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Unusual paediatric-type diffuse low-grade glioma in a toddler
  1. Nikhil Kumar1,
  2. Denise Malicki2,
  3. Michael Levy3 and
  4. John Ross Crawford1,4
  1. 1Pediatrics, University of California Irvine, Irvine, California, USA
  2. 2Pathology, Rady Children's Hospital University of California San Diego, San Diego, California, USA
  3. 3Neurosurgery, University of California San Diego, San Diego, California, USA
  4. 4Pediatrics, Children's Hospital Orange County, Orange, California, USA
  1. Correspondence to Dr John Ross Crawford; john.crawford{at}

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A previously healthy toddler presented to an outside hospital following a fall from the bed. The patient was slightly irritable at presentation without focal neurological signs on examination. Initial head CT scan demonstrated an area of hypoattenuation in the left basal ganglia (figure 1A) initially concerning for infarction, inflammation/demyelination or tumour (figure 1A). MRI demonstrated a non-specific T2-hyperintense lesion involving the left putamen, globus palidus, thalamus, and internal, external and extreme capsules without reduced diffusivity on apparent diffusion coefficient sequences and without evidence of contrast enhancement (figure 1B–D). Magnetic resonance spectroscopy of the lesion revealed elevated choline-to-creatine ratios without evidence of a lactate peak (figure 1E) that could be consistent but non-diagnostic of neoplasm. MRI of the spine was normal (not shown). The patient was treated with intravenous immunoglobulin at the outside hospital for presumptive diagnosis of a demyelinating disorder based on neuroimaging features. Inflammatory markers and cerebrospinal fluid (CSF) infectious/inflammatory studies were normal, and the patient was subsequently discharged.

Figure 1

Neuroimaging features of unusual paediatric-type diffuse low-grade glioma. (A) CT at presentation demonstrates an area of hypodensity involving the left basal ganglia. MRI shows diffuse infiltrative T2-hyperintense lesion of the left putamen and globus pallidus, with involvement of the internal, external and extreme capsules (B) without evidence of restricted diffusion on apparent diffusion coefficient weighted sequences (C) and without contrast enhancement (D). Magnetic resonance spectroscopy of the lesion (E) demonstrates elevated choline (CHO)-to-creatine (CR) ratio with normal N-acetylaspartic acid (NAA).

At 1 month post-discharge, the patient presented to our facility where follow-up MRI remained unchanged. Serum and CSF germ cell markers were performed to assess for an unusual germ cell tumour that were negative along with negative CSF cytology. Due to lack of radiographic improvement, the patient underwent a robotic-guided biopsy following obtaining informed consent, which demonstrated primarily white matter with marked oedema, within which was a paucicellular proliferation of infiltrating glial cells with mild nuclear pleomorphism and a myxoid background, specifically without vascular proliferation and necrosis (figure 2). Immunohistochemistry was positive for GFAP, synaptophysin (in enlarged axons and scattered neuron) and CD68 (in few scattered cells), and showed elevated Ki-67 (5% positivity) and negative for H3K27M consistent with a histological diagnosis of paediatric-type diffuse low-grade glioma. Next-generation sequencing and microarray testing of the tumour were normal as was a germline cancer gene panel. Methylation analysis clustered with low confidence (0.266) with the MYB subgroup and was non-diagnostic. Based on the negative genetic testing and non-diagnostic methylation analysis, the tumour was best classified as a paediatric diffuse type of low-grade glioma not elsewhere classified.1

Figure 2

Histological features of unusual paediatric-type diffuse low-grade glioma. H&E-stained sections obtained via stereotactic biopsy show an infiltrating glial neoplasm of low cellularity with elongated hyperchromatic nuclei and inconspicuous mitotic activity surrounding the larger neurons at 200× (A) and 400× (B) magnification.

Three years after initial diagnosis, the MRI remains unchanged in the absence of therapy, and the patient has normal development and a normal neurological examination.

Low-grade gliomas and glioneuronal tumours are neuroepithelial tumours that make up >30% of paediatric central nervous system cancers.2–4 Low-grade gliomas are classified based on genetic makeup, specifically FGFR1, MYB/MYBL1, BRAF, NF1 or IDH1/2 comprise the more common molecular alterations of paediatric low-grade glioma.5 6 Our patient’s tumour is unusual in that it does not fit any specific WHO categories of paediatric-type diffuse low-grade gliomas, which may be potentially due to variable tumour content. We present an unusual case of paediatric diffuse-type low-grade glioma with distinct neuroradiographic features found incidentally in a toddler with non-diagnostic genetic testing and non-classifiable by methylation, adding to the genetic diversity of paediatric-type diffuse low-grade glioma.

Learning points

  • WHO guidelines identify four types of paediatric-type diffuse low-grade gliomas: diffuse astrocytoma, MYB or MYBL1 altered; angiocentric glioma; polymorphous low-grade neuroepithelial tumour of the young and diffuse low-grade glioma, MAPK pathway altered.

  • We present a case of a rare paediatric-type diffuse-type low-grade glioma with unusual neuroimaging features that was unclassifiable by genetic testing and methylation adding to the diversity of paediatric low-grade glioma.

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  • Contributors NK was responsible for the design and writing of the case report. DM was responsible for the design and writing of the case report. ML was responsible for the design and writing of the case report. JRC was responsible for the design and writing of the case report.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.