Cardiac undifferentiated pleomorphic sarcomas (UPS) are exceptionally rare tumors, predominantly involving the left atrium [1]. They exhibit highly aggressive behavior, with survival typically ranging from 6 to 12 months [[2], [3], [4]]. Complete surgical resection is the primary treatment for cardiac sarcoma, with multimodality approaches including chemotherapy and radiation considered when complete surgical resection is not feasible due to its anatomy or patient’s medical condition [5,6]. However, the radiation-induced cardiotoxicity and pathological changes are under-recognized by clinicians and pathologists [7], and to our knowledge, there have been no reports of pathological features of radiation-induced changes of heart in patients with cardiac sarcoma.

Given the rarity of cardiac UPS, their pathogenesis remains poorly understood. Nonetheless, a growing body of evidence suggests a potential link between a subset of cardiac UPS and intimal sarcoma of the great vessels, characterized by shared morphological and genetic features, such as MDM2 amplification [[8], [9], [10]]. However, considering that MDM2 amplification can occur nonspecifically in a wide range of tumor types, there was concern that categorizing these cardiac UPS as intimal sarcoma could be premature [11]. Therefore, further evidence is needed to elucidate the relationship between cardiac UPS and intimal sarcoma.

Herein, we describe a patient with cardiac UPS treated with post-operative radiotherapy followed by heart transplantation. Our case report provides evidence of shared histological and molecular features between cardiac UPS and intimal sarcoma, along with a pathologic assessment of the response to post-operative radiation and the occurrence of radiation-induced cardiotoxicity.