ETMR-11.  PATZ1 -rearranged intracranial tumors in children: clinical, morphological, and molecular characteristics.

Introduction Intracranial tumors associated with PATZ1 gene rearrangements are extremely rare and poorly studied pathologies. These tumors are not currently included in the 2021 WHO Classification of CNS tumors. Objective To analyze and describe the clinical, morphological, and molecular characteristics of patients with PATZ1-rearranged intracranial tumors. Materials and Methods This study included eight pediatric patients with PATZ1-rearranged intracranial tumors. The initial morphological diagnoses included pleomorphic xanthoastrocytoma (4), ependymoma (2), papillary glioneuronal tumor (1), and high-grade glioma (1). Molecular genetic analyses were performed in all cases. Results The male-to-female ratio was 1:1 (4:4). The median age at the time of diagnosis was 8.1 years (range, 1–12.9). The initial symptoms included intracranial hypertension (4), seizures (3), and ataxia (1). The main radiological features were cystic-solid tumor structure (8) which located periventricular (7) and in the cerebellum (1). Gross total resection (GTR) was performed in four patients, while subtotal resection was performed in the other four cases. DNA methylation analysis was conducted for four patients, all of whom were classified as NET-PATZ1. RNA sequencing was performed for all eight patients, revealing a chimeric transcript of MN1::PATZ1 in five cases and EWSR1::PATZ1 in three cases. As first-line treatment, six patients received radiotherapy and one patient underwent chemotherapy. Among the patients who received GTR, two have been stable for 37 and 109 months, although four patients experienced disease progression, with two of them having multiple recurrences. At the time of follow-up, 7/8 patients are alive. The median follow-up is 3.6 years (1.6–9). Conclusion Intracranial tumors with PATZ1-rearrangements exhibit morphological and clinical variability, complicating their diagnosis and necessitating molecular diagnostic studies. In some cases, with GTR, observation may be sufficient.