Primary Pericardial Angiosarcoma Demonstrating Initial Response Followed by Progression on First‐Line Chemotherapy: A Case Report

ABSTRACT Primary pericardial angiosarcoma is an exceedingly rare and highly aggressive malignancy arising from pericardial endothelial cells, with a reported median survival of approximately 7 months. Owing to its non‐specific clinical presentation, diagnosis is frequently delayed, particularly in tuberculosis‐endemic regions, where symptoms may be attributed to tuberculous pericarditis. We report the case of a 25‐year‐old Nepalese male who presented with a six‐month history of progressively worsening dyspnea (MMRC grade 1 to 4) and an ECOG performance status of 3. Initial evaluation revealed a large pericardial effusion and a right atrial mass measuring 4.5 × 3.7 × 3.2 cm on MDCT. Based on trace Mycobacterium tuberculosis detection on sputum GeneXpert with indeterminate rifampicin resistance, the patient was initially diagnosed and treated as tuberculous pericarditis. However, symptoms persisted despite 2 weeks of antitubercular therapy. Subsequent pericardiocentesis yielded hemorrhagic fluid; repeat sputum and pericardial fluid testing were negative for tuberculosis, and pericardial fluid cytology was inconclusive for malignancy. Due to persistent diagnostic uncertainty, the patient underwent median sternotomy with creation of a bilateral pleuropericardial window. Histopathological examination revealed high‐grade angiosarcoma, with immunohistochemistry positive for CD31, CD34, and ERG, and a Ki‐67 proliferation index of 30%. Baseline systemic staging showed no definite evidence of distant metastasis. The patient received first‐line chemotherapy with ifosfamide and epirubicin. After 3 cycles, remarkable clinical improvement was observed, including improvement in ECOG performance status from 3 to 1, complete resolution of the pericardial effusion, and a 65% reduction in tumor volume. However, following completion of 6 cycles, MDCT demonstrated disease progression with new left para‐aortic deposits measuring 5.6 × 2.6 cm. Second‐line chemotherapy with nab‐paclitaxel and gemcitabine was subsequently initiated, with planned response assessment after 3 cycles. This case highlights the significant diagnostic challenges of pericardial angiosarcoma in tuberculosis‐endemic regions and underscores the need to consider malignant etiologies in patients with hemorrhagic pericardial effusion and cardiac masses. Although substantial initial responses to chemotherapy may occur, the disease remains highly aggressive with a high risk of progression. Early histopathological diagnosis and timely initiation of adaptive, multimodal treatment strategies are critical to optimizing clinical outcomes.