Cardiac fibroma presenting as hypoplastic left heart syndrome in a foetus: causal or coincidental?

Primary cardiac tumours are very rare. Cardiac tumours in the perinatal period are even more uncommon with a prevalence of 0.0017% to 0.28% in autopsy series. The majority of benign cardiac tumours are cardiac rhabdomyomas, followed by cardiac fibromas. Another rare congenital heart disease is hypoplastic left heart syndrome (HLHS). Here we present a 21-week-old foetus diagnosed antenatally with HLHS on foetal echocardiogram. An autopsy done on the foetus following medical termination of pregnancy revealed a cardiac fibroma in the ventricular septum. It is very uncommon to have a combination of two congenital heart diseases. An extensive literature review revealed only three cases that had rhabdomyoma and associated HLHS. This case presented with cardiac fibroma which in early gestation would have resulted in left ventricular outflow obstruction leading to the development of HLHS. Small cardiac tumours which are difficult to detect by echocardiogram in early gestation can lead to the development of HLHS. A thorough and hierarchical autopsy examination of such cases can help in a better understanding of the relationship between HLHS and cardiac tumours.

Mammalian target of rapamycin inhibitors: A new-possible approach for in-utero medication therapy.

The mammalian/mechanistic target of rapamycin (mTOR) is a protein kinase that plays a crucial role in regulating cellular growth, metabolism, and survival. Although there is no absolute contraindication for the use of mTOR inhibitors during pregnancy, the specific fetal effects remain unknown. Available data from the past 2 decades have examined the use of mTOR inhibitors during pregnancy in patients with solid organ transplantation, showing no clear link to fetal complications or structural abnormalities. Recently, a handful of case reports and series have described transplacental therapy of mTOR inhibitors to control symptomatic and complicated pathologies in the fetus. The effect of these agents includes a significant reduction in lesion size in the fetus and a reduced need for mechanical ventilation in neonates. In this context, we delve into the potential of mTOR inhibitors as in-utero therapy for fetal abnormalities, with a primary focus on lymphatic malformation (LM) and cardiac rhabdomyoma (CR). While preliminary reports underscore the efficacy of mTOR inhibitors for the treatment of fetal CR and fetal brain lesions associated with tuberous sclerosis complex, chylothorax, and LMs, additional investigation and clinical trials are essential to comprehensively assess the safety and efficacy of these medications.

Clinical outcomes of fetuses with cardiac rhabdomyoma: A case series from a tertiary center.

AIMS: The study aims to evaluate the genetic and clinical outcomes of fetal cardiac rhabdomyoma in our tertiary center. METHODS: Data of cases with cardiac rhabdomyoma detected by fetal echocardiography during antenatal follow-up were analyzed retrospectively. RESULTS: Nine cases were included in the study. The incidence of cardiac rhabdomyoma was 0.003%. The median fetal diagnosis time was 26th weeks, the most common location was the LV. There was no hemodynamic disorder requiring cardiovascular intervention in any of the cases. Of the eight genetically tested cases, four were tuberous sclerosis complex (TSC) gene-negative, one hereditary TSC2, one de novo TSC1, and two de novo TSC2 gene mutants. Postnatal first-year survival rate of the cases was 88.8%. CONCLUSIONS: Cardiac rhabdomyoma is a rare fetal and pediatric pathology that generally is a remarkable finding in the clinical process of TSC. Therefore, cases should be evaluated multisystemically and genetic counseling should be given to the family.

Surgical treatment of primary cardiac tumors in children.

OBJECTIVE: Summarizing the treatment experience of primary cardiac tumors in children. METHODS: The date of 24 children with primary cardiac tumors who underwent surgery in our department from July 2003 to September 2022 was collected and analyzed treatment efficacy. RESULTS: All patients completed the surgery successfully, including 21 cases of complete tumor resection, 2 cases of partial tumor resection, and 1 case of tumor biopsy. The location: 5 cases in the right atrium, 5 cases in the right ventricle, 6 cases in the left atrium, 6 cases in the left ventricle, 1 case in the left, right ventricle and ventricular septum, and 1 case in the ventricular septum. 23 cases were benign: 11 cases of myxoma, 7 cases of fibroma, 3 cases of rhabdomyoma, 1 case of infantile capillary hemangioma, and 1 case of lipoma. There was 1 case of borderline or malignant tumor. 23 patients were discharged successfully, 1 patient died of cardiac failure on the first day after operation. Follow-up was done from 5 months to 19 years and 2 months, 2 cases were lost to follow-up, and 1 case died of cardiac failure in the second year after operation due to severe mitral regurgitation. There was 1 case of tumor biopsy with space-occupying lesion gradually shrinking during follow-up. The prognosis of another 19 children with complete or partial tumor resection was good. There was no recurrence, enlargement, or reoperation of the tumor during the follow-up period. CONCLUSIONS: Primary cardiac tumors in children are mostly benign. Surgery is effective, but the timing of surgery depends on the patient's condition.

Surgical Treatment of Pediatric Refractory Ventricular Tachycardia Originating From a Left Ventricular Rhabdomyoma.

Cardiac tumors are very rare in children, and echocardiography is very important in their detection. The clinical presentation can vary greatly depending on arrhythmia or obstruction. One of the most important factors determining the surgical approach is the clinical process. In this case report, we report the surgical treatment of a rhabdomyoma that caused refractory ventricular tachycardia.

Long-term use of everolimus for refractory arrhythmia in a child with tuberous sclerosis complex.

Tuberous sclerosis complex is associated with the occurrence of cardiac rhabdomyomas that may result in life-threatening arrhythmia unresponsive to standard antiarrhythmic therapy. We report the case of an infant with multiple cardiac rhabdomyomas who developed severe refractory supraventricular tachycardia (SVT) that was successfully treated with everolimus. Pharmacological mTOR inhibition rapidly improved arrhythmia within few weeks after treatment initiation and correlated with a reduction in tumor size. Intermediate attempts to discontinue everolimus resulted in rhabdomyoma size rebound and recurrence of arrhythmic episodes, which resolved on resumption of therapy. While everolimus treatment led to successful control of arrhythmia in the first years of life, episodes of SVT reoccurred at the age of 6 years. Electrophysiologic testing confirmed an accessory pathway that was successfully ablated, resulting in freedom of arrhythmic events. In summary we present an in-depth evaluation of the long-term use of everolimus in a child with TSC-associated SVT, including the correlation between drug use and arrhythmia outcome. This case report provides important information on the safety and efficacy of an mTOR inhibitor for the treatment of a potentially life-threatening cardiac disease manifestation in TSC for which the optimal treatment strategy is still not well established.

Solitary atrial Rhabdomyoma in an infant with tuberous sclerosis: a case report and review of the literature.

BACKGROUND: Despite its rare incidence of 1/40,000, fetal cardiac rhabdomyoma (CR) represents the prevailing type of benign cardiac fetal tumors, which commonly affects the ventricles. Fetal CRs rarely occur in the right atrium. Thus, the presentation of atrial fibrillation and premature atrial contractions (PAC) due to a solitary cardiac rhabdomyoma is an extremely rare scenario. Our literature review found that only 2% (1 out of 61) of rhabdomyoma cases were found in the right atrium. The majority of fetal cardiac rhabdomyomas are associated with tuberous sclerosis complex (TSC). CASE PRESENTATION: A 7-day-old male neonate presented with arrhythmias and an atrial mass for further evaluation. Echocardiography revealed a hyperechoic, round, uniform right atrial mass (25 mm). An abdominal and testicular ultrasound showed multiple thin-walled cortical cysts in both kidneys and a scrotal hydrocele, respectively. His laboratory workup was insignificant except for hypomagnesemia. Electrocardiography revealed junctional rhythm and PACs with wave distortions. A brain magnetic resonance imaging scan revealed multiple subependymal lesions on the frontal and occipital horns of the lateral ventricles. These findings (Fig. 1), along with a family history of TSC, confirmed the diagnosis of TSC with associated CR. The patient was treated symptomatically with an anti-convulsant and monitored with regular follow-ups. Surgical resection was not required. CONCLUSION: Despite CR's predominance in the ventricles, a diagnosis of rhabdomyoma should be kept in mind in the presence of a solitary atrial mass and PACs. Physicians should evaluate systemic findings related to TSC and provide appropriate follow-up and family screening. Surgical resection is not always required, and symptom management can be achieved through medical treatment alone.

Extracardiac adult-type rhabdomyoma-Report of two cases in dogs.

This report describes the cytologic, histopathologic, and immunohistochemical features of adult-type rhabdomyoma located within the subcutaneous tissue in a 14-year-old female Border Collie (thigh) and a 13-year-old male Mongrel (flank). In both cases, fine-needle aspiration biopsy revealed cluster-forming, epithelial-like polygonal cells with abundant foamy cytoplasm, and moderate to marked anisocytosis and anisokaryosis; therefore, an epithelial tumor was suspected. After surgical excision, tumors underwent histopathologic examination with additional immunohistochemistry. Both tumors were well-demarcated and located within the subcutaneous tissue in the vicinity of the cutaneous muscle. The tumor mass consisted of densely packed round or polygonal cells with distinct vacuolation of the cytoplasm. Tumor cells expressed vimentin, desmin, and NSE and were cytokeratin and α-SMA negative. Based on histologic features and immunophenotyping, adult-type rhabdomyoma was diagnosed in both cases. This study highlights that the cytologic features of rhabdomyoma can be misleading and may suggest an epithelial tumor.

A single-center observational study on long-term neurodevelopmental outcomes in children with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare multisystem disorder caused by mutations in the TSC1 or TSC2 gene. More than 90% of patients with TSC develop neurological and/or neuropsychiatric manifestations. The aim of the present study was to determine the developmental and cognitive long-term outcomes of pediatric TSC patients. METHODS: This cross-sectional, monocenter study included pediatric TSC patients who received multidisciplinary long-term care with a last visit between 2005 and 2019. Neurological manifestations and cognitive development (BSID, K-ABC) were analyzed in relation to age and type of mutation. RESULTS: Thirty-five patients aged 13.5 ± 7.8 years were included in the study. Diagnosis was confirmed genetically in 65.7% of patients (TSC1, 26.1%; TSC2, 65.2%; NMI, 8.7%). Mean age at diagnosis was 1.3 ± 3.5 years; 74.3% of the patients had been diagnosed within the first year of life due to seizures (62.9%) or/and cardiac rhabdomyomas (28.6%). The most common TSC manifestations included structural brain lesions (cortical tubers, 91.4%; subependymal nodules, 82.9%), epilepsy (85.7%), and cardiac rhabdomyomas (62.9%). Mean age at seizure onset was 1.5 ± 2.3 years, with onset in 80.0% of patients within the first two years of life. Infantile spasms, which were the first seizure type in 23.3% of the patients, developed earlier (0.6 ± 0.4 years) than focal seizures (1.8 ± 2.5 years). Refractory epilepsy was present in 21 (70.0%) patients, mild or severe intellectual impairment in 66.6%, and autism spectrum disorders in 11.4%. Severe cognitive impairment (33.3%) was significantly associated with epilepsy type and age at seizure onset (p < 0.05). CONCLUSIONS: The results emphasized the phenotypic variability of pediatric-onset TSC and the high rate of neurological and neuropsychiatric morbidity. Early-onset refractory epilepsy was associated with impaired cognitive development. Children of all ages with TSC require multidisciplinary long-term care and individual early-intervention programs.

[Asymptomatic course of rhabdomyoma of the heart].

The article describes a clinical case of cardiac rhabdomyoma first diagnosed in an 18-year-old girl. At the age of 12 months, the patient first developed generalized, prolonged convulsive seizure with the eyeballs rolling upward, tonic arm tension, and profuse salivation. From 1.5 to 2 years, according to her mother, the girl had frequent "freezing" with fixed stare. Anticonvulsant therapy was not administered. From the age of 2 years 8 months, the child began to experience episodes of drowsiness, lethargy, blurred speech, and repeated vomiting lasting up to 2 weeks. The patient was regularly treated at the neurological department. According to CT at the age of four, the patient showed characteristic alterations in the brain and was diagnosed with tuberous sclerosis, symptomatic generalized epilepsy, and psychoorganic syndrome. Only at the age of 18, cardiac ultrasound detected a 7x6 mm hyperechoic formation with endogenous growth buried in the myocardium of the left ventricular (LV) anterior-lateral wall and another one in the area of the LV lateral wall with endogenous growth of 2×4 mm. Magnetic resonance imaging (MRI) revealed multiple focal formations with clear, even contours in the area of the middle anterior septal segment (closely adjacent to papillary muscles) in the region of the apex, buried in the myocardium. The formation sizes were 9×7 mm, 8×13 mm, and 7.5×6 mm, respectively, and they moderately accumulated the contrast agent. Lesions with identical characteristics and a diameter up to 4.5 mm were visualized on the anterior wall in the region of the apex, in the depth of the myocardium. Due to the absence of arrhythmias and hemodynamic disorders, immunosuppressive therapy was not administered. Follow-up and dynamic MRI control of the heart were recommended. If signs of tumor growth are detected, consider immunosuppressive therapy with everolimus. The case is of interest for a long asymptomatic growth of rhabdomyoma. Generally, cardiac rhabdomyomas are diagnosed in the postnatal period and may be the earliest manifestation of tuberous sclerosis.

Prenatal diagnosis of fetal pericardial rhabdomyoma resulting in fetal death.

We present a case of huge pericardial rhabdomyoma that progressed into the pericardial cavity, resulting in fetal death. Fetal ultrasound and neonatal echocardiography provide excellent diagnostic methods for fetal rhabdomyoma. When established, antenatal diagnosis enables a focused, specialized, and multidisciplinary approach with individual case management, potentially reducing perinatal morbidity and mortality.

Three-Year Follow-Up after Intrauterine mTOR Inhibitor Administration for Fetus with TSC-Associated Rhabdomyoma.

Tuberous sclerosis complex (TSC) is a multisystem disorder characterized by seizures, neuropsychiatric disorders, and tumors of the heart, brain, skin, lungs, and kidneys. We present a three-year follow-up of a patient with TSC-associated rhabdomyoma detected in utero. Genetic examination of the fetus and the parents revealed a de novo variant in the TSC2 gene (c.3037delG, p.Asp1013IlefsTer3). Oral everolimus was initiated in the pregnant mother to regress the fetal tumor, which was successful. To the best of our knowledge, there is very little information regarding the use of everolimus therapy during pregnancy. West-syndrome was diagnosed when the proband was four months old. The symptoms were well-manageable, however temporarily. Therapy-resistant focal seizures were frequent. The patient had good vitals and was under regular cardiological control, showed a balanced circulation, and did not require any medication. Subependymal giant cell astrocytoma (SEGA) identified by regular neuroimaging examinations remained unchanged, which may be a consequence of early intrauterine treatment. Early detection of the pathogenic TSC2 variant, followed by in utero administration of everolimus and early vigabatrin therapy, allowed the detection of a milder developmental delay of the proband. Our study emphasizes how early genetic testing and management of epilepsy are pivotal for proper neurodevelopmental impacts and therapeutic strategies.

Cutaneous rhabdomyoma in an 82-year-old White man.

This case highlights a primary cutaneous rhabdomyoma presenting as a slowly enlarging subcutaneous nodule on the mentum of an 82-year-old White man with a medical history of two intracranial rhabdomyomas. Although they are rarely syndromic, it is important to note that the most common demographic for presentation of rhabdomyomas includes older males presenting as a subcutaneous nodule on the head, neck, or oral cavity. They are most often seen in isolation but can be multifocal in up to 25% of all cases. Being a rare entity, there is no generally recognized treatment consensus; however, complete surgical excision is recommended to prevent recurrence and morbidity from local tissue destruction.

Cardiac and Pericardial Neoplasms in Children: Radiologic-Pathologic Correlation.

Primary cardiac and pericardial neoplasms are rare in the pediatric population and can include both benign and malignant lesions. Rhabdomyomas, teratomas, fibromas, and hemangiomas are the most common benign tumors. The most common primary cardiac malignancies are soft-tissue sarcomas, including undifferentiated sarcomas, rhabdomyosarcomas, and fibrosarcomas. However, metastatic lesions are more common than primary cardiac neoplasms. Children with primary cardiac and pericardial tumors may present with nonspecific cardiovascular symptoms, and their clinical presentation may mimic that of more common nonneoplastic cardiac disease. The diagnosis of cardiac tumors has recently been facilitated using noninvasive cardiac imaging. Echocardiography is generally the first-line modality for evaluation. Cardiac MRI and CT are used for tissue characterization and evaluation of tumor size, extension, and physiologic effect. The varied imaging appearances of primary cardiac neoplasms can be explained by their underlying abnormality. Treatment of these lesions varies from conservative management, with spontaneous regression of some lesions such as rhabdomyomas, to surgical resection, particularly in patients with associated heart failure. With adequate imaging techniques and knowledge of the pathologic basis of the neoplasm, it is often possible to differentiate benign from malignant tumors, which can greatly affect adequate and timely treatment. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.

Cardiac rhabdomyomas: clinical progression, efficacy and safety of everolimus treatment.

BACKGROUND: Primary cardiac tumors are extremely rare. Cardiac rhabdomyoma is the most common primary cardiac tumor. 50-80% of solitary rhabdomyomas and all multiple rhabdomyomas are associated with tuberous sclerosis complex. Due to spontaneous regression, surgery is necessary only in severe hemodynamic compromise and persistent arrhythmias. Everolimus, a mechanistic target of rapamycin (mTOR) inhibitor, can be used in the treatment of rhabdomyomas seen in tuberous sclerosis complex. We aimed to evaluate the clinical progression of rhabdomyomas followed-up in our center between the years 2014-2019 and evaluate the efficacy and safety of everolimus treatment on tumor regression. METHODS: Clinical features, prenatal diagnosis, clinical findings, tuberous sclerosis complex presence, treatment and follow-up results were evaluated retrospectively. RESULTS: Among 56 children with primary cardiac tumors, 47 were diagnosed as rhabdomyomas, 28/47 patients (59.6%) had prenatal diagnosis, 85.1% were diagnosed before one year of age and 42/47 patients (89.3%) were asymptomatic. Multiple rhabdomyomas were present in 51% and median diameter of tumors was 16mm (4.5 - 52 mm). In 29/47 patients (61.7%) no medical or surgical treatment were necessary while 34% of these had spontaneous regression. Surgery was necessary in 6/47 patients (12.7%). Everolimus was used in 14/47 patients (29.8%). Indications were seizures (2 patients) and cardiac dysfunction (12 patients). Regression in size of rhabdomyomas was achieved in 10/12 patients (83%). Although, in the long-term, the amount of tumor mass shrinkage was not significantly different between patients who received everolimus and untreated patients (p=0.139), the rate of mass reduction was 12.4 times higher in patients who received everolimus. Leukopenia was not detected in any of the patients, but, hyperlipidemia was noted in 3/14 patients (21.4%). CONCLUSIONS: According to our results, everolimus accelerates tumor mass reduction, but not amount of mass regression in the long term. Everolimus may be considered for treatment of rhabdomyomas which cause hemodynamic compromise or life-threatening arrhythmias before surgical intervention.

Childhood tuberous sclerosis complex in southern Sweden: a paradigm shift in diagnosis and treatment.

AIM: To investigate the complete clinical spectrum of individuals with paediatric tuberous sclerosis complex in southern Sweden and explore changes over time. METHODS: In this retrospective observational study, 52 individuals aged up to 18 years at the study start were followed-up at regional hospitals and centres for habilitation from 2000 to 2020. RESULTS: Cardiac rhabdomyoma was detected prenatally/neonatally in 69.2% of the subjects born during the latest ten years of the study period. Epilepsy was diagnosed in 82.7% of subjects, and 10 (19%) were treated with everolimus, mainly (80%) for a neurological indication. Renal cysts were detected in 53%, angiomyolipomas in 47%, astrocytic hamartomas in 28% of the individuals. There was a paucity of standardized follow-up of cardiac, renal, and ophthalmological manifestations and no structured transition to adult care. CONCLUSION: Our in-depth analysis shows a clear shift towards an earlier diagnosis of tuberous sclerosis complex in the latter part of the study period, where more than 60% of cases showed evidence of this condition already in utero due to the presence of a cardiac rhabdomyoma. This allows for preventive treatment of epilepsy with vigabatrin and early intervention with everolimus for potential mitigation of other symptoms of tuberous sclerosis complex.