Cardiac Sarcoma

Practice Essentials

Primary cardiac neoplasms are rare entities, with an autopsy prevalence of 0.001-0.28%, and most are benign.^{[1, 2, 3, 4]} The most common primary malignant tumor of the heart and pericardium is sarcoma. With the publication of the 5th edition of the World Health Organization's WHO Classification of Thoracic Tumours, cardiac sarcomas are now classified as follows^[5] :

• Angiosarcoma (AS)
• Undifferentiated pleomorphic sarcoma (UPS)
• Leiomyosarcoma (LMS)

Although a wide variety of primary sarcomas have been reported in the heart, AS, UPS, and LMS make up approximately 75% of cardiac sarcomas. Among the changes from the 4th edition, many of the rarer sarcomas of the heart—including rhabdomyosarcoma (embryonal and pleomorphic subtypes), osteosarcoma, dedifferentiated liposarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma—have been placed in a separate section, Mesenchymal Tumors of the Thorax. The remaining cardiac sarcomas include various differentiated tumors that are rarely primary cardiac lesions.^{[5, 6]}

The current edition also separates the entities of intimal sarcoma and UPS. Intimal sarcoma is distinguished from cardiac UPS by its intraluminal growth and origin within the great vessels, most commonly the pulmonary artery. Thus, it has been renamed pulmonary artery intimal sarcoma.^{[5, 6]}

The diagnosis of cardiac sarcoma is often not made preoperatively or even antemortem. It is overlooked because of the rarity of the lesion and the nonspecific nature of the symptoms and signs. These vary by site of involvement, as follows:

• Tumors that originate in the epicardium or pericardium and that lead to cardiac encasement may cause chest pain, hypotension, tachycardia, and malaise. Diminished cardiac sounds and a friction rub may be heard.
• Cardiac tamponade (usually from a persistent and bloody pericardial effusion) may eventually cause intractable cardiac failure.
• Myocardial involvement may lead to refractory arrhythmias, heart block, heart failure, angina, or infarction.
• Endomyocardial masses cause valvular obstruction or insufficiency. Rarely, a pedunculated tumor causes an audible plop from tumor prolapse through a valve.
• Tumor fragments may embolize from the right side of the heart to the lungs and cause dyspnea or hemoptysis.
• Left-sided emboli may lead to cerebrovascular accidents, peripheral organ infarctions, seizures, and distant metastases.
• Local extension of tumors may cause signs and symptoms such as superior vena cava syndrome, hemoptysis, and dysphonia.

Echocardiography is the preferred diagnostic procedure. Findings on echocardiography can direct further imaging workup.^[7]

For treatment of cardiac sarcoma, complete surgical excision remains the therapeutic mainstay, followed by radiotherapy with or without sequential chemotherapy. For more details, see Treatment.

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Pathophysiology

Cytogenetic analysis of these tumors may show numerical and structural chromosomal changes. Immunohistochemical analysis has revealed, in the case of a cardiac angiosarcoma, high expression of mutated p53 gene products.^[8]

Angiosarcoma (AS)

Accounting for approximately one third of primary cardiac sarcomas^[5] , nearly 80% of cardiac AS arise as mural masses in the right atrium. Typically, they completely replace the atrial wall and fill the entire cardiac chamber. They may invade adjacent structures (eg, vena cava, tricuspid valve).

On cardiac magnetic resonance imaging, angiosarcoma appears as a heterogeneous, nodular mass in the right atrium, and grossly, there are invariably areas of hemorrhage.

These tumors are both symptomatic and rapidly fatal. Extensive pericardial spread and encasement of the heart often occur. Pericardial angiosarcoma (without myocardial involvement) occurs rarely.

Leiomyosarcoma (LMS)​

Leiomyosarcoma account for approximately 10% of primary cardiac sarcomas.  LMS occur most often in the left atrium with no sex predilection. LMS exhibits immunoreactivity with smooth muscle markers (desmin and smooth muscle actin).^{[5, 6]}

Rhabdomyosarcoma

Rhabdomyosarcomas are derived from striated muscle and are rare, accounting for 0% to 5% of primary cardiac sarcomas. Most cases appear in children, at a mean age of approximately 14 years. Rhabdomyosarcoma has a predilection for the ventricle and the histologic features are usually of the embryonal subtype.^[9]  

Undifferentiated pleomorphic sarcoma

This tumor occurs primarily in the left atrium account for at approximately one third of cardiac sarcomas. A small proportion of undifferentiated pleomorphic sarcomas occur in other chambers, most frequently the left ventricle and right atrium.

Histologically, these tumors are heterogeneous, ranging from bland collagen-rich areas that may in small samples appear benign to low-grade sarcomas with myxoid background to areas of high pleomorphism and mitotic activity (undifferentiated pleomorphic sarcoma).^[9]  

These whitish lesions have a firm texture and exhibit infiltrative growth patterns. 

Tumors of the pericardium

Sarcomas of the pericardium are rare; the most common are synovial sarcoma (which also accounts for approximately 5% of cardiac sarcomas), angiosarcoma (which often involves both the pericardium and right atrium), and undifferentiated pleomorphic sarcoma. 

Metastatic cardiac sarcoma

Metastases to the heart and pericardium are 40 times more common than primary cardiac tumors. In fact, an estimated 25% of patients who die from metastatic soft tissue sarcoma have cardiac metastases. No particular gross pattern of myocardial spread exists (ie, diffuse, nodular). In children, rhabdomyosarcoma is the most common type of sarcoma that metastasizes to the heart.

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Epidemiology

Cardiac sarcoma occurs in less than 0.2% of decedents undergoing autopsy, both nationally and internationally.^[10] Sex predilection has not been defined for cardiac sarcoma. Cardiac sarcomas can occur at any age; however, children have an increased rate of cardiac rhabdomyosarcomas.

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Prognosis

In one series of patients with primary cardiac sarcomas, median survival was approximately 17 months in cases where complete surgical excision was achieved, versus 6 months in cases where surgical complete remission could not be achieved. Median survival of patients with metastatic disease was 5 months, versus 15 months in patients without metastatic disease.^[11]

A systematic review of 127 studies comparing overall survival in 162 patients receiving surgery, adjuvant chemotherapy and chemo-radiotherapy reported median survival more than doubled from 6 months among patients receiving surgery alone to 13 months for patients who received combined surgery and adjuvant chemotherapy.  However, treatment including surgery and chemo-radiotherapy offered the greatest survival benefit, with a median overall survival of 27 months.^[12]

Increasing age is associated with poor overall survival rates.^[13]  Wang et al reported the median survival times of patients with primary malignant cardiac tumors were 22.5, 11, 5, and 1 month for ages less than 20, 20-50, 51-80, and greater than 80 years, respectively.^[14]

Patients with angiosarcoma had a lower survival compared with patients with other histologies and longer survival is associated with left-sided lesions.^[15]

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History

No typical presentation of cardiac sarcoma exists because the common symptoms and signs are nonspecific. However, patients may complain of dyspnea, chest pain, and/or generalized fatigue.

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Physical

Cardiac sarcoma has no pathognomonic physical features that may be discovered on examination. However, the following signs may accompany cardiac sarcoma:

• Dyspnea
• Hemoptysis
• Diminished cardiac sounds
• Friction rub
• Rales
• Refractory arrhythmias
• Heart block
• Heart failure

An audible plop due to tumor prolapse through the mitral valve may be appreciated.

Left-sided embolization may lead to cerebrovascular accident, peripheral organ infarction, seizures, and distant metastases.

Upper extremity and facial congestion (suggestive of superior vena cava syndrome) and dysphonia may occur.

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Imaging Studies

Advances in diagnostic techniques have facilitated accurate, noninvasive assessment of cardiac sarcomas.^[16]

Echocardiography is the preferred diagnostic procedure for noninvasive imaging of cardiac tumors (2-dimensional and transesophageal echocardiography are complementary).^[17] Findings on echocardiography can direct further workup by cardiac magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and/or biopsy.^[7]

The role of other imaging studies includes the following:

• Chest radiography may reveal generalized cardiomegaly or right-sided heart enlargement, widened mediastinum, hilar adenopathy, pulmonary congestion, or pleural effusion.
• CT scanning is useful in detecting cardiac lesions, documenting local invasion of adjacent structures, and defining the presence of lung or liver metastases.
• Angiography can help assess coronary artery luminal status and document intracardiac and intravascular tumors as filling defects.
• MRI has the potential to define tumor histology, tumor location, and surrounding anatomy and to detect response to chemotherapy.^{[18, 19]} A study by Fussen et al found that comprehensive cardiovascular MRI is useful in risk stratification and clinical management in patients with suspected cardiac tumors.^[20]
• PET/CT) can characterize intracardiac masses and estimate tumor burden, as well as identify any extracardiac primary malignancy.^[21]

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Electrocardiography

More than 75% of patients with cardiac sarcomas have electrocardiography (ECG) abnormalities. These are generally nonspecifi, as follows:

• Myocardial tumors can cause arrhythmias or various degrees of heart block.
• Nonspecific ST and T wave changes may be observed.
• Pericardial lesions may cause tachycardia and decreased voltage.

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Procedures

Pericardiocentesis allows cytologic examination and may relieve tamponade.

Endomyocardial biopsy provides tissue to use in diagnosis; however, this biopsy is not absolutely necessary preoperatively because tissue is obtained during surgical exploration.

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Histologic Findings

Specific subtypes of cardiac sarcomas have characteristic gross and microscopic features (see Overview/Pathophysiology).

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Approach Considerations

Complete surgical excision remains the mainstay of therapy for primary cardiac sarcoma, followed by radiotherapy with or without sequential chemotherapy. Chemotherapy regimens containing anthracyclines, ifosfamide, or taxanes have been reported.^[22]

Neoadjuvant chemotherapy may also be considered. In one case report, preoperative chemotherapy reduced the size of an unresectable undifferentiated cardiac sarcoma, allowing complete resection of residual tumor.^[23]  In a case series of 44 patients with primary right-sided sarcomas, the addition of neoadjuvant chemotherapy increased survival from 9.5 months to 20 months.^[24]

Multimodality therapy has proved most effective. In a retrospective chart review, patients who received multimodality treatment (any combination of surgery, radiation therapy, and chemotherapy) had an estimated median survival of 36.5 months compared with 14.1 months for patients treated with surgery, radiation therapy, or chemotherapy only (P=0.05).^[15]

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Surgical Care

Cardiac sarcoma is rarely cured, but prolonged survival or significant palliation is possible with surgical resection.^{[25, 26]} Exploration with biopsy yields tissue for histologic diagnosis and assessment of the gross extent of the tumor.

The role of orthotopic heart transplantation for malignant cardiac tumors continues to be debated.^{[27, 28, 29, 30]} In a study of 46 patients who underwent orthotopic heart transplantation for unresectable primary cardiac sarcoma, median survival in those with angiosarcoma (the most common histologic type) was 9 months, versus 36 months in the patients with other histologic types (P = 0.002). Additionally, in patients with angiosarcoma, median survival in patients who received palliative care only was similar to that in patients who underwent transplantation (8 vs 9 months; P = 0.768).^[31]

Bench surgery (explantation and autotransplantation of the heart) may aid in achieving more complete tumor resection.^{[32, 33, 34]}

Complete or partial excision of primary or metastatic cardiac sarcoma can provide hemodynamic improvement and relief from congestive heart failure. Alternatively, a pericardial window or pericardiectomy may ameliorate symptoms.

Postsurgical radiation and chemotherapy have not proven consistently beneficial. However, adjuvant radiation or chemotherapy can be beneficial in ameliorating symptoms and improving quality of life.

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Long-Term Monitoring

No specific guidelines for follow-up care have been established; however, because of the low postoperative survival rate (median survival, 6 mo), pay careful attention postoperatively to the patient's cardiopulmonary status and overall physical state.

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