Cardiac tumors in infants and children are rare. Previously, their atypical clinical presentation prevented timely diagnosis, and the diagnosis was often postmortem. Currently, the widespread use of echocardiography and other noninvasive diagnostic imaging modalities has resulted in a marked increase in the detection of cardiac tumors during fetal life and childhood, when the patients are often asymptomatic. In turn, early recognition of cardiac tumors has resulted in better understanding of their natural history and, combined with advances in surgical and interventional techniques, an improved overall outcome.
It is difficult to ascertain the true incidence of cardiac tumors because of the tendency to base estimates on postmortem studies, case reports, and experiences of single institutions. The lack of noninvasive diagnostic imaging in earlier reports was another limiting factor. Based on the data of 22 large autopsy series, the incidence of cardiac tumors in all age groups has been reported at approximately 0.02%. Large pediatric studies performed in the era of echocardiography have reported an incidence of 0.17% to 0.2% in children and 0.14% in fetuses.
The majority of cardiac tumors in children are benign. Malignant tumors are exceedingly rare, with most being metastatic rather than primary. Overall, the most common pediatric cardiac tumor is rhabdomyoma. Fibromas and myxomas tend to be the next most common tumors in larger studies. Presentation is dependent on age, with myxomas being more common in older patients and rhabdomyomas and teratomas predominating in fetuses and infants. Table 52.1 shows the breakdown of 158 patients up to 18 years old diagnosed with cardiac tumors at four Chinese hospitals between 1998 and 2014. Table 52.2 shows the breakdown of 173 patients up to 21 years old diagnosed with primary cardiac tumors at Children’s Hospital Boston between 1968 and 2010. Table 52.3 shows the breakdown of 224 fetuses, stillborns, and neonates compiled from a meta-analysis of the literature performed in 2004.
| Type of Tumor | No. (%) | % Male | Age (Median) | Surgeries | Deaths |
|---|---|---|---|---|---|
| Rhabdomyoma | 100 (60.2) | 69 | 4 mo | 16 | 4 |
| Fibroma | 21 (12.7) | 57 | 9 mo | 11 | 1 |
| Myxoma | 15 (9) | 73 | 10 y | 13 | |
| Vascular | 6 (3.6) | 67 | 2.5 mo | 5 | |
| Lipoma | 5 (3) | 60 | 9 y | 3 | |
| Papillary fibroma | 2 (1.2) | 50 | 2 | ||
| Pericardial cyst | 1 (0.6) | 100 | |||
| Primary malignant | 8 (4.8) | 8 | 3 | ||
| Metastatic | 6 (3.6) | 2 | 4 | ||
| Unknown | 2 (1.2) | 2 | |||
| Overall | 166 (100) | 67 | 59 | 13 |
| Type of Tumor | N (%) | % Male | Median Age at Diagnosis (Range) | Asymptomatic (%) | Hemodynamic Changes (%) | Significant Arrhythmias (%) | Deaths (%) |
|---|---|---|---|---|---|---|---|
| Rhabdomyoma | 106 (61) | 46 | 2 mo (PN-18 y) | 76 (7 2) | 18 (17) | 17 (16) | 3 ( 3) |
| Fibroma | 25 (14) | 64 | 1 y (PN-10 y) | 4 (16) | 5 (20) | 16 (64) | 0 |
| Myxoma | 14 (8) | 43 | 9 y (3 wk–21 y) | 5 (36) | 6 (4 3) | 1 (7) | 0 |
| Vascular | 6 (4) | 67 | 11 y (PN-17 y) | 4 (66) | 0 | 1 (17) | 2 (3 3) |
| Teratoma | 4 (2) | 25 | 20 days (PN-3 y) | 0 | 4 (100) | 0 | 1 (25) |
| Lipoma | 3 (2) | 67 | 13 y (1 day–16 y) | 3 (100) | 0 | 0 | 0 |
| Other | 15 (9) | 67 | 1 y (1 day–16 y) | 1 (7) | 2 (1 3) | 7 (47) | 0 |
| Overall | 173 (100) | 55 | 7 mo (PN-21 y) | 93 (54) | 35 (20) | 42 (24) | 6 ( 3) |
| Type of Tumor | No. (%) | No. Alive | % Survival |
|---|---|---|---|
| Rhabdomyoma | 120 (53.8) | 72 | 60 |
| Teratoma | 40 (17.8) | 30 | 75 |
| Fibroma | 28 (12.4) | 8 | 29 |
| Purkinje cell tumor | 15 (6.6) | 1 | 7 |
| Vascular tumors | 13 (5.8) | 11 | 85 |
| Myxoma | 6 (2.7) | 1 | 17 |
| Malignant | 2 (0.9) | 0 | 0 |
| Overall number | 224 (100) | 123 | 55 |
a As reviewed by Isaacs H Jr. Fetal and neonatal cardiac tumors. Pediatr Cardiol. 2004;25:252–273.
Definitions
The word tumor is used in this chapter to refer to a neoplasm, or an abnormal growth of cells. This differentiates it from other tissue masses such as hematomas, thrombi, or vegetations.
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Benign tumors, as opposed to malignant tumors, do not invade adjacent tissues and do not metastasize to distant sites.
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Primary: located at site of tissue origin.
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Secondary: found at distant sites due to metastasis or direct invasion.
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Hamartomas: benign, characterized by overgrowth of normal tissue with few atypical changes, and the inability to undergo mitosis and metastasis.
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Polypoid, papillary, and villous: refer to the gross structure, resembling polyps, papillae, or villi, respectively.
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Sessile: attached to adjacent tissue by a broad base.
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Pedunculated: attached by a peduncle, or stalk.
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Circumscribed: confined to a limited area.
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Encapsulated: surrounded by a rim of connective tissue.
Clinical Signs and Symptoms
Although cardiac tumors are usually benign in children, they may induce life-threatening symptoms. Their clinical manifestations are often nonspecific. They may mimic many other diseases of the heart and lungs. Classically, the clinical presentation is divided according to whether it is the consequence of systemic, embolic, or cardiac effects ( Table 52.4 ).
| Symptoms/Signs | Remarks |
|---|---|
| SYSTEMIC | |
| Fever General malaise Weight loss Fatigue | May mimic endocarditis or malignant disease |
| Digital clubbing Raynaud phenomenon Myalgia and arthralgia | May mimic collagen, rheumatic, or malignant disease |
| EMBOLIC | |
| Systemic embolism | May affect almost any organ Caused by embolization of left-sided tumor fragments or thrombi aggregated at its surface |
| Pulmonary embolism | Caused by embolization of right-sided tumors |
| CARDIAC | |
| Arrhythmias | Almost any arrhythmias can occur Complete atrioventricular block and sudden death are seen as the extreme |
| Cardiac failure | May mimic dilated, restrictive, or hypertrophic obstructive cardiomyopathy May present with cardiomegaly, respiratory distress, hydrops, pulmonary edema, cyanosis |
| Pericardial effusion and tamponade | Seen mainly in teratoma, malignant tumors, and secondary lesions |
| Obstruction | May cause outflow tract or atrioventricular valve obstruction and mimic valvar disease May present with new murmur, syncope, sudden death, or acute pulmonary edema Symptoms and murmur may relate to the patient’s position |
| Tumor plop | Is almost the only specific sign (with the postural variation of a murmur) Results from sudden tension on the stalk of the tumor as it prolapses during diastole into the left ventricular cavity with the possible impact of the mass on the ventricular wall |
Systemic Manifestations
The systemic manifestations of tumors of the heart are manifold and include findings such as fever, general malaise, loss of weight, and fatigue. Digital clubbing, Raynaud phenomenon, myalgia, and arthralgia are usually associated with myxomas. All these features can mimic infective endocarditis, collagen vascular disease, rheumatic heart disease, or malignancy. The constitutional symptoms disappear when the tumor is removed. There is evidence to suggest that the inflammatory and autoimmune manifestations seen in the presence of myxomas may be the result of the production and release of the cytokine interleukin-6 by the tumor.
Embolic Manifestations
Embolic signs are not an uncommon manifestation of cardiac tumors, being reported in 30% of patients with left atrial myxomas. Embolism is also well described in children but is infrequent during fetal life or the neonatal period. There can be embolization of either fragments of the tumor itself ( Fig. 52.1 ), or thrombus aggregated at the surface of the tumor ( Fig. 52.2 ). Embolization of the entire tumor has been described in rare cases, often with tragic consequences. The distribution of such emboli depends largely on the localization of the primary tumor itself, along with the presence or absence of additional cardiac malformations, such as shunts or abnormal flow patterns. Embolization of tumor fragments occurs only when the tumor itself has an intracavitary extension. However, thromboembolic formation can occur also with primary intramural tumors that compromise the endocardium of the cardiac chamber, either by mechanical compression or by inducing a functional disturbance.
In general, left-sided tumors embolize to the systemic circulation. Hence they may affect almost any organ, even the heart itself. Sudden occlusion of a peripheral artery should always alert to the possibility of embolization from a primary intracardiac tumor and should alert to the possibility of cerebral embolism. Moreover, multiple systemic embolization may mimic systemic vasculitis or infective endocarditis, particularly when producing systemic manifestations.
Primary tumors in the right heart chambers may cause pulmonary embolism. This may be indistinguishable from pulmonary embolism secondary to venous thromboembolism. Perfusion defects in the lung due to embolization from a tumor do not usually resolve within a few weeks, as they do with venous embolization. Embolization from a tumor may also be suggested by complete absence of flow to one lung in the presence of a normal perfusion scan on the opposite lung. This is most unusual in patients with recurrent pulmonary venous thromboembolism.
Cardiac Manifestations
The cardiac events are largely dependent on the location and extent of the tumor within the heart. Tumors that are localized within the myocardium may be asymptomatic and discovered incidentally on imaging studies or at autopsy. Detection of a cardiac mass on routine obstetric sonographic scan is often the initial finding in fetuses.
Arrhythmias
Disturbances of cardiac rhythm can be the first manifestation of a primary cardiac tumor. Should the tumor be located in the region of the atrioventricular node or conduction axis, even small tumors may produce disturbances of atrioventricular conduction. Complete atrioventricular block and sudden death are seen as the extreme clinical manifestation, especially for rhabdomyomas. Moreover, the intramural location of primary tumors may underlie a wide variety of disturbances of rhythm, including atrial fibrillation or flutter, paroxysmal atrial tachycardia, atrioventricular junctional rhythm, partial or complete atrioventricular block, supraventricular tachycardia, atrial and ventricular premature beats, ventricular tachycardia, and ventricular fibrillation.
Cardiac Failure and Pericardial Effusion
Infiltrative tumors of the myocardium can cause hemodynamic compromise. This tends to occur late in the clinical course when there is substantial involvement of the myocardium or pericardium ( Fig. 52.3 ), producing symptoms of cardiac failure consequent to systolic and/or diastolic dysfunction. In some instances, the clinical presentation may mimic that of dilated, restrictive, or hypertrophic cardiomyopathy. Pericardial exudates, eventually with cardiac tamponade, may be the first symptom of the epicardial location of a tumor. This is mainly seen with teratomas, vascular tumors, malignant tumors, and secondary lesions.
Obstruction
Primary cardiac tumors with intracavitary extension may cause obstruction to inflow and outflow tracts, systemic and pulmonary veins and arteries, coronary arteries, and interfere with valvar function ( Fig. 52.4A ). The signs and symptoms are thus myriad and dependent on the chamber involved and the size and nature of the tumor. They can mimic valvar disease, left- and right-sided heart failure, coronary ischemia, and cardiac tamponade. All these obstructive manifestations may have a sudden onset, such as in the case of a pedunculated highly mobile left atrial tumor, which can cause syncope, sudden unexpected death, or acute pulmonary edema. Such findings are often intermittent and may relate to the posture of the patient. As stated before, the picture may be further complicated by pulmonary embolism and secondary pulmonary hypertension. In fetuses, obstruction is noted to happen at any stage of gestation, and obstructions to systemic venous return and/or both outflow tracts simultaneously are noted to be particularly worrisome.
Physical Examination
In general, physical examination is nonspecific. Murmurs, when present, are in themselves nonspecific, but certain atypical findings may suggest a cardiac tumor rather than primary valvar or myocardial disease. Such findings include postural variation in the intensity of the murmur, and the presence of a so-called tumor “plop.” The plop has been described particularly in patients with left atrial myxoma, being characteristic of a pedunculated and highly mobile tumor. This plop was heard in only approximately 16% of the patients in one large series. It most likely results from sudden tension on the stalk of the tumor as it prolapses during diastole into the left ventricular cavity, along with the possible impact of the mass on the ventricular wall.
Dermatologic findings can also alert the clinician to certain types of tumors. Tuberous sclerosis complex (TSC) is associated with rhabdomyomas and characteristic skin lesions such as facial angiofibromas, hypomelanotic macules, shagreen patches, and periungual fibromas. Carney complex is associated with atrial myxomas. These patients have a variety of skin pigmentation abnormalities, including intense freckling and blue nevuses. Gorlin syndrome is associated with fibromas and is characterized by multiple basal cell carcinomas.
Investigations
Laboratory Studies
These are nonspecific. Abnormal findings may include elevated erythrocyte sedimentation rate, C-reactive protein, hypergammaglobulinemia, thrombocytosis, thrombocytopenia, polycythemia, leukocytosis, and anemia.
Electrocardiography
The electrocardiogram may also be nonspecific. All types of disturbances of rhythm and conduction, and abnormalities of voltage and the ST-T segments, may be seen. The electrocardiogram may also display the typical pattern of atrial dilation or ventricular hypertrophy. Incidental low-voltage complexes may be registered, indicating possible pericardial involvement. Occasionally, it is possible to find the pattern of ventricular preexcitation. This is particularly the case when the accessory muscular atrioventricular pathways are composed of the intracardiac tumor.
Chest Radiography
Cardiac tumors may alter the contours of the heart, but the changes in themselves are most often nonspecific. The cardiac contour may be normal or may display enlargement of either the entire heart or any particular chamber. Gross and bizarre distortions of the cardiac contour occasionally occur that are then suggestive of a tumor. The overall picture may be further complicated by the presence of pericardial fluid. Radiographic signs of pulmonary venous obstruction with left atrial enlargement may be observed in patients with obstructive left-sided tumors. Calcification of a primary tumor may occasionally be so intense that it can be noted on the chest radiograph ( Fig. 52.5 ).
Echocardiography
Echocardiography is universally established as the first-line and main diagnostic modality for tumor assessment. Transthoracic echocardiography is highly portable and ubiquitous, with very high spatial and temporal resolution. It allows for accurate determination of the size, shape, texture, location, attachment, mobility, and hemodynamic consequences of the tumor. Echocardiography gives information as to whether the tumor is encapsulated and whether it is solid or cystic. Texture may be inferred by the grayscale appearance, although interpretation remains subjective. Color flow mapping has been applied to distinguish tumor mass from endocardium. Three-dimensional echocardiography may allow for improved visualization of morphologic and spatial characteristics of cardiac and paracardiac tumors, establishing their relationships with adjacent structures, and in certain cases may be superior to transthoracic echocardiography in the evaluation of the size of intracardiac masses ( Fig. 52.6 ).
Transesophageal echocardiography can be a useful adjunct to transthoracic imaging, notably in patients with suboptimal transthoracic windows. In such patients it is ideally suited for the examination of posterior structures such as the atriums, interatrial septum, caval veins, and atrioventricular valves. Another important application is the differentiation of true pathology from normal, or variants of normal, anatomy such as the terminal crest of the right atrium. In addition, transesophageal two- and three-dimensional imaging can be used intraoperatively to assist with surgical excision of cardiac tumors or to guide transvenous biopsy.
The diagnostic sensitivity of transthoracic and transesophageal approaches has been reported to be 93.3% and 96.8%, respectively. The sensitivity is greatest for endocardial lesions, where the contrast between tumor and an echolucent cavity is most apparent, permitting characterization of the size and mobility of the masses. In contrast, echocardiographic assessment of the pericardial tumors may be more limited due to their frequent position in the echocardiographic far field.
Prenatal echocardiographic screening ( Fig. 52.7 ) has permitted fetal tumors to be diagnosed as early as 15 weeks of gestation, with two-thirds of the tumors being rhabdomyomas. Prior knowledge of the existence of the tumor in some circumstances has permitted life-saving interventions, such as intrauterine pericardiocentesis or even intrauterine surgery. Prenatal diagnosis certainly permits optimization of postnatal care. Spontaneous regression of even symptomatic tumors has also been described when diagnosed during fetal life.
Magnetic Resonance Imaging and Computed Tomography
Cardiac magnetic resonance imaging (MRI) has emerged as a useful companion to echocardiography in the diagnosis of pediatric cardiac tumors. This is largely due in part to the ability of MRI to differentiate between tumor types based on their appearance on different imaging sequences.
A typical MRI examination begins with steady state free precession (bright blood) cine angiographic sequences in multiple cardiac planes. These sequences provide excellent visualization of the heart, pericardium, vasculature, and adjacent structures. Tumor size, location, and attachments are generally well visualized and can be assessed throughout the cardiac cycle to assess for obstruction. Ventricular function is also well visualized. Spin echo (black blood) sequences allow for tissue characterization based on T1 (fat enhancing) and T2 (water enhancing) weighting and the application of fat suppression. After gadolinium-based contrast administration, first pass perfusion sequences allow for assessment of tumor vascularity. Late gadolinium enhancement sequences can assess for fibrosis and are useful for identification of thrombus. Magnetic resonance angiography can demonstrate the relationship of the tumor to blood vessels, if applicable. Three-dimensional acquisitions can be performed with or without contrast and allow for multiplanar reconstructions and three-dimensional modeling and printing. MRI is unable to assess for calcification, which is best seen by x-ray–based techniques and echocardiography.
The signal intensity of the tumor on each sequence is assessed and compared with published tables for different tumor types. Certain tumors have pathognomonic features such as strong late gadolinium enhancement for fibromas, fat suppression for lipomas, and strong first-pass perfusion for vascular tumors ( Fig. 52.8 ). Features suggestive of malignancy are ill-defined boundaries, crossing of tissue planes within the heart, involvement of both cardiac and extracardiac structures, and linear growth through large blood vessels ( Fig. 52.9 ).
MRI allows for better visualization of cardiac structures than echocardiography in patients with poor acoustic windows. It also provides a wider field of view than echocardiography, allowing for clearer visualization of the heart and tumor relative to the adjacent mediastinum, lungs, or vascular structures. The spatial and temporal resolution of MRI may be limited compared with echocardiography, which may be better suited for anatomic visualization in the smallest patients and in cases with small mobile masses and very thin attachments. MRI is highly sensitive to ferromagnetic artifact from certain implantable devices and may be contraindicated in patients with devices such as pacemakers, defibrillators, and cochlear implants. MRI can be time consuming and difficult to obtain in patients with arrhythmias and requires deep sedation or general anesthesia in patients younger than 8 years. Compared with computed tomography (CT), it has the advantage of not requiring radiation or iodinated contrast.
CT scanning allows for multiplanar imaging with excellent spatial resolution. It is superior to MRI for assessment of calcifications but otherwise more limited in its ability for tissue characterization. It is also generally preferable to MRI for assessment of coronary arteries and their potential relationship to tumor. Modern high-pitch CT scanners allow for examination using a minimum of radiation exposure and are often fast enough to obtain diagnostic images in younger patients without sedation.
Catheterization and Angiocardiography
Once accepted as the gold standard for diagnosis, angiocardiography has waned in importance as a result of the availability and reliability of noninvasive imaging. Angiocardiography remains the gold standard for assessment of the coronary arterial relationship to tumor in cases where CT and MRI are equivocal. In certain select circumstances, endomyocardial biopsy may be preferable to surgical biopsy. Catheterization carries the inherent risk of placing a catheter near or across a friable tumor, a process that may lead to embolization.
Types of Tumor
Rhabdomyomas
Rhabdomyomas are by far the most frequent tumors found in fetuses, infants, and children. They occur almost exclusively in patients younger than 15 years, and approximately 75% are seen in patients younger than 1 year. There is a strong association between rhabdomyomas and TSC. Rarely, rhabdomyomas have been reported in association with congenital heart defects such as tetralogy of Fallot and Ebstein anomaly.
Rhabdomyomas are hamartomas characterized by grotesquely swollen myocytes, which present an almost empty cytoplasm traversed by tiny strands of cross-striated sarcoplasm. The nucleus may thus appear suspended within the cell, giving rise to the so-called spider cell ( Fig. 52.10 ). Rhabdomyomas present as circumscribed nonencapsulated lesions, varying in size from a few millimeters to several centimeters. Occasionally, the lesion may outgrow the size of the heart (see Fig. 52.1 ). Rhabdomyomas are usually multiple and have a distinct preference for the ventricles ( Fig. 52.11 ). Single and atrial rhabdomyomas are less common. The lesions may be limited to the myocardium or extend from their intramural location to occupy an intracavitary position (see Fig. 52.11 ).
