Primary cardiac myxofibrosarcoma: a case description and literature review of a highly rare entity

Introduction

Primary cardiac tumors are rare (incidence of 0.0017–0.33% in autopsy studies) and mostly benign (75%) (1). Myxomas are the most common benign subtype, while sarcomas are the most frequent malignant type (2,3). Primary cardiac myxofibrosarcoma is one of the rarest types of cardiac sarcoma and has only been described in a few isolated case reports (4). Myxofibrosarcoma is marked by its aggressive local invasion and pronounced tendency for distant metastasis, resulting in a poor prognosis (5). Several reports indicate that primary cardiac myxofibrosarcoma can metastasize to the brain, thoracic cavity, liver, and bones (6-9). To our knowledge, we present the first report of a case in which primary cardiac myxofibrosarcoma metastasized to the adrenal glands. The clinical and imaging presentation of primary cardiac myxofibrosarcoma often mimics that of cardiac myxoma, frequently resulting in misdiagnosis and subsequent delays in appropriate management. In this report, we describe a case of primary cardiac myxofibrosarcoma being misdiagnosed as myxoma and describe its clinical characteristics, imaging features, histological features, and clinical management, aiming to enhance clinicians and radiologists understanding of this rare condition.

Case presentation

All procedures described in this retrospective study were performed in accordance with the ethical standards of the relevant institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. The requirement for informed consent for the publication of this study and associated images was waived by the Ethics Management Committee of The Second Affiliated Hospital of Nanchang University. A 50-year-old woman presented with a 10-day history of progressive cough and sputum production of unknown etiology. Symptoms worsened to include pink frothy sputum during exacerbations, accompanied by chest tightness, palpitations, and fatigue. Since the onset of the disease, there was no fever, nausea, vomiting, or syncope. The patient had been in good physical condition and denied having a family history of cardiac tumors. Physical examination revealed a regular heart rhythm and a diastolic rumbling murmur in the apical region of the heart, bilateral coarse breath sounds, no crackles, and no pericardial fricative rub. The electrocardiogram (ECG) suggested sinus rhythm and prolonged QT interval. The N-terminal B-type natriuretic peptide precursor level was 1,497.00 pg/mL (normal range, 0–125 pg/mL). Computed tomography (CT) plain scan imaging demonstrated a hypodense lesion within the left atrium, measuring up to 3.6 cm in maximum transverse diameter. Concurrent bilateral pulmonary involvement was observed with extensive patchy opacities, indicative of pulmonary edema. Echocardiography indicated that the left atrial cavity was dilated and had a slightly lower echogenic tumor measuring 6.6 cm × 3.7 cm. The tumor had a clear boundary, irregular shape, and uneven internal echogenicity. It prolapsed into the mitral valve orifice during the diastolic period. There was severe stenosis complicated by mild regurgitation in the mitral valve orifice (Figure 1). The ultrasound findings were suggestive of a tumor. The primary clinical diagnosis was initially considered to be a myxoma.

Figure 1 Two-dimensional echocardiogram in the apical three-chamber view showed a left atrial tumor protruding into the left ventricle through the mitral valve orifice causing obstruction of blood flow at the mitral valve orifice. (A) Two-dimensional ultrasound images showed that the myxofibrosarcoma of the left atrium protruded toward the mitral valve orifice. (B) Color Doppler showed that the tumor caused obstruction of blood flow at the mitral valve orifice.

The patient underwent resection of the left atrial tumor 5 days after admission. Intraoperative exploration revealed a massive tumor (measuring 7 cm × 4 cm) in the left atrium, with its base attached to the interatrial septum. Macroscopically, the tumor section was gray-yellow, with a portion being mucoid and slightly tough. Histopathologically, the tumor cells were spindle-shaped and woven, with obvious nuclear division, branched blood vessels, and mucoid matrix in the interstitium (Figure 2). The immunohistochemistry results were as follows: cytokeratin (CK) (−), vimentin (+), smooth muscle actin (SMA) (−), S100 (−), desmin (partial+), CD34 (−), CD31 (−), P53 (10%+), P16 (+), MyoD1 (−), myogenim (−), Ki-67 index (30%+), and myoglobin focus (+). These histopathological and immunohistochemical features suggested a malignant tumor and were indicative of a diagnosis of myxofibrosarcoma, Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade 2. The symptoms of the patient were partially relieved after surgery, but she refused radiotherapy and chemotherapy due to financial reasons and personal preferences.

Figure 2 Histopathological findings of the excised specimen. (A) The tumor cells were arranged woven pattern with hypercellularity. (B) The stroma contains branched, thin-walled blood vessels and cells were arranged along these vessels. (C) The tumor cells were spindle-shaped and had a myxoid matrix. (D) Prominent mitotic figures were observed (green arrow), marked nuclear atypia (red arrow). Hematoxylin and eosin; magnification: A, ×4; B, ×10; C, ×20; D, ×40.

The patient underwent postoperative echocardiographic follow-up at 5, 35, and 121 days, which showed no evidence of recurrence. However, 24 months later, the patient presented with persistent low-grade fever and chest tightness lasting 3 days, which was not relieved by rest. Emergency echocardiography examination suggested a heterogeneous lower echogenic tumor measuring 6.0 cm × 4.1 cm, which was detected in the left atrium, and a an extremely low echogenic area measuring 3.0 cm × 2.0 cm inside the tumor (considered to be tumor ischemic necrosis). The tumor was found to occupy almost the entire left atrium and was attached to the mitral valve and the left atrial wall, with an unclear boundary (Video S1). Given the patient’s history of cardiac myxofibrosarcoma, the left atrial tumor was diagnosed as a recurrent disease. The patient underwent a whole-body positron emission tomography (PET)-CT examination to assess the presence of distant metastasis of the tumor. PET-CT revealed hypermetabolic lesions in both the left atrium (primary recurrence) and left adrenal glands (10-cm diameter, indicating distant metastasis) (Figure 3). The patient declined surgical operation and opted for traditional Chinese medicine treatment at a local hospital. Follow-up echocardiography 1 month later indicated disease progression: the left atrial tumor had enlarged to 6.7 cm × 4.7 cm, with new right atrial involvement (3.5 cm × 1.8 cm), indicative of aggressive biological behavior of the disease (Video S2). The patient died 1 month later.

Figure 3 Image from positron emission tomography-computed tomography. A strong hypermetabolic tumor was observed in the left atrium and the left adrenal region with increased fluorodeoxyglucose uptake.

Discussion

Cardiac tumors are predominantly secondary tumors, demonstrating a 20- to 40-times higher incidence compared to primary cardiac tumors (10). Primary cardiac tumors are extremely rare. Among them, only 25% are malignant tumors, and fewer than 1% are primary cardiac myxofibrosarcoma (11). The global medical literature includes fewer than 50 reported cases, with the available evidence limited primarily to individual case reports and small case series due to the tumor’s extraordinary rarity. The exact incidence remains challenging to determine, reflecting both the tumor’s infrequency and the lack of systematic epidemiological investigations. We conducted an extensive review of the literature on cardiac myxofibrosarcoma by searching PubMed, Web of science, and references cited by primary reports. The keywords were “myxofibrosarcoma” or “myxoid variant of malignant fibrous histiocytoma” and “cardiac” or “heart” (Figure 4). Data on gender, age, tumor location, size, pathological grade, recurrence/metastasis, and use of radiotherapy/chemotherapy were collected (Table 1).

Figure 4 Flowchart of literature selection.

Myxofibrosarcoma is a malignant soft tissue neoplasm of mesenchymal origin that predominantly affects the extremities and trunk in older adult populations and rarely occurs in the heart (12). Meanwhile, primary cardiac myxofibrosarcoma can occur in any cardiac chamber, with the left atrium being the most common tumor site (77.5%); other locations include the aorta, right ventricle, right ventricular outflow tract, and pericardium (13-16). The majority of tumors have a diameter of over 40 mm (70.0%) and exhibit heterogeneous clinical manifestations, primarily mechanical obstruction of cardiac blood flow and thromboembolic phenomena. The main symptoms include dyspnea, chest pain, syncope, and persistent chest tightness, which may correlate with hemodynamic disorders caused by the tumor and the subsequent ventricular dysfunction (17). Moreover, the friable nature of tumor tissue predisposes it to fragmentation, with embolization risk extending beyond coronary circulation to systemic vascular beds (18). Notably, some patients with primary cardiac myxofibrosarcoma exhibit rare symptoms such as hoarseness, limb pain, or seizures pose, which poses a diagnostic challenge (13,19,20). For atypical symptoms, cardiac tumors should be considered critical for differential diagnoses, and early cardiac imaging is crucial to preventing missed diagnoses and loss of optimal treatment timing. These pathognomonic features and nonspecific manifestations underscore the need for prompt diagnostic evaluation and timely therapeutic intervention to reduce severe complications.

In our case, histological findings of the myxofibrosarcoma indicated tumor cells arranged in a spindle-shaped and braided pattern, with abundant cell growth. Cell mitotic figures were frequent, and branched blood vessels and myxoid matrix were visible in the stroma. Myxofibrosarcoma is classified into low-grade, medium-grade, and high-grade types (21). Low-grade myxofibrosarcoma frequently recurs as higher-grade lesions, which suggests histological progression of the tumor (5). High-grade myxofibrosarcoma is more prone to recurrence and metastasis than is the low-to-medium-grade type and has a poorer prognosis (20). The literature contains 14 low-to-medium-grade (35.0%) and 11 high-grade (27.5%) cases. In our case, the mass first discovered in the patient had a clear boundary, no adhesion to adjacent tissues, and a high degree of mobility. At recurrence, the boundary of the mass was unclear, it adhered closely to both the mitral valve and the left atrial wall, and there was distant metastasis to the left adrenal glands. Notably, the tumor demonstrated marked growth within just 1 month and invaded the adjacent right atrium. These features collectively indicate the highly aggressive biological behavior of cardiac myxofibrosarcoma.

At present, reliable information for the diagnosis of cardiac myxofibrosarcoma remains considerably limited. Shiga et al. suggest that multimodal imaging techniques can provide supplementary information in the diagnosis of cardiac tumors (22). Early diagnosis of tumors can improve the survival rate and quality of life of patients (23). Echocardiography is the preferred method for diagnosing primary cardiac tumors. It can clearly display the location, size, shape, and mobility of the tumor, along with its relationship with surrounding tissues, while also dynamically assessing the hemodynamic changes of the heart. Although it is difficult to differentiate cardiac myxoma from myxofibrosarcoma via conventional echocardiography, their ultrasonic characteristics have some differences: (I) myxomas typically manifest as masses with moderate-to-high echogenicity, whereas myxofibrosarcomas predominantly display hypoechoic patterns. (II) Myxomas typically demonstrate echogenicity​, whereas myxofibrosarcomas frequently exhibit echogenicity. This sonographic distinction is primarily attributable to the proliferation rate​of malignant tumors, which renders them ​more susceptible to intratumoral necrosis, which occurred in our case​. (III) Myxomas present with clear boundaries and regular contours and often have a pedicle attachment. In contrast, myxofibrosarcomas lack a distinct pedicle structure and due to their frequent invasion of adjacent cardiac tissue structures (including the valves, pericardium, and nearby major blood vessels), result in irregular boundaries and unclear edges (24). The 2018 American Society of Echocardiography (ASE) guidelines incorporated contrast-enhanced echocardiography into the diagnostic criteria for cardiac masses (25). In contrast-enhanced ultrasound imaging, malignant myxofibrosarcomas show significant enhancement of contrast agent, while benign myxomas shows low contrast-agent perfusion. This is mainly due to the differences in the composition of the tissues. The tumor of myxofibrosarcoma has a disordered structure, abundant vascular network within the tissue, increased microvessels, and abnormal dilation of blood vessels. In contrast, the internal components of myxomas mainly consist of mucinous gelatinous substance, and the blood vessels are relatively sparse (26,27).

Compared to ultrasound, cardiac magnetic resonance (CMR) imaging has superior soft tissue resolution, significantly better spatial resolution, and a larger field of view; moreover, it has the distinct ability to perform localization and qualitative analysis of cardiac tumors and to assess myocardial lesions. CMR allows for a comprehensive histopathological analysis of cardiac tumors and assessment of the relationship between the tumor and the surrounding important structures, thereby providing important guidance for preoperative planning and intraoperative operations (28). In CMR, the tumor shows a low signal on T1-weighted imaging (T1WI), a high signal on T2-weighted imaging (T2WI), and significant enhancement on enhanced scans. When the tumor shows cystic changes or necrotic areas, the enhanced scan within the region does not show any enhancement. However, due to economic constraints, CMR examination was not performed on the patient described in this report before the operation, which limited our ability to comprehensively assess the tumor.

PET-CT demonstrates high sensitivity and high specificity in distinguishing malignant from benign cardiac masses. Malignant lesions show significantly increased ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) uptake, and the whole-body imaging capability allows for the detection of distant metastases, enabling assessment of systemic disease spread (29).

Complete surgical resection remains the cornerstone treatment for primary cardiac myxofibrosarcoma. However, due to the high tendency of primary cardiac myxofibrosarcoma to invade surrounding tissues near the heart and the unique structure of the heart, complete removal of the tumor is not always possible (7,30). Many patients may still experience recurrence and metastasis after the resection. According to our results, the recurrence rate (32.5%) and distant metastasis rate (32.5%) are comparable. The median survival time for patients with complete resection is more than four times that of incomplete resection (31). Furthermore, the prognosis of the patients is also related to the histological type of the tumor. High-grade tumors are more likely to recur and metastasize than are low-grade tumors and have a poorer prognosis (23).

For myxofibrosarcoma, radiotherapy and chemotherapy are often used as adjuvant treatments after surgery, but large-scale clinical trials and standardized treatment methods remain lacking (5). Patients with myxofibrosarcoma continue to have poor long-term survival outcomes and poor prognosis (32). According to a review of the literature, 20.0% of patients receive radiotherapy, 40.0% chemotherapy, and 37.5% die. The value of radiotherapy in controlling local recurrence after surgery for patients with myxofibrosarcoma is controversial (33-35). In particular, primary cardiac myxofibrosarcoma is characterized by its deep-seated and constant movement with the heart, and the heart is a radiation-sensitive organ. Inevitably, radiotherapy causes radiation damage to the heart and surrounding tissues when it eliminates tumor cells, which may lead to delayed and fatal complications such as pericardial disease, heart failure, and coronary artery disease (36,37). Chemotherapy is mainly used for palliative treatment in patients with metastatic myxofibrosarcoma, but there is a lack of large-sample clinical studies, and the therapeutic effect remains uncertain (5,38). Chemotherapy (especially the anthracycline-based type) has significant cardiotoxicity may cause secondary harm to patients with primary cardiac myxofibrosarcoma and poor cardiac reserve (39,40). Therefore, it is essential to fully assess the balance between the potential survival benefits and the fatal cardiotoxicity before radiotherapy and chemotherapy, which requires a comprehensive individualized evaluation by a multidisciplinary team (41).

Conclusions

In this report, we describe a rare case of primary cardiac myxofibrosarcoma that was initially misdiagnosed as a cardiac myxoma. Primary cardiac myxofibrosarcoma has a high degree of malignancy and tends to local tissue invasion and distant metastasis. Preoperative multimodal imaging examinations may help us detect tumors at an early stage. The complete resection of the tumor remains the primary treatment method. Postoperative radiotherapy and chemotherapy should be fully evaluated by a multidisciplinary team to balance the benefit of clinical efficacy with cardiac side effects.

Acknowledgments

None.

Footnote

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1464/coif). The authors have no 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 study 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. Informed consent for the publication of this study and associated images was exempted by the Ethics Management Committee of The Second Affiliated Hospital of Nanchang University.

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/.

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