Cardiac Rhabdomyoma

Etiology

Genetic modification during the development of striated muscle may cause rhabdomyoma.[3][4] No other causes have been identified. Between 80% and 90% of cardiac rhabdomyomas are linked to tuberous sclerosis. Surprisingly, only 43% to 67% of neonates with tuberous sclerosis have cardiac rhabdomyomas.[5][6]

Epidemiology

Primary cardiac tumors are rare and occur in 0.2% of children.[3] However, cardiac rhabdomyomas are the most common cardiac tumor in children, representing up to 43% in postmortem studies and from 50% to 78% in living cases.[3][4] This tumor is observed in both males and females, with male neonates being slightly more favored by the disease, without any documented proclivity for race.[5]

Pathophysiology

Cardiac rhabdomyoma is a hamartomatous tumor that typically develops within the myocardium and is most often detectable between 20 and 30 weeks of gestation. Prenatal detection rates have increased with advances in fetal imaging, and these tumors are more frequently identified in fetal than postnatal series. Common sites of involvement include the interventricular septum, both ventricles, and the atrioventricular valves. While cardiac rhabdomyomas can occur sporadically, there is a well-established association with tuberous sclerosis complex (TSC), an autosomal dominant disorder characterized by benign hamartomas in multiple organ systems.[6] TSC is usually diagnosed clinically, with confirmatory genetic testing for pathogenic variants in the TSC1 and TSC2 genes.[7]

Histopathology

On gross examination, rhabdomyomas typically appear as well-demarcated, nonencapsulated nodules that are white, gray, or yellow. Their size ranges widely, from as small as 1 mm up to 10 cm. While they most often arise within the ventricles, affecting the right and left sides equally, these tumors can also be seen in the atria, at the cavoatrial junction, embedded within the papillary muscles, the myocardial wall, the interventricular septum, or even on the epicardial surface. Notably, about 90% of cases involve multiple tumor sites. Although rhabdomyomas are usually intramural, they may extend into the cardiac chambers, sometimes filling an entire chamber and resulting in obstruction of inflow or outflow tracts. Even smaller lesions may involve the conduction system and precipitate arrhythmias.[3][8]Microscopically, rhabdomyomas consist of large, round, or polygonal cells characterized by clear cytoplasm rich in glycogen. The classic “spider cell” appearance is pathognomonic and features a central mass with the nucleus and thin cytoplasmic extensions radiating toward the periphery. Calcification and fibrosis within these tumors are uncommon.[9]

History and Physical

Cardiac rhabdomyoma can often be identified in utero as a cardiac mass using ultrasonography, with fetal echocardiography demonstrating increased sensitivity in detection compared to postnatal imaging.[10][11] Presentation in the fetus can range from incidental findings to serious complications such as heart block, hydrops fetalis, or pericardial effusion.[9] Large tumors may even lead to intrauterine fetal demise. Advances in imaging, including the use of deep learning algorithms like the AVRNet architecture, have shown remarkable accuracy—up to 99.85%—in identifying fetal cardiac rhabdomyomas, enhancing prenatal diagnostic precision.

Postnatally, cardiac rhabdomyomas are frequently asymptomatic; however, when symptoms occur, they often relate to arrhythmias or heart failure caused by obstruction of cardiac inflow or outflow tracts. Common presenting complaints include dyspnea, poor feeding, and signs of ventricular dysfunction. Physical examination may reveal murmurs from obstructive effects, irregular rhythms from arrhythmias, or signs of congestive heart failure such as hepatomegaly and respiratory distress. Given the strong association with TSC (Bourneville disease), patients may also exhibit characteristic dermatologic findings such as hypomelanotic “ash leaf” macules, shagreen patches, or facial angiofibromas, which can aid in clinical diagnosis. A thorough family history and examination for these stigmata are important components of patient evaluation.[12]

Evaluation

Evaluation of cardiac rhabdomyoma involves a combination of laboratory, imaging, and electrophysiological studies to confirm the diagnosis, assess tumor characteristics, and identify associated conditions such as TSC. Given the strong correlation between cardiac rhabdomyoma and TSC, genetic testing for TSC1 and TSC2 mutations is recommended to support diagnosis and guide family counseling. A baseline 12-lead electrocardiogram (EKG) is essential at diagnosis—even in asymptomatic patients—to detect conduction abnormalities or arrhythmias, with routine follow-up EKGs every 2 to 5 years. Holter or event monitoring may be necessary if intermittent arrhythmias are suspected. The imaging modality of choice for diagnosis and follow-up is pediatric transthoracic echocardiography, which typically reveals multiple echogenic nodular masses embedded within the ventricular myocardium.

These tumors may also protrude into the ventricular cavity. Atypical presentations, such as a single large tumor or involvement of the atria, can mimic other cardiac tumors like atrial myxoma, potentially complicating diagnosis. Cardiac magnetic resonance imaging is a valuable adjunct when echocardiographic findings are unclear, offering superior delineation of tumor margins, more accurate assessment of ventricular systolic function, and aiding surgical planning when resection is considered.[9] Additional radiographic studies, such as chest x-rays, may reveal cardiomegaly or pulmonary congestion but are nonspecific. A comprehensive approach combining clinical, genetic, EKG, and advanced imaging assessments is critical to optimizing diagnosis, management, and long-term surveillance of patients with cardiac rhabdomyoma.

Treatment / Management

Cardiac rhabdomyomas are asymptomatic and regress spontaneously. In rare instances of hemodynamic compromise and congestive heart failure, pharmacotherapy with angiotensin-converting enzyme inhibitors, digitalis, and diuretics is indicated. Prostaglandin E1 can manage hemodynamic instability in critically ill newborns with ventricular outflow obstruction. Prostaglandin E1 infusion keeps the arterial duct open and allows systemic and pulmonary blood mixing.

Oral mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, are increasingly used as the primary treatment for rhabdomyomas. Multiple case reports document the successful use of mTOR inhibitors to treat life-threatening cardiac rhabdomyomas in infants, often associated with TSC. A 2023 systematic review pooled 31 reports (48 patients) and found that everolimus, in 83% of cases, or sirolimus shrank cardiac rhabdomyomas by an average of 57%, with improvement in hemodynamic status in most infants. Median therapy duration was 2 months. Common adverse effects were manageable.[13] In 1 notable case study, transplacental sirolimus reduced fetal cardiac rhabdomyoma considerably through maternal oral intake.[14]

mTOR inhibitors are traditionally known for halting the multiplication of T- and B-lymphocytes and preventing in-stent restenosis, which is why they are used in transplant and angioplasty. Their mechanism of action is through binding to the FK-binding protein 12, forming a complex that disrupts the mTOR enzyme, a key regulator of cell growth in G phase, that functions as a central node in eukaryotic cell signaling, and integrates a vast array of intracellular and extracellular cues. mTOR inhibitors have been used in cardiothoracic trials for delaying pulmonary vein stenosis and the treatment of primary lung and cardiac cancers.[15][16] While effective, these medications carry cardiovascular risks; patients may experience hypertension, edema, and high cholesterol or triglyceride levels.[17] Additionally, they can lead to electrolyte disturbances like hypokalemia.[18][19]

Antiarrhythmics are useful when conduction defects or other ventricular arrhythmias are present. Partial or complete surgical resection of the mass is indicated in cases of hemodynamic compromise and congestive heart failure due to a large tumor.[20] Partial resection is preferred if there is a high risk of damage to the myocardial mass or vital structure by complete excision.[21] Orthotopic heart transplantation is considered in infrequent occasions when the tumor is so large that it has replaced the normal myocardial tissue. If the patient can not tolerate the long waiting times for a heart transplant, single ventricle palliation, artificial heart, or left ventricle assist devices can be performed as a bridge to transplant or total correction.(B2)

Differential Diagnosis

The differential diagnosis includes:

• Cardiac fibroma
  • This condition is associated with Gorlin syndrome. MRI shows a low T2 signal and intense late gadolinium enhancement due to fibrous content; calcification signs on CT scans help differentiate it from rhabdomyoma. Microscopic examination would reveal dense collagen, spindle-shaped fibroblasts, and possibly entrapped cardiomyocytes.
• Atrial myxoma
  • This is usually not embedded in the myocardium; instead, stalked or pedunculated, with a tendency to attach to the interatrial septum from the left atrial chamber side. Histologically, myxoid stroma is abundant with dispersed stellate cells.
• Hemangioma
  • The transthoracic echocardiogram shows it as echogenic with prominent blood flow. MRI reveals a high T2 signal with intense contrast enhancement due to vascularity.
• Teratoma
  • Rare, predominantly in fetuses and newborns, sometimes part of a congenital cystic mediastinal teratoma. Contains tissues from all 3 germ layers (eg, cartilage, neural tissue, epithelium).
• Thrombus
  • This is a nontumorous mass that is common in adults with atrial fibrillation, left ventricular dysfunction, or aneurysm. On imaging, it may appear echolucent or laminated, avascular on Doppler or contrast imaging, and nonenhanced and layered on CT or MRI.
• Inflammatory myofibroblastic tumor
  • This condition is sporadic and can affect people of any age. Cardiac inflammatory myofibroblastic tumors constitute a small subset of inflammatory pseudotumors. On imaging, they appear as a solid mass, often heterogeneous, with variable enhancement. They can mimic malignant lesions. Histologically, they show myofibroblastic spindle cells with inflammatory infiltrates (plasma cells, lymphocytes). Anaplastic lymphoma kinase is positive in 50% of cases.

Treatment Planning

If the patient is asymptomatic, watchful waiting is advised as most tumors regress on their own; if symptomatic, the patient requires admission to the cardiac intensive care unit. The mTOR inhibitors are a consideration in cases associated with tuberous sclerosis, and no regression is observed. 

Prognosis

The patients who have had surgery for the removal of rhabdomyoma have a fair to good prognosis. The highest risk is among cardiac rhabdomyomas. They may grow and obstruct the left ventricular outflow tract, thus causing abnormalities in the flow, or may cause ventricular tachycardias or heart blocks.[9] The presence of fetal cardiac rhabdomyoma may be a sign of tuberous sclerosis, and thus, other structures should be evaluated, ie, the renal or brain parenchyma for tumors; this is because cardiac rhabdomyoma is often the first symptom of tuberous sclerosis, followed by neurological involvement and impairment.[22]

Complications

The complications of cardiac rhabdomyoma include the following:

• Infections
• Arrhythmias (bradycardia and tachycardia)
• Congestive heart failure
• Hemodynamic compromise