Diffuse Midline Glioma (H3K27M mutant) in Adult: A Diagnostic Challenge

  • Sonal Paul Department of Pathology, Lokmanya Tilak Medical college and General Hospital, Sion, Mumbai
  • Nitin M Gadgil Department of Pathology, Lokmanya Tilak Medical college and General Hospital, Sion, Mumbai
  • Chetan Chaudhari Department of Pathology, Lokmanya Tilak Medical college and General Hospital, Sion, Mumbai
Keywords: Adult, Diffuse midline glioma, H3K27M mutation


Introduction: Diffuse midline glioma (DMG), H3K27M mutant is an infiltrative midline high grade glioma with predominantly astrocytic differentiation and K27M mutation in either H3F3A or HIST1H3B/C. Case Report:  A 45-year-old female presented with complaints of headache and memory loss for 3 months. MRI was suggestive of an infiltrative mass lesion in the quadrigeminal plate cistern suggestive of pineal neoplasm. Squash and histomorphology showed a low-grade astrocytic tumour with infiltrative growth pattern. Microvascular proliferation and necrosis were absent. Immunohistochemistry showed loss of ATRX protein, focal positivity for p53 proteinand IDH1R132H negativity. On molecular analysis, H3K27M mutation was noted and the case was labelled as DMG H3K27Mmutant (WHO IV) Conclusion: DMG (H3K27M) is a newly added entity in the WHO 4th revised editionof 2016. It presents with a diagnostic challenge as it has varied histomorphology, not requiring atypia, mitosis, endothelial hyperplasia and necrosis for diagnosis as Grade IV.


1. David N Louis, Hiroko Ohgaki, Otmar D.Wiestler, Webster K. Cavenee (Eds): WHO Classification of Tumours of the Central Nervous System (Revised 4th edition). IARC; Lyon 2016.
2. Meyronet D, Esteban-Mader M, Bonnet C, Joly MO, Uro-CosteE, Amiel-Benouaich A et al. Characteristics of H3 K27M-mutant gliomas in adults: Neuro Oncol.2017;19:1127–1134.
3. Hu J, Western S, Kesari S. Brainstem Glioma in Adults. Front Oncol. 2016; 6: 180
4. LullaRR, Saratsis AM, HashizumeR. Mutations in chromatin machinery and pediatric high-grade glioma. Sci Adv.2016;2: e1501354.
5. Castel D, Philippe C, CalmonR, LeDret L, Truffaux N, Boddaert N et al. Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes.Acta Neuropathol.2015;130:815–27
6. Stowe HB, Miller CR, Wu J, Randazzo DM, Ju AW. Pineal Region Glioblastoma, a Case Report and Literature Review. Front. Oncol. 2017;12:123.
7. Solomon DA, Wood MD, Tihan T, Bollen AW, Gupta N, Phillips J et al.Diffuse Midline Gliomas with Histone H3-K27M Mutation: A Series of 47 Cases Assessing the Spectrum of Morphologic Variation and Associated Genetic Alterations.Brain Pathol. 2016;26:569–80.
8. Schreck KC, Ranjan S, Skorupan N, Bettegowda C, Eberhart CG, Ames HM et al. Incidence and clinicopathologic features of H3 K27M mutations in adults with radiographically-determined midline gliomas. J Neuro-Oncol. 2019;143:87–93.
9. Grasso CS, Tang Y, Truffaux N, Berlow NE, Liu L, Debily MA et al. Functionally defined therapeutic targets in diffuse intrinsic pontine glioma. Nat Med. 2015;21:555–9.
10. Louis DN, Giannini C, Capper D, Paulus W, Figarella-Branger D, Lopes MB 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;135:639-642.
Case Report