A case of surgically resected cardiac rhabdomyoma with progressive left ventricular outflow tract obstruction.

Cardiac rhabdomyoma is the most prevalent cardiac tumors in the pediatric population, in close association with tuberous sclerosis complex. It is usually detected antenatally or postnatally by echocardiography. Clinical presentations depend greatly on the size and position of the tumor mass. Interestingly, rhabdomyoma has a propensity to regress spontaneously and is not usually operated upon, unless the patient becomes hemodynamically compromised. Herein, we report an unusual case of surgically treated cardiac rhabdomyoma in a baby boy presented at birth with a progressive enlarging intraventricular mass, complicated with left ventricular outflow tract obstruction 7 weeks later. Histopathological examination of the intracardiac mass revealed sheets of tumor cells with spider-like morphology (known as "spider cells"), confirmed the diagnosis of rhabdomyoma. Close disease monitoring of patient's hemodynamic status in a newly diagnosed cardiac rhabdomyoma is inevitable as the tumor, although rare, may progress.

Clinical Treatment of Pediatric Primary Cardiac Tumors: A Single-Institute 12-Year Experience.

BACKGROUND: Primary cardiac tumors in children are extremely rare. This study aimed to analyze clinical treatment and follow-up of pediatric primary cardiac tumors. PATIENTS AND METHODS: We performed a retrospective analysis by searching the medical records of 75 patients diagnosed with pediatric primary cardiac tumors from June 2005 to August 2017 in our institution. We followed operative patients every half year in the first postoperative year and then at least every year. If the patients had no serious symptoms or hemodynamic changes, they received nonoperative management and were followed regularly every year. RESULTS: Nineteen patients underwent surgery at our department for serious symptoms and critical hemodynamic changes. Four patients had postoperative complications. Two died of low cardiac output syndrome and arrhythmia after surgery. One patient with myxomas had tumor recurrence and one had been found of another rhabdomyoma after surgery. The other 14 patients recovered well. Fifty-six patients had nonoperative management. Four were lost in follow-up. Two patients with malignant tumors died of unknown causes after discharge. The remaining patients had no severe symptoms or tumor growth during follow-up. CONCLUSIONS: Clinical treatment of pediatric primary cardiac tumors should be performed individually. Most pediatric primary cardiac tumors are benign, and spontaneous regression is possible, especially for rhabdomyomas. The principle purpose of surgical treatment is to restore normal hemodynamics and protect important structures and cardiac tissue.

Giant cardiac tumours in the newborn: an unusual image.

Primary heart tumours in the paediatric population are very rare and they range from 0.01% to 0.04%. Most are benign lesions of which about half are rhabdomyomas. Rhabdomyoma tumour diagnosis is associated with a 75-80% risk of tuberous sclerosis complex (TSC). TSC are characterised with numerous changes of hamartoma-type located in the brain, kidneys, skin and other organs including the heart. More than two-thirds of newborns with TSC present rhabdomyomas in the heart. These changes may be asymptomatic, but in some cases they may cause heart failure, arrhythmias and death. We present a case report of an infant with giant rhabdomyoma tumours in the course of TSC.

Early appearance of tuberous sclerosis complex on cerebral ultrasound in extremely preterm infant.

Tuberous sclerosis complex (TSC) is an inherited neurocutaneous disorder. Diagnosis of early onset TSC in newborn infants is usually made by cardiac ultrasound because of circulatory problems due to cardiac rhabdomyoma. Early appearance of cortical tubers on cerebral ultrasound in newborn infants is very rare. Mostly TSC is diagnosed on MRI and not by cerebral ultrasound. Subependymal nodules are the usual presenting sign of TSC on cerebral ultrasound in neonates, which are often misdiagnosed as subependymal hemorrhage, calcifications or ischemic lesions after intrauterine germinal matrix hemorrhage. In this case report, multiple cortical and subcortical tubers are demonstrated in an extremely preterm infant, which were not observed on antenatal ultrasound. Together with cardial rhabdomyoma and the identification of the TSC2 pathogenic mutation in DNA from normal tissue the diagnosis of TSC has been confirmed. To our knowledge this is the first case report of early appearance of disseminated cortical tubers on cerebral ultrasound postnatal in an extremely preterm infant with TSC.

Pediatric cardiac tumors: a 45-year, single-institution review.

BACKGROUND: Cardiac tumors in children are rare. Of the cases reported in the literature, nearly all are benign and managed conservatively. METHODS: This is a retrospective, observational study of pediatric patients <18 years who presented for surgical evaluation of a cardiac tumor, between 1969 and 2014 at a tertiary care children's hospital. Presentation, pathology, management, and outcomes were evaluated. RESULTS: Over the last 45 years, 64 patients were evaluated for surgical resection of a cardiac tumor. Rhabdomyoma was the most common neoplasm (58%), and 17% of the tumors had malignant pathologies. While 42% of benign cardiac neoplasms required surgical intervention for significant hemodynamic concerns, 73% of malignant neoplasms underwent radical excision, if possible, followed by adjuvant chemotherapy. Despite a 37% mortality in patients with malignant pathology, an aggressive surgical approach can yield long-term survival in some patients. There were no deaths among patients with benign tumors and 17% had postoperative complications mostly related to mitral regurgitation. CONCLUSION: Cardiac tumors in children are rare but can be managed aggressively with good outcomes. Benign tumors have an excellent survival with most complications related to tumor location. Malignant tumors have a high mortality rate, but surgery and adjuvant chemotherapy allow for prolonged survival in selected patients.

Use of mTOR inhibitor everolimus in three neonates for treatment of tumors associated with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex is characterized by the growth of benign tumors in multiple organs, caused by the disinhibition of the mammalian target of rapamycin (mTOR) protein. mTOR inhibitors, such as everolimus, are used in patients with tuberous sclerosis complex, mainly to reduce the size of renal angiomyolipomas and subependymal giant cell astrocytomas. There are minimal data available regarding its use during the neonatal period. METHODS: We report clinical and pharmacological data of three neonates treated with the mTOR inhibitor everolimus (two hemodynamically significant cardiac rhabdomyomas and one voluminous subependymal giant cell astrocytoma). RESULTS: Beneficial clinical responses were observed in all three patients and the medication was generally well-tolerated. Optimal dose was 0.1 mg orally once daily and was confirmed with therapeutic drug monitoring. CONCLUSION: Everolimus is a promising pharmacological approach to treat clinically significant inoperable cardiac rhabdomyomas or subependymal giant cell astrocytoma associated with tuberous sclerosis complex during the neonatal period.

Cardiac rhabdomyoma mimicking haemodynamics of hypoplastic left heart syndrome.

Cardiac rhabdomyomas are rare and often regress spontaneously. However, the management of rhabdomyoma with severe inflow and outflow obstructions is a challenge. An infant with a massive left ventricular rhabdomyoma mimicking the haemodynamics of hypoplastic left heart syndrome is reported. Surgery could not be contemplated because the mitral valve leaflets and chordae were imbedded in the tumour mass. The arterial duct (AD) was kept open to perfuse the systemic circulation and palliations with pulmonary artery branch banding and AD stenting were planned. However; while waiting for spontaneous regression of the tumour, the child died of circulatory collapse when 4 weeks old.

ECG phenomena: pseudopreexcitation and repolarization disturbances resembling ST-elevation myocardial infarction caused by an intraatrial rhabdomyoma in a newborn.

As is known from other reports, a rhabdomyoma or tumor metastasis may alter intracardiac electrical conduction, producing electrical phenomena like pseudopreexcitation or repolarization disturbances resembling ST-elevation myocardial infarction or Brugada's syndrome. We present a newborn with a giant atrial rhabdomyoma and additionally multiple ventricular rhabdomyomas. He presented with several electrocardiogram (ECG) phenomena due to tumor-caused atrial depolarization and repolarization disturbances. Except from the cardiac tumors, the physical status was within normal range. Initial ECG showed a rapid atrial tachycardia with a ventricular rate of 230 bpm, which was terminated by electrical cardioversion. Afterwards, the ECG showed atrial rhythm with frequent atrial premature contractions and deformation of the PR interval with large, broad P waves and loss of discret PR segment, imposing as pseudopreexcitation. The following QRS complex was normal, with seemingly abnormal ventricular repolarization resembeling ST-elevation myocardial infarction. The atrial tumor was resected with consequent vast atrial reconstruction using patch plastic. The ventricular tumors were left without manipulation. After surgery, pseudopreexcitation and repolarization abnormalities vanished entirely and an alternans between sinus rhythm and ectopic atrial rhythm was present. These phenomena were supposably caused by isolated atrial depolarization disturbances due to tumor-caused heterogenous endocardial activation. The seemingly abnormal ventricular repolarization is probably due to repolarization of the atrial mass, superimposed on the ventricular repolarization. Recognizably, the QRS complex before and after surgical resection of the rhabdomyoma is identical, underlining the atrial origin of the repolarization abnormalities before surgery.

Delta-like 1 homolog (dlk1): a marker for rhabdomyosarcomas implicated in skeletal muscle regeneration.

Dlk1, a member of the Epidermal Growth Factor family, is expressed in multiple tissues during development, and has been detected in carcinomas and neuroendocrine tumors. Dlk1 is paternally expressed and belongs to a group of imprinted genes associated with rhabdomyosarcomas but not with other primitive childhood tumors to date. Here, we investigate the possible roles of Dlk1 in skeletal muscle tumor formation. We analyzed tumors of different mesenchymal origin for expression of Dlk1 and various myogenic markers and found that Dlk1 was present consistently in myogenic tumors. The coincident observation of Dlk1 with a highly proliferative state in myogenic tumors led us to subsequently investigate the involvement of Dlk1 in the control of the adult myogenic programme. We performed an injury study in Dlk1 transgenic mice, ectopically expressing ovine Dlk1 (membrane bound C2 variant) under control of the myosin light chain promotor, and detected an early, enhanced formation of myotubes in Dlk1 transgenic mice. We then stably transfected the mouse myoblast cell line, C2C12, with full-length Dlk1 (soluble A variant) and detected an inhibition of myotube formation, which could be reversed by adding Dlk1 antibody to the culture supernatant. These results suggest that Dlk1 is involved in controlling the myogenic programme and that the various splice forms may exert different effects. Interestingly, both in the Dlk1 transgenic mice and the DLK1-C2C12 cells, we detected reduced myostatin expression, suggesting that the effect of Dlk1 on the myogenic programme might involve the myostatin signaling pathway. In support of a relationship between Dlk1 and myostatin we detected reciprocal expression of these two transcripts during different cell cycle stages of human myoblasts. Together our results suggest that Dlk1 is a candidate marker for skeletal muscle tumors and might be involved directly in skeletal muscle tumor formation through a modulatory effect on the myogenic programme.

Cardiac rhabdomyomas associated with tuberous sclerosis complex in 11 children: presentation to outcome.

Cardiac rhabdomyomas (CRs) are the most common heart tumors in children and closely associated with tuberous sclerosis complex (TSC). This study was performed to assess the presentation type, clinical course, treatment modalities, and outcome of the patients with rhabdomyoma, associated with TSC. We reviewed our patients with cardiac rhabdomyomas (CRs), who had received a diagnosis of TSC previously or during the follow-up period between June 1996 and January 2012, retrospectively. Thirty-two patients with TSC were evaluated and among them 11 patients (34%) were associated with CRs. Five patients (45%) had multiple tumors and consequently a total of 29 CRs were analyzed in our study. The median follow-up period was 2 years (range: 1 week-15 years). Clinical presentation was cardiac murmur in three patients, cyanosis in two patients and arrhythmia in one patient. Five patients were asymptomatic at the diagnosis and CRs were detected during routine cardiac evaluation for TSC. Cardiac tumors were diagnosed prenatally in two patients. Spontaneous regression rate was 31% and we experienced a complete regression of a tumor with an echogenic bordered tissue defect and septal thinning in a patient. Three patients had hemodynamically significant tumor obstruction; two of them underwent surgery. The other patient, who had multiple CRs, was treated medically with everolimus because of high-risk potential of surgery. Although surgical resection is the preferred treatment in most of the patients with hemodynamic instability, we need novel alternative medical therapies in some critically ill patients who cannot be operated due to various reasons.

Cardiac tumours in infancy.

Cardiac tumours in infancy are rare and are mostly benign with rhabdomyomas, fibromas and teratomas accounting for the majority. The presentation depends on size and location of the mass as they tend to cause cavity obstruction or arrhythmias. Most rhabdomyomas tend to regress spontaneously but fibromas and teratomas generally require surgical intervention for severe haemodynamic or arrhythmic complications. Other relatively rare cardiac tumours too are discussed along with an Indian perspective.

Implantable cardioverter defibrillator as a bridge to recovery in an infant with cardiac rhabdomyoma.

Multiple cardiac rhabdomyomas in an infant presented with recurrent life-threatening ventricular arrhythmias refractory to medical treatment and necessitating the placement of an implantable cardioverter defibrillator (ICD). The device functioned effectively as a bridge to recovery during a 2-year follow-up period, when the tumor showed spontaneous regression, along with an almost complete resolution of the ventricular arrhythmias. We conclude that childhood cardiac rhabdomyomas causing severe drug-refractory ventricular arrhythmias can be managed by ICD therapy.

Neonatal rhabdomyoma causing right ventricular inflow obstruction with duct-dependent pulmonary blood flow: successful stenting of PDA.

We describe an infant with the antenatal diagnosis of a large intracardiac rhabdomyoma causing tricuspid inflow obstruction. Postnatal cyanosis and arterial hypoxemia prompted commencement of intravenous prostaglandin E1 with immediate improvement in saturations. Clinical and genetic testing confirmed diagnosis of tuberous sclerosis. To secure ductal patency, two tandem coronary stents were implanted via an antegrade approach. Several episodes of long RP atrio-ventricular re-entrant tachycardia were observed. At 7(1/2) months of age, the tumor was no longer obstructive to tricuspid inflow, ductal flow was highly restrictive and there was no recurrence of supraventricular tachycardia.

Cardiac rhabdomyoma with long-term conduction abnormality: progression from pre-excitation to bundle branch block and finally complete heart block.

BACKGROUND: Cardiac rhabdomyoma, a benign smooth muscle hamartoma, is the commonest heart tumor encountered in children. Arrhythmias and conduction disorders have been described with these tumors, although most electrocardiographic abnormalities will resolve over time, concomitant with the resolution of the tumor. CASE REPORT: The case of a child, diagnosed with cardiac rhabdomyomas in fetal life, is reported in whom the tumors regressed in size over a four-year period whilst displaying a spectrum of conduction disturbances. He finally developed potentially lethal complete heart block. CONCLUSIONS: Cardiac rhabdomyomas may be asymptomatic, cause hemodynamic compromise, or be associated with rhythm disorders. In the presence of conduction disorders, close monitoring is required with regular electrocardiograms to detect potential lethal conduction disorders.

Submandibular rhabdomyoma: a case report.

BACKGROUND: The cytologic diagnosis of extracardiac rhabdomyoma is frequently hampered by its rarity and resemblance to various tumors. In this regard, the infrequent occurrence has hindered its prompt and early recognition. It is also confused with other tumors because of similarities in clinical and cytologic presentations. CASE: A submandibular rhabdomyoma occurred in an otherwise-healthy, 62-year-old man. The neoplasm was firstly diagnosed by fine needle aspiration cytology (FNAC. Complete local excision without radical surgery was performed. Histologic findings confirmed the cytologic diagnosis of adult rhabdomyoma. Treatment-related complications were minimal, and there was no evidence of recurrent disease 6 years later. CONCLUSION: Helpful FNAC features and immunocytochemical results permitted an early diagnosis and spared the patient unnecessary radical surgery.

Right atrial rhabdomyoma acting as the substrate for Wolff-Parkinson-White syndrome in a 3-month-old infant.

We report a 3-month-old infant girl who presented with supraventricular tachycardia, who was detected to have a large right atrial rhabdomyoma and evidence of Wolff-Parkinson-White (WPW) syndrome with an accessory pathway corresponding to the position of the tumour. In view of the resistant cardiac arrhythmia and large size of the tumour, the infant underwent surgical excision of the tumour. The evidence of WPW syndrome disappeared from the surface electrocardiogram immediately upon removal of the tumour. A second resolving tumour in the interventricular septum was also detected during the investigation. Although there are no other stigmata of tuberous sclerosis at present, our infant requires close follow-up. Right atrial rhabdomyomas are rare and to our knowledge this is the first reported instance where we could document clearly that the tumour itself formed the substrate for the WPW syndrome.