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Case Report Open Access

Conserved methylation signature accurately predicts heavily irradiated CNS tumour with perplexing histopathology: A case report

  • Authors:
    • Handoko
    • Eka Susanto
    • Renindra Ananda Aman
    • Tiara Aninditha
    • Heri Wibowo
    • Tiara Bunga Mayang Permata
    • Soehartati A. Gondhowiardjo
  • View Affiliations / Copyright

    Affiliations: Department of Radiation Oncology, Faculty of Medicine, Cipto Mangunkusumo National General Hospital, University of Indonesia, Jakarta 10430, Indonesia, Department of Anatomical Pathology, Faculty of Medicine, Cipto Mangunkusumo National General Hospital, University of Indonesia, Jakarta 10430, Indonesia, Department of Neurosurgery, Cipto Mangunkusumo National General Hospital, Faculty of Medicine, University of Indonesia, Jakarta 10430, Indonesia, Department of Neurology, Cipto Mangunkusumo National General Hospital, Faculty of Medicine, University of Indonesia, Jakarta 10430, Indonesia, Integrated Laboratory, Faculty of Medicine, University of Indonesia, Jakarta 10430, Indonesia
    Copyright: © Handoko et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 165
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    Published online on: August 14, 2025
       https://doi.org/10.3892/br.2025.2043
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Abstract

Diagnosing central nervous system (CNS) tumours post‑radiation therapy is often complicated by treatment‑induced histological changes. Molecular diagnostics, such as methylation profiling, offer robust tools to aid in accurate tumour classification. The present study reported a case of a 48‑year‑old woman with a recurrent parasellar mass previously treated with stereotactic radiosurgery. Despite imaging suggestive of meningioma, histopathology and immunohistochemistry yielded ambiguous findings. Low‑coverage whole genome methylation profiling using Oxford Nanopore sequencing provided a conclusive diagnosis of meningioma, with a classifier confidence score of 0.791, supported by t‑distributed stochastic neighbor embedding clustering and characteristic copy number variations. The present case illustrated the diagnostic utility of methylation profiling in post‑treatment CNS tumours with perplexing histopathology. Integration of molecular diagnostics can enhance classification accuracy and inform clinical decision‑making.
View Figures

Figure 1

T1 contrast-enhanced brain magnetic
resonance imaging revealing the parasellar lesion in axial and
sagittal sections (A) before SRS, (B) 6 months post-SRS, (C) 12
months post-SRS, (D) 18 months post-SRS, (E) 6 months post-surgery
and (F) 1 year post-surgery. SRS, stereotactic radiosurgery

Figure 2

Overview of the molecular testing
process through correlation with clinical and imaging data to
establish a definite diagnosis. FFPE, formalin-fixed
paraffin-embedded; NGS, next-generation sequencing.

Figure 3

Histopathology and
immunohistochemical findings. (A) Haematoxylin and eosin staining.
(B-H) Immunohistochemical staining of the following markers: (B)
Vimentin, (C) EMA, (D) AE1/3, (E) S100, (F) PR, (G) Ki-67 and (H)
synaptophysin. All images were obtained at a magnification of x100.
EMA, mucin 1, cell surface associated. EMA, mucin 1, cell surface
associated; AE1/3, pan-cytokeratin antibody cocktail; S100,
calcium-binding proteins; PR, progesterone receptor.

Figure 4

Methylation classification results.
(A) Methylation class and methylation class family assignements,
(B) low-coverage copy number variation profile and (C) t-SNE
clustering map demonstrating clustering consistent with
meningioma.
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Copy and paste a formatted citation
Spandidos Publications style
Handoko , Susanto E, Aman RA, Aninditha T, Wibowo H, Permata TB and Gondhowiardjo SA: Conserved methylation signature accurately predicts heavily irradiated CNS tumour with perplexing histopathology: A case report. Biomed Rep 23: 165, 2025.
APA
Handoko, , Susanto, E., Aman, R.A., Aninditha, T., Wibowo, H., Permata, T.B., & Gondhowiardjo, S.A. (2025). Conserved methylation signature accurately predicts heavily irradiated CNS tumour with perplexing histopathology: A case report. Biomedical Reports, 23, 165. https://doi.org/10.3892/br.2025.2043
MLA
Handoko, , Susanto, E., Aman, R. A., Aninditha, T., Wibowo, H., Permata, T. B., Gondhowiardjo, S. A."Conserved methylation signature accurately predicts heavily irradiated CNS tumour with perplexing histopathology: A case report". Biomedical Reports 23.4 (2025): 165.
Chicago
Handoko, , Susanto, E., Aman, R. A., Aninditha, T., Wibowo, H., Permata, T. B., Gondhowiardjo, S. A."Conserved methylation signature accurately predicts heavily irradiated CNS tumour with perplexing histopathology: A case report". Biomedical Reports 23, no. 4 (2025): 165. https://doi.org/10.3892/br.2025.2043
Copy and paste a formatted citation
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Spandidos Publications style
Handoko , Susanto E, Aman RA, Aninditha T, Wibowo H, Permata TB and Gondhowiardjo SA: Conserved methylation signature accurately predicts heavily irradiated CNS tumour with perplexing histopathology: A case report. Biomed Rep 23: 165, 2025.
APA
Handoko, , Susanto, E., Aman, R.A., Aninditha, T., Wibowo, H., Permata, T.B., & Gondhowiardjo, S.A. (2025). Conserved methylation signature accurately predicts heavily irradiated CNS tumour with perplexing histopathology: A case report. Biomedical Reports, 23, 165. https://doi.org/10.3892/br.2025.2043
MLA
Handoko, , Susanto, E., Aman, R. A., Aninditha, T., Wibowo, H., Permata, T. B., Gondhowiardjo, S. A."Conserved methylation signature accurately predicts heavily irradiated CNS tumour with perplexing histopathology: A case report". Biomedical Reports 23.4 (2025): 165.
Chicago
Handoko, , Susanto, E., Aman, R. A., Aninditha, T., Wibowo, H., Permata, T. B., Gondhowiardjo, S. A."Conserved methylation signature accurately predicts heavily irradiated CNS tumour with perplexing histopathology: A case report". Biomedical Reports 23, no. 4 (2025): 165. https://doi.org/10.3892/br.2025.2043
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