Fetal rhabdomyoma in a Thoroughbred filly.

A newborn Thoroughbred filly presented with a large mass located on the ventro-rostral aspect of the mandible. The mass was surgically removed under general anaesthesia. Upon gross examination, the mass was well circumscribed with a heterogeneous lobulated appearance. The results of histopathology and immunohistochemistry were consistent with a diagnosis of congenital fetal rhabdomyoma. On follow-up at six months post-surgical excision, no abnormalities were noted on clinical examination.

Cardiac Rhabdomyomas Presenting with Critical Cardiac Obstruction in Neonates and Infants: Treatment Strategies and Outcome, A Single-Center Experience.

Cardiac rhabdomyomas are the most common benign pediatric heart tumor in infancy, which are commonly associated with tuberous sclerosis complex (TSC). Most rhabdomyomas are asymptomatic and spontaneously regress over time. However, some cases especially in neonates or small infants can present with hemodynamic instability. Surgical resection of the tumor, which has been the gold standard in alleviating obstruction, is not always possible and may be associated with significant morbidity and mortality. Recently, mammalian target of rapamycin inhibitors (mTORi) have been shown to be safe and effective in the treatment of TSC. We present the outcomes of neonates and an infant who received treatment for symptomatic rhabdomyomas at a tertiary cardiology center. Medical records were reviewed to obtain clinical, demographic, and outcome data. Six patients received interventions for symptomatic rhabdomyomas, median age at presentation was 1 day old (range from 1 to 121 days old), and 67% of the patients had a pathogenic mutation in TSC gene. One patient underwent surgical resection of solitary tumor at right ventricular outflow tract (RVOT) successfully. In the four patients with left ventricular outflow tract (LVOT) obstruction, two patients received combined therapy of surgical debulking of LVOT tumor, Stage I palliation procedure, and mTORi and two patients received mTORi therapy. One patient with RVOT obstruction underwent ductal stenting and received synergistic mTORi. Four of the five patients had good response to mTORi demonstrated by the rapid regression of rhabdomyoma size. 83% of patients are still alive at their latest follow-up, at two to eight years of age. One patient died on day 17 post-LVOT tumor resection and Hybrid stage one due to failure of hemostasis, in the background of familial factor VII deficiency. Treatment of symptomatic rhabdomyoma requires individualized treatment strategy based on the underlying pathophysiology, with involvement of multidisciplinary teams. mTORi is effective and safe in inducing rapid regression of rhabdomyomas. A standardized mTORi prescription and monitoring guide will ensure medication safety in neonates and infants with symptomatic cardiac rhabdomyoma. Although the majority of tumors responded to mTORi, some prove to be resistant. Further studies are warranted, ideally involving multiple international centers with a larger number of patients.

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.

Adult-type rhabdomyoma of the lung: A case report.

ABSTRACT: Adult rhabdomyoma is an uncommon and benign striated muscle tumor consisting of striated muscular tissue. This neoplasm usually originates from cardiac muscle, and extracardiac rhabdomyoma is extremely rare. Herein, we report a case of adult rhabdomyoma in the lung, which has only been reported once in the 1970s. A 62-year-old woman presented to our hospital with a solid nodule on the right upper lobe. We performed tumor resection surgery and confirmed the diagnosis of adult rhabdomyoma by postoperative pathological examination. Herein, we report the clinical and pathologic characteristics of pulmonary adult rhabdomyoma (PAR) and review the literature about adult rhabdomyoma.

Genetics of Cardiac Tumours: A Narrative Review.

Cardiac tumours can occur in association with genetic syndromes. Rhabdomyomas have been reported in association with tuberous sclerosis, myxomas with Carney's complex, cardiac fibromas with Gorlin syndrome, and paragangliomas with multiple endocrine neoplasm syndrome. The presentation and prognosis of cardiac tumours associated with genetic syndromes differ compared with sporadic cases. Knowledge about the associated syndromes' genetic features and extracardiac manifestations is essential for the diagnosis, prognosis, and management of cardiac neoplasms. Moreover, identifying genetic mutations in benign and malignant cardiac tumours is needed to personalise management and improve treatment outcomes. Thus, this review discusses the genetic abnormalities associated with cardiac tumours, the current genetic screening recommendations, and the effect of those genetic mutations on the outcomes.

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.

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 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.

Benign mesenchymal tumours of the tongue: A report of adult-type rhabdomyoma and granular cell tumour with a review of the literature.

The cytomorphological features of benign mesenchymal tumours of the tongue have rarely been reported. Herein, we present the cytomorphological features of adult-type rhabdomyoma, which occurred in the tongue of a female patient, and granular cell tumour (GCT), which occurred in the tongue of a male patient; both patients were in their mid-50s. The cytological features of the adult-type rhabdomyoma case included large polygonal to ovoid cells with abundant and granular cytoplasm with predominantly peripherally located, uniform, round to oval nuclei and small nucleoli. Cross-striation and crystalline intracytoplasmic structures were not seen. The cytological features of the GCT case included large cells with abundant granular pale cytoplasm, small round nuclei and small distinct nucleoli. The cytological differential diagnoses of these tumours overlap; thus, the cytological findings of the different entities included in their differential diagnoses are discussed.

Multiple cardiac rhabdomyomas, prenatal diagnosis. Case report / Rabdomiomas cardiacos múltiples, diagnóstico prenatal. Reporte de casos.

Cardiac tumors are rare in children, having a maximum reported incidence of 0.027% in prenatal diagnosis, increasing the incidence in necropsy diagnosis; rhabdomyomas are the most frequent cardiac tumors, some cases are associated with tuberous sclerosis. We present the report of two cases in our unit that were diagnosed prenatal with follow-up after birth and one of them was associated with tuberous sclerosis. Both cases were admitted in a third level center, uncomplicated, without requiring surgical treatment, and could be discharged.

Los tumores cardiacos son raros en la población infantil, teniendo una incidencia máxima reportada del 0.027% en el diagnóstico prenatal, incrementándose la incidencia en el diagnóstico por necropsia. Los rabdomiomas son los tumores cardiacos más frecuentes, algunos casos pueden asociarse con esclerosis tuberosa. Presentamos el reporte de dos casos en nuestra unidad a los cuales se les realizó diagnóstico prenatal con seguimiento posterior al nacimiento y asociándose uno de ellos a esclerosis tuberosa. Ambos casos recibieron atención en un centro de tercer nivel, sin complicaciones, sin requerir tratamiento quirúrgico, pudiendo ser egresados.

Prostatic Rhabdomyoma in a Toddler: A Case Report With Molecular Characterization.

We present a 29-month-old male patient in follow-up due to pyelocaliceal dilation with a prostatic nodule incidentally found during ultrasound evaluation. Cysto video endoscopy was performed and a prostate biopsy, obtained. Microscopic evaluation showed a haphazardly distributed population of muscular cells with cross striations without evidence of mitosis or necrosis. Immunohistochemistry was positive for myogenin and desmin and negative for smooth muscle actin. Next generation sequencing was performed without finding any pathogenic variant or fusion in the tumor RNA. The patient received no further treatment, remained asymptomatic and continues in follow up, 3 years after initial diagnosis. We report a case of prostate rhabdomyoma in a toddler, an exceptional location that raises concern about differential diagnosis with its malignant counterpart, rhabdomyosarcoma, especially at this age.

Detection of TSC1/TSC2 mosaic variants in patients with cardiac rhabdomyoma and tuberous sclerosis complex by hybrid-capture next-generation sequencing.

BACKGROUND: Fetal cardiac rhabdomyoma (CR) is strongly associated with tuberous sclerosis complex (TSC), which is caused by variants in TSC1 and TSC2. However, in 10%-15% of patients with clinically confirmed TSC, no TSC1/TSC2 variants are identified by panel sequencing or multiplex ligation-dependent probe amplification (MLPA). METHODS: We analyzed eight fetuses with CR and their families. No TSC1/TSC2 variants had previously been identified for six of these fetuses, and we suspected the other two families of gonadal mosaicism. We performed next-generation sequencing (NGS) using CR tissue, umbilical cord tissue, and parental blood. All positive results, involving two paternal semen, were verified by droplet digital polymerase chain reaction (ddPCR). RESULTS: Four fetuses carried low-level mosaic variants (0.05%-14.89%), and two only exhibited somatic mosaic variants in the CR tissue (15.76% and 37.69%). Two fathers had gonadal mosaicism (9.07% and 4.86%). We identified nine pathogenic variants in eight fetuses, including one fetus with a second-hit variant. CONCLUSION: The fetuses assessed in this study carried low-level and somatic mosaic variants, and CR tissue from one fetus exhibited a second-hit variant. Heterozygous gonadal variants can exist in patients with low-level mosaicism. Combining NGS with ddPCR improves the accuracy of prenatal TSC diagnosis.

[Ballantyne syndrome associated with fetal cardiac rhabdomyoma: a case report]. / Syndrome de Ballantyne associée à un rhabdomyome cardiaque fœtal: à propos d´un cas.

Ballantyne syndrome or mirror syndrome was first described in 1892. It is a disorder affecting pregnant women describing the association of fetal anasarca complicated by more or less generalized maternal edema and albuminuria (and sometimes anemia). It is a rare clinical entity. Diagnosis is based on a triad consisting of fetal hydrops, generalized maternal edema and placentomegaly. It can be associated with fetal hydrops from any cause. Diagnostic should be suspected in patients with maternal edema syndrome associated with fetal anasarca. Guarded fetal prognosis can be associated with high maternal morbidity; hence the need for early diagnosis, resting on a clear determination of its cause, and aimed to implement antenatal treatment improving maternal and fetal prognosis. We here report a unique case of Ballantyne syndrome which has never been described in the literature. The study involved a 32-year-old female patient with fetal hydrops caused by fetal cardiac rhabdomyoma.

Rhabdomyomatous mesenchymal hamartoma presenting as telangiectasia in a 57-year-old man.

Rhabdomyomatous mesenchymal hamartoma (RMH) is a rare congenital malformation of the dermis and subcutaneous tissue. Usually, RMH occurs in the midline of the face and neck region. We described a case of RMH presenting as telangiectasia in a 57-year-old man with a history of pityriasis lichenoides chronicus. Histopathological examination revealed a subepidermal haphazard proliferation of striated muscular tissue perpendicular to the epidermis. These bundles of striated muscular tissue were admixed with adnexal structures. The diagnosis was consistent with RMH. RMH is more common in the neonatal period or in young children, but we should consider it as part of a differential diagnosis in older adults as well.