Angiosarcoma of the heart, with pericardial encasement by hemorrhagic tumor. Image courtesy of Dr. K. Marchant.
Primary cardiac neoplasms are rare entities,[1, 2, 3] with an autopsy prevalence of 0.001-0.28%. The most common primary malignant tumor of the heart and pericardium is sarcoma. With the publication of the 4th edition of the WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart, cardiac sarcomas are now classified as follows[4] :
Among the changes from the 3rd edition, cardiac sarcomas with a predilection for the left atrium (the most common site in the heart), have been simplified. This group of sarcomas previously included low-grade lesions (fibrosarcoma, myxofibrosarcoma, myxosarcoma, fibromyxosarcoma), and intermediate- to high-grade lesions (myxoid malignant fibrous histiocytoma, malignant fibrous histiocytoma). High-grade sarcomas are now classified as undifferentiated pleomorphic sarcoma to conform with the WHO classification of soft-tissue tumors. The older designations of the lower-grade sarcomas have also been combined under the classification of myxofibrosarcoma.[4]
Another change in classification of cardiac sarcomas is that of tumors with bone matrix formation. In the third edition, sarcomas with osteosarcoma or chondrosarcoma were classified as a subtype of undifferentiated pleomorphic sarcoma. Partly to conform to the WHO classification of soft-tissue tumors, the current edition places these tumors in a separate category of osteosarcoma analogous to extraskeletal osteosarcomas of the soft tissue.[4]
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. 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.
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.[5]
Angiosarcoma
Nearly 80% of cardiac angiosarcomas 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.
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.[6]
Together, this group of tumors that occur primarily in the left atrium account for at least 50% 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).[6]
These whitish lesions have a firm texture and exhibit infiltrative growth patterns. Myxofibrosarcoma may have a better prognosis than does undifferentiated pleomorphic sarcoma.
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.
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.
Cardiac sarcoma occurs in less than 0.2% of decedents undergoing autopsy, both nationally and internationally.[7] 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.
Data from one series of patients with primary cardiac sarcomas showed that median survival is approximately 17 months for those who undergo complete surgical excision and 6 months for those who do not.[8]
Patients with angiosarcoma had a lower survival compared with patients with other histologies and longer survival is associated with left-sided lesions.[9]
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.
Cardiac sarcoma has no pathognomonic physical features that may be discovered on examination. However, the following signs may accompany cardiac sarcoma:
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.
Advances in diagnostic techniques have facilitated accurate, noninvasive assessment of cardiac sarcomas.[10]
Echocardiography is the preferred diagnostic procedure for noninvasive imaging of cardiac tumors (2-dimensional and transesophageal echocardiography are complementary).[11]
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.
Chest radiography may exhibit generalized cardiomegaly or right-sided heart enlargement, widened mediastinum, hilar adenopathy, pulmonary congestion, or pleural effusion.
MRI has the potential to define tumor histology, tumor location, and surrounding anatomy and to detect response to chemotherapy.[12, 13]
A study by Fussen et al found that comprehensive cardiovascular magnetic resonance examination is useful in risk stratification and clinical management in patients with suspected cardiac tumors.[14]
More than 75% of patients with cardiac sarcomas have abnormalities that are generally nonspecific on ECGs.
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.
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.
Specific subtypes of cardiac sarcomas have characteristic gross and microscopic features (see Pathophysiology).
For treatment of cardiac sarcoma, complete surgical excision remains the therapeutic mainstay, followed by radiotherapy with or without sequential chemotherapy. Chemotherapy regimens containing anthracyclines, ifosfamide or taxanes have been reported.[15]
In one case report, preoperative chemotherapy reduced the size of an unresectable undifferentiated cardiac sarcoma, so that residual tumor could then be completely resected.[16] In a case series of 44 patients with primary right-sided sarcomas, survival was doubled (20 months vs 9.5 months) with the addition of neoadjuvant chemotherapy.[17]
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).[9]
Cardiac sarcoma is rarely cured, but prolonged survival or significant palliation is possible with surgical resection.[18, 19] 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.[20, 21, 22, 23] The results of a study analyzing the outcomes of 46 patients who underwent orthotopic heart transplantation for unresectable primary cardiac sarcomas found that median survival time after heart transplantation for patients with angiosarcoma was much less than that of other histologic types (9 vs 36 months; P = 0.002). Additionally, it was similar to the median survival of 8 months for patients with angiosarcoma receiving palliative care (P = 0.768).[24]
Bench surgery (explantation and autotransplantation of the heart) may aid in achieving more complete tumor resection.[25, 26, 27]
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 adjuvant radiation and chemotherapy have not proven consistently beneficial. However, adjuvant radiation or chemotherapy can be beneficial in ameliorating symptoms and improving quality of life.
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.
Angiosarcoma of the heart, with pericardial encasement by hemorrhagic tumor. Image courtesy of Dr. K. Marchant.
