Original articles

Vol. 117: Issue 5 - October 2025

The contribution of methylation profiling in neuropathological diagnosis of central nervous system tumors in children, adolescent and young adults

Authors

Anna Maria Buccoliero , Laura Giunti , Mirko Scagnet , Milena Guidi , Debora Vergani , Rina Agushi , Federico Mussa , Barbara Spacca , Flavio Giordano , Lorenzo Innocenti , Abramo Ponticelli , gianluca Mattei , Maura Calvani , Manila Antonelli , Ludovico D'Incerti , Lorenzo Genitori , Iacopo Sardi

Key words: Methylation profile, central nervous system tumor, diffuse midline glioma H3.3K27-altered, pilocytic astrocytoma FGFR1-altered, leptomeningeal glioneuronal tumor
DOI: 10.32074/1591-951X-1226
Publication Date: 2025-12-16

Abstract

Methylation of CpG islands plays a crucial role in the regulation of gene expression. The study of DNA methylation profiles offers deep insights into key oncogenic processes and facilitates the differentiation of tumor entities at the epigenetic level. Methylation profiling was performed on 8 CNS tumors (6 children, 1 adolescent, 1 young adult) with inconclusive diagnoses, available frozen tissue, and surgeries dating back over 5 years. Our goal was to correlate the resulting methylation classes with the clinical-radiological data and to evaluate the diagnostic and prognostic power of this analysis. The resulting molecularly defined diagnoses were: pilocytic astrocytoma (3 cases), pilocytic astrocytoma subclass FGFR1 altered (1 case), ganglioglioma (2 cases), diffuse leptomeningeal glioneuronal tumor subtype 1 (1 case), and diffuse midline glioma H3.3K27-altered, subtype H3K27 mutant or EZHIP-expressing (1 case). Clinico-pathological features of each tumor in our series are discussed. The clinical behavior was consistent with the molecular diagnosis in all cases but one that was lost to follow-up. In our series, the initial diagnostic failure in 3 of the 8 cases was due to the fact that the pathological entities—diffuse midline glioma, H3 K27-altered, pilocytic astrocytoma with FGFR1 alteration and diffuse leptomeningeal glioneuronal tumor —had not yet been fully characterized or widely recognized in the literature at the time of diagnosis. In the remaining cases, the lack of distinctive histopathological features hindered a definitive diagnosis. In conclusion, according to our experience, DNA methylation profile analysis represents a very attractive diagnostic tool and provides important support for the diagnosis and classification of CNS tumors.

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Authors

Anna Maria Buccoliero - MEYER CHILDREN'S HOPSOTAL IRCCS

Laura Giunti - Neuro-Oncology Unit, Meyer Children's Hospital IRCCS, Florence Italy https://orcid.org/0009-0009-8081-3039

Mirko Scagnet - Neuro-Surgery Unit, Meyer Children's Hospital IRCCS, Florence Italy

Milena Guidi - Neuro-Oncology Unit, Meyer Children's Hospital IRCCS, Florence Italy

Debora Vergani - Medical Genetics, Meyer Children's Hospital IRCCS, Florence Italy https://orcid.org/0000-0002-3339-2237

Rina Agushi - Neuro-Surgery Unit, Meyer Children's Hospital IRCCS, Florence Italy

Federico Mussa - Neuro-Surgery Unit, Meyer Children's Hospital IRCCS, Florence Italy

Barbara Spacca - Neuro-Surgery Unit, Meyer Children's Hospital IRCCS, Florence Italy https://orcid.org/0009-0009-2195-8035

Flavio Giordano - Functional and Epilepsy Surgery, Meyer Children's Hospital IRCCS, Florence Italy; Department NEUROFARBA, University of Florence, Italy https://orcid.org/0000-0002-9006-9225

Lorenzo Innocenti - Pathology Unit, Meyer Children's Hospital IRCCS, Florence Italy

Abramo Ponticelli - Pathology Unit, Meyer Children's Hospital IRCCS, Florence Italy

gianluca Mattei - Unit of Translational and Precision Medicine, Meyer Children's Hospital IRCCS, Florence Italy

Maura Calvani - Unit of Translational and Precision Medicine, Meyer Children's Hospital IRCCS, Florence Italy

Manila Antonelli - Dipartimento di Scienze Radiologiche e Anatomo Patologiche, Università Sapienza, Roma Italy; IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli Italy

Ludovico D'Incerti - Neuroradiology, Meyer Children's Hopsital IRCCS, Florence Italy https://orcid.org/0000-0002-4092-9290

Lorenzo Genitori - Neuro-Surgery Unit, Meyer Children's Hospital IRCCS, Florence Italy

Iacopo Sardi - Neuro-Oncology Unit, Meyer Children's Hospital IRCCS, Florence Italy

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Copyright

Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology

How to Cite
Buccoliero, A. M., Giunti, L., Scagnet, M., Guidi, M., Vergani, D., Agushi, R. ., Mussa, F., Spacca, B., Giordano, F. ., Innocenti, L., Ponticelli, A., Mattei, gianluca, Calvani, M., Antonelli, M., D’Incerti, L., Genitori, L., & Sardi, I. (2025). The contribution of methylation profiling in neuropathological diagnosis of central nervous system tumors in children, adolescent and young adults. Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology, 117(5). https://doi.org/10.32074/1591-951X-1226
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