Cardiac angiosarcoma (CA), a rare and highly aggressive malignancy originating from endothelial cells, presents significant diagnostic challenges owing to its non-specific clinical manifestations and variable imaging features. Given its biological behavior and poor prognosis, early and accurate CA diagnosis is critical for optimizing therapeutic strategies and improving patient outcomes. Multimodal imaging tools, such as transthoracic echocardiography (TTE), contrast-enhanced ultrasound (CEUS), computed tomography angiography (CTA), and positron emission tomography (PET), are indispensable for the detection, characterization, and staging of CA. While CA typically exhibits hyperenhancement and hypermetabolism on imaging, this report presents two cases of CA with contrasting enhancement and metabolic patterns, highlighting the diversity of enhancement and metabolic pattern combinations in this malignancy. By presenting these cases, we aim to underscore the importance of considering a wide range of imaging and metabolic findings in the diagnosis and management of CA.

Angiosarcoma is a rare and aggressive soft tissue tumor originating from endothelial cells of blood or lymphatic vessels. It is commonly detected in the extremities, particularly the lower limbs, followed by the trunk, head, and neck. CA is exceptionally rare, accounting for 25%–30% of all primary malignant cardiac tumors, with the RA being the most frequent site of origin (3). The incidence of CA is higher in males (63.1%) than females, with a median age at onset of 50.5 years (4). CA often presents with nonspecific clinical symptoms such as dyspnea, chest pain, fever, and pericardial effusion, which may result from its aggressive nature. Up to 80% of cases initially present with pericardial infiltration, potentially leading to misdiagnosis as constrictive pericarditis (5). Pericardial effusion drainage and cytological biopsy have limited diagnostic success rates for CA (6) and the gold standard for diagnosis remains immunohistochemical analysis of tissue specimens, with markers of positivity including CD31, CD34, ERG, FLI-1, and von Willebrand factor. Among these factors, FLI-1 and ERG demonstrate superior specificity and sensitivity (7, 8).

On two-dimensional echocardiography, CA typically appears as a nodular or lobulated hypoechoic mass. RA-originating CA often presents with a broad-based attachment, accompanied by pericardial effusion or thickening (9). In Case 1, CA invasion into the pericardium caused diffuse thickening and adhesion, leading to restricted movement of the ventricular free wall. In Case 2, the RA mass invaded the superior vena cava, resulting in increased blood flow velocity at the vena cava entrance. Although the diagnostic value of echocardiography for CA is limited, its specificity for detecting intracardiac tumors is as high as 95%, making it the preferred screening method for cardiac tumors (10).

Contrast-enhanced ultrasound provides critical insights into the perfusion characteristics of tumors and serves as a valuable tool for differentiating benign from malignant lesions (11). In Case 1, the complete perfusion defect initially led to misdiagnosis as an atrial thrombus. Notably, 3.6% of malignant tumors exhibit reduced perfusion due to ischemic necrosis (12), and, in Case 1, the perfusion defect was attributed to extensive intratumoral hemorrhaging and necrosis, a hallmark of poorly differentiated CA (8). In contrast, Case 2 demonstrated moderate heterogeneous enhancement on CEUS, consistent with the histopathological findings of abundant irregular vascular lacunae and minimal necrosis. The striking disparity in CEUS enhancement patterns between the two cases (complete perfusion defect vs. moderate heterogeneous enhancement) underscores the significant impact of tumor vascular architecture on perfusion characteristics.

On contrast-enhanced CT, CA typically presents as a homogeneous or heterogeneously dense mass with broad-based attachment and infiltrative margins (13). Characteristic filling defects are observed when the tumor involves the tricuspid annulus or cavoatrial junctions (14). Here, Case 1 exhibited a non-enhancing hypodense lesion initially mistaken for a thrombus, while Case 2 demonstrated heterogeneous enhancement, aligning with classical CA features. These contrasting enhancement patterns—non-enhancing versus heterogeneously hyperenhancing—reflect the stark differences in tumor necrosis and vascular supply between these cases. Furthermore, as previously mentioned, the enhancement patterns on CEUS and CT were consistent in both cases, highlighting their complementary roles in characterizing CA vascularity.

Fluorodeoxyglucose (¹⁸F-FDG) PET/CT is a crucial imaging modality for assessing tumor metabolic activity (15). Yamakuni et al. established a diagnostic threshold of SUV _max ≥3.5, demonstrating 100% sensitivity and 80% specificity for CA diagnosis (16). In Case 1, focal arcuate-shaped uptake (SUV _max 7.29) was observed in the RA lateral wall, suggestive of localized hypermetabolic activity. Wan et al. detected potential associations between atrial wall hypermetabolism and atrial fibrillation (1, 2). Given the presence of atrial fibrillation, elevated D-dimer levels, and the absence of significant metabolic activity in the RA mass, the initial diagnosis favored thrombus. However, postoperative pathological analysis revealed that the tumor primarily consisted of hemorrhagic and necrotic tissue, with atrial wall thickening and increased metabolism attributable to tumor infiltration. In contrast, Case 2 demonstrated intense heterogeneous uptake (SUV _max 11) within the pericardium-invading mass, consistent with typical CA findings. The marked metabolic heterogeneity between the two cases paralleled the disparities observed on CEUS and contrast-enhanced CT. Notably, Case 1 exhibited low Ki-67 levels, which correlate with the cell division cycle and differentiation status, indicative of poor differentiation (8, 17) and potentially explaining the hypometabolic phenotype.

Owing to the marked heterogeneity in CA differentiation (18), multimodal imaging analysis combining contrast-enhanced and PET metabolic patterns reveals diverse phenotypic combinations, including hyperenhancement with hypermetabolism, hypoenhancement with hypermetabolism, heterogeneous enhancement with hypermetabolism, and heterogeneous enhancement with heterogeneous metabolism. We present the first report of two CA cases exhibiting contrasting enhancement-metabolism patterns, including a rare hypoenhanced-hypometabolic phenotype (Case 1) that has not been previously documented in the literature. This striking dichotomy not only expands the imaging spectrum of CA but also highlights the considerable diversity of enhancement-metabolism pattern combinations.

CA is a rare yet highly aggressive malignancy that poses significant diagnostic challenges owing to its atypical clinical presentation. The two cases reported here demonstrated strikingly contrasting enhancement-metabolism patterns (hypoenhanced-hypometabolic vs. hyperenhanced-hypermetabolic), reflecting not only the diversity of imaging phenotypes and metabolic patterns but also providing critical insights into the underlying biological heterogeneity of CA.