Abstract

   
      The most common tumours of the heart are metastatic in origin, but the most common primary cardiac tumour in adults is a myxoma. We present a recent classic case of myxoma and review the topic of cardiac tumours as a whole. Heart Views. 2008;9(2): 64-70. © Gulf Heart Association 2008.

Keywords: ¨ Cardiac tumour, myxoma

Introduction

The most common tumours of the heart are metastatic in nature occurring in 5% of patients dying of disseminated cancer, and these are 40 times more common than primary cardiac tumours. Cardiac tumours may be intracavitary or intramural but can also involve the pericardium with or without an effusion. The most common primary cardiac tumour is myxoma, being most frequent in adults, with rhabdomyomas the most frequent type in children. 75% of primary cardiac tumours are benign and therefore potentially curable. We present a recent classic case of a cardiac myxoma which is followed by a comprehensive review of cardiac tumours.

Case Summary


  
      A 38 year old woman was admitted with dyspnoea, orthopnoea, chest pain and fever. She gave a history of progressive dyspnoea for the preceding month. She was dyspnoeic at rest and desaturated to 84% on room air. She had a blood pressure of 100/60mmHg and had bilateral crackles in her lung fields, but there were no murmurs or added heart sounds. Chest X-ray showed bilateral infiltrates and an initial diagnosis of community acquired pneumonia was made. She was mildly anaemic with a haemoglobin of 11.2g/dl and an erythrocyte sedimentation rate (ESR) of 56mm/hr. There was no improvement after 2 days of intravenous antibiotics and the differential then included pulmonary oedema. Transthoracic Echocardiography (TTE) followed by transesophageal echocardiography (TEE) was performed which revealed a large heterogenous globular mass measuring 6.5cm x 2.3cm and occupying more than two-thirds of the left atrium with a clear attachment to the interatrial septum (Fig.1). The mass was prolapsing into the mitral valve inflow with evidence of functional mitral stenosis with a mean gradient of 13mmHg, with effective valve inflow area of 1.4cm2 and mild mitral regurgitation. The left atrium was enlarged and there was normal left ventricular ejection fraction (55%), right ventricular enlargement with poor contractility, mild tricuspid regurgitation and an RVSP of 59mmHg.

     In view of her pulmonary oedema and severe dyspnoea she underwent urgent surgery. At operation the right ventricle was found to be dilated with poor function. A biatrial approach was used to reveal a large gelatinous mass. The attachment to the interatrial septum was excised with a cuff of macroscopically normal septum (Fig.2), with the defect closed using a pericardial patch. The patient was then weaned slowly from cardiopulmonary bypass. She made a gradual recovery post-operatively and was discharged home in a good general condition. Histology confirmed benign cardiac myxoma.

 

Fig.1: TEE showing a large mass (M), in the left atrium with attachment to interatrial septum and prolapsing through the mitral valve into the left ventricular cavity in diastole. (M = myxoma). .

 

Pathology of Cardiac Tumours


  
   
Metastatic cardiac tumours occur in approximately 5% of patients dying of disseminated malignancy, with the most common sources being breast and lung cancer, with either local direct spread or through haematogenous/ lymphatic routes1. Disseminated malignant melanoma has the highest predilection for the heart, with cardiac metastases occurring in 50-65% of affected patients2.

     In contrast primary cardiac tumours occur with an incidence of 0.002-0.3% of autopsy series and according to most sources the five most common primary cardiac tumours are myxoma (24-31%), sarcoma (12-19%), lipoma (8-11%), papillary fibroelastoma (8-10%) and rhabdomyoma (7-9%)3. In children the most common cardiac tumours are rhabdomyomas and fibromas4.



Clinical Presentation
    

      Presentation and clinical findings depend on the type and location of the tumour. Generally malignant lesions present rapidly with heart failure due to valvular or myocardial infiltration. The cardiac symptomatology arises from valvular obstruction, cardiac failure and arrhythmias. Patients with myxomas can have strange manifestations such as the systemic symptoms of fever, weight loss and anaemia and may require a high index of suspicion for diagnosis. Signs of systemic embolisation can be the presenting feature as well as mitral valve obstruction which can cause the characteristic early diastolic sound, shortly after S2, or ‘tumour plop’. Cardiac fibromas are more typical in the paediatric group and grow slowly invading the conduction system resulting in arrhythmias which may be fatal.

Symptoms cardiac:   angina, dyspnoea, syncope and palpitations.
systemic: fever, malaise, fatigue, weight loss, arthralgia, embolic events.

Signs cardiac:    murmur, tumour plop, pulmonary oedema.
systemic: pyrexia of unknown origin, clubbing.


Location


  
    Endocardial tumours tend to cause embolic events or obstruction. Emboli may travel to the pulmonary, carotid, coronary or peripheral arteries. Myxomas have an embolisation rate of 30-40%5. Cerebral emboli can present as transient ischaemic attacks, cerebrovascular accidents or even seizures6. Myocardial tumours tend to cause arrhythmias or conduction disturbances. Valvular tumours usually present with obstruction or emboli. Pericardial tumours can cause pain, constriction or tamponade. Pericardial invasion most commonly occurs with spread from the breast or lung.

   Left atrial myxomas are associated with pulmonary hypertension in 70%, anaemia in 33%, a raised ESR in 33% and an audible tumour plop in 33%7. Left ventricular and right atrial tumours can remain silent until quite large. Right atrial tumours can interefere with the tricuspid valve function leading to hepatomegaly, oedema and ascites. Elevated right atrial pressure can lead to opening of a patent foramen ovale leading to right to left shunting and arterial oxygen desaturation and thereby cause polycythaemia8. Right ventricular tumours lead to venous congestion and oedema. Tumour emboli to the pulmonary vasculature can lead to cor pulmonale. Pericardial tumours can be painless, but can cause dyspnoea and cough. Tamponade is suggested by tachycardia, tachypnoea, narrow pulse pressure and pulsus parodoxus. There may also be a pericardial friction rub.
 

Primary Benign (75%) Myxoma   Rhabdomyoma   Papillary fibroelastoma   Fibroma   Lipoma   Teratoma (arise in the pericardium) Malignant (25%) Sarcomas   Lymphoma   Teratoma Secondary  Metastatic Carcinoma 67%   Sarcoma 20%   Melanoma 12%

Table. 1.

 

Fig.2: Operative specimen showing large gelatinous mass (7x5cm).

 
   Investigations

           The aim is to determine whether the patient has a cardiac tumour, the exact location in the heart, and if possible whether it is benign or malignant. This information is vital in planning further evaluation and treatment.

     
   
   Laboratory


     
         Raised ESR, gamma globulins and liver enzymes, as well as anaemia and thrombocytopenia are common to many cardiac tumours, particularly myxomas.

  
     

  Echocardiography
         
     
         This is the diagnostic modality of choice. Its sensitivity is highest for endocardial lesions. TEE provides more information locating the site of attachment and morphological features. Following myxoma resection regular echocardiography is recommended as there is a 5% recurrence rate9.
 

Computerised Tomography
         
     
         This is most useful in diagnosing paracardiac masses related to the pericardium. Soft-tissue characterization and contrast enhancement can help the differentiation. This imaging modality may also be useful when the mediastinum, pleura and lungs also need to be examined10.


Magnetic Resonance Imaging
         
     
         This can be used to supplement information provided by echocardiography. MRI can be useful in cases of invasion of surrounding structures and also has the potential for tissue characterization10.

Cardiac Catheterisation
         
     
         Coronary arteriography is indicated in patients over 50 years of age or younger if there is high risk for coronary artery disease, prior to resection. A ‘tumour blush’ due to opacification of tumour vasculature may also be present.

No imaging modality can reliably distinguish between benign and malignant cardiac tumours. Clinical information and any laboratory information needs to be assessed alongside the imaging and these should lead to the further management, but ultimately tissue is needed for definitive diagnosis.

Histology
         
      

All systemic peripheral emboli retrieved at embolectomy should be sent for histology, as occasionally myxomas will be picked up ‘incidentally’ this way.

 

Differential Diagnosis
         
      

The differential diagnosis of cardiac masses includes tumours, thrombus, vegetations, prolapsing valve leaflets, coronary artery aneurysms, and pericardial cysts. Clinical features help in narrowing the differential. Constitutional symptoms, embolic phenomena and known primary malignancy may suggest tumour. Left atrial thrombi occur with mitral valve disease, an enlarged left atrium and atrial fibrillation. Ventricular thrombi are associated with cardiomyopathies and myocardial infarcts. Right atrial thrombi can complicate indwelling central venous lines and pacemaker wires. Even a ‘disseminated’ disease such as tuberculosis can produce cardiac masses that resolve on antituberculous treatment11.


Specific Cardiac Tumours – Benign Myxomas
         
      


Myxomas have 2 epidemiological patterns of occurrence – sporadic and familial. Sporadic types are usually found between 30 and 60 years old, with a mean age of 51, occur predominately in women and typically occur in the left atrium. Fewer than 10% of myxomas are familial, which usually occur in younger patients (mean age 25 years) and can be found anywhere in the heart and can be multiple at presentation. All first-degree relatives of patients with multiple myxomas should undergo echocardiographic screening as familial myxomas can be inherited in an autosomal dominant pattern. 10% of patients with myxomas may be completely asymptomatic12.

   Complex cardiac myxomas or the familial Carney’s complex may include such features as multiple pigmented skin lesions, myxoid fibroadenomas of the breast, tumours of the pituitary and testes, and primary pigmented nodular adrenocortical disease13. Patients with familial or complex myxomas are more likely than those with sporadic myxomas to have multiple (30-50%) and recurrent (12-22%) tumours. This occasional recurrence and a few reported cases of invasion of surrounding tissue by the tumour suggest that myxomas may have some low-grade malignant features14,15.

    Myxomas are the most common primary cardiac tumour (24-31% of primary tumours but account for 75% of all benign tumours) and can be smooth and round or gelatinous and friable. 35% of tumours are friable or villous and these tend to present with emboli16. Histologically they are composed of scattered cells within a mucoplysaccharide stroma. The cells originate from a multipotent mesenchyme that is capable of neural and endothelial differentiation17. Myxomas may grow rapidly with a case report of a patient with a large myxoma detected 11 months after a normal echocardiographic study18.

   Myxomas can occur in any cardiac chamber but 75% are found in the left atrium attached by a pedicle to the fossa ovalis of the left atrial septum, 18% occur in the right atrium, 4% in the right ventricle and 4% in the left ventricle6. When a myxoma occurs in the ventricles it originates from the free wall. On 2D echocardiographic imaging they usually appear gelatinous, sometimes globular and can have frond like projections. Large tumours are usually mobile and if it appears fixed it is less likely to be a myxoma. TEE is superior to TTE in visualizing the attachments and for the detection of small myxomas. Careful evaluation of all chambers is necessary as about 5% of myxomas are biatrial and cases of concurrent primary cardiac tumours have been reported previously with atrial myxoma and papillary fibroelstoma found in the same patient at the time of surgery19. The systemic manifestations of cardiac myxomas such as pyrexia, a high ESR and anaemia have been linked to the release of the cytokine interleukin6. The treatment of choice for benign tumours is excision20.

Fig.3: Diagram of excision of rim of normal tissue around the attachment to the interatrial septum.

Other Benign Tumours
         
      

Rhabdomyomas are rare cardiac tumours and occur mainly in the paediatric group, presenting in the first year of life. They can occur in any chamber, be multiple, but spare the valves and range in size from a few millimeters to a few centimeters and are white to yellow in colour21. They are often associated with tuberous sclerosis, with 90% of cases having multiple tumours. These tumours can regress spontaneously and only symptomatic lesions require surgery21.

     Papillary fibroelastomas are usually found in patients older than 60 years of age and typically appear as papillary fronds (like a sea anemone) attached to the endocardial surface of the valve by a small pedicle. They can form a nidus for thrombus formation and are associated with cerebral and coronary embolization22. They are usually small (< 1cm in diameter) and often grow on valves or chordae and can mimic vegetations echocardiographically. They arise on the left-sided valvular structures more commonly than on the right. Surgical excision is recommended in symptomatic individuals22.

    Fibromas are more common in children and most frequently affect the ventricular myocardium. These tumours can grow in the myocardium rather than expand into the chambers and can be large (4-7cm) and are associated with ventricular arrhythmias and cardiac failure. Those located in the ventricular septum can be associated with sudden death. The large size can make complete excision difficult23.

    Lipomas are usually solitary, circumscribed, encapsulated tumours and can be intramuscular, subendocardial, subepicardial and are often asymptomatic. Symptomatic lipomas should be resected24. Lipomatous septal hypertrophy arises in the atrial septum and is just an exaggerated growth of normal fat rather than a tumour. It is seen in older patients, particularly the obese25.
 

Specific Cardiac Tumours – Malignant
         
      

Primary malignant cardiac tumours are quite rare and carry a very poor prognosis. Sarcomas are the most common malignant cardiac tumours, and are highly malignant affecting men more commonly (75%). Angiosarcomas are the most common followed by rhabdomyosarcoma, fibrosarcoma and osteosarcomas. Angiosarcomas usually occur in the right atrium or pericardium and most patients present with right-sided cardiac failure, pericardial disease or vena caval obstruction. The tumours infiltrate extensively and metastases are frequently found at the time of presentation. Fibrosarcomas occur equally on either side of the heart are often multiple and protrude into cardiac chambers. Osteosarcomas usually originate near the entrance of the pulmonary veins and can present with arrhythmias or obstructive symptoms26. Cardiac involvement is seen in lymphoma patients, but primary cardiac lymphoma is extremely rare. Intracavitary lesions cause obstruction, infiltrative lesions cause conduction abnormalities or cardiac failure.

    Mesotheliomas of the pericardium are not linked to prior asbestos exposure and present with ‘pericarditis’ or pericardial effusion and are twice as common in men. They cover both the parietal and visceral surfaces encasing the heart with minimal invasion of the myocardium27.

Metastatic and Secondary Tumours of the Heart and Pericardium  

These are 20-40 times more frequent than primary cardiac tumours. Common primary sites included breast, lung, melanoma and lymphoma. The tumour is often visible in the RA or in the IVC. Pericardial effusion is the most common finding and metastatic tumours can be confused with primary cardiac tumours, vegetations, thrombi or prominent muscular trabeculations.


Treatment  


Surgery is the treatment of choice for benign lesions but with inadequate resection there is a risk of recurrence14,15. Most benign lesions are resectable and potentially curable. With myxomas it is important to resect a rim of normal tissue around the attachment to prevent future recurrence (Figure 4).

   With the exception of lymphoma, most malignant primary and metastatic lesions are resistant to chemotherapy and radiotherapy and carry a very poor prognosis, and surgery is usually only for diagnostic/palliative purposes. Sarcomas proliferate rapidly, most patients develop recurrence and die even if their original tumour was completely resected. Heart transplantation has been used for patients with locally advanced disease, for example when the infiltration by a fibroma is too extensive for excision, or multiple recurrences of benign lesions, but there is always the risk of further tumour events due to the immunosupression28.
 
    Most cardiac tumours require surgical intervention because of embolic or obstructive phenomena. For the benign lesions this is potentially curative, for malignant lesions this may palliate but may also be for diagnostic purposes only. Myxomas should be removed urgently because of there high embolic potential5. Lipomas are often asymptomatic and do not necessarily require further treatment. Because of the risk of thromboembolic events from papillary fibroelastomas resection is the recommended treatment. Symptomatic rhabdomyomas only should be resected as many can regress spontaneously. They can be difficult to resect as they are non-encapsulated and embedded in the myocardium. Fibromas can be large and should be promptly and completely excised as they can be a focus for ventricular arrhythmias.

     Malignant tumours may be resected to relieve compressive or obstructive symptoms but remains palliative with a high mortality. Adjuvant therapies are not very effective and overall the prognosis for malignant cardiac tumours is extremely poor. Radiotherapy may have some benefit especially in those with pericardial metastases. Pericardiocentesis and pericardial resection procedures may be necessary to palliate those with recurrent symptomatic pericardial effusions.
 

Prognosis  


Surgical resection usually results in cure of benign cardiac tumours. There is a small rate of recurrence within 10-15 years, especially those that are familial or syndrome-related. Patients should be followed by annual echocardiography for 15 years or life. Primary malignant tumours carry a very poor prognosis because of early metastatic spread, local spread or rapid recurrence. Post-operative survival is approximately 6 months.¨


Acknowledgements: Dr. Hesham Hussein Khalil, Specialist, Non-Invasive Cardiac Laboratory, Hamad Medical Corporation, for performing the ecocardiography study.

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