Michele A. Frommelt1 and Rebecca S. Beroukhim2 1 Children’s Hospital of Wisconsin, Milwaukee, WI, USA 2 Boston Children’s Hospital, Boston, MA, USA Cardiac masses are abnormal growths of tissue within the heart or pericardium, and are categorized as tumors or non‐neoplastic masses. Tumors of the heart in the pediatric age group are typically characterized by a proliferation of tissue normally present at the site of origin. Cardiac tumors can comprise muscle (rhabdomyoma), fibrous tissue (fibroma), vascular tissue (hemangioma), mixed tissue (teratoma), fatty tissue (lipoma) and, rarely, metastatic tissue. Tumors of the heart can be defined as primary or secondary to other disease processes, as well as benign or malignant. Primary cardiac tumors are much more common in children, with almost all being histologically benign. This is in contrast to adults, where most cardiac tumors are secondary and related to metastatic disease. Non‐neoplastic masses include pericardial cysts, vascular malformations (arising from capillary, venous, arterial and/or lymphatic tissue), infectious and inflammatory masses among others. This chapter reviews the most common cardiac masses found in the pediatric population. Cardiac masses are rare in children, with an estimated incidence of 0.03–0.4%. In a review of 11,000 pediatric autopsies from the Boston Children’s Hospital, reported by Nadas and Ellison in 1968, cardiac masses were present in 0.027% [1]. In the New England regional study of more than 2000 infants with congenital heart disease, nine had primary cardiac tumors (0.4%) [2]. In an 8‐year review of more than 14,000 fetal echocardiograms, cardiac masses were present in 19 pregnancies, an incidence of 0.14% [3]. Almost all cardiac masses in these studies were benign, with the most common being rhabdomyoma. Over the past few decades, the recognition of cardiac masses has increased. This is likely not related to an increase in their prevalence, but may be explained by the widespread availability and increased sensitivity of 2‐dimensional (2D) echocardiography. This is demonstrated in a study by Beghetti et al., a 15‐year review of more than 27,000 pediatric patients with cardiac disease [4]. The overall incidence of a primary cardiac tumor was 0.2%, with an increase in incidence over each successive 5‐year period (from 0.06% in the period 1980–1984 to 0.32% in the period 1990–1995). More than half of the patients were less than 1 year old at the time of diagnosis, and 12 of the 56 patients were diagnosed prenatally. Table 34.1 summarizes the most common types of cardiac tumors in the pediatric age group. Rhabdomyoma is the most common primary tumor, comprising about 60–80% of cases (Table 34.1). Cardiac fibromas have the second highest incidence (6–25%), followed by myxoma (8%). Hemangiomas and lipomas are much less common. It is important to remember that many of the primary cardiac tumors in children are associated with hereditary syndromes [5]; for this reason, a consultation with a geneticist is generally recommended for children who present with a prenatal or postnatal diagnosis of a cardiac mass. A genetic diagnosis is not only used as a diagnostic aid but also useful in predicting the natural history of the mass, heritability, and comorbidities. At the initial echocardiographic evaluation, the tissue diagnosis is usually unknown. Therefore, a comprehensive study of the mass should involve a complete assessment of the morphology and size of the mass, involvement of adjacent cardiac structures, and thorough assessment of valves and ventricular function. The mass is evaluated from multiple views and angles with 2D and 3D echocardiography to measure size, location, and tissue appearance (echogenicity, homogeneity, or cystic appearance). Color Doppler imaging with low Nyquist limit is used to assess for vascularity. 3D imaging may aid in evaluation of ventricular size and function when the chamber is distorted by the mass (for example in patients with large fibromas). Local effects of the mass on adjacent cardiac structures, such as valves or outflow tracts, should be evaluated with color and spectral Doppler imaging. Finally, an evaluation for associated pericardial and/or pleural effusion is performed. Table 34.1 Characteristics of common cardiac masses in childhood * Characteristics of malignant tumors vary by type of tumor. ** From Hinton RB, Prakash A, Romp RL, et al. Cardiovascular manifestation of tuberous sclerosis complex and summary of the revised diagnostic criteria and surveillance and management recommendations from the International Tuberous Sclerosis Consensus Group. J Am Heart Assoc 2014;3:e001493. ‡ Percent of cases evaluated by cardiac MRI (pending publication). † Note that all masses have been reported in atypical locations. CMR, cardiac magnetic resonance; RICH, rapidly involuting congenital hemangioma. Rhabdomyomas, also known as hamartomas, are defined as an anomalous, benign proliferation of primitive myocardial tissue displaying typical “spider cells” on histopathology [6]. They are the most common benign congenital tumor, and are frequently associated with the tuberous sclerosis complex in nearly all patients with multiple tumors and approximately one‐third of patients with solitary ventricular tumors [7,8]. Tuberous sclerosis is a genetic disorder that affects cellular differentiation and proliferation, resulting in hamartoma formation in many organs, including the heart. Although it has an autosomal dominant inheritance pattern, more than half of the cases have been attributed to spontaneous mutations. There are two known genetic loci, one mapping to chromosome 9 and the other to chromosome 16 (also termed TSC1 and TSC2). The genetic mutations in the tuberous sclerosis complex lead to defects in proteins that regulate cellular growth and differentiation (tuberin and hamartin), resulting in proliferation of embryonal myoblasts. This typically yields multiple solid masses, which may arise anywhere in the atrial or ventricular myocardium. The presence of multiple cardiac masses is nearly pathognomonic for a diagnosis of tuberous sclerosis [7,9]. Notably, spontaneous regression of these cardiac tumors after birth is the rule [10–13]. Although the classic echocardiographic feature of the cardiac rhabdomyoma is the presence of multiple tumors, some rhabdomyomas present as solitary tumors involving the atrium or ventricle (Video 34.1). The tumors appear nodular and embedded in the myocardium, but often protrude into the involved cardiac chamber. They are typically homogeneous and hyperechoic compared with normal myocardium (Figure 34.1). Cardiac rhabdomyomas have a distinct preference for the ventricles. In a study by Nir et al., of 109 patients with tuberous sclerosis, 47 (43%) had cardiac rhabdomyoma. The tumors were most commonly located in the left (LV) and right (RV) ventricles (68 and 66%, respectively); only three patients (6%) were found to have right atrial tumors, and no tumors were found in the left atrium [14]. Figure 34.1 Four different patients with tuberous sclerosis complex and cardiac rhabdomyomas. (a, b) Classically, multiple echo‐bright, homogeneous nodular masses of varying sizes are seen arising from the ventricular myocardium and protruding into cardiac chambers. (c) Occasionally rhabdomyomas may be seen in the atria. (d) Atypical presentation of solitary rhabdomyoma protruding into the pericardial space. LA, left atrium; RA, right atrium. 2D imaging as well as color and pulsed‐wave (PW) Doppler from standard acoustic windows should be performed. The goals of the examination include determination of tumor size, location, and number. Hemodynamic abnormalities associated with the tumor are assessed, with quantification of inflow or outflow tract obstruction as well as valvar insufficiency. Evaluation of ventricular function is important, as replacement of the ventricular myocardium by noncontractile tumor tissue may mimic cardiomyopathy [15]. In the fetus, it is also important to evaluate cardiac rhythm, and to investigate the serous cavities for effusions. Serial echocardiographic evaluation is critical, both pre‐ and postnatally. Several studies have reported significant growth of cardiac rhabdomyoma in mid‐gestation, suggesting that hormonal stimulation in utero plays a role in the growth process [3,14]. If there is a family history of tuberous sclerosis, it is important to remember that prenatal ultrasound rarely detects tumors prior to 20 weeks’ gestation [16]. Therefore, an early screening ultrasound may be falsely reassuring. After birth, most cardiac rhabdomyomas undergo spontaneous regression. This phenomenon has been extensively studied and, indeed, is one of the hallmarks of these tumors [10–13]. Of note, rapid tumor growth has been reported postnatally when the patient is treated with corticosteroids. The size of cardiac rhabdomyomas should be followed carefully in patients receiving this and other types of drug therapy [17], as well as those followed expectantly. The clinical course is generally benign and largely determined by tumor size and the presence of inflow or outflow tract obstruction. Rarely, global ventricular function may be depressed if there is significant tumor replacement of normal myocardium. Cardiac arrhythmias are well reported, and may be related to interruption of the normal conduction pathways. In several studies, the presence of Wolff–Parkinson–White syndrome was more frequent in patients with tuberous sclerosis compared with the normal population. Incessant ventricular arrhythmias, although rare, can be life threatening [18–20]. The timing of presentation also influences clinical course. In the older child referred to the echocardiography laboratory with a new diagnosis of tuberous sclerosis, it would be unusual to find a cardiac rhabdomyoma of clinical significance. However, when the diagnosis of tuberous sclerosis is suspected prenatally, the fetus may present with demise secondary to severe outflow tract obstruction or sustained arrhythmias. In a retrospective 7‐year review by Geipel et al., 12 cases of cardiac tumors were observed prenatally. Eleven of the 12 were ultimately found to be rhabdomyomas, with one fibroma. Presenting symptoms were common in this age group, and included hydrops fetalis in five patients and arrhythmias in four patients. There were three elective terminations of pregnancy, one intrauterine demise related to severe left ventricular outflow tract (LVOT) obstruction, and three neonatal deaths, all related to massive tumor infiltration of the ventricular septum [21]. Since the first description in 2011, multiple case reports have been published demonstrating the efficacy of oral mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, in rapidly reducing the size and hemodynamic burden of large neonatal rhabdomyomas [22–34]. Furthermore, one report describes effective management of a hydropic fetus with transplacental sirolimus [35]. The mTOR inhibitors have also been successfully used to treat rhabdomyoma‐associated arrhythmias [36]. Given these data, it would be reasonable to attempt medical management prior to more invasive measures in hemodynamically unstable infants. Although clinical practice is evolving toward medical rather than surgical management, the medium‐ and long‐term outcomes of medical management remain unknown. Cardiac fibroma is a benign tumor of connective tissue derived from fibroblasts. It is the second most common type of primary cardiac tumor occurring in the pediatric age group (see Table 34.1). Cardiac fibromas are generally large solitary tumors, averaging 5 cm in diameter, with the larger lesions able to obstruct outflow tracts, compress cardiac chambers, and cause atrioventricular (AV) valve regurgitation. Their growth is typically within the myocardial mass itself and they occur most frequently within the anterior LV free wall or the interventricular septum. Rarely, a fibroma can be located in the RV free wall or in the atria. In contrast to rhabdomyomas, fibromas are more often associated with symptoms, more often require surgery, and do not spontaneously regress [4,15,37,38]. Although most cardiac fibromas in children occur as an isolated tumor, approximately 3–5% of children with this tumor will have the nevoid basal cell carcinoma syndrome (Gorlin syndrome) [39]. Gorlin syndrome is an autosomal dominant disorder characterized by the development of basal cell carcinomas at an early age, jaw keratocysts, and palmar or plantar pits. Patients with Gorlin syndrome may have multiple fibromas. The syndrome results from mutations in the PTCH1 (patched) gene, which has been mapped to chromosome 9. This gene is thought to function primarily as a tumor suppressor. Fibromas are often associated with ventricular arrhythmias such as premature ventricular contractions, ventricular tachycardia, and ventricular fibrillation with cardiac arrest. The arrhythmia mechanism has been linked to regions of entrapped myocardium, allowing for a mechanism of slow conduction and re‐entry (Figure 34.2) [40]. Cardiac fibromas are solitary lesions that usually arise from the LV free wall or ventricular septum. They typically appear spheroid and well‐circumscribed with surrounding myocardium. Fibromas can be massive, markedly distorting the cardiac muscle and chamber geometry. The acoustic signal is typically inhomogeneous with a hyperechoic periphery and hypoechoic centrally compared with normal myocardium. Overall, fibromas are less hyperechoic than rhabdomyomas. Calcification is frequent and an important diagnostic imaging feature (Figure 34.3). Areas of focal necrosis and cystic degeneration are common in larger tumors. It is important to note that a large septal fibroma can mimic hypertrophic obstructive cardiomyopathy. Distinguishing features include absence of thickening/hypertrophy of other cardiac walls and calcifications, which do not occur in hypertrophic cardiomyopathy. Fibromas may cause ventricular dysfunction, inflow or outflow tract obstruction, mitral and tricuspid regurgitation, and pulmonary vein compression in cases of massive tumors. 2D imaging from multiple views is performed to identify the location and morphology of the tumor, including assessment of ventricular size and function. Color and pulsed Doppler interrogation of the AV valves, outflow tracts, and pulmonary veins is employed as appropriate (Figure 34.4, Video 34.2). Although fibromas have a characteristic ultrasound appearance, the diagnosis may be difficult to distinguish from other cardiac masses by echocardiography. Fibromas have a classic pattern of late gadolinium enhancement on cardiac magnetic resonance (CMR) imaging that is nearly pathognomonic for the diagnosis [41]. Thus, in patients with suspected fibroma, CMR should be considered as a noninvasive diagnostic modality following initial diagnosis. Most cardiac fibromas present either as a mass during prenatal ultrasound, or during the first several years of life due to symptoms, heart murmur, or as an incidental finding on chest x‐ray or other form of chest imaging. Infants may present with life‐threatening arrhythmias or symptoms related to severe left or right ventricular outflow tract obstruction. The older child may be asymptomatic, but life‐threatening arrhythmias and sudden cardiac death have been reported in adolescents and older adults (Figure 34.5) [42]. Figure 34.2 Gross and histologic pathology of fibroma. (a) Typically fibromas are large intramyocardial masses involving the left ventricular wall or interventricular septum, and compress adjacent structures. (b) The mechanism of ventricular arrhythmias in fibroma is thought to be related to regions of entrapped myocardium, allowing for regions of slow conduction and re‐entry. Source: Reprinted from Carreon CK, Sanders SP, Perez‐Atayde AR, et al. Interdigitating myocardial tongues in pediatric cardiac fibromas: plausible substrate for ventricular tachycardia and cardiac arrest. JACC Clin Electrophysiol 2019;5:563–75. © Elsevier. Figure 34.3 Four different patients with fibroma. (a) Typical large, hyperechoic mass (arrow) involving the lateral wall of the left ventricle (LV). (b) The intramyocardial location of fibromas (arrow) can often be demonstrated well by echocardiography. (c) A large fibroma within the interventricular septum (arrow), which should not be confused with hypertrophic cardiomyopathy. (d) A speckled appearance of fibroma by echocardiography is usually due to calcifications within the tumor. LA, left atrium; RV, right ventricle.
CHAPTER 34
Cardiac Masses
Introduction
Incidence
Association with syndromes
Echocardiographic evaluation
Type
Rhabdomyoma
Fibroma
Myxoma
Teratoma
Hemangioma
Malignant*
Incidence‡
0.01–0.06% population**
61% of masses
14% of masses
8% of masses
2% of masses
4% of masses
Rare
Typical age of presentation
Fetal/neonatal
Neonatal, young children
Older children
Fetal/neonatal
Wide range
Older children
Associated genetic diagnosis
Tuberous sclerosis
Gorlin syndrome
Carney complex
None
None
Variable
Typical location†
Ventricle, intramyocardial and intracavitary
Ventricle, intramyocardial
Left atrium, endocardial, pedunculated
Intrapericardial, compressing right atrium and superior vena cava
Various, usually right atrium or right ventricle: endocardial, intramyocardial, intrapericarial, mediastinal
Inferior vena cava, right atrium, infiltrative appearance
Pericardial effusion common
No
Yes
No
Yes
Yes
Yes
Echocardiographic appearance
Multiple
Large, solitary
Solitary
Solitary
Solitary
Solitary
Very hyperechoic
Hyperechoic, well circumscribed
Mixed echogenicity
Solid/multicystic
Mixed echogenicity
Mixed echogenicity
CMR characteristics
Similar to myocardium
Bright with dark patchy areas on late gadolinium enhancement imaging
Variable
Variable
Perfusion on first pass perfusion imaging
Variable
Other associations
Atrial and ventricular arrhythmias
Ventricular arrhythmias
Tumor or thromboemboli
Commonly metastatic
Spontaneous regression
Yes
No
No
No
Yes, if RICH
No
Rhabdomyoma
Classification
Echocardiography
Clinical course
Fibroma
Classification
Echocardiography
Clinical course
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