Cardiac tumours in infants and children are rare. Their atypical clinical presentation prevented timely diagnosis in the past, when cardiac tumours were often a postmortem finding. The widespread use of echocardiography, and other non-invasive diagnostic methods, in recent years has resulted in a marked increase in the detection of cardiac tumours during childhood, when the patients are often asymptomatic, and also in fetal life. 1,2 In turn, early recognition of cardiac tumours has resulted in better understanding of their natural history and, combined with advances in surgical techniques, an improved overall outcome. 1,3
It is difficult to ascertain the true incidence of cardiac tumours because of the tendency to base estimates on postmortem studies, case reports, and experiences of single institutions. The lack of non-invasive diagnostic imaging in earlier reports was another limiting factor. In the general population, and based on the data of 22 large autopsy series, the incidence of cardiac tumours was reported at around 0.02%. 4 The reported incidence in infants and children varied from 0.027% as assessed from autopsy records, 5 to 0.49% in the clinical series analysed in the New England Regional Infant Cardiac Program. 6 Another analysis 2 showed that the incidence of cardiac tumours in children had seemingly increased from 0.06% over the period 1980 to 1984, to 0.32% for the period 1990 to 1995. Review of data from the Armed Forces Institute of Pathology, combined with personal experience from the Cardiovascular Pathology Registry in the Academic Medical Center, Amsterdam, shows that, among a total of 386 primary tumours of the heart collected between 1976 and 1993, only 55 occurred in infants and children below the age of 16 years ( Table 51-1 ). 7 Of these, one-fifth were considered malignant. Table 51-2 shows a detailed breakdown of the types of tumours reported in stillbirths, fetuses, and neonates. 1
| Benign | N = 44 | Malignant | N = 11 |
|---|---|---|---|
| Rhabdomyoma | 20 (19) | Rhabdomyosarcoma | 3 (1) |
| Fibroma | 13 (8) | Angiosarcoma | 1 (0) |
| Myxoma | 4 (0) | Malignant fibrous histiocytoma | 1 (0) |
| Vascular tumour | 2 (1) | Leiomyosarcoma | 1 (1) |
| Tumour of the atrioventricular node | 2 (1) | Fibrosarcoma | 1 (0) |
| Purkinje cell tumour | 2 (2) | Myxosarcoma | 1 (0) |
| Teratoma | 1 (1) | Unclassified | 3 (1) |
∗ The numbers of subjects below the age of 1 year are shown in parentheses.
| Type of Tumour | No. (%) | No. Alive | Percent Survival (%) |
|---|---|---|---|
| Rhabdomyoma | 120 (53.8) | 72 | 60 |
| Teratoma | 40 (17.8) | 30 | 75 |
| Fibroma | 28 (12.4) | 8 | 29 |
| Purkinje cell tumour | 15 (6.6) | 1 | 7 |
| Vascular tumours | 13 (5.8) | 11 | 85 |
| Myxoma | 6 (2.7) | 1 | 17 |
| Malignant | 2 (0.9) | 0 | 0 |
| Overall number | 224 (100) | 123 | 55 |
∗ As reviewed by Isaacs H Jr: Fetal and neonatal cardiac tumors. Pediatr Cardiol 2004;25:252–273.
CLINICAL SIGNS AND SYMPTOMS
Although cardiac tumours are usually benign in children, they may induce even life-threatening symptoms. Their clinical manifestations are often non-specific. 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 51-3 ).
| Symptoms/Signs | Remarks |
|---|---|
| |
| May mimic endocarditis or malignant disease |
| May mimic collagen, rheumatic or malignant disease |
| |
| Systemic embolism |
|
| Pulmonary embolism | Caused by embolisation of right-sided tumours |
| |
| Arrhythmias |
|
| Cardiac failure |
|
| Pericardial effusion and tamponade | Seen mainly in teratoma, malignant tumours, and secondary lesions |
| Obstruction |
|
| Tumour plop |
|
| Investigation | Remarks |
|---|---|
| Blood |
|
| Electrocardiogram |
|
| Chest radiograph |
|
| Echocardiogram |
|
| Magnetic resonance imaging |
|
Systemic Manifestations
The systemic manifestations of tumours of the heart are manifold, and include findings such as fever, general malaise, loss of weight, and fatigue. Digital clubbing, Raynaud’s phenomenon, myalgia, and arthralgia are usually associated with myxomas. All these features can mimic infective endocarditis, collagen vascular disease, rheumatic heart disease, or malignancy. 8 The constitutional symptoms disappear when the tumour is removed. 8 During the last 15 years, much evidence has accrued to suggest that 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 tumour. 8–11
Embolic Manifestations
Embolic signs are not an uncommon manifestation of cardiac tumours, being reported in three-tenths of patients with left atrial myxomas. 12 Embolism is also well described in children, 13 but is infrequent during fetal life or the neonatal period. 1 There can be embolisation of either fragments of the tumour itself ( Fig. 51-1 ), or thrombus aggregated at the surface of the tumour ( Fig. 51-2 ). The distribution of such emboluses depends largely on the localisation of the primary tumour itself, along with the presence or absence of additional cardiac malformations, such as additional shunts or abnormal patterns of flow. Embolisation of tumour fragments occurs only when the tumour itself has an intracavitary extension. Thromboembolic formation, however, can occur also with primary intramural tumours that compromise the endocardium of the cardiac chamber, either by mechanical compression or by inducing a functional disturbance. Generally speaking, left-sided tumours embolise to the systemic circulation. Hence, they may affect almost any organ, even the heart itself. 14 Sudden occlusion of a peripheral artery should always alert to the possibility of embolisation from a primary intracardiac tumour, and should alert to the possibility of cerebral embolism. 13 Moreover, multiple systemic embolisation may mimic systemic vasculitis or infective endocarditis, particularly when producing systemic manifestations.
Primary tumours in the right heart chambers may cause pulmonary embolism. 15 This may be indistinguishable from pulmonary embolism secondary to venous thromboembolism. Perfusion defects in the lung due to embolisation from a tumour do not usually resolve within a few weeks, as they do with venous embolisation. Embolisation from a tumour 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 the extent of the tumour within the heart. Tumours that are localised within the myocardium may occasionally pass unnoticed clinically. They may be discovered as incidental findings at echocardiography or postmortem. Detection of a cardiac mass on routine obstetric sonographic scan is often the initial finding in fetuses. 1
Arrhythmias
Disturbances of cardiac rhythm can be the first manifestation of a primary cardiac tumour. 16 Should the tumour be located in the region of the atrioventricular node or conduction axis, even small tumours may produce disturbances of atrioventricular conduction. Complete atrioventricular block and sudden death are seen as the extreme clinical manifestation, especially for rhabdomyomas. 1 Moreover, the intramural location of primary tumours may underlie a wide variety of disturbances of rhythm, including atrial fibrillation or flutter, paroxysmal atrial tachycardia, atrioventricular junctional rhythm, Wolff-Parkinson-White syndrome, atrial and ventricular premature beats, ventricular tachycardia, and ventricular fibrillation. 16–19
Cardiac Failure and Pericardial Effusion
Infiltrative tumours of the myocardium can cause haemodynamic compromise. This tends to occur late in the clinical course when there is substantial involvement of the myocardium or pericardium ( Fig. 51-3 ), producing symptoms of cardiac failure consequent to systolic and or diastolic dysfunction. 1 In some instances, the clinical presentation may mimic that of dilated, restrictive, or hypertrophic obstructive cardiomyopathy. 20,21 Pericardial exudates, eventually with cardiac tamponade, may be the first symptom of the epicardial location of a tumour. 22,23 This is mainly seen with teratomas, malignant tumours, and secondary lesions.
Obstruction
Primary cardiac tumours with intracavitary extension may cause obstruction, or may interfere with valvar closure ( Fig. 51-4 ). 1,3 The signs and symptoms are then highly dependent upon the chamber involved, and the size of the tumour. The embolic effects, which are a frequent complication, similarly relate directly to the site of the tumour. Left atrial tumours may produce mitral stenosis (see Fig. 51-4 ) or insufficiency, and may mimic valvar disease, with new murmurs as a frequent presenting sign in infants and children. 1,24 Intracavitary left ventricular tumours may also cause inflow or outflow obstruction, or atrioventricular valvar insufficiency, along with the anticipated accompanying signs and symptoms. All these obstructive manifestations may have a sudden onset, particularly in the case of a pedunculated highly mobile left atrial tumour, which can cause syncope, sudden unexpected death, or acute pulmonary oedema. 1,3 Such findings are often intermittent, and may relate to the posture of the patient.
Location of Tumour within the Heart
Intracavitary tumours within the right atrium frequently produce symptoms of right-sided cardiac failure. 25 The manifestations may result from either obstruction of the tricuspid orifice or tricuspid valvar insufficiency, the latter secondary to interference with valvar closure. Caval venous obstruction may be seen as a leading feature. 26 Right ventricular intracavitary tumours may similarly produce signs and symptoms of tricuspid valvar obstruction, but can also produce outflow obstruction or atrioventricular valvar insufficiency. 24,27–30 Right-sided failure is often the leading manifestation. As with all cardiac tumours, the physical signs may vary considerably, depending upon their site and size. As stated before, the picture may be further complicated by pulmonary embolism and secondary pulmonary hypertension. Tumours in the right ventricle, therefore, may mimic congenital pulmonary stenosis, restrictive cardiomyopathy, or even cyanotic cardiac disease, especially in the neonate. 1 Atypical chest pain may occur. This is caused by coronary arterial obstruction, either from compression by the tumour itself, or because of coronary arterial embolism (see Fig. 51-2 ). 14 Hence, intracavitary left ventricular tumours may mimic other conditions, such as aortic and subaortic stenosis, asymmetric septal hypertrophy, and endocardial fibroelastosis. 31–35
PHYSICAL EXAMINATION
Physical examination is, in general, non-conclusive. Murmurs, when present, are in themselves non-specific, but certain atypical findings may suggest a cardiac tumour 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 tumour plop. The plop has been described particularly in patients with left atrial myxoma, being characteristic of a pedunculated and highly sessile tumour. The plop was heard in one-sixth of the patients in one large series. 12 It most likely results from sudden tension on the stalk of the tumour as it prolapses during diastole into the left ventricular cavity, along with the possible impact of the mass on the ventricular wall. 36
INVESTIGATIONS
Laboratory Studies
These are non-specific ( Table 51-4 ). Abnormal findings include an elevated erythrocytic sedimentation rate, and increased levels of C-reactive protein in the serum, along with hypergammaglobulinaemia, thrombocytosis or thrombocytopenia, polycythaemia, leucocytosis, and anaemia.
Electrocardiography
The electrocardiogram is also non-specific. All kinds of disturbances of rhythm and conduction, and abnormalities of voltage and the ST-T segments, may be seen. 1,16 The electrocardiogram may also display the typical pattern of atrial dilation or ventricular hypertrophy. 1,12 Incidental low-voltage complexes may be registered, indicating possible pericardial involvement. Occasionally, it is possible to find the pattern of ventricular pre-excitation. 1 This is particularly the case when the accessory muscular atrioventricular pathways are composed of the intracardiac tumour. 37,38
Chest Radiography
Cardiac tumours may alter the contours of the heart, but the changes in themselves are most often non-specific. The cardiac contour may be normal, or may display enlargement of either the entire heart or any particular chamber. 39–41 Gross and bizarre distortions of the cardiac contour occasionally occur that are then suggestive of a tumour. 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 tumours. Calcification of a primary tumour may occasionally be so intense that it can be noted on the chest radiograph ( Fig. 51-5 ). 39,40
Echocardiography
Echocardiographic examination is now universally established as the main, and usually the only, diagnostic modality required for children. It allows accurate determination of the size, shape, texture, location, attachment, mobility, and haemodynamic consequences of the tumour. For most patients, it obviates the need for cardiac catheterisation and angiography. 2,3,42,43 Use of the technique, in some hands, 44 has resulted in dramatic increase in the annual incidence of cardiac neoplasms over a period of 5 years, combined with an equally dramatic reduction in unexpected intra-operative findings. Echocardiography is also the method of choice for follow-up, as spontaneous regression of tumours diagnosed during infancy is frequent. 45 The diagnostic sensitivity of transthoracic and transoesophageal approaches has been reported to be 93.3% and 96.8%, respectively. 46 The sensitivity is greatest for endocardial lesions, where the contrast between tumour and an echolucent cavity is most apparent, permitting characterisation of the size and mobility of the masses. In contrast, echocardiographic assessment of the pericardial tumours may be limited because of the echo density and their frequent position in the echocardiographic farfield. While involvement of the pericardium, and the extracardiac mediastinum, by the tumour may be revealed by scanning from multiple positions, this being mandatory when assessing any pericardial effusion of unknown aetiology, magnetic resonance imaging is a more capable and reliable technique for this task. Texture may be inferred by the gray-scale appearance, although interpretation remains subjective. 47 Colour processing of the cross sectional gray-scale image has also been applied to distinguish tumour mass from endocardium. 48,49 In recent years, contrast echocardiography has been shown to provide better visualisation of the interface between myocardium and blood. 50 Contrast perfusion imaging of cardiac masses with gray-scale power modulation also facilitates the differential diagnosis. 51 Echocardiography also gives information as to whether the tumour is encapsulated, and whether it is solid or cystic. 52 Cardiac tumours have the tendency to occur at multiple sites. Hence, echocardiographic evaluation should be thorough, encompassing the whole heart and pericardium. 3
Transoesophageal echocardiography can be a useful adjunct to transthoracic imaging, notably in patients with suboptimal transthoracic windows. It is ideally suited for the examination of suspected tumours involving the atriums, interatrial septum, caval veins, atrioventricular valves, and, to a lesser extent, the great arteries. 53 Another important application is the differentiation of true pathology from normal, or variants of normal, anatomy. For example, a prominent terminal crest may simulate a mass during transthoracic imaging of the morphologically right atrium. Transoesophageal echocardiography can demonstrate this to be a normal structure. In addition, transoesophageal imaging can be used intra-operatively to assist with surgical excision of cardiac tumours, or to guide transvenous biopsy. 3,54 Dynamic three-dimensional echocardiography allows a view of the contents of an intracardiac tumour. 55 It is a valuable way of defining the morphological and spatial characteristics of cardiac and paracardiac tumours, establishing their relationships with adjacent structures, and might be superior to transthoracic echocardiography in the evaluation of the size of intracardiac masses ( Fig. 51-6 ). 42,55–58 When used preoperatively, it may yield important additional information and improve the operative planning. 59 Prenatal echocardiographic screening ( Fig. 51-7 ), performed usually for the assessment of intrauterine growth, or occasionally as part of investigations for fetal arrhythmias or non-immune hydrops and high-risk pregnancies, has permitted fetal tumours to be diagnosed as early as 19 weeks of gestation, 1,60–62 with two-thirds of the tumours being rhabdomyomas. 1 Prior knowledge of the existence of the tumour in some circumstance has permitted life-saving interventions, such as intra-uterine pericardiocentesis, or even intra-uterine surgery. Prenatal diagnosis certainly permits optimisation of postnatal care. 61–64 Spontaneous regression of even symptomatic tumours has also been described when diagnosed during fetal life. 1
Magnetic Resonance Imaging and Computed Tomography
Since the mid-1980s, magnetic resonance imaging has been increasingly used for the detection and diagnosis of cardiac neoplasms, with various studies comparing its value to transthoracic echocardiography. 40,65–67 Resonance imaging shows better the contrast with soft tissue, and offers a larger field of view, showing the extent of the tumour relative to the adjacent mediastinum, lungs, or vascular structure ( Figs. 51-8 and 51-9 ). 65–70 The inherent natural contrast between the intracardiac and vascular spaces and the surrounding walls of cardiovascular structures enables sharp delineation of the myocardium, with negligible interference by bony or lung tissue. 71 Resonance imaging is unquestionably the superior investigative approach in pericardial lesions, and provides information on the haemodynamic consequences of the tumour. Contrast-enhanced imaging with paramagnetic agents and radio-frequency labelling permits further differentiation of tumour from viable myocardium. 72 With the recent improvement in pulse sequences for cardiac imaging, the motion artefact has been reduced, giving an even better quality to the images. 68 Spin-echo and cine-gradient-echo techniques provide additional valuable information concerning mobility, site of attachment, and effects on myocardial and valvar function. 73 The use of resonance imaging in children, nonetheless, is not free of limitations. Heavy sedation is often required to suppress deep respiration and other movements. In those with arrhythmias, interference can still cause significant motion artefact despite electrocardiographic gating, thus compromising the quality of imaging. 68 Furthermore, in contrast to echocardiography, the machine is not portable, and is not suitable for patients requiring intensive care. The technique is also incapable of demonstrating the presence of calcium. 68 Computed tomography, in contrast, is able to detect calcification, of value in the differential diagnosis of cardiac tumours. 67 Computed tomographic scanning is also faster and easier to perform than magnetic resonance imaging. 67 Recently, multi-slice computerised tomography has emerged, permitting detailed delineation of intra- and pericardial masses. 74
