Left Atrial Myxoma: Definition and Pathophysiology
Definition
Left atrial myxoma is the most common primary benign cardiac tumor, accounting for approximately 50% of all benign cardiac neoplasms, arising from primitive multipotent mesenchymal cells in the endocardium. 1, 2
Epidemiology: Cardiac myxomas occur in only 0.02% of people based on large autopsy series, making them rare but clinically significant when present 3, 1
Anatomic location: Myxomas occur most frequently in the left atrium, typically attached to the interatrial septum at the fossa ovalis region 3, 4
Demographics: Most cases occur sporadically (approximately 90%), with peak incidence between the 4th and 6th decade of life, and are more common in women 5, 6
Pathophysiology
Cellular Origin and Development
The tumor originates from undifferentiated mesenchymal cells in the endocardium, with characteristic microscopic architecture that determines its clinical behavior. 5, 4
Cellular composition: The tumor contains polygonal to stellate-shaped myxoma cells (lepidic cells) with eosinophilic cytoplasm, arranged singly or in small clusters, along with stromal spindle cells embedded in abundant myxoid matrix 1, 2
Extracellular matrix: The myxoid stroma is composed of loose, gelatinous mucopolysaccharide-rich material (hyaluronic acid and chondroitin sulfate) that appears basophilic on H&E staining 1, 2
Vascular architecture: Thin-walled blood vessels of varying caliber are scattered throughout the tumor, with frequent hemorrhage and hemosiderin deposition, especially in larger tumors 1, 2
Genetic Factors
Sporadic cases: Approximately 90% occur without familial inheritance, with unclear etiology 5
Familial cases: About 10% have autosomal dominant inheritance, often as part of Carney complex (multiple neoplasia and lentiginosis syndrome), presenting at younger ages with higher recurrence rates (up to 20% versus 1-5% in sporadic cases) 5
Mechanisms of Clinical Manifestations
The pathophysiology of symptoms involves three distinct mechanisms that determine clinical presentation and risk profile. 3
1. Mechanical Obstruction
Mitral valve obstruction: The tumor causes intermittent obstruction of blood flow across the mitral valve during diastole, reducing left ventricular filling and cardiac output, leading to syncope, heart failure symptoms, or sudden death 2
Positional symptoms: Symptoms may vary with body position as the mobile tumor shifts within the atrium 7
2. Embolic Complications
Thromboembolic mechanism: Stroke occurs either from embolization of thrombus that forms on the tumor surface or from embolization of tumor fragments themselves 3
Embolic risk: The overall embolism rate is 25% in patients with cardiac myxomas, with embolic stroke being the presenting symptom in up to 50% of cases 1, 2
Morphologic determinants: Villous or papillary surface architecture is associated with significantly higher embolic and thromboembolic potential due to friable surfaces that readily generate thrombus or tumor fragments 3, 5
3. Constitutional Symptoms
- Systemic manifestations: Patients may present with fever, weight loss, and elevated inflammatory markers, though the mechanism is not fully understood 7
Histopathologic Features
Immunohistochemistry confirms the diagnosis with characteristic staining patterns. 1
Positive markers: Vimentin and calretinin 1
Negative markers: Cytokeratin and S100, helping distinguish myxoma from other cardiac tumors 1
Clinical Pitfalls
Atypical presentations: While most myxomas are attached to the interatrial septum, rare cases may have broad-based attachments extending from the septum to the atrial wall, or may arise from other cardiac chambers 8
Size considerations: Giant myxomas (>6 cm) are associated with worse prognosis and higher risk of mechanical complications 6
Misdiagnosis risk: Longstanding dyspnea may be incorrectly attributed to other conditions like asthma, delaying diagnosis 7