What Causes Atrial Myxoma?
Atrial myxomas are benign primary cardiac tumors whose exact cause remains largely unknown, though they arise from primitive multipotent mesenchymal cells in the endocardium, with approximately 90% occurring sporadically and 10% having a familial autosomal dominant inheritance pattern. 1, 2
Sporadic Atrial Myxomas (90% of cases)
The vast majority of atrial myxomas occur without identifiable genetic or environmental triggers. 3
- Origin: These tumors develop from primitive mesenchymal cells within the endocardium, most commonly at the fossa ovalis region of the interatrial septum 4, 5
- Location pattern: Approximately 75% occur in the left atrium, 10-20% in the right atrium, and the remainder in atypical locations including ventricular chambers 5, 6
- Incidence: Autopsy series demonstrate an occurrence rate of 0.02% in the general population, making them the most common primary cardiac tumor 2, 4
Familial Atrial Myxomas (10% of cases)
A distinct subset of patients develops myxomas through autosomal dominant inheritance, often as part of familial syndromes. 1, 3
- Genetic transmission: Several chromosomal loci have been identified in familial cases, transmitted as an autosomal dominant trait 1
- Associated syndromes: Atrial myxomas occur with increased frequency in patients with familial multiple neoplasia and lentiginosis syndrome (Carney complex) 1
- Clinical implications: Familial cases typically present at younger ages, involve multiple cardiac chambers simultaneously, and have significantly higher recurrence rates (up to 20%) compared to sporadic cases (1-5%) 4, 3
Pathophysiological Development
The microscopic architecture reveals the tumor's mesenchymal origin with characteristic myxoid matrix proliferation. 4
- Cellular composition: Myxomas contain lepidic cells (polygonal to stellate-shaped with eosinophilic cytoplasm), stromal spindle cells, and endothelial-lined vascular channels embedded in abundant mucopolysaccharide-rich myxoid matrix 4
- Growth pattern: The tumor typically attaches to the atrial septum via a stalk, though 10% arise from other sites including the posterior wall, anterior wall, or atrial appendages 5, 7
- Surface characteristics: Villous or papillary surface architecture correlates with higher embolic potential, as these friable surfaces readily generate thrombus or tumor fragments 2, 4
Associated Conditions (Not Causative)
While certain conditions may coexist with atrial myxomas, they do not cause the tumor:
- Structural heart disease: Atrial myxomas can occur alongside atrial septal defects, though this represents coincidental occurrence rather than causation 7
- Cardiomyopathy: Isolated case reports describe myxomas in patients with hypertrophic cardiomyopathy, but no causal relationship exists 8
Critical Clinical Pitfall
Do not confuse conditions that predispose to atrial fibrillation (valvular disease, hypertension, heart failure) with causes of atrial myxoma—these are entirely separate pathophysiological entities. 9 The evidence regarding atrial fibrillation mechanisms 1 and mitral valve prolapse pathology 1 is irrelevant to myxoma etiology.
Screening Recommendations
First-degree relatives of patients with documented atrial myxomas must undergo echocardiographic screening for occult tumors, given the 10% familial inheritance pattern. 3