*Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Illinois at Chicago, 820 South Wood Street M/C 808, Room 250, Chicago, Illinois 60612-7313, Ph 312-996-3204, Fax 312-996-4238

Synonyms: Hamartoma.

Definition: An anomalous, benign proliferation of tissue displaying typical "spider cells" on histopathology.

Prevalence: Any cardiac tumor 1-2:10,000; over 90% are benign^1-3. Rhabdomyoma is the most common benign congenital tumor⁴.

Etiology: Unknown.

Pathogenesis: Unclear, proliferation of embryonal myoblasts, yielding single or, more commonly, multiple solid masses which may arise anywhere in the atrial or ventricular myocardium and may project into a cardiac chamber.

Associated anomalies: Tuberous sclerosis (50-86%)^5-8, cardiac dysrhythmia⁹, non-immune hydrops^10,11.

Differential diagnosis: Teratoma, myxoma, hemangioma, mesothelioma.

Prognosis: Dependent on size, location and number of tumors and presence of associated anomalies.

Recurrence risk: Frequent in patients with tuberous sclerosis^12,13.

Management: Dependent on presence or absence of cardiac outflow obstruction. Most regress after birth^7,14. Careful evaluation for the presence of tuberous sclerosis is indicated for patient and family.

MESH Heart-Neoplasms -congenital, complications, diagnosis, complications, pathology. MIM 191100 POS 3417 ICD9 212.7 (benign tumor of the heart), 746.8 (other specified anomalies of the heart) CDC 746.990 (cardiac anomaly) 759.500 (tuberous sclerosis)

Introduction

Congenital heart disease is estimated to occur in 8 to 9 cases per 1000 live births^15,16. The presence of a primary congenital tumor of the heart, however, is a rare occurrence. The most common benign tumor is a rhabdomyoma which may occur as a single lesion or as multiple lesions usually located within the ventricle. Cardiac rhabdomyomas are frequently associated with tuberous sclerosis. We present a case in which the prenatal diagnosis of a primary intracardiac rhabdomyoma was made which was not clearly associated with tuberous sclerosis.

Case report

A 16-year-old, G₂P₀₀₁₀ healthy patient was referred after a routine obstetrical ultrasound to confirm gestational age revealed fetal ascites. Her pregnancy was uncomplicated to this point. Routine prenatal laboratory studies including maternal serum a-fetoprotein were within normal limits and her blood type was 0 positive. There were no significant findings on review of the patients past medical, surgical, or family history.

Sonographic evaluation of the fetus at the time of referral revealed symmetrical biometric measurements of the fetal head, abdomen and long bones consistent with an estimated gestational age of 27 weeks. Cross-sectional evaluation of the fetal thorax revealed cardiomegaly as well as a large homogeneous, solid, echogenic mass measuring 25 x 25 mm (fig. 1). The heart occupied 68% of the cross-sectional area of the chest and the outer biventricular diameter during diastole was greater than the 95^th centile when compared with the biparietal diameter¹⁷. The mass was primarily located within the left atrium with downward displacement of a functioning mitral value on echocardiography. There was no evidence of a pericardial effusion, ascites or dysrythymia. Fetal aortic and umbilical artery Doppler studies were within normal limits for gestational age. Careful examination of remaining fetal structures, especially intracranial and renal anatomy, revealed no other fetal anomalies. The sonographic appearance and location of the mass were consistent with the diagnosis of a cardiac rhabdomyoma.

Figure 1: Axial view of the thorax at the level of the four- chamber view with an echogenic mass located mainly within the left atrium.

The patient was counseled regarding the diagnosis and the association of cardiac rhabdomyomas with tuberous sclerosis. A detailed genetic and family history was negative for evidence of tuberous sclerosis. A genetic amniocentesis was performed on request revealing a 46XY karyotype. Serial ultrasound examinations demonstrated progressive growth of the tumor, primarily into the left ventricular cavity with obstruction of mitral valve excursion. A bright, hyperechoic, crescent-shaped lesion developed within the tumor on subsequent sonograms which was thought to be the stenotic mitral valve leaflet (fig. 2). While growth of the tumor occurred with advancing gestational age, tumor size relative to heart and chest size decreased slightly (table 1). Normal fetal growth occurred and at no time did the fetus demonstrate signs of congestive heart failure. Amniotic fluid volume as well as antepartum testing were reassuring and Doppler velocimetry remained within normal limits for gestational age.

Figure 2: Cross-section view of fetal thorax at level of four chamber view. Note the bright, shaped lesion in the area of the mitral valve.

Spontaneous labor occurred at 39 weeks gestational age. There were no intrapartum fetal heart rate abnormalities noted on continuous monitoring. A secondary arrest of labor occurred and a primary cesarean section was performed yielding a 3073g male infant with an Apgar score of 3 and 9 at one and 5 minutes, respectively.

Table 1: Fetal measurements (in mm.).

Postnatal course

The neonate exhibited mild respiratory distress requiring temporary oxygen therapy in the form of a head hood. Physical exam revealed a hyperdynamic precordium with both systolic and diastolic murmurs. Cardiomegaly was evident on chest X-ray and the EKG revealed a normal sinus rhythm with a shortened PR interval and intraventricular conduction delay consistent with Wolf-Parkinson-White syndrome. Head CT-scan and EEG were normal. Echocardiography revealed a multilobular echo dense mass involving the left ventricle and atrium along the ventricular septum, mild mitral stenosis, moderate mitral regurgitation, a patent foramen ovale with left to right shunting and a patent ductus arteriosus. The ductus arteriosus closed spontaneously. The infants cardiovascular and respiratory status remained stable, with no evidence of congestive heart failure, and he was subsequently discharged home. No surgical intervention was required and subsequent echocardiograms have documented a decrease in the size of the tumor. The infant remains asymptomatic at this time. Detailed physical and radiologic examination of both mother and infant failed to show any evidence of tuberous sclerosis.

Discussion

Primary cardiac neoplasms are rare constituting only a small fraction of the incidence of congenital heart disease occurring in the general population. Cardiac tumors are estimated to occur in 1-2:10,000 patients and over 90% of these are benign^1-3. Rhabdo­myomas are the most common benign cardiac neoplasms occurring in the fetus and neonate, with most identified within the first year of life⁴.

Pathogenesis

The etiology is unknown. A rhabdomyoma resembles a hamartoma derived from embryonal myo­blasts in which there is an abnormal proliferation of tissue yielding single or multiple solid circumscribed, unencapsulated tumors of variable size. They may arise anywhere in the myocardium, most commonly the ventricle, but not from a valve, and may project into a cardiac chamber. Grossly the appear as yellow-tan solid, circumscribed, unencapsulated tumors. Microscopically, the characteristic spider cell is seen which is a large clear cell with cytoplasmic strands composed of glycogen extending to the plasma membrane.

Associated anomalies

There is a very strong association between cardiac rhabdomyomas and tuberous sclerosis, occurring in 50-86% of patients with cardiac rhabdo­myomas^18,19. Tuberous sclerosis is an autosomal dominant disorder with variable expressivity and high penetrance²⁰. However, between 50 and 80 percent of cases are new mutations¹³. The gene for tuberous sclerosis has been localized on chromosome 9 (9q34) ²¹. Clinical manifestations of tuberous sclerosis include skin lesions (depigmented marks, adenoma sebaceum, shagreen patches), cerebral abnormalities (periventricular calcifications or nodules, seizures, cerebral atrophy) and retinal phakomata. Renal angiomyolipomas and hamartomas are very common in patients with tuberous sclerosis but usually develop later in life and progress slowly. Of the dermatologic lesions, hypomelanotic macules are usually present at birth, are diffuse and do not follow linear patterns. Skin biopsy or Woods light examination of these lesions establishes the diagnosis. There is no association of cardiac rhabdomyoma with any genetic or familial disorders with the exception of tuberous sclerosis.

Differential diagnosis

The differential diagnosis of fetal cardiac tumors includes, in order of descending frequency, rhabdomyoma, teratoma, fibroma, myxoma and hemangioma. Sonographically, these tumors appear as single or multiple, homogeneous, echogenic masses within the myocardium. Teratomas may appear as complex masses, typically involve the pericardium and are usually associated with pericardial effusions. Fibromas tend to be discrete single lesions usually found in the left ventricular wall. Myxomas are very rare lesions, usually involving the left atrium, and appear similar to rhabdomyomas.

Prognosis

The prognosis depends on the number, size and location of the tumors as well as the presence or absence of associated anomalies. Intracavitary growth of the tumors may cause disruption of intracardiac blood flow leading to congestive heart failure and hydrops. Cardiac dysrhythmias, caused by compression of the conducting system, are also frequently identified. Rhabdomyomas grow slowly in utero but tend to regress spontaneously after birth¹⁴. Fenogiol et al. has shown that rhabdomyomas cells lose there ability to divide over time which may account for the spontaneous regression of these tumors noted clinically²².

Management

When the diagnosis of a cardiac tumor is made prior to fetal viability, pregnancy termination may be offered. Serial ultrasonic evaluations should be performed to identify signs of congestive heart failure or dysrhythmia. Standard obstetrical management is appropriate for uncomplicated cases. Delivery should take place in a tertiary care center were a pediatric cardiologist is available. Conservative neonatal management is indicated in the asymptomatic patient with surgery reserved for those with hemodynamic compromise.

When the fetal rhabdomyoma is diagnosed, careful evaluation of other fetal structures should be performed looking for signs of tuberous sclerosis. Particular attention should be directed toward the central nervous system and kidneys. A detailed family history, particularly of mental retardation and epilepsy, should be obtained and first degree relatives should undergo a physical examination to identify clinical evidence of tuberous sclerosis. In the absence of a family history, a fetal cardiac rhabdomyoma should imply the diagnosis of tuberous sclerosis, whether the disease is clinically manifest or not²³.

References

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20. Hunt A, Lindenbaum RH. Tuberous sclerosis: a new estimate of prevalence within the Oxford region. J Med Genet 21:272-77, 1984.

21. Smith M, Simpson NE. Report of the committee on the genetic constitution of chromosomes 9 and 10. Cytogent Cell Genet 49:71-8, 1988.

22. Fenogilo JJ, McAllister HA, Ferrans VJ. Cardiac rhabdomyoma: a clinicopathologic and electron microscopy study. Am J Cardiol 38:241-51, 1976.

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