Cardiac tumors

Cardiac tumors represent a heterogenous group, potentially involving any of the heart structures.

They can be primary or secondary, may be related to the heart muscle or pericardium, and may be direct extensions of primary tumors or metastases from adjacent structures.

Secondary malignancies are the most common, occurring 20-40 times more frequently than primary tumors.

Primary cardiac tumors are extremely rare, accounting for less than 0.1% of all cases in large autopsy studies, with 75% of them being benign.

The majority of cardiac tumors are found incidentally during routine cardiac imaging.

In symptomatic patients, a mass can almost always be detected by echocardiography, MRI, and/or CT.

Although transthoracic echocardiography is simpler and usually can identify a tumor, transesophageal echocardiography (TEE) may be more informative. 

Clinical manifestation

Depending on location and morphology, cardiac tumors can produce four types of clinical manifestations:

• Systemic – constitutional (fever, arthralgias, weight loss, fatigue) and paraneoplastic syndromes (primary cardiac tumors).
• Embolic – pulmonary and/or systemic by tumor/thrombo emboli.
• Cardiac – mass effect interfering with myocardial function, blood flow, electric impulse formation and conduction, pericardial fluid dynamics.
• Secondary to metastatic disease of a primary malignant cardiac tumor – manifestations depending on site of metastasis.

Primary cardiac tumors

1) Benign - myxoma, papillary fibroelastoma, hemangioma, lymfangioma, fibroma, lipoma, rhabdomyoma, hamartoma, cardinoid heart disease

2) Malignant - angiosarcoma, rabdomyosarcoma, fibrosarcoma, malignant mezotelioma

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Cardiac myxoma

• Most common primary cardiac tumor
• Most are sporadic (90%)
• Familial myxomas, also known as “syndrome myxoma” or “Carney complex” (10%) - autosomal dominant condition comprising myxomas of the heart and skin, hyperpigmentation of the skin (lentiginosis), and endocrine overactivity (Cushing syndrome, etc.); testicular cancer, particularly Sertoli cell type, is associated with Carney syndrome, thyroid and pancreas cancer may also occur.
• Female preponderance
• Most frequently discovered 3rd to 6th decades
• Can arise anywhere within the heart
• left atrium (75%), right atrium (23%), rarely in the ventricles
• usually connected to the atrial septum (fossa ovalis) by a narrow stalk; depiction of site and type of tumor attachment is important when differentiating from thrombus

Clinical presentation

• Constitutional, embolic or obstructive symptoms 

• Many detected asymptomatically

Echocardiographic features

-globular, smooth – surfaced or irregular, friable surface with multilobular appearance

-4 to 8 cm in size

-heterogeneous echogenicity with areas of echolucency and sometimes calcifications

-myxomas have a poor blood supply, with partial and lower than normal myocardium enhancement on contrast echocardiography

-myxomas have variable mobility depending on size and narrow/broad implantation stalk. Usually, they protrude into the ventricles through the mitral or tricuspid valves in diastole -diastolic filling impairment can be assessed by color Doppler imaging and further quantified by continuous Doppler trace analysis, showing signs of mitral/tricuspid stenosis.

The diagnosis of an atrial myxoma warrants resection due to the risk of embolization, cardiovascular complications and sudden death.

Surgical resection is associated with a low operative mortality and good long-term outcome.

Video 1  TTE, Cardiac myxoma of right atrium, A4C view - a round echogenic structure at a size around 30x32 mm is inserted into the interatrial septum and the top of the RA with diastolic protrusion into the atrial cavity. The surface appears smooth and the mass is heterogeneous with a central echolucency area.

Video 2  TTE, Cardiac myxoma, PSAX view - the same patient viewed in the PSAX view at the level of aortic valve. The insertion point of the myxoma is seen more clearly.

Image 1  Cardiac myxoma size measurement (30x32 mm) in A4C view.

Video 3  Giant myxoma in the left atrium, TTE A3C view - a myxoma is seen protruding through the mitral valve in the diastole. The myxoma is round with clean edges.

Video 4  A giant myxoma in the left atrium shown on TEE - the myxoma is seen inserted into the interatrial septum and shows forward movement in the diastole, leaning onto the mitral valve. This obstruction caused severe mitral stenosis.

Video 5  Giant myxoma in the left atrium, colour Doppler applied - the presence of myxoma causes severe mitral stenosis with moderate mitral regurgitation.

Image 2  Size measurement of the myxoma (60x49mm)

Image 3  Severe Mitral stenosis caused by myxoma, CW Doppler (Pmean = 18,28 mmHg)

Video 6  Myxoma of the left atrium, TEE short axis view – a myxoma is seen in the left atrium protruding from the interatrial septum with a wide stalk. Its size is approx. 35x22x22 mm. 

‍Video 7  Myxoma of the left atrium, TEE – the myxoma is seen moving at the top

‍Video 8  Myxoma of the left atrium, 3D TEE assessment of the tumour

‍Video 9 Multilobular myxoma at the level of fossa ovalis, A4C view – the myxoma protrudes from the interatrial septum into the left atrium, size approx. 11x13mm.

‍Video 10  Multilobular myxoma at the level of fossa ovalis, zoomed for details – the myxoma appears to have an irregular surface with multiple villous appendages.

‍Video 11  Multilobular myxoma at the level of fossa ovalis, 3D TEE assessment – the myxoma is viewed in 3D with better details

‍Video 12  Myxoma of the right atrium, A4C view – a mobile myxoma adjacent to the posterior leaflet of the tricuspid valve in the right atrium.

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Lipoma

• second most common primary cardiac tumor (10-20%)
• usually asymptomatic, but may cause arrhythmias or valvular dysfunction
• anywhere in the heart, most frequently in the left ventricle, right atrium, and atrial septum
• the majority of these arise in the subendocardium, but they can also occur in the pericardium and on the cardiac valves

Echocardiographic features

-well demarcated

-homogeneous

-broad based masses (not diagnostic)

-immobile, without pedicle

-their appearance varies with location: in the pericardial space they arise from the epicardium and are hypoechogenic, while intracavitary lipomas are hyperechogenic

Lipomatous hypertrophy of the interatrial septum is due to fatty infiltration of the proximal and distal portions of the atrial septum, generally with sparing of the fossa ovalis and most commonly seen in the elderly and obese. It is not a true tumor, although it can be mistaken for one, namely a myxoma or lipoma.

Differentiation between this lesion and true tumor is critical and may prevent unnecessary surgery. 

On echocardiography, the lipomatous hypertrophy of the atrial septum has a characteristic appearance with massive, hyperechogenic, thickening of the atrial septum that spares the fossa ovalis, taking a “dumbbell” or “hourglass” shape.

Video 13  Lipomatous hypertrophy of the interatrial septum, TTE, PSAX view - massive thickening of the IAS reaching up to 26 mm in diameter with the typical fossa ovalis sparing. 

‍Video 14  Lipomatous hypertrophy of the interatrial septum, TTE, A4C view - another view of the same patient. Note the hourglass shape of the thickened IAS.

‍Image 4  Lipomatous hypertrophy of the interatrial septum, PSAX measurement of the IAS (30x32mm)

Papillary fibroelastoma

• most common tumor involving cardiac valves
  - Aortic valve is the most common location – Both surfaces show equal prevalence
  - May involve other cardiac structures/chambers (15-25%)
• rarely causes valvular dysfunction
• significant embolic potential recognized

Due to the need for differential diagnosis with vegetations, thrombi, valvular calcifications or Lambl's excrescences, TEE is often required.

Echocardiographic features

-small size

-independent motion 

-attachment to an endocardial surface 

-especially on TEE, the borders appear stippled or shimmering, which is due to the vibration at the tumor–blood interface due to the finger-like projections

-distinguishing a PFE from a Lambl’s excrescence may be difficult, but the latter is typically smaller and more linear

Video 15 Papillary fibroelastoma, TEE – papillary fibroelastoma is seen at the level of mitral annulus and P1 scallop of the posterior mitral leaflet protruding into the left atrium with a wide stalk (4-5mm) and gelatinous structure. It’s freely moving with the blood flow and its size is approx. 19x12mm.

‍Video 16  Papillary fibroelastoma,  3D TEE – the position and relation to the mitral valve is better viewed in the 3D reconstruction of the fibroelastoma.

Video 17 Papillary fibroelastoma on a left coronary cusp of aortic valve (10 mm)

Video 18 Papillary fibroelastoma on aortic valve

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‍Surgical excision is recommended for larger (≥1 cm), left-sided PFEs in patients who are deemed appropriate surgical candidates (young age, low surgical risk) or at the time of cardiac surgery for another cardiovascular condition.

Right-sided PFEs should be removed only if large or mobile and associated with hemodynamically significant obstruction or risk of embolism such as can be seen with a patent foramen ovale with right-to-left shunting.

Excision dramatically decreases the risk of stroke from a PFE.

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Lambl's excrescences

• common
• 70-80% adults
• linear, filiform fronds
• ventricular surface of semilunar valves
• atrial surface of mitral valve
• multiple
• located at closure lines

Video 19 Lambl excrescences on Aortic valve

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Rhabdomyoma

• the most common primary cardiac tumor in infants and young children
• the majority are associated with tuberous sclerosis (80%)
• in more than half of the patients they regress in size and number after infancy
• most often occur in the right and left ventricular myocardium
• depending on their location and size they may induce arrhythmias or blood flow obstruction

Echocardiographic features

-multiple

-homogeneous

-hyperechogenic 

-located intramurally or pedunculated, protruding into the ventricular cavity

-ranging from few mm to few cm in size

Fibroma

• the second most common benign cardiac tumor in the pediatric population
• in 70% of cases, fibromas cause symptoms by impeding intracavitary blood flow or causing ventricular arrhythmias
• invariably located in the ventricular myocardium, usually in the left ventricular free wall or interventricular septum
• may mimic hypertrophic cardiomyopathy
• do not spontaneously regress
• patients with multiple basal cell carcinomas should be screened for cardiac fibromas (Gorlin syndrome)

Echocardiographic features

-distinct 

-well-demarcated

-non-contractile and solid

-highly echogenic mass within the myocardium

-calcification is possible

-size ranges from 1 to 10 cm

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Cardinoid heart disease

Neuroendocrine tumors (NETs, originally termed “carcinoids”) create a relatively rare group of neoplasms with an approximate incidence rate of 2.5 to 5 cases per 100 000 persons. ‍

The great majority of the tumors is benign, and <10% are malignant.

Roughly 30% to 40% of subjects with NETs develop carcinoid syndrome (CS) - release of vasoactive substances (serotonin, 5-hydroxytryptophan, histamine, bradykinin, tachykinins, and prostaglandins) that are not deactivated by the liver.

20% to 50% of subjects with CS are diagnosed with carcinoid heart disease (CaHD).

‍The long-standing exposure to high serum serotonin concentration is one of the crucial factors in CaHD development.

White plaque-like deposits (consist of intercellular mass, smooth muscle cells and are covered by endothelium) on the endocardial surface of heart structures with valve leaflets and subvalvular apparatus thickening (fused and shortened chordae; thickened papillary muscles) are characteristic for CaHD.

NT pro-BNP and 5-hydroxyindoleacetic acid are the 2 most useful screening markers.

Long-acting somatostatin analogs are the standard of care in symptoms control. They are also the first-line treatment for tumor control in subjects with a metastatic somatostatin receptor avid disease.

In cases refractory to somatostatin analogs, several options are available. We can increase a somatostatin analog to off-label doses, add telotristat ethyl or administer peptide receptor radionuclide therapy.

Cardiac surgery, which mainly involves valve replacement, is presently the most efficient strategy in subjects with advanced CaHD and can relieve unmanageable symptoms or be partly responsible for better prognosis.

Image 5 ECHO features of Carcinoid heart disease

Adapted from: Bober B, Saracyn M, Kołodziej M, Kowalski Ł, Deptuła-Krawczyk E, Kapusta W, Kamiński G, Mozenska O, Bil J. Carcinoid Heart Disease: How to Diagnose and Treat in 2020? Clin Med Insights Cardiol. 2020 Oct 27;14:1179546820968101. doi: 10.1177/1179546820968101. PMID: 33192110; PMCID: PMC7597558.

Video 20  Carcinoid heart disease (CaHD) causing massive tricuspid regurgitation with mild tricuspid stenosis, A4C view - the leaflets of the tricuspid valve are almost akinetic, infiltration of the leaflets and subvalvular apparatus.

Video 21 Carcinoid heart disease (CaHD) causing massive tricuspid regurgitation with mild tricuspid stenosis, A4C view with colour Doppler - large central regurgitant jet that reaches the atrial wall

Video 22 Carcinoid heart disease (CaHD) causing massive tricuspid regurgitation with mild tricuspid stenosis

Video 23 Carcinoid heart disease (CaHD) causing severe pulmonary regurgitation and mild pulmonary stenosis, PSAX view with colour Doppler - the valve is almost akinetic due to carcinoid plaques restricting its movement. Pulmonary stenosis (mean gradient 9mmHg), regurgitant jet is seen. 

Video 24 Carcinoid heart disease (CaHD) causing severe pulmonary regurgitation and mild pulmonary stenosis, PSAX view

Image 6 CW Doppler measurement of severe pulmonary stenosis with mild pulmonary stenosis caused by CaHD, PSAX view - max gradient 22,05 mmHg

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Malignant tumors

• constitute 15% of primary cardiac tumors
• a tumor present only on the right side of the heart has an almost 50% chance of being malignant
• it is very rare for a malignant cardiac tumor to occur exclusively in places other than those within the cardiac chambers
• typically have rapid expansion
• precordial pain usually indicates a malignant rather than a benign process

Video 25 Malignant mesenchymal tumor of the right atrium, TTE, PSAX view - a heterogeneous echogenic mass is seen inserted into the lateral wall of the right atrium, protruding into the atrial cavity. The tumor takes up a significant part of the atrium with close contact with the tricuspid valve. Although the movement of the valve is not restricted.

Video 26  Malignant mesenchymal tumor of the right atrium, TTE, A4C view - you can see that the tumor surpasses the tricuspid valve and has grown into the basal part of the lateral wall of the RV. The size is measured at 39x21 mm. Note that the tumor is hyperechogenic compared to the surrounding myocardium.

Video 27  Malignant mesenchymal tumor of the right atrium, subcostal view - the same tumour is viewed in more detail in the subcostal window. 

Sarcomas

• 95% of primary malignant cardiac tumors
• occur between the third and fifth decades of life, equally in both genders
• typically in the left atrium (differential diagnosis is a myxoma)

Echocardiographic features

-undifferentiated sarcomas appear as a broad-based mass

-with heterogeneous echogenicity

-hypoechogenic areas may indicate tumor necrosis

-based on characteristics on echocardiography, it’s not possible to differentiate between histological subtypes of sarcomas

Any type of sarcoma may develop in the heart, but the most common is the angiosarcoma. These tumors have a predilection for the right chambers, particularly for the right atrium. 

On ECHO they emerge as lobulated masses near the inferior vena cava, extending intracavitary and into the pericardium, occasionally invading the caval veins or tricuspid valve, distinctly heterogeneous with an area of necrosis or hemorrhage.

They have no stalk, differentiating them from myxomas or PFEs. 

Video 28  Sarcoma in left atrium, TEE – the sarcoma infiltrated the LV from the opening of the coronary sinus in RA, across the AV junction to mid ventricular level of LV inferior wall. Ovoid mass is seen in the LA leaning into the posterior leaflet of MV. Diastolic forward motion of the sarcoma pushes it into the MV opening and causes a mild obstruction at rest (max gradient 16mmHg).

‍Video 29 Sarcoma in left atrium, TEE  with colour Doppler – the colour Doppler reveals the obstruction caused by the sarcoma

‍Video 30 Sarcoma in left atrium, TEE – short axis view of the mitral valve shows the sarcoma protruding into the MV opening.

‍Video 31 Sarcoma of the interventricular septum, A4C view – an oval mass is seen in the interventricular septum at the midventricular level. Its size is approx. 31x25 mm.

‍Video 32  Sarcoma of the interventricular septum, PSAX view – the sarcoma is seen as an oval mass in the septum.

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‍Rhabdomyosarcoma

‍Is the most common cardiac malignancy in infants and children.

They can arise from any cardiac structure; they do not seem to have a preference for any particular location. In 60% of cases there are multiple.

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Leimyosarcomas, osteosarcomas, fibrosarcomas and undifferentiated sarcomas are other rare primary cardiac sarcomas. ​​

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Lymphoma

• extremely rare, representing 5% of primary cardiac malignancies
• defined as non-Hodgkin’s lymphoma located initially only in the heart or pericardium
• involve more often the right side of the heart and usually associate with pericardial effusion

On echocardiography, they can appear as homogeneous, infiltrating masses leading to ‘wall thickening’ and restrictive hemodynamics or as nodular masses intruding into the heart chambers, preferentially the right heart chambers and especially the right atrium

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Pericardial mesothelioma 

• extremely rare 
• unlike pleural and peritoneal mesotheliomas has no definite correlation with exposure to asbestos
• symptoms include chest pain, cough and palpitations

Echocardiographic findings are pericardial effusion, pericardial thickening or constrictive physiology. Invasion of other cardiac structures is rarely seen.

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Secondary (metastatic) cardiac tumors

• at least 20-to-40 times more common than primary tumors
• breast and lung cancer encountered most commonly 
• malignant melanoma has the highest propensity for metastasis to the heart
• echocardiography should be performed in all patients with a history of malignancy and cardiac symptoms 
• cardiac metastases are predominantly located in the pericardium, with pericardial effusion being the most frequent finding

Hematogenous/Lymphatic spread

• melanoma, lymphoma, breast 

Direct extension

• lung, breast, esophageal

Invasion via venous structures

• Vena cava (renal, uterine, hepatocellular)
• Pulmonary veins (lung, breast, thyroid)

Video 33 Lung cancer metastasis of right atrium and ventricle, A4C view - tumorous mass infiltrates the lateral wall of RA, going across tricuspid annulus and into RV free wall (length around 90mm, walls thickened up to 24 mm).

Video 32 - Lung cancer metastasis of right atrium and ventricle, subcostal 4 chamber view - infiltration of the RV wall

‍Video 33 - Lung cancer metastasis of right atrium and ventricle, application of contrast (SonoVue) - the tumour shows partial filling of contrast as it is vascularized

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References

1. Mankad R, Herrmann J. Cardiac tumors: echo assessment. Echo Res Pract. 2016 Dec;3(4):R65-R77. doi: 10.1530/ERP-16-0035. Epub 2016 Sep 6. PMID: 27600455; PMCID: PMC5292983.
2. Cardiac tumors. European Society of Cardiology [online]. Copyright © 2021 European Society of Cardiology. All rights reserved. [cit. 20.08.2021]. Available from: https://www.escardio.org/Education/Practice-Tools/EACVI-toolboxes/3D-Echo/cardiac-tumors
3. Dennis A. Tighe. Cardiac Masses. Online. Available from: https://asecho.org/wp-content/uploads/2016/04/4.17-Tighe-Cardiac-Masses.pdf

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