Clinical Research Coordinator Children's Hospital of Los Angeles Los Angeles, California, United States
Introduction: High-grade neuroepithelial tumors with MN1 alteration (HGNET,MN1) are defined by a shared DNA methylation profile and recurrent gene rearrangements involving MN1. The 2021 5th edition of the WHO Classification of CNS Tumors introduced a new category “astroblastoma, MN1-altered” since many of these tumors share astroblastoma-like histology, but several studies have shown divergent histologies in this methylation class. Outcome data for MN1 altered CNS tumors is limited. This study examined clinical features and treatment outcomes of our patients with MN1-altered CNS tumors
Methods: Cases with methylation profiles of HGNET,MN1 were identified from an institutional neuropathology archive. Clinical, radiographic, and outcome data were extracted from the medical record.
Results: Three female subjects, aged 6-16 years at diagnosis, were identified. All tumors were supratentorial and showed variable histologic patterns including papillary neoplasm NOS (case 1), astroblastoma (case 2), and ependymoma (case 3). RNA sequencing of cases 1-2 showed MN1::BEND2 fusion, RNA analysis of case 3 was not available. Case 1 underwent gross total resection (GTR) followed by craniospinal irradiation and chemotherapy and remains disease free; case 2 underwent resection only initially, and has had multiple recurrences treated variably with resection, tumor bed irradiation/reirradiation, and chemotherapy; case 3 suffered recurrence after resection only, and then underwent GTR and tumor bed irradiation without subsequent recurrence. All patients remain alive at 3.7 to 16.6 years after diagnosis.
Conclusion : This limited case series suggests that MN1-altered tumors follow a variable clinic course, may benefit from multimodal therapy that includes maximal resection and radiation, and may have prolonged survival despite recurrence. Multi-institutional prospective evaluation is essential for better prognostication and development of appropriate therapies for this rare disease.
