Clinicopathological Features and Outcomes of H3K27-Altered Diffuse Midline Gliomas: An Immunohistochemistry-Based Study from a Tertiary Cancer Centre in Western India
DISCOVERIES (ISSN 2359-7232), 2026, Volume 14, Issue 3
Original Article
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CITATION: Rai V, Trivedi P, Manimaran P, Saha A, Maru P. Clinicopathological Features and Outcomes of H3K27-Altered Diffuse Midline Gliomas: An Immunohistochemistry-Based Study from a Tertiary Cancer Centre in Western India. Discoveries 2026, e232. DOI: 10.15190/d.2026.11
Clinicopathological Features and Outcomes of H3K27-Altered Diffuse Midline Gliomas: An Immunohistochemistry-Based Study from a Tertiary Cancer Centre in Western India
Varnika Rai¹, Priti Trivedi²,*, Poornima Manimaran², Anurag Saha², Paheli Maru²
¹ Homi Bhabha Cancer Hospital and Mahamana Pandit Madan Mohan Malaviya Cancer Centre, Varanasi, India
² Gujarat Cancer and Research Institute, Ahmedabad, India
Corresponding author: Dr Priti Trivedi; Onco-pathology Department, Gujarat Cancer and Research Institute, Ahmedabad; E-mail address: priti_patho@yahoo.co.in
Abstract
Diffuse midline gliomas (DMGs) arise in central brain structures. The 2021 World Health Organization (WHO) classification redefined “H3K27-mutant DMG” (DMG-H3K27M-mutant) as “H3K27-altered DMG” (DMG-H3K27Alt), encompassing four epigenetically distinct subtypes. This study aimed to identify DMG-H3K27Alt cases in midline locations using H3K27M and H3K27me3 immunohistochemistry (IHC), evaluate the clinicopathological profile, compare them with their H3K27 wild counterparts, and assess their prognostic outcomes. The study included all midline-located diffuse gliomas (WHO grades 2–4) diagnosed between January 2020 and June 2023, in our institution. Using IHC for H3K27M and H3K27me3, cases were classified as H3K27-altered or wild-type (DMG-H3K27Wt). Statistical analysis was performed using SPSS version 29.0. Of the 72 cases, 37 (51.4%) were DMG-H3K27Alt, age range 4 to 60 years (mean:28.8years) with a male-to-female ratio of 2.08:1. The thalamus was the most frequent site overall. High-grade morphology was significantly more common in DMG-H3K27Alt (p = 0.008), whereas low-grade gliomas were more frequent in DMG-H3K27Wt (p < 0.001). Brisk mitosis, necrosis, and microvascular proliferation were significantly associated with H3K27-altered tumours (p = 0.014, p < 0.001, and p = 0.017, respectively). H3K27M positivity was observed in 89.2% of DMG-H3K27Alt cases, while 10.8% were H3K27M-negative and showed isolated H3K27me3 loss. Infratentorial DMG-H3K27Alt were high-grade, occurred in younger patients, and retained ATRX expression. Mean survival was shorter in DMG-H3K27Alt group (p = 0.009), although not statistically significant by log-rank test (p = 0.15). Compared with previous reports, our paediatric DMG-H3K27Alt cohort was slightly older than the corresponding wild-type cohort, and low-grade morphology predominantly involved the thalamus rather than the brainstem, highlighting the clinicopathological heterogeneity of DMG-H3K27Alt. This study highlights the utility of combined H3K27M and H3K27me3 immunohistochemistry for identifying DMG-H3K27Alt in routine practice, particularly in resource-limited settings where comprehensive molecular testing is unavailable.