Language

English

Publication Date

8-18-2025

Journal

Acta Neuropathologica Communications

DOI

10.1186/s40478-025-02097-7

PMID

40826136

PMCID

PMC12363008

PubMedCentral® Posted Date

8-18-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Introduction: Modern molecular diagnostic techniques such as DNA methylation profiling are leading to the reclassification of several central nervous system malignancies and discovery of novel diagnostic entities, such as high-grade glioma with pleomorphic and pseudopapillary features (HPAP).

Methods: We performed a retrospective chart review of all patients with HPAP confirmed with methylation profiling at a single institution between 2023 and 2025. Demographic, radiographic, surgical, and outcome data were collected.

Results: Three patients were identified: two females and one male with a mean age of 49.7 years (range 25-62). No patients had a prior cancer history. One patient had an incidentally discovered tumor, while the other two patients underwent imaging for symptoms of headache, vision changes and extremity weakness. Mean tumor size was 4.0 cm (range 2.8-6) with a wide variation in imaging characteristics. All patients underwent surgical resection and radiographic gross total resection was achieved in all cases. All patients underwent radiation therapy without concurrent chemotherapy. After a median 20 months follow up (range 4.5 to 108.9), two patients experienced tumor progression at 2.7 months and 86.5 months respectively. All patients were alive at last follow up.

Conclusion: HPAP is a novel clinical entity demonstrating variable molecular signatures sharing a common DNA methylation profile which demonstrates a relatively favorable clinical course when compared with other high grade gliomas. Further study is needed to determine the optimal treatment and factors that influence survival.

Keywords

Humans, Male, Female, Middle Aged, Adult, Glioma, Brain Neoplasms, Retrospective Studies, DNA Methylation, Neoplasm Grading

Published Open-Access

yes

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