Primary cardiac angiosarcoma: From pathogenesis to therapeutic strategies.

Abstract

Primary cardiac angiosarcoma (PCAS) is a rare yet highly aggressive malignancy arising from cardiac vascular endothelial cells. This tumor predominantly affects young to middle-aged males and carries a dismal prognosis, typically characterized by a median survival of less than one year. Owing to its nonspecific manifestations and rapid infiltrative growth, most patients present at an advanced or metastatic stage. Recent genomic and transcriptomic studies have revealed molecular drivers in PCAS, including recurrent mutations in POT1, KDR/VEGFR2, and PLCG1, loss of CDKN2A, and aberrant angiogenic cascade activation. In parallel, an immunosuppressive tumor microenvironment dominated by exhausted T cells and tumor-associated macrophages may collectively contribute to tumor progression and therapeutic resistance. Multimodal imaging, integrating echocardiography, cardiac magnetic resonance, computed tomography, and PET/CT, plays a central role in detection, tissue characterization, and systemic staging. Histopathology with immunohistochemistry remains the diagnostic gold standard. Current treatment strategies rely on multimodal approaches, including surgery, chemotherapy, and radiotherapy, with emerging targeted therapies and immunotherapies under active investigation. Despite recent advances, clinical outcomes remain poor, highlighting the urgent need for improved mechanistic understanding and more effective personalized therapeutic strategies.