenesis of diffuse gliomas in adults and children. J Neurooncol 2017; 132 (1): 1–11. doi: 10.1007/s11060-016-2349-9.

13. Takami H, Yoshida A, Fukushima S et al. Revisiting TP53 mutations and immunohistochemistry-a comparative study in 157 diffuse gliomas. Brain Pathol 2015; 25 (3): 256–265. doi: 10.1111/bpa.12173.

14. Brat DJ, Aldape K, Colman H et al. cIMPACT-NOW update 3: recommended diagnostic criteria for “Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV”. Acta Neuropathol 2018; 136 (5): 805–810. doi: 10.1007/s00401-018-1913-0.

15. Hegi ME, Diserens AC, Hamou MF etal. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J M 2005; 352 (10): 997–1003. doi: 10.1056/NEJMoa043331.

16. Wick W, Platten M, Meisner C et al. Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol 2012; 13 (7): 707–715. doi: 10.1016/S1470-2045 (12) 70164-X.

17. Malmström A, Grønberg BH, Marosi C et al. Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol 2012; 13 (9): 916-926. doi: 10.1016/S1470-2045 (12) 70265-6.

18. Mansouri A, Hachem LD, Nassiri F et al. MGMT promoter methylation status testing to guide therapy for glioblastoma: Refining the approach based on emerging evidence and current challenges. Neuro Oncol 2019; 21 (2): 167–178. doi: 10.1093/neuonc/noy132.

19. Lakomý R, Kazda T, Poprach A et al. The role of chemotherapy in the treatment of low-grade gliomas. Klin Onkol 2017; 30 (5): 343–348. doi: 10.14735/amko2017343.

20. Kazda T, Lakomý R, Poprach A et al. Controversy in the postoperative treatment of low-grade gliomas. Klin Onkol 2017; 30 (5): 337–342. doi: 10.14735/amko2017337.

21. Kazda T, Dziacky A, Burkon P et al. Radiotherapy of glioblastoma 15 years after the landmark Stupp’s trial: More controversies than standards? Radiol Oncol 2018; 52 (2): 121–128. doi: 10.2478/raon-2018-0023.

22. Weller M, van den Bent M, Tonn JC et al. European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol 2017; 18 (6): e315–e329. doi: 10.1016/S1470-2045 (17) 30194-8.

23. Berghoff A, van den Bent M. How I treat anaplastic glioma without 1p/19q codeletion. ESMO Open 2019; 4 (Suppl 2): e000534. doi: 10.1136/esmoopen-2019-000534.

24. Ellison DW, Hawkins C, Jones DTW et al. cIMPACT-NOW update 4: diffuse gliomas characterized by MYB, MYBL1, or FGFR1 alterations or BRAF (V600E) mutation. Acta Neuropathol 2019; 18 (6): 683–687. doi: 10.1007/s00401-019-01987-0.

25. Ryall S, Tabori U, Hawkins C. A comprehensive review of paediatric low-grade diffuse glioma: pathology, molecular genetics and treatment. Brain Tumor Pathol 2017; 34 (2): 51–61. doi: 10.1007/s10014-017-0282-z.

26. Sturm D, Witt H, Hovestadt V et al. Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell 2012; 22 (4): 425–437. doi: 10.1016/j.ccr.2012.08.024.

27. Louis DN, Wesseling P, Paulus W et al. cIMPACT-NOW update 1: Not otherwise specified (NOS) and not elsewhere classified (NEC). Acta Neuropathol 2018; 135 (3): 481–484. doi: 10.1007/s00401-018-1808-0.

28. Huang T, Garcia R, Qi J et al. Detection of histone H3 K27M mutation and post-translational modifications in pediatric diffuse midline glioma via tissue immunohistochemistry informs diagnosis and clinical outcomes. Oncotarget 2018; 9 (98): 37112–37124. doi: 10.18632/oncotarget.26430.

29. Kleinschmidt-DeMasters BK, Donson A, Foreman NK et al. H3 K27M mutation in gangliogliomas can be associated with poor prognosis. Brain Pathol 2017; 27 (6): 846–850. doi: 10.1111/bpa.12455.

30. Orillac C, Thomas C, Dastagirzada Y et al. Pilocytic astrocytoma and glioneuronal tumor with histone H3 K27M mutation. Acta Neuropathol Commun 2016; 4 (1): 84. doi: 10.1186/s40478-016-0361-0.