Atrial Myxoma and Other CardiacTumors¶

Chapter 282 | Part 6: Disorders of the Cardiovascular System · Part 6 – Cardiovascular Disorders · Chapter 282

Key Clinical Points¶

Primary cardiac tumors are rare (approximately 1 in 2000 cases in autopsy series); ~75% are benign (myxomas) and ~25% are malignant (sarcomas).
Atrial myxoma is the most common primary cardiac tumor in adults; ~90% are sporadic, while ~10% are familial (associated with Carney complex).
Myxomas typically arise from the interatrial septum near the fossa ovalis (especially in the left atrium) and are often pedunculated.
A characteristic 'tumor plop' is heard during early/mid-diastole due to tumor impact against the mitral valve.
Constitutional symptoms (fever, weight loss, malaise, etc.) occur in myxomas due to cytokine (e.g., IL-6) secretion; these can lead to misdiagnosis as endocarditis or systemic inflammatory disease.
Rhabdomyomas are the most common cardiac tumors in infants/children and are associated with tuberous sclerosis (TSC1/TSC2 mutations).
Angiosarcomas are the most common malignant primary cardiac tumor in adults, typically involving the right side of the heart.
Surgical excision is the definitive treatment for my1xomas; recurrence rates are 1-2% in sporadic cases but 12-22% in familial cases.
Cardiac MRI is preferred over TTE/TEE for tissue characterization and differentiating tumor from thrombus when TTE is inconclusive.
Paragangliomas are rare, highly vascular chromaffin cell tumors that may be hormonally active, causing uncontrolled hypertension.

DEFINITION & OVERVIEW¶

• Primary vs. Secondary: ◦ Primary tumors arise in the heart; secondary involvement of the heart or pericardium occurs in up to 20% of patients with end-stage metastatic cancer. ◦ All cardiac tumors, regardless of pathology, have the potential to cause life-threatening complications. • Diagnostic Differentiation: ◦ Must be distinguished from other masses: vegetation, thrombus, inflammatory myofibroblastic tumors, or myocardial hypertrophy. • Classification of Primary Tumors: ◦ Benign: Myxomas (most common in adults), Rhabdomyomas (most common in infants/children), Fibromas, Lipomas, Papillary fibroelastomas, Teratoma, Chemodectoma, Neurilemoma, Granular cell myoblastoma, Hemangiomas, Mesotheliomas, Paragangliomas. ◦ Malignant: Sarcomas (almost all malignant primary cardiac tumors), Angiosarcomas (most common in adults), Rhabdomyosarcomas (most common in children), Cardiac lymphomas (more common with systemic disease).

EPIDEMIOLOGY¶

• Myxomas: ◦ Occur at all ages, most commonly in the 3rd through 6th decades; female predilection. ◦ ~90% are sporadic (solitary, interatrial septum origin); ~10% are familial (autosomal dominant). • Rhabdomyomas: ◦ Found in ~50% of children with tuberous sclerosis. • Sarcomas: ◦ More common in men and the elderly; typically involve the right side of the heart.

Familial vs. Sporadic Myxomas¶

• Sporadic (90%): ◦ Solitary, often pedunculated on a fibrovascular stalk. ◦ Arise from interatrial septum near fossa ovalis (especially left atrium). ◦ Recurrence rate: 1-2%. • Familial (10%): ◦ Often part of Carney complex; occur in younger individuals. ◦ Frequently multiple and may be ventricular in location. ◦ Recurrence rate: 12-22% due to multifocal lesions.

ETIOLOGY & PATHOPHYSIOLOGY¶

• Myxoma Structure: Gelatinous structures; myxoma cells in a stroma rich in glycosaminoglycans. • Rhabdomyomas: ◦ Likely hamartomatous growths; multiple in 90% of cases. ◦ Associated with mutations in tumor-suppressor genes TSC1 and TSC2. ◦ Tend to regress completely or partially. • Fibromas: ◦ Usually single, ventricular location, often calcified. ◦ May be associated with mutations in tumor-suppressor gene PTCH1. • Sarcomas: ◦ Rapid progression; death within weeks to months from presentation. ◦ ~1/3 are metastatic at initial diagnosis (typically lung). ◦ Frequently invade pericardial space; may obstruct chambers or venae cavae. ◦ Angiosarcomas: most common in adults. ◦ Rhabdomyosarcomas: most common in children. • Paragangliomas: ◦ Rare chromaffin cell tumors (extra-adrenal pheochromocytomas). ◦ Located in the roof of the left atrium; highly vascular. ◦ May be hormonally active → uncontrolled hypertension. ◦ Identified via CT, MRI, or 131I-metaiodobenzylguanidine scan.

Carney Complex Genetics¶

• Genetic Basis: Inactivating mutations in PRKAR1A (approx. 70% of patients). ◦ PRKAR1A encodes the protein kinase A type I-α regulatory subunit. • Syndrome Features: ◦ Myxomas (cardiac, skin, and/or breast). ◦ Lentigines and/or pigmented nevi. ◦ Endocrine overactivity (primary nodular adrenal cortical disease, testicular tumors, pituitary adenomas).

CLINICAL FEATURES¶

• General Manifestations: ◦ Chest pain, syncope, CHF, murmurs, arrhythmias, conduction disturbances. ◦ Pericardial effusion/tamponade; embolic phenomena (TIA, stroke, MI). • Myxoma-Specific Features: ◦ 'Tumor plop': Low-pitched sound in early/mid-diastole from tumor impact against the mitral valve. ◦ Obstructive Symptoms: ◦ Mimics mitral valve disease (stenosis from prolapse; regurgitation from trauma/distortion). ◦ Ventricular myxomas → outflow tract obstruction (similar to subaortic or subpulmonic stenosis). ◦ Positional Nature: Symptoms may be sudden or change with gravity. • Constitutional Symptoms: ◦ Fever, weight loss, cachexia, malaise, arthralgias, rash, digital clubbing, Raynaud's phenomenon. ◦ Mechanism: Secretion of cytokines (e.g., IL-6). ◦ Clinical Trap: Often misdiagnosed as endocarditis, collagen vascular disease, or paraneoplastic syndrome. • Rhabdomyoma Symptoms: ◦ Mechanical obstruction; mimics valvular stenosis; CHF; restrictive/hypertrophic cardiomyopathy; pericardial constriction. • Sarcoma Symptoms: ◦ Rapid progression; hemodynamic compromise; local invasion; distant metastases.

Embolic Phenomena¶

• Result from embolization of tumor fragments or tumor-associated thrombus. ◦ Can cause TIA, stroke, or myocardial infarction.

DIFFERENTIAL DIAGNOSIS¶

• General Cardiac Masses: ◦ Vegetation, Thrombus, Inflammatory myofibroblastic tumors, Myocardial hypertrophy. • Mimics of Constrictive Pericarditis: ◦ Cor pulmonale: Advanced pulmonary disease present; Kussmaull's sign is negative. ◦ Tricuspid stenosis: Characteristic murmur and accompanying mitral stenosis usually present. ◦ Restrictive cardiomyopathy. • Clinical Importance of Differentiation: ◦ Constrictive pericarditis can be corrected surgically. ◦ Tumor vs. Thrombus differentiation is critical for treatment planning.

INVESTIGATIONS & DIAGNOSIS¶

Initial Imaging: Transthoracic Echocardiography (TTE). ◦ Assess location, size, and impact on adjacent structures (valves, pericardium).
Advanced Echo: Transesophageal Echocardiography (TEE). ◦ Improved characterization/spatial resolution; aids in determining surgical approach.
Tissue Characterization: Cardiac Magnetic Resonance Imaging (MRI) with gadolinium. ◦ Superior for defining size, identifying local invasion, and differentiating tumor from thrombus. ◦ Preferred when TTE/TEE is inconclusive.
Alternative Imaging: Gated Cardiac Computed Tomography (CT). ◦ Used if MRI is not feasible (e.g., implantable devices) or to assess calcified lesions and extracardiac involvement.
Nuclear Imaging (FDG-PET): ◦ Defines extracardiac disease; useful for neuroendocrine tumors.
Procedure Note: ◦ Cardiac catheterization/angiography not mandatory if noninvasive data is sufficient. ◦ Caution: Catheterization carries risk of tumor embolization.
Screening: Echocardiographic screening of first-degree relatives (especially if patient is young, has multiple tumors, or myxoma syndrome features).

Table 282-1 Summary (Imaging Modalities): • TTE: Assessment of location/size and impact on structures. • TEE: Improved characterization; aids surgical planning. • MRI: Superior tissue characterization; differentiates tumor from thrombus. • CT: Anatomic assessment; useful for calcified lesions or when MRI is contraindicated. • Nuclear (FDG-PET): Identifies extracardiac disease; useful for neuroendocrine tumors.

MANAGEMENT & TREATMENT¶

Myxoma Treatment: ◦ Procedure: Surgical excision using cardiopulmonary bypass. ◦ Efficacy: Generally curative regardless of size. ◦ Preoperative Step: Coronary arteriography for patients aged >50 years to exclude CAD.
Malignant Tumor Treatment: ◦ Primary Goal: Complete resection (if possible). ◦ Note: Many are too advanced for surgery at presentation; prognosis is generally poor.
Other Benign Tumors: ◦ Rhabdomyomas: Surgery only if causing obstruction. ◦ Fibromas: Complete resection when possible (due to growth, arrhythmias, and obstruction). ◦ Papillary fibroelastomas: Resect even if asymptomatic; conservative approach for small, right-sided lesions. ◦ Lipomas: Resect if producing symptoms (mechanical interference, arrhythmia, conduction issues). ◦ Paragangliomas: Extensive surgical resection required. ◦ Hemangiomas/Mesotheliomas: Generally small; may cause AV conduction disturbances or sudden death.

Surgical Considerations¶

• Recurrence Risk: ◦ Familial: 12-22% (due to multifocality). ◦ Sporadic: 1-2% (due to incomplete resection). • Cardiac Decortication: ◦ Benefits are progressive over months. ◦ Risks depend on myocardial penetration, atrophy, and renal/hepatic function.

COMPLICATIONS & PROGNOSIS¶

• General Complications: ◦ Obstructive signs; embolic phenomena (TIA, stroke, MI); ◦ Constitutional symptoms; ◦ Hemodynamic compromise; local invasion; distant metastases; ◦ Pericardial effusion/tamponade; arrhythmias; conduction disturbances; valve dysfunction. • Myxoma Prognosis: ◦ Generally good with surgery; recurrence depends on etiology (familial vs. sporadic). • Malignant Tumor Prognosis: ◦ Rapid progression; death within weeks to months. ◦ High rate of metastasis at diagnosis (approximately one-third); often involves lungs. ◦ Frequently invade pericardium or obstruct chambers/venae cavae. • Rhabdomyoma Prognosis: ◦ Tend to regress partially or completely; surgery only for obstructive cases. • Fibroma Prognosis: ◦ Tend to grow and cause arrhythmias/obstruction; resection recommended.

SPECIAL CONSIDERATIONS¶

• Pediatrics (Rhabdomyomas): ◦ Most common in infants/children. ◦ Often in ventricles; may mimic valvular stenosis, CHF, restrictive cardiomyopathy, or pericardial constriction. ◦ Associated with Tuberous Sclerosis. • Fibromas: ◦ Usually single, ventricular, often calcified; associated with PTCH1 mutations. • Paragangliomas: ◦ Rare chromaffin cell tumors; highly vascular; may cause catecholamine-induced hypertension. • Hemangiomas & Mesotheliomas: ◦ Small, intramyocardial; can cause AV conduction disturbances or sudden death due to proximity to the AV node.

Carney Complex¶

• Definition: Familial variety of myxoma; part of a syndrome complex. ◦ Myxomas (cardiac, skin, and/or breast). ◦ Lentigines and/or pigmented nevi. ◦ Endocrine overactivity (primary nodular adrenal cortical disease, testicular tumors, pituitary adenomas). ◦ Genetics: Inactivating mutations in PRKAR1A (~70% of cases).

Tuberous Sclerosis¶

• Association: Rhabdomyomas occur in ~50% of children with Tuberous Sclerosis. ◦ Genetics: Associated with mutations in tumor-suppressor genes TSC1 and TSC2. ◦ Management: Tend to regress; surgery only for obstructive cases.

KEY PEARLS & CLINICAL TRAPS¶

• Myxoma Prevalence: Most common primary cardiac tumor in adults (1/3 to 1/2 of all cases at autopsy). ◦ Clinical Trap: Constitutional symptoms from IL-6 often lead to misdiagnosis as endocarditis or systemic inflammatory disease. • Tumor Plop: Characteristic low-pitched sound in early/mid-diastole due to mitral valve impact. ◦ Differentiation: Myxomas can mimic mitral valve disease (stenosis or regurgitation) and present with positional symptoms. • Imaging Hierarchy: TTE is initial → MRI for tissue characterization and differentiation from thrombus → CT for calcified lesions or non-MRI patients. • Surgical Goal: Excision is curative for myxomas; recurrence is significantly higher in Carney Complex cases (12-22%) due to multifocality. • Rhabdomyoma/Fibroma: Common in children; rhabdomyomas often regress; fibromas usually grow and cause arrhythmias.

Reference Tables¶

TABLE 282-1 Imaging Modalities and Their Utility in the Evaluation of Cardiac Tumors MODALITY Transthoracic…¶

Harrison's 22e, p.2085

MODALITY	UTILITY IN CARDIAC TUMOR EVALUATION
Transthoracic echocardiography (TTE) (including two-dimensional, three-dimensional, and contrast)	Assessment of tumor location and size and its impact on adjacent structures (e.g., valves, pericardium).
Cardiac magnetic resonance imaging (MRI) with gadolinium contrast	Improved tissue characterization, definition of tumor size, and identification of local invasion when compared with TTE or TEE. May differentiate tumor from thrombus.
Nuclear imaging (including 18F-fluorodeoxyglucose positron emission tomography [FDG-PET])	Definition of extracardiac disease. May be useful in diagnosis of certain cardiac tumors (e.g., neuroendocrine tumors), but assessment of smaller tumors may be limited by surrounding myocardial FDG uptake.