ID #1031 Neuroepithelial Tumors with PATZ1 Gene Fusions: Diagnostic Challenges, Molecular Reclassification, and Clinical Implications – Case Report and Literature Review
Malgorzata A Krawczyk, Amelia Kot, Ewa Bien, Mohamed AbdelbakiAbstract
Background
Neuroepithelial tumors (NEpT) harboring PATZ1 gene fusions represent a rare and biologically heterogeneous group of central nervous system neoplasms characterized by marked histopathological variability and incompletely defined clinical behavior. Historically, tumor classification relied predominantly on histopathological assessment. The introduction of next-generation sequencing (NGS) has significantly improved tumor stratification by identifying recurrent molecular alterations, enabling more precise diagnosis, prognostication, and potential therapeutic targeting. PATZ1 fusion tumors are most frequently supratentorial and are generally associated with favorable outcomes, although clinical experience remains limited due to their rarity.
Methods
We present a case of a pediatric patient with tumor reclassification following molecular diagnostics and provide a review of the current literature on NEpT with PATZ1 gene fusions, including clinical, histopathological, and molecular characteristics.
Results
A 16-year-old female was initially diagnosed with anaplastic ganglioglioma (WHO grade III) located in the right frontal lobe. Following surgical resection, she received multimodal oncological treatment consisting of chemotherapy according to a national protocol (lomustine and temozolomide) and adjuvant radiotherapy to the tumor bed (59.4 Gy in 33 fractions). Clinical evaluation revealed features consistent with neurofibromatosis type 1 based on established diagnostic criteria. Comprehensive molecular testing results became available after completion of oncological treatment and identified an EWSR1::PATZ1 gene fusion, leading to final reclassification as neuroepithelial tumor with PATZ1 fusion.
Conclusions
This case highlights the critical role of molecular diagnostics in the accurate classification of rare pediatric CNS tumors. Identification of PATZ1 gene fusions may significantly impact diagnostic interpretation, prognostic assessment, and future therapeutic decision-making. Increasing integration of molecular profiling into routine clinical practice is essential to improve diagnostic precision and optimize individualized patient management in rare neuroepithelial tumors.