Primary cardiac tumors are rare, 75% are benign and have a reported incidence of 0.03–0.32%. Cardiac fibromas are the second most common primary cardiac tumor after rhabdomyoma in children. They are primarily composed of connective tissue and fibroblast and although benign, can be symptomatic due to intracavitary obstruction, inflow and outflow tract obstruction, coronary artery compromise, thromboembolic events, conduction defects, and can also lead to sudden death. Pediatric cardiac tumors carry associations with genetic conditions, for example, rhabdomyomas have an association with tuberous sclerosis, and about 3% of patients with nevoid basal cell carcinoma syndrome (NBCCS), also called Gorlin syndrome, have cardiac fibromas.
Gorlin syndrome exists as an autosomal dominant, multisystem disorder due to mutations in the PTCH1 or SUFU tumor suppressor genes which has a prevalence of 1/31,000 to 1/164,000; mostly inherited from an affected parent but can also arise de novo in 20–30% cases.
Cardiac fibroma is a tumor that primarily affects children. Most cases are detected in infants or in utero. Cardiac fibromas typically present in infancy, but in patients with NBCCS, they have been reported to develop up to the age of 60 years. They are the second most common benign cardiac tumor in children (after rhabdomyoma), and the second most common in fetuses, because of prenatal diagnosis. There is a slight male predominance.
The most common site is the left ventricle (approximately 57% of the cases), followed by right ventricle (27.5%), and interventricular septum (17%). There is a hypothesis that the tumor increases in size with physiological cardiac growth and stops growing when the growth of the heart completes, usually at 17 to 20 years of age. Hence, with somatic growth, the size of fibroma decreases relative to cardiac mass, but unlike rhabdomyoma, fibromas never resolve completely. Septal involvement and age less than 17 years old at the time of diagnosis are associated with a poor prognosis. It is probably because younger patients have a smaller heart and high tumor-to-heart ratio compared to older individuals, generating low cardiac output leading to poor outcomes. Fibromas involving interventricular septum frequently induce conduction system disease with resulting rhythm abnormalities.
In contrast to cardiac rhabdomyoma, cardiac fibroma rarely regress spontaneously and often present with arrhythmias (32%), mostly ventricular tachycardia (risk exceeding 50%), ventricular fibrillation, murmur (20%), and abnormal chest x-ray (20%). Coronary arteries are usually not involved, but there have been reports of coronary compression by large fibromas.
Cardiac fibroma is composed of monomorphic fibroblasts that demonstrate little or no atypia. The margins infiltrate into cardiac muscle. The degree of cellularity often decreases with the age of the patient, and the amount of collagen increases. Mitoses are generally present only in tumors occurring in infants. There can be occasional perivascular aggregates of lymphocytes and histiocytes or sparse chronic inflammation at the junction of the tumor and uninvolved myocardium. Calcification is a common finding with these fibromas in patients of all ages.
Cardiac fibromas may be asymptomatic. Common presentations of cardiac fibromas include:
Nevoid basal cell carcinoma syndrome carries associations with lamellar or early calcification of the falx, jaw keratocysts, palmar and plantar pits, with a predisposition for basal cell carcinomas. Characteristic facial features include macrocephaly, frontal bossing, and hypertelorism. Skeletal anomalies, early childhood medulloblastoma, cleft lip/ palate, and there are reports of ovarian fibromas in female patients with NBCCS.
Imaging using magnetic resonance imaging (MRI) shows an encapsulated mass with no vascularization and delayed enhancement. Histology is not always a requirement for diagnosis in the presence of clinical phenotype and MRI findings. Electrocardiogram (ECG) in most fibroma patients shows T-wave abnormalities, and VT morphologies on ECG are mostly consistent with an origin near the tumor site. In adults, it is also reported to present as a fixed defect on myocardial perfusion imaging.
Due to the rarity of cardiac fibromas (1 in 280,000 births), the best clinical management is not yet well defined, and it presents as a challenging entity for pediatric cardiologists. Suggestions for different management strategies exist in the literature including surgical resection, single ventricle palliation, cardiac transplant, and even conservative treatment with antiarrhythmic medications.
Defibrillator placement to prevent malignant arrhythmia after cardiac arrest is associated with a high risk of complications in infants and should only be considered after exploring all options with the risks and benefits explained to the parents. One of the common strategies is to place an endocardial defibrillator lead around the back of the heart in the epicardial space and use epicardial pace/sense leads. Alternatively, use epicardial pace/sense leads and tunnel an endocardial defibrillator lead along the intercostal space is also a reported option. With epicardial defibrillator, the risk of lead fracture is high with a reported 5-year failure rate of 50%.
Medical management with amiodarone and beta-blockers seems to be effective. Small and apically located fibromas respond well to antiarrhythmic medications and are probably better managed without defibrillators. Surgical resection has shown to provide curative treatment, alleviating the need for a defibrillator and long-term antiarrhythmic medications. It is also a viable treatment for large fibromas with positive results. A significant hurdle is the rarity of cardiac centers with experience in removing these tumors. Optimal time reported for surgery is between 1 to 3 years. Factors like the severity of arrhythmias, medication tolerance, defibrillation lead integrity, and symptoms are often considerations and dictate the appropriate time for surgery. Location and size of the tumor can complicate surgery, but even for large fibromas operative morbidity and mortality are low. Given that there are a limited number of patients, it is difficult to test the comparative effectiveness of these treatments.
In patients with tumors not amenable to resection owing to its size and extensive involvement of cardiac structures, several reported cases of “single ventricle palliation” exist. In one case with a large right ventricle fibroma, single ventricle palliation was performed by doing balloon atrial septostomy, placement of a systemic-to-pulmonary shunt to allow an unobstructed venous return to the left atrium and left ventricle to support both systemic and pulmonary circulations. This and other methods of ventricle palliation provided a bridge to heart transplantation.
Differentials include cardiac rhabdomyoma, myxoma, teratoma, lipoma, and hemangioma.
Cardiac fibromas in infancy that are not surgically resectable because of size and extensive myocardial infiltration have a poor prognosis and may require defibrillator implantation or cardiac transplantation. Tumors that can are resectable (even incompletely) have a good prognosis. In one study, the median survival of patients with cardiac fibromas after successful surgery was 27 years.
If cardiac fibromas are left untreated, there is an increase in the risk of fatality, particularly due to lethal ventricular arrhythmia.
New diagnosis of NBCCS should obtain referrals to dermatologists, pediatricians, and geneticists, obstetrics-gynecology and psychology evaluations to implement cancer surveillance as per guidelines and early identification of potential complications.
Because of a predisposition to basal cell carcinoma, patients with NBCCS are encouraged to apply sunscreen, limit sun exposure, and avoid ionizing radiation.
Nevoid basal cell carcinoma syndrome, given its wide phenotypic variations, is challenging to diagnose and needs a high level of suspicion to achieve prompt and early diagnosis. In sporadic cases, diagnosing NBCCS in proband should trigger genetic testing of other family members. Once identified, management implications include appropriate cancer screening and precautions, for example, screening for basal cell carcinoma (with encouragement to apply sunscreen, limit sun exposure and avoid ionizing radiation) and early childhood medulloblastoma (children less than eight years of age are recommended to have annual brain MRI with contrast). Diagnosis of cardiac fibroma, which rarely is a presenting manifestation, should prompt an evaluation for NBCCS along with a careful assessment of the patient’s past medical and family history. (Bree, Shah, et al. 2011)
As mentioned earlier, patients diagnosed with NBCCS are at an increased risk of benign and malignant neoplasms at an early stage. Experts have recommended coordinated multispecialty care for surveillance of NBCCS patients. [V-Case series, studies with no controls and expert opinion]