Rhabdomyosarcoma With Alveolar Morphology and a Novel NCOA1::ZNF143 Fusion in a 4-Year-Old Girl: A Case Report

Abstract

Rhabdomyosarcoma with alveolar morphology is a diagnostically challenging tumor pattern, particularly in cases lacking canonical FOXO1-associated fusions. In the current WHO framework, molecular fusion status plays a central role in classification and risk stratification. However, a subset of tumors lacks canonical rearrangements and harbors alternative genetic events. We report a case of a 4-year-old girl with a massive parameningeal rhabdomyosarcoma presenting with cranial nerve dysfunction and airway compromise. Histological examination confirmed rhabdomyosarcoma with alveolar morphology. Fluorescence in situ hybridization revealed no rearrangements of FOXO1 or PAX3. Targeted RNA sequencing identified a novel NCOA1::ZNF143 fusion transcript. Despite intensive multimodal treatment including chemotherapy, radiotherapy, surgery, and metronomic therapy, the disease demonstrated multiple relapses with subsequent metastatic progression involving the spinal cord and central nervous system, ultimately leading to a fatal outcome.