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Pathology
Unusual low-grade neuroepithelial tumour in a child
  1. Leia Salongo1,
  2. Ali Nael2,3,
  3. Pournima Navalkele4 and
  4. John Ross Crawford4,5
  1. 1University of California Irvine, Irvine, California, USA
  2. 2Department of Pathology, Children's Hospital of Orange County, Orange, California, USA
  3. 3Pathology, University of California Irvine Medical Center, Orange, California, USA
  4. 4Pediatrics, Children's Hospital of Orange County, Orange, California, USA
  5. 5Pediatrics, University of California Irvine, Irvine, California, USA
  1. Correspondence to Dr John Ross Crawford; john.crawford{at}choc.org

https://doi.org/10.1136/bcr-2024-262692

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    A previously healthy patient in early childhood presented with 6 weeks of intermittent headaches and vomiting. Neurological examination revealed left homonymous hemianopsia on confrontation testing, otherwise normal cranial nerves, strength, reflexes, coordination and gait. MRI of the brain demonstrated a cystic right parieto-occipital cystic mass with a fluid level, no evidence of reduced diffusivity or susceptibility-weighted artefact and peripheral rim enhancement on postgadolinium sequences (figure 1A–F). The neuroradiographical differential included a pilocytic astrocytoma, ependymoma or atypical glioneuronal tumour. Following gross total resection, neuropathology demonstrated a cellular tumour with spindle-to-round nuclei and globose cytoplasm within a loose myxoid background and immunohistochemical reactivity for glial fibrillar acidic protein and Olig2 with a Ki67 proliferation index of 3–5% (figure 2A–D). Additional immunohistochemistry staining was negative for BRAF V600E and IDH1 R132H staining and retained ATRX expression in tumour cells consistent with a histological diagnosis of low-grade astrocytoma. Chromosomal microarray demonstrated several complex gains on chromosome 7 (7p12.3, 7p22.3, 7q31.1, 7q31.2, 7q36.1 and 7q36.2). The next-generation sequencing performed on the tumour was negative for BRAF mutations/rearrangements and FGFR mutations, and revealed two somatic variants of unknown significance in ATRX (c2764G>A) and LRP1B (c.6179G>A.). Germline testing was not performed. Methylation tumour analysis was consistent with a diagnosis of glioma, subtype dysembryoplastic neuroepithelial tumour (DNET) with a high confidence score (0.947). More than 4 years after surgery, the patient has stable left homonymous hemianopsia without evidence of disease recurrence.

    Figure 1
    Figure 1

    Neuroimaging features of low-grade neuroepithelial tumour. MRI reveals a right parietal occipital mass without reduced diffusivity on (A) diffusion-weighted or (B) apparent diffusion coefficient sequences and (C) a rim of susceptibility-weighted artefact. The mass was cystic with a fluid level on (D) T2-weighted sequences and (E) a rim of enhancement on T1 postgadolinium axial and (F) sagittal sequences.

    Figure 2
    Figure 2

    Pathology features of low-grade neuroepithelial tumour. H&E-stained sections demonstrate (A) a cellular tumour with spindle-to-round globose cytoplasm within a loose myxoid background. The tumour was positive for (B) glial fibrillar acidic protein and (C) Olig2 by immunohistochemistry. (D) The Ki67 proliferation index was between 3% and 5%. These findings were consistent with a histological diagnosis of low-grade glioma.

    DNETs are a subtype of low-grade glioma (LGG), comprising 1% of all neuroepithelial tumours seen in patients under the age of 20.1 DNETs are classified as long-term epilepsy-associated tumours, located predominantly in cortical-based regions.2 3 MRI features include hypointensity in T1-weighted and hyperintensity in T2-weighted sequences2–5 and may have other atypical features making neuroradiographical diagnosis challenging.6 Histologically, DNETs take on many forms, including simple, complex, diffuse or nonspecific, and have similar features to many other tumour types, including ganglioglioma.2 3 Complete resection of the tumour when feasible is the preferential treatment for DNETs and has been shown to be effective in minimising seizures.5

    DNA methylation has become increasingly important in the WHO classification of paediatric CNS tumours,7 including LGG and glioneuronal tumours.8 Methylation profiling is useful for distinguishing tumour types and subtypes and has the potential to predict response to therapeutic agents and survival.9 In the case of DNET, methylation has been used for classification in cases of malignant transformation.10 Our case is unusual in that the genetical alterations were atypical of LGG and DNET compared with what has been previously reported,11 and there was a discrepancy between the histological, molecular and methylation analysis in achieving an integrated diagnosis. The role of the reported variants in ATRX and LRP1B on tumorigenesis, if any, remains to be determined.

    In summary, we report a case of an unusual low-grade neuroepithelial tumour with unique neuroimaging features and novel molecular findings, classified by methylation analysis with high confidence, highlighting the role of methylation in LGG diagnosis and the diversity of low-grade neuroepithelial tumours.

    Learning points

    • Low-grade neuroepithelial tumours are a distinct subset of paediatric central nervous system tumours with varied molecular and neuroradiographical features.

    • DNA methylation analysis is an increasingly important tool for enhancing paediatric CNS tumour classification.

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    Patient consent for publication

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    Footnotes

    • Contributors The following authors were responsible for drafting of the text, sourcing and editing of clinical images, investigation results, drawing original diagrams and algorithms, and critical revision for important intellectual content: LS, PN, AN, JRC. The following authors gave final approval of the manuscript: LS, PN, AN, JRC. JRC is the guarantor of the manuscript.

    • 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.