Primary malignant cardiac tumor of the left atrium masqueraded as multiple myxomas

Introduction

Cardiac tumors can be classified as benign, malignant, and tumors of uncertain behavior. Based on large autopsy series, primary cardiac tumors are rare, with an incidence rate of less than 0.03% (1-4). Among them, primary malignant cardiac tumors of mesenchymal origin are particularly uncommon, accounting for a very small subset of all cardiac neoplasms. The most frequent malignant subtypes include angiosarcoma, leiomyosarcoma and undifferentiated pleomorphic sarcoma, typically arising from the right atrium, while less commonly located in the left atrium (1).

Differentiating malignant cardiac tumors from benign myxomas on echocardiography remains challenging. Tumors arising from different cardiac chambers or walls may present distinct clinical implications depending on their location and pattern of invasion. In addition, the clinical manifestations are highly variable, ranging from incidental findings in asymptomatic individuals to manifestations including exertional dyspnea, arrhythmias, embolic events, or constitutional symptoms. Due to the atypical and various clinical manifestations, as well as the limited awareness among clinicians, delayed diagnosis may occur (1,4).

This report presents a distinctive primary malignant tumor of mesenchymal origin located in the left atrium, extending toward the mitral valve orifice, and affecting the blood flow through the pulmonary vein.

Case presentation

A 59-year-old male patient was referred to our hospital after a transthoracic echocardiogram performed at a local hospital, which revealed multiple abnormal masses in the left atrium, initially suspected to be atrial myxomas.

The patient presented with recurrent episodes of dizziness and chest tightness, accompanied by diplopia and vertigo, but denied orthopnea or paroxysmal nocturnal dyspnea. Physical examination revealed a diastolic rumbling murmur at the cardiac apex. He had no notable past medical history. All procedures performed in this case were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case description and accompanying images and videos. A copy of the written consent is available for review by the editorial office of this journal.

Differential diagnosis

The differential diagnosis encompassed multiple cardiac myxomas, secondary cardiac tumors, and thrombus, highlighting the complexity of cardiac mass identification.

Investigations

Laboratory tests revealed an elevated high-sensitivity C-reactive protein (CRP) level of 30.66 mg/L (normal range, <10 mg/L) and a lipoprotein a level of 344 mg/L (normal range, <300 mg/L). The patient’s electrocardiogram was unremarkable. Transthoracic echocardiography revealed a left ventricle (LV) with normal morphology and chamber dimensions, preserved segmental wall motion, and normal systolic function, with an ejection fraction of 66%. However, the left atrium was enlarged, and an irregular mass with a broad-based attachment was identified along the atrial roof and lateral wall (Figure 1A, Videos 1,2). The mass exhibited multiple thick, elongated extensions projecting into the left atrial cavity—resembling tentacle-like or seaweed-like strands—measuring approximately 40 mm, 30 mm, and 19 mm in length, respectively. These intracavitary, mobile-appearing, lobulated components contributed to the preliminary impression of multiple myxomas at the referring hospital. Although part of the mass protruded toward the mitral valve orifice, the transvalvular flow velocity remained within normal limits (Vmax =1.3 m/s, mean pressure gradient =2.2 mmHg) (Figure 1B). Simultaneously, the base of the lesion appeared contiguous with the pulmonary veins. A faint linear hypoechoic shadow was noted within the right superior pulmonary vein, and accelerated flow was observed at the left atrial inlets of the left inferior, right superior, and right inferior pulmonary veins (Figure 1C). Pulmonary vein Doppler demonstrated an S-wave velocity of 1.2–1.4 m/s (1.2 m/s shown in the figure) and a D-wave velocity of approximately 1.0 m/s (Figure 1D, Videos 3,4). Contrast-enhanced echocardiography was not performed because cardiac magnetic resonance (CMR) and positron emission tomography-computed tomography (PET-CT) were promptly obtained for comprehensive tissue characterization and staging.

Figure 1 Transthoracic echocardiographic findings of the patient. (A) Transthoracic echocardiography reveals multiple thick, elongated protrusions (arrow) extending into the left atrial cavity. (B) Pulsed-wave Doppler measurement of blood flow across the mitral valve orifice. (C) Color Doppler flow imaging shows accelerated blood flow through the pulmonary veins. (D) Pulsed-wave Doppler measurement of blood flow through the pulmonary veins. LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

Coronary CT demonstrated focal thickening of the left atrial wall with a nodular outward bulge. Contrast-enhanced images showed tubular and patchy enhancement within the lesion, raising suspicion for a possible neoplastic process. CMR imaging demonstrated diffuse heterogeneous thickening of the left atrial wall with focal nodular protrusion into the atrial cavity (Figure 2A, Video 5). The intracavitary component showed marked mobility synchronized with the cardiac cycle. The lesion appeared hyperintense on T2-weighted imaging, isointense on T1-weighted imaging, and iso- to mildly hyperintense on diffusion-weighted imaging, with corresponding iso- to mildly hypointense signal on the apparent diffusion coefficient (ADC) map. Contrast-enhanced sequences revealed heterogeneous enhancement with focal surface hypoenhancement. The lesion involved the orifices of all pulmonary veins, with focal areas of surface hypoenhancement possibly representing overlying thrombosis (Figure 2B, Video 6). These findings suggested a malignant neoplastic process, most consistent with cardiac angiosarcoma. Cardiac chambers, myocardial signal, wall motion, and valvular function were otherwise unremarkable.

Figure 2 Cardiac magnetic resonance findings of the patient. (A) Diffuse heterogeneous thickening of the left atrial wall was observed, with focal nodular protrusions extending into the atrial cavity (arrow). (B) The mass exhibited infiltrative growth around the inferior pulmonary vein, accompanied by partial thrombosis (arrow). LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

PET-CT revealed multiple nodular foci of increased fluorodeoxyglucose (FDG) uptake along the left atrial wall (Figure 3). The largest lesion measured approximately 2.8 cm × 1.5 cm, showing markedly elevated metabolism with a maximum standardized uptake value (SUVmax) of 11.1. Some hypermetabolic extensions were noted along the left pulmonary vein trunk and the right inferior pulmonary vein. These findings were highly suggestive of a malignant neoplastic process. Multiple small lymph nodes were seen in the mediastinum and bilateral hila without increased FDG uptake, consistent with reactive hyperplasia. No other abnormal hypermetabolic foci were detected elsewhere.

Figure 3 Positron emission tomography-computed tomography indicated the mass (arrows) had tumorous characteristics, with a high probability of malignancy. LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

Under combined transthoracic echocardiographic and cardiac angiographic guidance, a transvenous biopsy was performed via the femoral venous approach. A steerable sheath was advanced across the interatrial septum into the left atrium, where it was positioned against the intracavitary mass. Tissue samples were obtained using a biopsy needle. The procedure was uneventful, and the patient remained hemodynamically stable, being discharged on postoperative day 4 without complications.

Management

Histopathological examination of the left atrial mass revealed a small amount of tumor tissue, partially forming slit-like spaces. The neoplastic cells were predominantly oval to short spindle-shaped, exhibiting enlarged, hyperchromatic, and pleomorphic nuclei with occasional mitotic figures (Figure 4). Based on these morphological findings, the lesion was diagnosed as a malignant mesenchymal neoplasm, not otherwise specified (NOS). Immunohistochemical staining and further ancillary studies were not performed because the endomyocardial biopsy yielded limited tissue.

Figure 4 Histopathology of the left atrial mass showing oval-to-short spindle-shaped mesenchymal cells with enlarged hyperchromatic nuclei and occasional mitoses. Findings are consistent with a malignant mesenchymal tumor (hematoxylin and eosin staining, 100×).

After multidisciplinary evaluation, cardiothoracic surgeons determined that complete excision was unlikely and that reconstruction of the left atrial wall and pulmonary veins would be technically challenging, with high risk of bleeding and perioperative complications. Consequently, the patient was referred to a specialized oncology hospital for concurrent chemoradiotherapy.

Follow-up

After discharge, the patient was referred to a specialized oncology hospital and received two courses of concurrent chemoradiotherapy:

• First course: 30 Gy in 6 fractions to the atrial mass, defined as planning target volume generated from the gross tumor volume (PTV_GTV), with docetaxel + nedaplatin.
• Second course: 25 Gy in 5 fractions to the same target with low-dose docetaxel + nedaplatin (DP regimen).

Following treatment, the patient underwent regular follow-up every 2 to 3 months. Approximately one year after the initial diagnosis, transthoracic echocardiography revealed pulmonary artery dilation and elevated estimated pulmonary pressure. CMR imaging demonstrated stable heterogeneous thickening of the left atrial wall with reduced vascularity and moderate pericardial effusion (Figure 5, Video 7).

Figure 5 Approximately one year after the initial diagnosis, the degree of heterogeneous thickening of the left atrial wall (arrow) remained stable, but vascularity was reduced. LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

However, chest and abdominal CT revealed multiple osseous metastases with bone destruction involving the T6 vertebral body, sternum, bilateral clavicular heads, and right humeral head, indicating systemic disease progression. Consequently, further oncologic therapy was discontinued, and the patient was managed conservatively with cardiovascular and bone-protective medication and continued follow-up every 2 to 3 months.

Discussion

Cardiac masses constitute a rare yet critical entity in the field of cardio-oncology. They are broadly classified into benign and malignant tumors, as well as tumor-like conditions. Among primary malignant cardiac tumors, sarcomas account for over two-thirds of all cases, although they constitute only a minority of all cardiac masses.

Diagnosing left atrial masses via echocardiography remains particularly challenging. Common entities in this location include thrombus, myxoma, sarcoma, lipoma, and metastatic lesions, while myxoma and thrombus being the most frequently encountered (1). Echocardiography typically identifies myxomas as mobile masses attached to the endocardium by a stalk, often originating from the fossa ovalis. In contrast, thrombi often present with variable morphologies and motilities. Lipomas tend to be broad-based, immobile, well-circumscribed, and homogeneous masses without a pedicle or calcification. Angiosarcomas, the most frequently encountered sarcomas, usually manifest as echogenic, nodular or lobulated masses, with pericardial effusion or direct pericardial extension (1,2).

In general, echocardiography serves as a valuable tool for the initial differentiation between benign and malignant cardiac masses. Several echocardiographic features might provide clues to malignancy, such as location, irregular or lobulated morphology, broad-based attachment, the invasion of adjacent structures or pericardium, and the presence or severity of pericardial effusion. According to a recent study, six echocardiographic “red-flag” indicators have been identified as suggestive of malignancy, including infiltrative growth pattern, polylobate mass configuration, significant pericardial effusion, sessile attachment, inhomogeneous internal echotexture, and non-left-sided localization (5).

Distinguishing between different types of cardiac masses can be challenging, as overlapping echocardiographic appearances may lead to diagnostic uncertainty. For instance, differentiating malignant mesenchymoma from multiple cardiac myxomas can be challenging. Khattab et al. described a case of left atrial mesenchymoma that was surgically resected, including its site of attachment (6). Despite postoperative radiotherapy, the patient succumbed to disease progression six months later due to the poor prognosis of this infiltrative malignancy. In addition, rare primary cardiac sarcomas may also masquerade as myxoma-like lesions. For example, embryonal rhabdomyosarcoma has been reported as multifocal atrial disease and may present with intracavitary masses that mimic benign tumors on echocardiography, ultimately requiring surgical excision for definitive diagnosis (7).

Echocardiography revealed a large, mobile, lobulated mass arising from the left atrial roof, prolapsing through the mitral valve orifice during diastole and causing acceleration of blood flow. In contrast, Bourgeois et al. reported a patient with Carney complex presenting with multiple cardiac myxomas and acromegaly (8). Echocardiography revealed three large masses located in the right ventricular free wall, left lateral wall, and left atrium, one of which protruded into the LV during diastole but did not cause obstruction or regurgitation. Moreover, primary cardiac synovial sarcoma, although exceptionally rare and often reported in right-sided structures or involving the outflow tract, can also present as an obstructive intracardiac mass (9). Collectively, these cases highlight that myxoma-like features (e.g., mobility, intracavitary protrusion, and lobulated morphology) are not pathognomonic, and rare malignant tumors should remain in the differential diagnosis when imaging or clinical features are atypical.

This case emphasizes the crucial role of multimodal imaging in the differential diagnosis and management of cardiac tumors. Given the diversity of cardiac tumor types, their variable morphology and locations, echocardiography remains the first-line modality for assessing tumor size, shape, location, and involvement of the valves or pericardium (5). It also provides important information on hemodynamic impact and allows initial differentiation between benign and malignant masses (10). Although contrast-enhanced echocardiography has been shown to improve diagnostic accuracy in characterizing cardiac masses (11), it was not performed in this patient. Instead, coronary CT, cardiac MRI, and whole-body PET-CT offered detailed insights into the tumor’s morphology, vascularity, metabolic activity, and local invasion. In addition, echocardiography-guided transvenous biopsy provided sufficient tissue for histopathological diagnosis and guided subsequent therapeutic decision-making. Although endoscopic ultrasound (EUS) was not performed in this case due to institutional availability, it has been increasingly recognized as a valuable imaging modality for detecting cardiac masses and simultaneously reducing the risk of esophageal injury (12,13).

In terms of treatment, surgical resection remains the mainstay of therapy for cardiac tumors, although the specific strategy varied depending on the tumor’s location, size, and relationship to adjacent structures. According to previous reports, partial atrial wall resection with subsequent reconstruction, pulmonary vein reconstruction, or even cardiac auto-transplantation may be considered under different clinical circumstances (14). However, the infiltrative nature of these tumors and their proximity to critical structures such as the pulmonary veins often make complete resection difficult, leading to a high recurrence rate and poor long-term prognosis.

For unresectable or metastatic cardiac tumors, multimodal palliative strategies may be considered, including chemoradiotherapy and, in selected cases, transcatheter arterial embolization (TAE) might serve as a less invasive alternative, to reduce the tumor’s blood supply, limit its growth, alleviate symptoms without compromising the heart’s integrity and stabilize disease progression (15,16).

Overall, this case highlights the value of a multidisciplinary, imaging-guided approach, where advanced imaging contributes not only to precise diagnosis but also to optimal therapeutic decision-making in patients with cardiac malignancies.

Looking ahead, digital health innovations may further strengthen imaging-guided pathways for complex and rare diseases such as cardiac tumors. Internet of Medical Things (IOMT) (17)-enabled perioperative monitoring and workflow integration could facilitate real-time surveillance, streamlined coordination, and, when appropriate, remote multidisciplinary consultation or tele-mentoring during challenging procedures. In parallel, artificial intelligence (AI) (18,19) may augment cardiothoracic surgical practice through risk stratification, image-based planning, intraoperative guidance (e.g., computer vision-assisted navigation and decision support), and postoperative surveillance for early complication prediction. Despite these promising applications, substantial challenges remain, including data quality and interoperability, ethical and privacy considerations, and the need for rigorous external validation and governance before such technologies can be widely integrated into routine clinical practice.

Conclusions

This report describes a rare malignant cardiac tumor of mesenchymal origin located in the left atrium, extending toward the mitral valve orifice and altering pulmonary venous flow dynamics. The patient underwent concurrent chemoradiotherapy following histopathological diagnosis. Cardiac mesenchymoma represents a highly aggressive malignancy with a poor prognosis, primarily due to its rapid growth, local infiltration, and early metastatic potential. Only a few cases have been reported in the medical literature. Multimodal imaging plays a pivotal role in achieving accurate diagnosis, assessing disease extent, and guiding treatment planning. Further research and detailed case reports are necessary better to understand the optimal management strategies for this aggressive tumor.

Acknowledgments

None.

Footnote

Funding: This work was supported by the General Program of the Natural Science Foundation of Guangdong Province (No. 2023A1515011294, to F.J.Y.).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2026-1-0020/coif). F.J.Y. reports funding from the General Program of the Natural Science Foundation of Guangdong Province (No. 2023A1515011294). The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this case were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case description and accompanying images and videos. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Tyebally S, Chen D, Bhattacharyya S, Mughrabi A, Hussain Z, Manisty C, Westwood M, Ghosh AK, Guha A. Cardiac Tumors: JACC CardioOncology State-of-the-Art Review. JACC CardioOncol 2020;2:293-311. [Crossref] [PubMed]
2. Casavecchia G, Lestuzzi C, Gravina M, Corrado G, Tusa M, Brunetti ND, Manuppelli V, Monte IP. Cardiac Tumors. J Cardiovasc Echogr 2020;30:S45-53. [Crossref] [PubMed]
3. Scicchitano P, Sergi MC, Cameli M, Miglioranza MH, Ciccone MM, Gentile M, Porta C, Tucci M. Primary Soft Tissue Sarcoma of the Heart: An Emerging Chapter in Cardio-Oncology. Biomedicines 2021;9:774. [Crossref] [PubMed]
4. Çobankent Aytekin E, Behzatoğlu K, Akçay A, Özgün Şahin A, Kökbudak N, Kılınç F, Okçu Heper A, Kurtulan O, Özbilim G, Eğilmez R, Koç T, Özdemir Kara D, Ocak E, Aköz A, Özbudak İH. Primary Cardiac Tumors: Clinical Presentations and Pathological Features in a Multicenter Cohort. Diagnostics (Basel) 2025;15:1951. [Crossref] [PubMed]
5. Angeli F, Bodega F, Bergamaschi L, Armillotta M, Amicone S, Canton L, et al. Multimodality Imaging in the Diagnostic Work-Up of Patients With Cardiac Masses: JACC: CardioOncology State-of-the-Art Review. JACC CardioOncol 2024;6:847-62. [Crossref] [PubMed]
6. Khattab MN, Alkounsol K, Soleman R. Primary left atrial malignant mesenchymoma: A rare case of cardiac malignancy. Int J Surg Case Rep 2024;114:109186. [Crossref] [PubMed]
7. Panagiotopoulos I, Katinioti A, Mousafeiris V, Leivaditis V, Skevis K, Tasios K, Antzoulas A, Pitros C, Verras GI, Mulita F, Prapas S. Multifocal, biatrial, primary cardiac embryonal rhabdomyosarcoma. Prz Menopauzalny 2023;22:173-6. [Crossref] [PubMed]
8. Bourgeois T, Van den Bruel A, Vandelanotte S, Vergauwen W, Debonnaire P. Multiple cardiac myxomas and acromegaly revealing carney complex. Eur Heart J Cardiovasc Imaging 2021;22:e142. [Crossref] [PubMed]
9. Bi Y, LeGout JD, Lukens FJ. A Rare Cause of Shortness of Breath. Clin Gastroenterol Hepatol 2021;19:e28. [Crossref] [PubMed]
10. Lyon AR, López-Fernández T, Couch LS, Asteggiano R, Aznar MC, Bergler-Klein J, et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J 2022;43:4229-361. [Crossref] [PubMed]
11. Yang Z, Niu Y, Ma H, Gong W, Yu L, Liu L, Zheng M. Contrast-enhanced echocardiographic diagnosis of benign and malignant cardiac tumors and its correlation with pathology. Front Cardiovasc Med 2023;10:1182334. [Crossref] [PubMed]
12. Elhakim A, Heinisch F, Elhakim M, Sauter P, Rode M, Seiche M, Radke PW, Saad M. The role of endosonography in cardiac tumor assessment: a case report. Int J Cardiovasc Imaging 2025;41:1621-6. [Crossref] [PubMed]
13. Elhakim A, Karkour K, Sauter P, Rode M, Elhakim M, Radke PW, Saad M. The role of endosonography in cardiology: case series and literature review. Eur Heart J Imaging Methods Pract 2023;1:qyad002. [Crossref] [PubMed]
14. Sá MP, Osho AA, Bloom JP. Cardiac Tumors in the Left Atrium: A Challenge in Diagnosis and Surgical Treatment. JACC Case Rep 2024;29:102668. [Crossref] [PubMed]
15. Chen CJ, Kan CD. Left Ventricular Mesenchymal Hamartoma: Exploring Diagnostic Approaches and Potential Therapeutic Strategies. JACC Case Rep 2025;30:103636. [Crossref] [PubMed]
16. Delanian S, Awad S, de Gramont A. New curative approach using embolization followed by moderate-dose radiotherapy after surgical failure for large right heart metastasis. Clin Transl Radiat Oncol 2022;32:1-5. [Crossref] [PubMed]
17. Mulita F, Verras GI, Anagnostopoulos CN, Kotis K. A Smarter Health through the Internet of Surgical Things. Sensors (Basel) 2022;22:4577. [Crossref] [PubMed]
18. Leivaditis V, Maniatopoulos AA, Lausberg H, Mulita F, Papatriantafyllou A, Liolis E, Beltsios E, Adamou A, Kontodimopoulos N, Dahm M. Artificial Intelligence in Thoracic Surgery: A Review Bridging Innovation and Clinical Practice for the Next Generation of Surgical Care. J Clin Med 2025;14:2729. [Crossref] [PubMed]
19. Leivaditis V, Beltsios E, Papatriantafyllou A, Grapatsas K, Mulita F, Kontodimopoulos N, Baikoussis NG, Tchabashvili L, Tasios K, Maroulis I, Dahm M, Koletsis E. Artificial Intelligence in Cardiac Surgery: Transforming Outcomes and Shaping the Future. Clin Pract 2025;15:17. [Crossref] [PubMed]