Spinal ependymoma, MYCN-amplified with multiple extra-CNS metastases

Abstract Spinal ependymoma, MYCN -amplified was first recognized in the 5th edition of the WHO Classification of Tumors as a clinically aggressive entity with high-grade histologic features, frequent recurrence, and cerebrospinal fluid dissemination. Extra-central nervous system (CNS) metastasis is exceptionally rare in ependymoma, emerging years after resection of the intracranial or spinal primary, and has not yet been described in spinal ependymoma, MYCN -amplified. Herein, we describe a 68-year-old man who presented with urinary retention and paraplegia. MRI revealed a T2-3 intradural extramedullary solid and cystic enhancing mass with intramedullary extension and confluent subarachnoid drop metastases at lower spinal levels. He underwent subtotal resection followed by a negative cerebrospinal fluid (CSF) cytology at postoperative week three. The histopathological diagnosis was spinal ependymoma, CNS WHO grade 3. Next-generation sequencing (NGS) identified MYCN amplification. The patient received adjuvant craniospinal irradiation. At one year, leptomeningeal disease was stable, but the follow-up imaging identified a right paraspinal soft tissue mass. At three years, he presented with a fall and was found to have a nondisplaced pathologic right femoral neck fracture through a lytic lesion. Staging imaging revealed multiple pulmonary and hilar masses, perihilar masses, and mediastinal and hilar lymphadenopathy, without intracranial disease. Fine-needle aspiration (FNA) and endobronchial biopsy of hilar lymph nodes were performed, along with resection of the proximal femoral mass. Histopathologic examination and fluorescence in situ hybridization of the thoracic lymph node and femoral biopsies showed metastatic grade 3 MYCN -amplified ependymoma morphologically consistent with the primary tumor, which was confirmed with methylation and copy number profiling. He underwent long-stem hip hemiarthroplasty with prophylactic femoral fixation, followed by radiation therapy to the femur and systemic temozolomide and lapatinib. This case expands the spectrum of clinical behavior and molecular pathological understanding of this recently defined entity.