Abstract
Tumors within the heart and pericardium are often initially detected by cardiac ultrasound. This chapter reviews the primary and secondary tumors of the heart. Their characteristics, benign versus malignant nature, locations, echocardiographic appearance, and effects on the heart and the patient are discussed.
Keywords
cancer of the heart, cardiac neoplasms, cardiac tumors, fibroelastoma, myxoma
Introduction
The first demonstration of a left atrial myxoma by ultrasound occurred in Germany in 1959. Since then echocardiography has evolved to become the usual initial modality for detecting a cardiac tumor. Cardiac neoplasms are found in only 1%–2% of cases in general autopsy series. For this reason, routine screening to rule out cancer in the heart is not appropriate and would undoubtedly lead to many false positives. This is generally true even in cancer patients, in whom there is higher risk (autopsy incidence reported in up to 4%–8%) of cardiac tumors. However, there are exceptional circumstances, such as familial tumor syndromes and carcinoid, in which screening may be justified. Because of the rarity of primary malignancies, the best data available originate from autopsy studies and larger specialized single-center studies, supplemented by case reports in the literature.
A fair proportion of heart tumors are clinically silent and discovered as incidental findings in the process of ancillary testing or workup prior to a surgery. In other cases, systemic embolization or pericardial involvement with hemodynamic effect may be the sentinel event that initiates a cardiac workup. Even more rarely, large masses of the heart may impede cardiac inflow or outflow, cause valvular regurgitation, and hence cause heart failure or syncope.
With knowledge of the general distribution of cardiac tumors and by taking the patient’s age and comorbidities into consideration, along with the location and echocardiographic features of the mass, the clinician can make an educated guess as to the likely nature of the tumor. After the possibilities are narrowed down, one can formulate a diagnostic and therapeutic plan, which may involve further imaging with intravenous (IV) echo contrast, three-dimensional (3D) echocardiography, transesophageal echocardiography (TEE), or other modalities to better define the tumor boundaries and stage before deciding upon observation, surgery, or other treatment. Echocardiography also serves to monitor for growth, recurrence after treatment, or adverse sequelae of tumors.
Tumor Types
Primary Versus Secondary Tumors
The best data for the actual frequency distribution of cardiac tumors are decades old and come from autopsy series, as summarized in Fig. 37.1 . Primary tumors of the heart (see Fig. 37.1A and B ) occur in only 0.02% of autopsy series and represent only 2%–5% of all cardiac tumors. The vast majority are secondary, metastastic neoplasms (see Fig. 37.1C ). Although most clinicians recognize the significance of this binary classification system, the World Health Organization (WHO) has updated and refined their classification and nomenclature in 2015 to better describe rare tumors and those with variable or unknown natural history.
Primary Benign Tumors
Of the primary tumors, approximately 75% are benign, and approximately 30% of these in the general population (up to 50% in adults) are myxomas. The next most common primary tumors are lipomas (10%) and papillary fibroelastomas (8% of general population). Echocardiographic characteristics and patient demographics are often enough to distinguish these three entities. (Of note, the prevalence of tumors reported in the literature from living patients may differ slightly from incidence rates reported from autopsy series, particularly for benign tumors).
Myxoma
Cardiac myxomas are the most common type of primary cardiac tumor, particularly in adults. They are believed to arise from endocardial (mesenchymal) cells. The classic myxoma arises in the left atrium (in 75% of the cases), but 20% of cases arise in the right atrium, and the remaining 5% occur in the ventricles. It is common for the myxoma to be attached to the interatrial septum near the fossa ovalis via a stalk or pedicle, although attachments to the mitral valve have also been described.
On echocardiography, myxomas often appear as compact, gelatinous-appearing masses that can be globular, ovoid, or multilobular ( Fig. 37.2 and 
). However, there exists a spectrum of morphologies. Smaller tumors are often more papillary or villous in appearance, are friable, and are more prone to embolization. In contrast, larger bulky myxomas tend to be more discrete, with a smoother surface or “cluster of grapes” appearance. These can grow large enough to fill the left atrium and are renowned for causing both mitral stenosis, with a diastolic rumble and a tumor “plop” on auscultation, as the mass prolapses into the left ventricle in diastole ( 
). TEE can help determine if the myxoma extends into the pulmonary veins or vena cavae.
. (A) Parasternal long-axis view. (B) M-mode view showing the mass prolapsing into the left atrium in systole. (C) Apical four-chamber view. (D) Transmitral gradients (mitral stenosis) as shown by continuous wave Doppler, with peak and mean gradients of 23 and 12 mm Hg. (E) Gross pathologic specimen of a left atrial myxoma, which appears as a clusterlike, gelatinous myxoid mass with an attached fragment (arrow) of atrial myocardium and interatrial septum. There is an autosomal dominant form of myxoma, which constitutes approximately 7% of cases, that tend to present earlier in life (i.e., second decade) than the sporadic myxomas. Individuals affected by this mutation in the PRKAR1A gene (which encodes a regulatory subunit of protein kinase A) or alternatively by a chromosome 2p16 mutation, tend to develop myxomas in atypical locations, even extracardiac locations, with multiple and recurrent sites. The “Carney complex” is a syndrome associated with these mutations that consists of myxomas, hyperpigmented skin spots (lentiginosis), and endocrine overactivity. First-degree relatives of identified patients should be screened by echocardiography, and the patients themselves must be surveyed frequently for recurrence of myxoma.
Lipoma
Lipomas represent slightly more than 8% of benign cardiac tumors. The tumor consists of benign fat cells that are encapsulated. They can arise anywhere in the heart but have been described most frequently in the left ventricle, right atrium, and atrial septum, usually in the subepicardial or subendocardial regions. On echocardiograms, they appear as homogeneous circumscribed masses that may be hyperechoic or hypoechoic. Those in the interatrial septum need to be distinguished from lipomatous hypertrophy, which is a normal finding (see Chapter 39 ). Lipomas tend to grow progressively and may intrude into the pericardial space. Accordingly, they are surgically excised if the patient becomes symptomatic due to mass effect or arrhythmia. An example, along with differential diagnoses and corresponding cardiac magnetic resonance imaging (MRI), is shown in Fig. 37.3 .
Papillary Fibroelastoma
Papillary fibroelastomas are the most common valvular tumor and have recently surpassed myxomas in being the most commonly excised cardiac masses. They represent approximately 8% of benign cardiac tumors and most commonly develop in older adults. Most (>80%) arise on the left-sided valves, and a minority may be multivalvular. They often appear on the aortic valve, less frequently on the mitral valve; a fraction manifest at multiple valves. On echocardiogram, fibroelastomas may appear irregular, frequently threadlike or fingerlike in shape, can often branch or have flowerlike fronds, and be quite mobile. They may attach to either left ventricular outflow tract (LVOT) or aortic aspect of the aortic valve ( Fig. 37.4A and 
). They tend to occur more on the atrial side of the mitral valve but have been found attached to mitral chordae or papillary muscles as well (see Fig. 37.4B and 
). Pathologically, fibroelastomas appear to be endocardial papillary growths that are larger and more exuberant forms of Lambl’s (degenerative) excrescences. Studies indicate that fibroelastomas larger than 1 cm in length have greater potential to embolize and hence are often resected (with preservation of the underlying valve) for primary or secondary prevention. Interestingly, up to 30% of papillary fibroelastomas are findings discovered incidentally upon echocardiography, cardiac surgery, or autopsy.
. (B) Papillary fibroelastoma of the left ventricle (LV). This three-dimensional (3D) transthoracic echocardiogram (TTE) apical four-chamber view shows the fibroelastoma (arrow) attached to a mitral chorda. See also corresponding 
. Ao, Aorta; RV, left ventricle. Rhabdomyomas
Rhabdomyomas are less common primary tumors, representing approximately 7% of total population, but represent the most common primary heart tumor in children. Greater than 95% of rhabdomyomas occur in young children, often before a year of age or even detected on prenatal ultrasonography. Approximately half of all cases are associated with the genetic disorder tuberous sclerosis, but these tumors can also arise spontaneously. They appear as well-demarcated, round, homogeneously hyperechoic masses or discrete foci of thickened myocardium, most frequently located in the ventricles (80% of cases, with 15% arising in the right ventricle). They frequently occur in multiples and have not been reported to arise on cardiac valves. Rhabdomyomas carry a relatively good prognosis because they tend to regress, partially or completely, with time. For this reason, unless they cause severe obstruction, valve dysfunction, or intractable arrhythmias, they are observed expectantly.
The remaining tumors, which together make up less than 10% of primary benign cardiac tumors, include fibromas, hemangiomas, and teratomas. The fibromas and teratomas also occur predominantly in the pediatric population. Fibromas are the second most common benign cardiac tumor found in children and fetuses and appear as a solid very echodense mass of fibroblasts and collagen (an example is shown in Fig. 37.5 ). They typically arise in the ventricular myocardium, usually the LV free wall or interventricular septum (where they may mimic hypertrophic cardiomyopathy). They are always solitary and may have calcified centers (in contrast to rhabdomyomas). Unlike rhabdomyomas, the growth of fibromas appears to be variable. Some can grow over time and cause ventricular arrhythmias (often reentrant ventricular tachycardia) or less often obstruction or valvular dysfunction, in which case surgical resection may be necessary. Others have been observed over decades and shown regression, although they may never resolve completely. Of the remaining benign cardiac tumors, hemangiomas may be distinguished as being highly vascularized and hence may take up IV echocardiographic contrast ( Fig. 37.6 ). These are rare, can be found at any age, and are mostly located in the right atrium (particularly in children) and ventricles. The natural history is variable. Teratomas are usually found in the anterior mediastinum rather than intracardiac locations, particularly in the pericardium, where they may be attached to the ascending aorta and hemorrhage. These tumors are distinct in that they may possess elements of all three germ cell layers, as well as hair, skin, and muscle, and the propensity for malignancy is related to the degree of differentiation.
Benign Versus Malignant
Primary Malignant Tumors
Approximately one-fourth of all primary cardiac tumors are malignant, and most are sarcomas. Histologically, sarcomas can be subclassified as: angiosarcomas, sarcomas of varying lines of differentiation (undifferentiated, myxofibrosarcomas, sarcomas with bone matrix elements), and rhabdomyosarcoma. Angiosarcomas are the most common type in adults ( Fig. 37.7 ). These have a predilection for the right atrium, where they may invade the vena cava and tricuspid apparatus. They often appear bulky and multilobular, are broad based, grow rapidly in an exophytic manner, and present with intracardiac obstruction. The next most common primary heart malignancy is the rhabdomyosarcoma, which can arise in any cardiac chamber and is often multifocal. With all cardiac sarcomas, those that affect the left heart tend to present more often with congestive heart failure. Mesothelioma, fibrosarcoma, and cardiac lymphoma are rarer cardiac malignancies. Regardless of the histologic type of sarcoma, the treatment options and prognosis are usually dictated largely by the tumor’s anatomic location and effect on the heart. All the primary cardiac malignancies share a predilection for rapid invasive growth and metastasis with frequent extension to the pericardium, which may limit the options for complete resection. All confer a poor prognosis even with complete resection and systemic chemotherapy or radiotherapy. Unlike the benign cardiac tumors, there have been no demonstrated linkages of these malignancies with specific genetic mutations.
