143 Neuroepithelial tumour with PATZ1 fusion (NEPTP) - a novel molecularly defined CNS tumour type

Abstract Introduction Neuroepithelial tumour with PATZ1 fusion (NEPTP) is a novel entity not currently recognised as a distinct entity in the WHO-2021 CNS5 Classification of CNS Tumours. It is diagnostically challenging as is molecularly defined and shows histological heterogeneity. We present a retrospective case series of two young adults diagnosed with this fusion. Methods Two patients (aged 18 and 30 years) were identified. Histological evaluation, immunophenotyping, Illumina methylation array analysis, and copy number profiling were performed. Clinical presentation, radiological findings, treatment, and follow-up data were reviewed. Results Patient 1 presented with seizures. Histology was low grade, with features raising pleomorphic xanthoastrocytoma (PXA) as a working diagnosis. Methylation profiling classified the tumour as NEPTP (calibrated score 0.99 ≥0.9). Copy number analysis demonstrated losses of chromosome 17 and chromosome 22. The patient underwent gross total resection in 2023 and remains recurrence-free on MRI surveillance in 2024 and 2025. Patient 2 presented with headaches with a right temporal solid-cystic lesion. Histology was high-grade with mitotic activity and necrosis. The histological differentials were wide in view of mixed glioneuronal immunophenotype. Methylation profiling confirmed NEPTP (calibrated score 0.99 ≥0.9). Copy number alterations included losses of chromosomes 1p, 6, 10, and 11, and gains of 1q, 5, and 7. The patient received radical radiotherapy with concurrent temozolomide. Conclusion NEPTP represent heterogeneous tumours encompassing both low- and high-grade morphologies. Diagnosis is reliably achieved through methylation profiling. No formal WHO grade is provided currently but evidence suggests a behaviour consistent with an intermediate-grade neoplasm. Currently those with high grade features are treated with conventional glioma-directed therapy but further molecular characterisation of this fusion-defined subgroup may enable more refined risk stratification and therapeutic approaches in the future.