A Fetus of Cardiac Myxoma with a Tuberous Sclerosis Complex 2 Variant: The First Case Report

Dear Editor, Fetal cardiac tumors are rare conditions, with an incidence ranging from 0.08% to 0.2%.[1] Among the various histological types, the three most common in fetal and pediatric individuals are rhabdomyoma, teratomas, and fibromas. Fetal cardiac myxomas are even rarer. These histological types are classified as benign tumors since malignant variants are exceedingly uncommon in fetuses. However, fetal tumors can be associated with genetic syndromes. We here present the first documented case of a fetal myxoma identified in a prenatal case diagnosed with a tuberous sclerosis Complex 2 (TSC2) variant. A 26-year-old woman, G1P0, was referred to our unit for further evaluation during her second trimester due to abnormal findings on fetal ultrasound. At 12 weeks of gestation, she underwent cell-free DNA screening for aneuploidies following a normal first-trimester sonographic scan, which yielded a normal result. Upon referral at 22 weeks’ gestation, a detailed anatomical ultrasound revealed a fetal cardiac mass located in the right atrium without extracardiac anomalies. A fetal echocardiogram demonstrated a solitary homogeneous isoechogenic mass measuring 13 mm × 7 mm × 10 mm situated in the lateral wall of the right atrium [Figure 1a]. The mass exhibited regular morphology and moved synchronously with atrial contraction; Doppler imaging did not show any blood flow associated with it. The woman was informed that the nature of the cardiac mass remained uncertain.Figure 1: A fetal case of cardiac myxoma with a tuberous sclerosis Complex 2 variant, (a) A solitary fetal atrial mass (arrow) identified at 24 weeks’ gestation showing homogeneous isoechogenicity with regular boundary, (b) Schematic diagrams of the TSC2 showing the variant c.3611-2A>C (arrow) in the fetus, but not in the parents, (c) The microscopic appearance of cardiac myxoma showing minimal cellularity with only scattered spindle or stellate cells being present in a loose myxoid stroma (H and E, ×20), and the myxoma cell being round, oval, polygonal, fusiform or stellate shaped with bland nuclei and light pink cytoplasm (H and E, ×40) (d)Amniocentesis was performed utilizing exome sequencing as the first-tier test, given the low risk of chromosomal abnormalities suggested by a negative cell-free DNA screening result. This approach identified a heterozygous TSC2 variant (c.3611-2A>C) in the fetus that arose de novo [Figure 1b]; this variant was classified as likely pathogenic according to the ACMG guidelines. Notably, no variants were identified in the PRKAR1A gene, which has been associated with cardiac myxoma.[2] Following genetic counseling regarding TSC-associated neuropsychiatric disorders, which may include autism spectrum disorder and cognitive disabilities, the couple opted to terminate the pregnancy at 24 weeks’ gestation. Autopsy confirmed the presence of an atrial mass, while histological examination established a diagnosis of myxoma [Figure 1c and d].Abbreviations ACMG American College of Medical Genetics and Genomics DNA Deoxyribonucleic acid G1P0 Gravida 1, para 0 H and E Hematoxylin and eosin PRKAR1A Protein kinase cAMP-dependent type I regulatory subunit alpha TSC Tuberous sclerosis complexPrenatal diagnosis for TSC is essential for affected families. This diagnosis primarily relies on sonographic detection of fetal cardiac rhabdomyomas, which can typically be identified as early as 20 weeks into the second trimester. The likelihood of a TSC diagnosis increases with the number of tumors present; approximately 80% of cases exhibit two or more tumors.[3] Currently, odontogenic myxoma has been reported exclusively in patients with TSC and myxomas.[4,5] We present a case involving a fetal cardiac myxoma associated with a TSC2 variant. The clinical progression associated with fetal myxomas is generally benign, with relatively few instances leading to adverse cardiac events due to critical hemodynamic effects.[6] Prenatal echocardiography serves as a reliable diagnostic tool capable of detecting cardiac myxomas; however, differentiating these from other types of fetal cardiac tumors poses significant challenges and may ultimately require pathological examination for definitive diagnosis. Our case suggests that when encountering a fetal atrial mass, even one lacking typical features indicative of rhabdomyoma, prenatal molecular testing should be considered necessary. Identifying genetic conditions within those with benign cardiac tumors will facilitate personalized clinical management and enhance treatment outcomes. Ethics statement This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and its amendments. The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.