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Pediatric midline H3K27M-mutant tumor with disseminated leptomeningeal disease and glioneuronal features: case report and literature review

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Abstract

Background

H3K27M-mutant midline lesions were recently reclassified by the World Health Organization (WHO) as “diffuse midline glioma” (DMG) based entirely on their molecular signature. DMG is one of the most common and most lethal pediatric brain tumors; terminal progression is typically caused by local midbrain or brainstem progression, or secondary leptomeningeal dissemination. H3K27M mutations have also been infrequently associated with a histologically and prognostically diverse set of lesions, particularly spinal masses with early leptomeningeal spread.

Case presentation

A 15-year-old girl after 1 week of symptoms was found to have a T2/FLAIR-hyperintense and contrast-enhancing thalamic mass accompanied by leptomeningeal enhancement along the entire neuraxis. Initial infectious workup was negative, and intracranial biopsy was inconclusive. Spinal arachnoid biopsy revealed an H3K27M-mutant lesion with glioneuronal features, classified thereafter as DMG. She received craniospinal irradiation with a boost to the thalamic lesion. Imaging 1-month post-radiation demonstrated significant treatment response with residual enhancement at the conus.

Conclusions

This case report describes the unique presentation of an H3K27M-mutant midline lesion with significant craniospinal leptomeningeal spread on admission and atypical glioneuronal histopathological markers. With such florid leptomeningeal disease, spinal dural biopsy should be considered earlier given its diagnostic yield in classifying the lesion as DMG. Consistent with similar prior reports, this lesion additionally demonstrated synaptophysin positivity—also potentially consistent with a diagnosis of diffuse leptomeningeal glioneuronal tumor (DLGNT). In atypical DMG cases, particularly with leptomeningeal spread, further consideration of clinical and histopathological context is necessary for accurate diagnosis and prognostication.

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Data availability

There are no associated datasets for this manuscript. Related queries can be directed to the corresponding author.

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Acknowledgments

We would like to acknowledge the contributions of Dr. Nora Kim, Dr. Karen Tang, Dr. Sharon Gardner, Dr. Stephanie Livingston, Dr. Benjamin Cooper, and Dr. Theodore Nicolaides from NYU Langone Health for their contributions to this manuscript.

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Author notes

  1. Ralph E. Navarro and Danielle Golub contributed equally to this work and should be considered co-primary authors.

Authors and Affiliations

  1. Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Grossman School of Medicine, NYU Langone Health, New York, NY, USA

    Ralph E. Navarro, Travis Hill, Michelle W. McQuinn, David Zagzag & Eveline Teresa Hidalgo

  2. Department of Neurosurgery, Zucker School of Medicine at Hofstra/Northwell, Northwell Health, 300 Community Drive, 9 Tower, Manhasset, NY, 11030, USA

    Danielle Golub

  3. Department of Pathology, NYU Grossman School of Medicine, NYU Langone Health, New York, NY, USA

    Christopher William & David Zagzag

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Contributions

Manuscript drafting (REN, DG, TH, MWM); Clinical data collection and interpretation (DG, TH, MWM, CW, DZ, ETH); Figure design (REN, DG, CW, DZ); Manuscript editing and revision (TH, CW, DZ, ETH); Literature review (REN, DG, TH, MWM, CW, DZ); Research team management and oversight (CW, DZ, ETH).

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Correspondence to Danielle Golub.

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Written informed consent regarding the submission and potential publication of this manuscript was obtained from the case study patient. Additionally, consent for treatment was likewise obtained in the usual fashion during the course of the patient’s hospitalization.

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Navarro, R.E., Golub, D., Hill, T. et al. Pediatric midline H3K27M-mutant tumor with disseminated leptomeningeal disease and glioneuronal features: case report and literature review. Childs Nerv Syst 37, 2347–2356 (2021). https://doi.org/10.1007/s00381-020-04892-0

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