Atrial myxoma

• An atrial myxoma is a benign, jelly-like tumour that hangs from the wall between the two upper chambers of the heart, most often into the left atrium.
• It is the commonest primary tumour of the heart in adults in most series (papillary fibroelastoma rivals it in surgical series), and it is more common in women.
• It declares itself in three ways, alone or together: it blocks blood flow through the mitral valve (mimicking mitral stenosis), it sheds fragments that cause strokes and other emboli, and it releases inflammatory signals that cause fever, weight loss and a raised erythrocyte sedimentation rate (ESR).
• Echocardiography finds it. A mobile mass on a stalk attached to the atrial septum is almost diagnostic.
• Surgical removal on cardiopulmonary bypass is the only cure and should not be delayed, because fragments can embolise at any time.

By the end of this page you should be able to:

1. Describe where myxomas arise, what they look like, and why they are "benign but dangerous".
2. Explain the obstructive, embolic and constitutional features from the tumour's structure, and recognise the "tumour plop".
3. Plan the investigation of a suspected myxoma and tell it apart from thrombus, vegetations and other cardiac masses.
4. Explain why surgery is urgent, what the operation involves, and the cautions about anticoagulation and thrombolysis.
5. Recognise Carney complex and say who needs genetic testing and long-term surveillance.
6. Outline the other primary cardiac tumours and how they differ from a myxoma.

Myxomas do not usually invade or spread, which is why they are called benign. Yet one review describes them as "functionally malignant", because a soft tumour inside a pumping chamber can fragment and send emboli to the brain, and can block a valve and cause collapse.^[1] That contrast is the key to the whole topic.

This page also covers the other primary cardiac tumours briefly, so that you can place the myxoma among them.

Cardiac myxoma is rare. Reported incidence is about 0.5 to 1 new case per million people per year, although a recent Spanish study found a higher figure of 1.6 to 2.1 per million.^[1] Myxomas make up roughly 50 to 85% of benign primary cardiac tumours.^[1] They are the commonest primary cardiac tumour in adults in most series, but reviews of surgically removed masses find papillary fibroelastoma removed almost twice as often as myxoma.^[5][6]

Primary heart tumours of any kind are uncommon: they turn up in about 0.01% of autopsies, whereas tumours that have spread to the heart from elsewhere are about 100 times more common, and about three-quarters of primary tumours are benign.^[4]

• Age. Myxomas occur at any age. Mean ages in published surgical series range from 42 to 66 years.^[2]
• Sex. Women are affected more often. Large series report between 53% and 77% women,^[2] and one review gives a female-to-male ratio of about 3 to 1.^[1]
• Sporadic or familial. About 95% of myxomas are sporadic, occurring in someone with no family history.^[1] Around 5% occur in the inherited condition Carney complex, discussed below.^[5]

Younger patients, tumours outside the atria, and multiple tumours should make you think of the inherited form.^[5]

The cause of sporadic myxomas is not established; the favoured view is that they arise from a primitive multipotent mesenchymal cell.^[1] There is no known modifiable risk factor. Familial myxoma is the main identified risk factor: Carney complex is caused by inactivating mutations of the PRKAR1A gene and is inherited in an autosomal dominant pattern (see below).^[1][3] Female sex is also associated with the tumour.^[2]

Roughly three-quarters of myxomas are in the left atrium, 15 to 23% in the right atrium, and only a few percent in the ventricles; the valves are involved only rarely.^[1][2] The usual point of attachment is the rim of the fossa ovalis, the thin oval patch on the interatrial septum that marks where the foramen ovale closed after birth.^[1]

Sporadic myxomas are usually single. Familial myxomas may be multiple, may involve both atria or several chambers, and may start from unusual sites.^[1]

A myxoma is a gelatinous, friable mass, often lobulated or shaggy, with areas of haemorrhage or cavity formation, usually attached by a short, narrow stalk.^[5][6] Mean size in series is about 3 to 6 cm, and a few reach enormous proportions ("giant" myxomas).^[1][2]

Two shapes matter clinically.^[1]

• Polypoid (about two-thirds of cases): firm, compact, rounded and often larger. These tend to block the valve and are less likely to break up.
• Papillary or villous (about one-third): soft, shaggy, with many finger-like projections. These fragment easily and are the type most often linked to emboli.

Under the microscope the tumour is made of myxoma cells, which are star-shaped, spindle-shaped or polygonal, scattered singly, in cords or in small nests, and often gathered around small blood vessels. They lie in an abundant loose stroma rich in proteoglycans (the mucopolysaccharide ground substance that gives the tumour its jelly-like feel).^[1][4] Old bleeding leaves haemosiderin-laden macrophages, and some tumours calcify or even form bone.^[4]

On immunohistochemistry the cells characteristically stain for calretinin, vimentin and endothelial markers such as CD31 and CD34.^[1][6] The cell of origin is still debated; the favoured view is a primitive multipotent mesenchymal cell.^[1]

Histology on the resected tumour is the gold standard that confirms the diagnosis.^[1]

Everything the myxoma does follows from three facts: it is a soft mass on a stalk, it lives in a chamber with fast-moving blood, and its cells are metabolically active.

Obstruction. In diastole the left atrium empties into the left ventricle through the mitral valve. A pedunculated left atrial myxoma swings with this flow and can sit in or prolapse through the valve opening, acting like a ball valve.^[2] Filling of the ventricle falls and the pressure behind it rises, so the lungs become congested and the patient is breathless (this is also why a myxoma can raise pulmonary pressures).^[1][4] When the opening is blocked more completely, cardiac output collapses and the patient faints; since the tumour shifts with the patient's position, symptoms can change with posture.^[2] A right atrial myxoma does the same at the tricuspid valve and causes right-sided failure.^[1]

Embolism. Pieces of friable tumour, or clot that forms on its surface, break off and travel on the arterial side from a left-sided tumour or into the lungs from a right-sided one. Embolism occurs in about 30 to 40% of patients in some reviews, though individual series report anything from under 5% to about 40%.^[1][2] The soft papillary tumours shed most.^[1]

Inflammation. Myxomas release cytokines, above all interleukin-6 (IL-6), a signalling protein that drives the acute-phase response. IL-6 explains the fever, malaise, anaemia and raised ESR and C-reactive protein (CRP) that can make the tumour look like infection or a connective tissue disease.^[1][5] Constitutional symptoms are reported more often in women, in right-sided tumours, and in large or multiple tumours.^[1]

A myxoma is unusual in that its symptoms depend on its position, size and mobility rather than on a single pattern.^[1] Between about 3% and 46% of patients have no symptoms (series differ), and between 10% and 50% are found by chance when an echocardiogram is done for another reason.^[1][2] Dyspnoea is the commonest symptom overall.^[2]

• Exertional breathlessness, orthopnoea and sometimes pulmonary oedema, from raised left atrial pressure.^[4]
• Syncope or presyncope, often related to posture.^[2]
• Heart failure, particularly right-sided failure with a right atrial tumour.^[1]
• Sudden death, rarely, when a large mobile tumour jams the valve.^[2]

The target depends on which side of the heart the tumour is on.

• Left-sided tumours most often embolise to the brain, causing stroke or TIA (transient ischaemic attack), and to the kidneys, spleen, limbs, gut and coronary arteries. In a series of 162 patients, 20% had an embolic event and most of these were cerebral.^[1] Neurological complications are reported in 20 to 25% of patients across the literature.^[2]
• Retinal artery embolism can cause sudden loss of vision, and cerebral emboli have also been linked to aneurysm formation.^[1]
• Coronary embolism is rare but well documented, and can cause a myocardial infarction.^[1]
• Right-sided tumours can cause pulmonary embolism.^[1]

Embolism can be the first sign of a myxoma, so an embolus in a young patient without atrial fibrillation or another obvious source needs an echocardiogram.^[2]

Fever, malaise, loss of appetite, weight loss, arthralgia, anaemia and raised ESR and CRP may dominate.^[1] Leucocytosis can also occur.^[5] IL-6 may be a more sensitive marker of inflammation than CRP in these patients.^[1] Because of these features, myxoma can masquerade as pyrexia of unknown origin, vasculitis, connective tissue disease, tuberculosis and infective endocarditis.^[1] A myxoma can itself become infected, giving high fever, positive blood cultures and multiple emboli.^[1]

Palpitations and atrial arrhythmias can occur, and AF (atrial fibrillation) occurs in some patients: in one multicentre study 8 of 41 patients were in AF when assessed, though AF was the presenting complaint in only 2.^[2][7] But rhythm is not a reliable clue: one review notes that, in contrast to the findings in mitral valve disease, AF is uncommon in myxoma, and no ECG pattern is diagnostic.^[1][2] A normal ECG therefore never excludes a myxoma. AF also complicates the picture because it is itself a cause of left atrial thrombus.

Use the approach in cardiac physical examination. The findings mimic mitral stenosis (see valvular heart disease), or tricuspid stenosis if the tumour is on the right:^[1]

• a loud, widely split first heart sound, because the tumour delays valve closure;
• a tumour plop: a low-pitched sound early in diastole, just after the second heart sound, produced when the tumour impacts the heart wall or reaches the end of its stalk's excursion;
• a low-pitched diastolic rumble, and sometimes a mitral or tricuspid regurgitant murmur;
• a loud pulmonary second sound if pulmonary pressure is raised, and a prominent a wave in the jugular venous pulse in some patients;
• findings that change with the patient's position.

Two questions arise. First, when the patient presents with symptoms, what else could cause obstruction, emboli or fever? Second, when a mass is seen on echo, what else could it be? The clinical mimics are mitral or tricuspid stenosis, infective endocarditis, vasculitis, connective tissue disease, lymphoma and tuberculosis, and each is separated by echo and by tests such as blood cultures. For the mass itself, use the table.

Transthoracic echocardiography (TTE, an ultrasound through the chest wall) is the first test. It is quick, safe and widely available, and shows the tumour's size, site and attachment.^[1][2] Typically it shows a mobile mass on a stalk fixed to the atrial septum, moving to and fro and often prolapsing through the mitral or tricuspid valve in diastole.^[1] Accuracy of echo for myxoma is reported as 90 to 96%.^[2]

Transoesophageal echocardiography (TEE, a probe in the oesophagus) gives clearer pictures of the atria. In one European study TEE detected the myxoma in 100% against 95% for TTE, and identified the point of attachment in 95% against 65%.^[1] It is also useful for small, multiple or atypically placed tumours and for planning surgery.^[1]

Contrast echocardiography shows how much blood supply the mass has: malignant tumours enhance strongly, a myxoma enhances partially and less than the surrounding muscle, and thrombus does not enhance at all.^[1]

Echo is not infallible. In a Korean surgical series, only 66% of 265 masses called myxoma on echo were myxomas at histology.^[1]

Cardiac magnetic resonance imaging (MRI) shows tissue characteristics, mobility and attachment and is the best test for telling a myxoma from thrombus. Myxoma is bright on T2-weighted images and shows little or no enhancement after contrast.^[5] Computed tomography (CT) is less reliable for separating myxoma from thrombus but shows calcification (present in 10 to 30%) and helps with surgical planning.^[1][5] When malignancy is a concern, CT of the chest and abdomen is used for staging. Positron emission tomography (PET) is not usually needed for a typical myxoma.^[1][2]

When the appearance is classic, with a mobile mass on a septal stalk, biopsy is not needed before surgery. If there is no stalk, no septal origin, or invasion, a malignant tumour or a metastasis must be considered.^[5]

• ECG and chest radiograph. Nonspecific. The ECG may show atrial enlargement, and the chest radiograph may suggest mitral stenosis or pulmonary venous congestion; see ECG interpretation.^[1]
• Blood tests. No blood test diagnoses a myxoma.^[2] ESR and CRP are usually raised, anaemia may be present, and IL-6 is raised when constitutional symptoms are marked.^[1] Take blood cultures if the picture could be endocarditis.
• Pre-operative work-up. Coronary assessment is needed before surgery; one review uses conventional angiography in patients over 40 and CT coronary angiography in younger patients, while another notes that catheter manipulation during angiocardiography risks dislodging tumour fragments.^[1][2] Head, chest and abdominal CT can find silent emboli and other disease.^[2]
• Histology and genetics. The excised tumour goes to the laboratory. In a young patient, with multiple tumours or a family history, test for the PRKAR1A gene.^[1][3]

Surgical resection is the only definitive treatment.^[5] It should be done promptly once the diagnosis is made, because the behaviour of the tumour cannot be predicted from its size or consistency; even a small one can embolise, and a mobile one can block a valve suddenly.^[2] Some reviews call for emergency surgery in selected patients.^[1] Evidence that an emergency operation does better than an urgent planned one is lacking, and the timing may be adjusted for a recent stroke or other serious condition.^[2]

After a stroke, the risk of a further embolus rises with time, and the authors of one pooled analysis recommend resection as early as the clinical state allows.^[8]

• Anticoagulation. Evidence is limited to case series and reviews, and no guideline settles the question. If you are unsure whether a mass is thrombus or tumour, it is reasonable to give therapeutic anticoagulation and re-image, because thrombus usually shrinks.^[5] Do not let this delay surgery for a confirmed myxoma.
• Intravenous thrombolysis in stroke. Thrombolysis in myxoma-related stroke is controversial. A review cited in one paper reported intracranial haemorrhage in 22.7% and parenchymal haematoma type II in 18.2%. The authors say safety and efficacy are not established, but that thrombolysis should not be withheld when a myxoma-related stroke is highly suspected, and should be critically discussed only when stroke secondary to infective endocarditis cannot be excluded. None of their thrombolysed patients improved rapidly.^[8] This is a decision for the stroke team.
• Mechanical thrombectomy. In a pooled analysis of 35 cases, 91.8% of occlusions were reopened and 60% of patients had a favourable functional outcome, but the data are small and not controlled.^[8]
• Catheters. Manipulating a catheter in the heart carries a risk of dislodging tumour fragments.^[1]

Look for embolic damage, including a recent stroke, pulmonary embolism or limb ischaemia, because these add to the operative risk and may affect timing.^[2] If infection of the tumour is suspected, send blood cultures and treat according to the organism before surgery.^[2]

The operation is done on cardiopulmonary bypass through a median sternotomy.^[2] The surgeon handles the heart as little as possible before the aorta is clamped, to avoid squeezing out fragments, and removes the myxoma before doing any other procedure.^[2] For tumours of the septum or left atrium a biatrial approach is favoured, which also lets all four chambers be inspected.^[2] The stalk's base is cut out with the full thickness of the adjacent septum, and the resulting defect is closed with a patch of pericardium or synthetic material.^[1][2] Intra-operative TEE checks the repair and any valve that was repaired or replaced.^[2] Concomitant coronary or valve surgery is needed in 5 to 25% of patients, because of age.^[2]

Minimally invasive and robotic resection have been reported in small series, but one review considers the evidence too limited to confirm a benefit.^[2]

The operation has a low complication rate. Atrial fibrillation is the commonest complication after surgery, and stroke, bleeding and infarction are rare.^[2] Thirty-day mortality ranges from 0 to 10% in published series (small, low-volume series show the highest figures), and long-term survival is generally 85 to 96%.^[2] In one retrospective series survival after resection did not differ from the general population of the same age and sex.^[7]

• Embolism, above all stroke, but also limb, visceral, coronary and pulmonary emboli.^[1][2]
• Valve obstruction, with heart failure, syncope or, rarely, sudden death.^[2]
• Infection of the tumour, with high fever, positive blood cultures and multiple emboli.^[1]
• After surgery, atrial fibrillation is the commonest complication.^[2]
• Recurrence, which is uncommon but can appear years later (see below).^[2]

Recurrence in sporadic disease is low: about 0 to 5% in most series, up to 7.4% in one, months or years after surgery.^[2] Familial cases are more likely to have recurrent tumours or a new tumour in another site.^[4] A sporadic tumour usually recurs only after incomplete resection.^[5]

Reviews agree that every patient needs long-term follow-up with transthoracic echo, because recurrence can appear years later, and many patients are lost to follow-up.^[2] They do not agree on a fixed schedule, and one review says the extent of surveillance still needs study.^[5] The interval should follow local practice. The one clear recommendation is annual echo for patients with a syndromic myxoma (Carney complex).^[5]

Carney complex is a rare dominantly inherited syndrome of spotty skin pigmentation, myxomas at several sites, endocrine overactivity and tumours of the nerve sheath. It was formerly described as two separate syndromes, "NAME" (naevi, atrial myxoma, myxoid neurofibroma, ephelides) and "LAMB" (lentigines, atrial myxoma, mucocutaneous myxoma, blue naevi).^[3]

• Genetics. Caused by inactivating mutations of the PRKAR1A gene on chromosome 17, which codes for a regulatory subunit of protein kinase A. The condition is autosomal dominant, with roughly 70 to 75% of patients having an affected relative and the rest carrying a new mutation.^[1][3] Genetic testing finds a mutation in only about 60% of patients, so a negative test does not exclude the diagnosis. This and the figures below come from a 2013 chapter and may be out of date; newer reviews should be checked.^[3]
• Cardiac features. Myxomas in Carney complex appear earlier (as young as 3 years), can occur in any chamber, may be multiple and recur, and are responsible for over half of the deaths in the syndrome.^[3] In a series of 338 patients, 53% had a cardiac myxoma.^[3]
• Other features. Spotty pigmentation (lentigines on the lips, eyelids and mucosae) and blue naevi, skin and breast myxomas, primary pigmented nodular adrenocortical disease causing Cushing syndrome, growth-hormone-secreting pituitary adenoma, testicular Sertoli cell tumour, thyroid nodules or cancer, and psammomatous melanotic schwannoma.^[1][3]
• Diagnosis. Stratakis criteria: two of the twelve major manifestations, or one manifestation plus an affected first-degree relative or a PRKAR1A mutation.^[1][3]
• Surveillance. For children, cardiac ultrasound from the first 6 months, at least yearly thereafter, and about every 6 months after a myxoma has occurred. For everyone with the syndrome, a full clinical work-up at least yearly, starting in infancy. First-degree relatives should be tested if a mutation is found, with an echocardiogram at the time of testing.^[3]
• Counselling. Each child of an affected person has a 50% chance of inheriting the condition.^[3]

Myxoma is generally reported as the commonest primary cardiac tumour in adults, although a recent pathology review states that papillary fibroelastoma is the most frequently removed.^[1][6] The table gives the main others.

Children. Myxoma is rare in childhood and, when it occurs, often signals Carney complex or another familial form, so look for skin and endocrine features and test the gene.^[1][3] The commonest cardiac tumour in children is rhabdomyoma, not myxoma.^[6]

Pregnancy. Myxomas are sometimes found for the first time during pregnancy. A single review of 51 pregnant patients reported favourable maternal and fetal outcomes after surgery; this is limited evidence.^[1] Management of an individual patient is for a team of obstetric, cardiology and cardiac surgery specialists.

Families. When Carney complex is suspected, offer testing to first-degree relatives and echocardiographic screening to carriers (see above).^[3]

Any mobile atrial mass seen on echocardiography, and any unexplained embolus in a patient without an obvious source, should be discussed with cardiology and cardiac surgery the same day, because fragments can embolise at any time.^[2] Refer early too when a "mitral stenosis" has signs that change with position, or when fever and emboli persist despite negative cultures.

• A transthoracic echocardiogram, available even in emergency departments, is the one test that makes the diagnosis; learn to look for a mobile mass in the atria in any patient with a "mitral stenosis" that does not fit, with a stroke at a young age, or with fever and weight loss.^[2]
• If echo is not available, suspect the diagnosis from the postural variation in the signs and symptoms and refer.
• Fever, emboli and a murmur look like endocarditis. If cultures are negative and the patient does not respond to antibiotics, look again for a myxoma.
• The treatment needs cardiopulmonary bypass. If this is not available locally, refer early to a cardiac surgery centre.
• Send every resected tumour for histology.