Novel EWSR1 :: TEAD3 Fusion in an Adolescent With a Highly Aggressive Peritoneal Mesothelioma

Malignant peritoneal mesothelioma (MPM) is an exceptionally rare entity in children and adolescents, exhibiting distinct clinicopathological features compared to its adult counterpart. Unlike adult cases, it typically occurs without a history of asbestos exposure or BAP1 inactivation. Although several driver gene fusions have been documented, the primary oncogenic triggers and molecular pathways involved remain largely undefined. Herein, we present an 18‐year‐old male who presented with ascites and abdominal distension. Computed tomography imaging revealed diffuse thickening of the peritoneum, including the omentum and mesentery. Histopathological examination showed a neoplasm composed of a mixture of atypical epithelioid and spindled cells infiltrating the adipose tissue. Immunohistochemically, the tumor cells were positive for cytokeratin, calretinin, CK5/6, and D2‐40, and negative for CK20, MOC‐31, and Ber‐EP4, supporting the diagnosis of a biphasic mesothelioma. Molecular genetic studies identified a novel EWSR1::TEAD3 gene fusion. This is the first reported case of a peritoneal mesothelioma harboring this fusion.