Paediatric diffuse leptomeningeal tumor with glial and neuronal differentiation harbouring chromosome 1p/19q co-deletion and H3.3 K27M mutation: unusual molecular profile and its therapeutic implications

Diffuse leptomeningeal glioneuronal tumor (DL-GNT) is a newly introduced tumor entity of uncertain prognosis characterised by a primary diffuse leptomeningeal growth pattern, oligodendroglial-like morphology and dual glial/neuronal differentiation. Predominantly occurring in children, these tumors present as chronic meningitis and mimic infectious/inflammatory diseases. They are surgically challenging tumors with a high incidence of delayed morbidity and mortality despite low-grade histology. Their molecular genetic profile is not fully elucidated and few reports have identified chromosome 1p and 19q deletions, and BRAF alterations. We present a rare instance of a DL-GNT in a 13-year-old female who presented with slowly progressive and sequential neurological deficits over a 12-month duration. Imaging showed leptomeningeal thickening and spinal lesions. Biopsy from the spinal mass showed histomorphological features characteristic of DL-GNT. Further molecular analysis revealed 1p and 19q co-deletion and H3K27M mutation, while no mutation were identified in IDH, TERT, or BRAF genes. Patient died 4 months after diagnosis. Only one previous case of DL-GNT has been reported to harbour H3K27M mutation. Although H3K27M mutations have been described in rare examples of low-grade glial and glioneuronal tumors, whether DL-GNTs with H3K27M represent a rare growth pattern of the aggressive H3K27M-mutant diffuse midline gliomas needs further clarification.