of the heart are diffusely infiltrated by rhabdomyoma type cells and fibrosis rather than forming discrete tumors The few reported cases of this entity have presented as sudden cardiac death and were diagnosed on autopsy.86 Because most infants with rhabdomyomas will show a spontaneous regression during the first year of life, surgical intervention should be recommended only in the presence of severe hemodynamic disturbances or refractory life-threatening arrhythmias.1 Tuberous Sclerosis Complex and Related Issues: Rhabdomyomas, Myocardial Fatty Foci, and Pharmacologic Tumor Regression Although the cardiac prognosis for fetuses or infants with rhabdomyomas is generally good, concerns are raised because of their common association with TSC TSC is an autosomal dominant genetic disease resulting from mutations in the TSC1 (hamartin) or TSC2 (tuberin) genes that result in proliferation of hamartomas in multiple organs such as the heart, brain, kidneys, eyes, and skin TSC is present in more than half of those found to have rhabdomyomas When the tumors are multiple, as many as 80% to 95% of have the disease.1,51,72 Conversely, rhabdomyoma is present in two-thirds of TSC patients younger than 2 years.71 Clinical manifestations depend on the organs affected Most patients have characteristic skin lesions, and a majority of patients have epilepsy or neuropsychiatric disorders In a series of neonates and infants, rhabdomyomas (56%), seizures (34%), hypomelanotic macules (15%), and family history (12%) were the most common presenting findings.87 Recently, multiple groups have noted the presence of tumors described as MFF in 35% to 64% of adolescent and adult TSC patients.88–90 The tumors are noted to be well circumscribed, midmyocardial, noninvasive, and often multiple Most patients appear to have no cardiac symptoms, although cases of unexplained sudden death have been reported.91 The presence of MFF has been associated with the presence of brain, thoracic, and renal tumors, and the number of MFF has been correlated with noncardiac tumor burden.88,89 Postmortem analyses of these tumors have shown mature fat cells in three patients91,92 and angiomyolipoma in one.88 Given the tendency for rhabdomyoma regression, MFF have been considered separate and unrelated entities Interestingly, a large serial echocardiographic study of 152 TSC patients noted a higher prevalence of rhabdomyomas in adolescents than in 2- to 11-year-olds and described new or growing tumors in six adolescent females.71 Given the very similar appearance of rhabdomyomas and MFF on echocardiography, these findings may be explained by de novo appearance of MFF In addition, there may be evidence for transformation of rhabdomyomas into MFF Our group follows an adolescent female with TSC, multiple cardiac tumors, and ventricular tachycardia (unpublished data) where some tumors had MRI characteristics of rhabdomyoma as a neonate but fatty characteristics in adolescence Rhabdomyomas in TSC patients have been noted to both grow and regress in response to different medications There are case reports of rapid enlargement of rhabdomyomas in patients with TSC who received corticotropin therapy for infantile spasms.93,94 In 2011 a case report described a 7-year-old with TSC who underwent nearly complete resolution of a previously stable cardiac rhabdomyoma after initiation of everolimus treatment for a brain tumor.95 Everolimus inhibits the mammalian target of rapamycin (mTOR), which is normally suppressed by a tumor suppressor complex that is inactivated in TSC Since then, there have been a handful of reports describing accelerated resolution of TSC-related cardiac rhabdomyomas with mTOR inhibitors.96–98 One retrospective case series found that treated infants had a cardiac tumor regression rate nearly 12 times faster than a historic control group, with an average time of 1.1 months to 50% tumor reduction.99 Rebound tumor growth has been demonstrated after drug discontinuation, and important side effects are mostly related to immunosuppression Further investigation into the potential role of mTOR inhibitors is needed, but it may be a viable option for avoiding surgical intervention in patients with significant morbidity Fibromas Cardiac fibromas rank second or third frequency among primary cardiac tumors.1,5,8,10 These tumors are seen throughout childhood, although they are less common in fetuses and newborn infants In up to 5% of cases, cardiac fibromas are associated with nevoid basal cell carcinoma syndrome (Gorlin syndrome), an autosomal dominant disease characterized by neoplasms in multiple organ systems, most commonly basal cell carcinomas.1,100 Cardiac fibromas are characteristically solitary intramural lesions seen in the ventricular septum or left ventricular free wall Right ventricular involvement is less common, and atrial fibromas have been reported.54 Intracavitary fibromas and multiple fibromas have also been described The gross appearance of cardiac fibromas is relatively uniform They present as solid, firm, whitish lesions, with a distinct fibromatous architecture when seen in cut sections (Fig 52.13) Their circumscribed appearance suggests an encapsulated nature, but microscopic studies reveal intermingling of the tumor with the adjacent myocardium.1,31 Calcification within the lesions is not uncommon.1 Lesions may vary in size from 1 to 9 cm.1 Those producing functional impairment are usually several centimeters in size Moreover, satellite nodules may be present FIG 52.13 Cut edge of a resected fibroma showing the typical fibromatous architecture Fibromas are solitary, slow-growing, and potentially aggressive lesions Spontaneous regression has not been observed On echocardiography, fibromas are echo bright and may be distinguished from rhabdomyomas by inhomogeneity due to the presence of calcifications, necrosis, or cystic degeneration.74 Large lesions, particularly septal ones, may mimic hypertrophic cardiomyopathy The pathognomonic finding on MRI is intense late gadolinium enhancement with or without a central dark core.54 Symptoms are most commonly due to ventricular arrhythmia, although atrioventricular conduction disturbances and ventricular obstruction have also been reported In one large single-center study, 64% of fibroma patients had clinically significant arrhythmias, all ventricular tachycardia or ventricular