Cardiologists evaluate cardiac masses after clinical symptoms lead to a positive imaging study, or because of an incidental mass found at imaging, usually echocardiography. Cardiac masses range from non-neoplastic lesions to high grade malignancies (box 1) and occur over a wide range of ages (table 1). Ninety per cent of primary cardiac tumours are either myxomas, which are cured by resection, or sarcomas, which have a dismal prognosis regardless of treatment (table 1).1^–5

Although the vast majority of heart tumour patients are readily referred to the surgeon (and eventually oncologist in the case of sarcoma), the rare patient with a heart tumour causes great interest among clinical cardiologists. Cardiac myxomas have a wide range of clinical presentations that may mimic a variety of non-neoplastic conditions. Most cardiac masses are not amenable to percutaneous biopsy; therefore definitive diagnosis often awaits surgical excision and allows for a time of suspense during which differential diagnoses are discussed. The 10% of heart tumours that are not myxoma or sarcoma comprise a quite varied group of lesions.

Cardiac masses that are discovered by imaging can be considered in three groups: paediatric tumours, which are mostly hamartomas and are associated in many cases with genetic syndromes; benign tumours, both non-neoplastic masses and benign neoplasms, which are generally cured by surgery; and malignancies, which are mostly primary cardiac sarcomas, but which include lymphoma and metastases (with known or occult primary) (box 1). In this article, tumours will be presented based on usual site in the heart, as differential diagnosis varies greatly by site (table 2). Primary tumours may arise in adults most frequently from the endocardium, followed by the cardiac muscle, and, most infrequently, the pericardium. Interestingly, the rate of metastatic lesions is the reverse; the pericardium is by far the most common site, especially for epithelial malignancies, with endocardial lesions common only for those tumours growing into the great veins.

IMAGING OF CARDIAC TUMOURS

Echocardiography has the best spatial and temporal resolution of the cardiac imaging modalities, providing excellent anatomic and functional information. It is generally the only imaging modality required preoperatively, although angiography may be performed to exclude coronary artery disease in older patients. Echocardiography is the optimal imaging modality for imaging small masses (<1 cm) or masses arising from valves. Echocardiography can image velocities with Doppler, which allows for assessment of presence, degree, and location of obstructions to blood flow or valve regurgitation. Magnetic resonance imaging (MRI) has the highest soft tissue contrast of the imaging modalities, which makes it the most sensitive modality for detection of tumour infiltration, and is more manipulable than other imaging modalities.6 For example, a T2 weighted standard or fast spin echo sequence distinguishes tumours with high water content, such as haemangioma, from tumours with low water content, such as fibroma. MRI can characterise tumour vascularity with intravenous contrast and does allow assessment of wall motion, allowing for characterisation of ventricular function, inflow or outflow obstruction and valve regurgitation. ECG gated computed tomography (CT) scans with multidetector scanners or electron beam scanners are also very useful for cardiac imaging. The advantages and disadvantages of CT are intermediate between those of echocardiography and MRI.7 CT scanners have spatial resolution, better than that of MRI, but not as high as echocardiography. CT has better soft tissue contrast than echocardiography, and can be used to definitively characterise fatty content and calcifications; however, the overall soft tissue contrast and ability to characterise tumour infiltration and tumour type is less than that of MRI.8

CLINICAL FEATURES OF HEART TUMOURS

Cardiac tumours present with a variety of symptoms, including those related to obstruction, embolism, and elaboration of substances resulting in constitutional symptoms. The presenting symptom is generally related less to the tumour type than to the site in the heart, and friability of the lesion. Myxomas, especially those with an irregular surface, and papillary fibroelastomas have a high rate of embolism. Other than lymphomas, treatment of neoplasms is primarily surgical, with complete excision if possible. Optimal treatment of malignant cardiac tumours awaits more sophisticated surgical techniques and chemotherapeutic regimens. Cardiac transplantation and autotransplantation will likely become a more established treatment for primary cardiac neoplasms that are inoperable.

TUMOURS OCCURRING PRIMARILY IN THE LEFT ATRIUM

Cardiac myxoma

Cardiac myxoma is an endocardial based neoplasm of uncertain histogenesis that, morphologically, is unique and not seen in extracardiac locations. In surgical series, cardiac myxomas account for the majority of heart tumours (table 2). The mean age at presentation is 50 years,9 and approximately two thirds of patients are women. Almost 90% of myxomas occur in the left atrium as polypoid lesions attached to the oval fossa, and most of the rest occur in the right atrium.

In over 50% of patients left atrial myxomas cause symptoms of mitral valve stenosis or obstruction (dyspnoea and orthopnoea from pulmonary oedema or heart failure). Right atrial myxomas may obstruct the tricuspid valve and cause symptoms of right sided heart failure.9 Embolic phenomena occur in 30–40% of patients. Frequent sites of embolisation include the central nervous system, kidney, spleen and extremities. Smooth surfaced tumours (fig 1A) are more likely to produce valvular obstruction, while polypoid and myxoid ones are more likely to embolise. Anaemia, leucocytosis and raised erythrocyte sedimentation rate (ESR) are the most common laboratory findings. Constitutional symptoms (possibly related to interleukin IL-6 production by tumour cells) seen in approximately 20% of patients include myalgia, muscle weakness, arthralgia, fever, fatigue and weight loss. About 20% of cardiac myxomas are asymptomatic; incidental myxomas are usually smaller than 40 mm. Abnormal, but non-specific, electrocardiographic changes may be identified in 20–40% of patients and include atrial fibrillation or flutter and left and right bundle branch block.

• Download figure
• Open in new tab
• Download powerpoint

Figure 1 Cardiac masses in the atria. (A) Gross photograph of a smooth surfaced myxoma that has been sectioned down the middle. (B) Axial chest computed tomography (CT) demonstrates a mass within the left atrium apparently attached to the interatrial septum. (C) Gross specimen of atrial leiomyosarcoma demonstrates multilobulated irregular mass. (D) Axial chest CT demonstrates a large soft tissue mass, which fills the left atrium. (E) Gross photograph of resected atrial thrombus demonstrates surface thrombus (brown in fixed state), organised white thrombus underneath, and a portion of the excised atrial septum at the bottom. (F) Axial chest CT demonstrates soft tissue mass contiguous with the posterior wall of the right atrium and the interatrial septum. The imaging impression was atrial myxoma; histology (not shown) was organised thrombus. There was no history of coagulation disorder.

At echocardiography cardiac myxomas typically appear as a mobile mass attached to the endocardial surface by a stalk, usually arising from the fossa ovalis.7 Myxomas with this appearance can be confidently diagnosed by echocardiography and further imaging is not necessary. Because myxomas are usually small and mobile, they are typically better defined by echocardiography than by either MRI or CT, because echocardiography has the best spatial and temporal resolution. If the narrow stalk is not visible, the diagnosis cannot be made by echocardiography and further imaging, MRI or CT, is necessary to show the tumour’s margins and to exclude tumour infiltration (fig 1B).

Less than 5% of myxomas form a component of the myxoma complex,9 which includes abnormal skin pigmentation (lentigines and blue nevi), calcifying Sertoli-Leydig testicular tumours, cutaneous myxomas, myxoid breast fibroadenomas, pigmented adrenal cortical hyperplasia, pituitary hyperactivity, psammomatous melanotic schwannoma and thyroid tumours. In contrast to patients with sporadic tumours, who have a 1% recurrence rate, about 10% of patients with familial myxomas either have recurrent tumours or develop another tumour in a different location.10 Patients with myxoma complex have cardiac myxomas at a young age, and are more likely to have multiple tumours or tumours in locations other than the atria.

Because embolisation is the major complication of myxoma, especially of myxoid, friable, familial ones, identification of first degree relatives of patients with documented myxoma syndrome is important. Intracranial aneurysm caused by embolisation is also a rare, but potentially morbid, complication. The aetiology of these aneurysms is unclear but histologic verification of myxoma cells in arterial walls has been reported.

As the majority of left atrial myxomas arise from the interatrial septum, the tumours can be removed en bloc with a 5 mm margin of normal tissue. The fossa ovalis, where the pre-tumour cells of myxomas are thought likely to exist, should also be excised if possible. Resection of the attachment, and 5 mm of normal tissue including endocardium and underlying myocardium, is generally recommended. Despite anecdotal reports of recurrence after incomplete excision,3 there are no data that clearly link negative margins at the time of surgery with an increase in the recurrence rate.

Cardiac sarcoma

Cardiac sarcomas are pathologically classified by histologic type and, unlike myxomas, are histologically similar to their counterparts in extracardiac soft tissue. There are three categories of primary cardiac sarcomas. Angiosarcoma is usually found in the right atrium, and is discussed separately below. Endomyocardial based tumours, which usually have features of smooth muscle or fibroblastic differentiation, form the majority of cardiac sarcomas and are typically located in the left atrium. Despite the fact that the bulk of the heart is formed of striated muscle, rhabdomyosarcomas (striated muscle differentiation) are the rarest of heart sarcomas, and are typically ventricular lesions in children or young adults.

Sarcomas with myo- or fibroblastic differentiation are the most pathologic diverse of cardiac sarcomas, often have heterologous elements such as bone, and typically form endoluminal masses that are most frequently found in the left atrium. There is no evidence that they are malignant counterparts of cardiac myxoma.11 They have been subclassified as malignant fibrous histiocytoma (recently designated undifferentiated pleomorphic sarcoma), osteosarcoma, leiomyosarcoma, and fibrosarcoma or myxofibrosarcoma. Any of the histologic subtypes may be associated with myxoid change. Grossly they are less haemorrhagic than myxoma (fig 1C), and often infiltrate the atrial wall. Imaging reveals features similar to myxoma, but invasion into adjacent atria or valves may sometimes be demonstrated by MRI or CT (fig 1D).

Cardiac sarcomas may be graded based on cell type, presence of necrosis, and mitotic activity. Complete resection of malignant primary cardiac tumours can rarely be achieved, but palliative surgery is usually undertaken because many patients present with mechanical obstruction. Adjunctive chemotherapy, radiation therapy or both are sometimes used; however, the optimal protocol and efficacy are unclear.

TUMOURS AND TUMOUR MIMICKERS OCCURRING PRIMARILY IN THE RIGHT ATRIUM

Mural thrombi

Endocardial thrombi in the atria are generally left sided, occur in the setting of organic heart disease, and as such do not mimic cardiac tumours. However, even left atrial thrombi, if they have an unusual imaging configuration such as pedunculation, are occasionally removed surgically, and may be clinically and pathologically misdiagnosed as myxomas. However, the majority of surgically excised atrial thrombi are right sided, occur in patients without heart disease, and are seen in patients with either documented or occult coagulation disorders (fig 1E and F).

One of the more common coagulopathies diagnosed in patients with mural thrombi is the antiphospholipid syndrome, but a wide variety of conditions may be a predisposing factor, including essential thrombocytosis, protein C or S deficiency, and Behçet’s disease. If venous emboli become dislodged into the right ventricle, a mistaken preoperative diagnosis of right ventricular tumour may be made.

Echocardiography, cineangiography, and magnetic resonance imaging have been used to make a diagnosis of mural cardiac thrombus both in patients with organic heart disease, and patients with presumed coagulopathies and normal cardiac function. In some cases, the imaging findings are indistinguishable from primary cardiac tumours, such as myxoma, when the location is intra-atrial.

Right sided myxoma

Approximately 10% of cardiac myxomas occur in the right atrium. Unlike multiple or ventricular myxomas, there is no significant increase in recurrence, age at presentation, or rate of myxoma syndrome. Histologically and radiographically, however, right sided myxomas are more likely to be calcified and may, on occasion, become heavily calcified. Because of location, patients are often asymptomatic, although tricuspid obstruction and pulmonary embolism can occur.

Lipomatous hypertrophy

Lipomatous hypertrophy of the atrial septum is an exaggeration of the normal accumulation of brown fat within the atrial septum, which is only weakly associated with obesity. The typical imaging findings are those of a right sided mass, with fat density on MRI. Lipomatous hypertrophy is removed incidentally during open heart surgery for other causes or for relief of cardiac symptoms, such as supraventricular arrhythmias, congestive heart failure or vena caval obstruction. The indications for surgery are somewhat controversial, as the detection of incidental masses may lead to unnecessary surgery for a benign lesion that may simply be an exaggeration of normal. Histologically, there is a mixture of mature and brown fat, which ultrastructurally contains abundant mitochondria.12 Entrapped, enlarged myocytes are common and may lead to the false diagnosis of sarcoma, or the brown fat clusters may be mistaken for lipoblasts.

Angiosarcoma

Angiosarcomas are the most common malignant cardiac neoplasms with specific cell type differentiation. They occur over a wide age range (36 months to 80 years) with a peak incidence in the fourth decade. Cardiac angiosarcoma most often arises in the right atrium near the atrioventricular groove (80%), but has been reported in the other three chambers as well as in the pericardium. The most common presenting symptoms are chest pain, and symptoms related to right sided heart failure, haemopericardium and supraventricular arrhythmias.

At echocardiography, angiosarcomas typically appear as an echogenic, nodular or lobulated mass in the right atrium with pericardial effusion or direct pericardial extension.7 MRI sequences sensitive for haemorrhage (T1 weighted images) may show areas of haemorrhage which may be diffuse or nodular. After administration of intravenous contrast (gadolinium-DTPA), enhancement along vascular lakes may be seen which has been described as a “sunray” appearance. Cardiac angiosarcomas have an especially poor prognosis because they typically present with metastasis, most frequently to the lung and then the liver. Angiosarcoma is generally treated by a combination of surgery (sometimes with modifications including explantation and ex situ resection) and radiation with or without sarcoma-type chemotherapy; heart transplantation is a consideration if metastatic disease is not identified.

TUMOURS OCCURRING PRIMARILY ON CARDIAC VALVES

Papillary fibroelastoma

Also known as fibroelastic papilloma, this unusual lesion occurs exclusively on endocardial surfaces, most commonly on valve leaflets. There is no gender predominance, and there is a wide range of age at presentation, with a mean age of approximately 60 years.13 Papillary fibroelastomas occasionally occur in areas of previous endocardial damage or in patients with pre-existing heart disease.14 Most symptoms arise from left sided lesions that shower fibrin clots into the cerebral circulation or prolapse into the coronary orifice. Unlike Lambl’s excrescences, which are likely a precursor lesion, papillary fibroelastomas can become quite large, and occur on any valve surface or area of the endocardium. Histologically, they are avascular papillary structures lined by endothelial cells, and are often mistaken for cardiac myxoma. Asymptomatic patients could be treated surgically if the tumour is mobile, as the tumour mobility is the independent predictor of death or non-fatal embolisation. Asymptomatic patients with non-mobile lesions can be followed up closely with periodic clinical evaluation and echocardiography, and receive surgical intervention when symptoms develop or the tumour becomes mobile. Recurrences are rare, and valve sparing surgery should be considered whenever possible, as regrowth of partially resected lesions does not always occur.

VENTRICULAR AND MISCELLANEOUS LESIONS OCCURRING WITHOUT PARTICULAR SITE PREDILECTION

Cardiac hamartomas

Cardiac hamartomas, or non-neoplastic benign lesions, occur primarily in children. Cardiac fibromas usually occur in the ventricular free wall or interventricular septum (fig 2). Most cardiac fibromas are discovered in children and often before 1 year of age. However, cases are also reported in adults and even as incidental findings in the elderly.15 Approximately 3% of patients with Gorlin syndrome have cardiac fibromas. At echocardiography fibromas typically appear as a large, well circumscribed, solitary mass in the septum or ventricular free wall,7 and in some cases may be confused with hypertrophic cardiomyopathy. The tumours are frequently very large and may cause obstruction, which can be assessed by colour Doppler. MRI also shows a large, solitary, homogeneous myocardial mass centred in the ventricles.7 Because of the fibrous nature of the tumour, the signal intensity is often less than that of adjacent uninvolved myocardium, and contrast enhanced imaging usually demonstrates a hypoperfused tumour core. CT also shows a large, solitary, ventricular mass, which is usually of low attenuation on CT, which may detect calcification—a helpful feature in making a confident diagnosis.7

• Download figure
• Open in new tab
• Download powerpoint

Figure 2 Ventricular mass: cardiac fibroma. (A) Gross photograph of the lesion—a dense, white, homogeneous, whorled fibrous mass. (B) Post-contrast, delayed magnetic resonance (MR) image in the horizontal long axis shows the mass involving the free wall of the right ventricle. On this late enhancement image, the signal of normal myocardium is nulled, whereas the mass exhibits increased MR signal resulting from delayed accumulation of gadolinium.

Cardiac fibroma is benign, but its slow continuous growth may cause conduction defects and arrhythmias. Extension into the ventricular free walls may result in atrioventricular valve inflow or arterial outflow obstruction. Spontaneous regression, as can occur with congenital rhabdomyoma, has not been observed. If the mass is too large for resection, heart transplantation may be considered with or without pre-transplant palliation or cardiomyoplasty. However, favourable late results even after incomplete excision have been reported.

Cardiac rhabdomyoma is the most common cardiac tumour of children. It is associated with tuberous sclerosis, an autosomal dominant disorder involving brain, kidney, pancreas, retina and skin. Patients with tuberous sclerosis have a 40–86% incidence of cardiac rhabdomyoma. Rhabdomyomas occur in any location in the heart, but are more common in the ventricles. In patients with tuberous sclerosis, tumours are usually multiple. Clinical and haemodynamic findings are related to the number, position and size of the tumours.16 Children with “rhabdomyomatosis” or diffuse microscopic involvement of the myocardium may present as though they have a cardiomyopathy. Conduction abnormalities are common, and consist of bundle branch block, pre-excitation, and first to third degree atrioventricular block. At echocardiography, rhabdomyomas appear as homogeneous, well circumscribed echogenic masses in the ventricular myocardium, possibly protruding into the ventricular cavity. At MRI, rhabdomyomas appear as well circumscribed masses with signal characteristics similar to that of normal myocardium.17 Compared with the signal from uninvolved myocardium, the masses are hypointense on post-gadolinium imaging. At CT, rhabdomyomas also appear as multiple nodules, which may be hyper- or hypo-attenuating compared to normal myocardium. With MRI or CT, the rest of the body can be imaged for signs of tuberous sclerosis. However, because rhabdomyoma has many imaging features similar to normal myocardium, echocardiography, MRI and CT may be complementary as rhabdomyomas that are not visible by one modality may be visible with another.17

The familial form of tuberous sclerosis, which is present in up to 50% of patients with cardiac rhabdomyoma, exhibits autosomal dominant inheritance. Two disease genes have been identified: TSC-1 at chromosome 9q34, and TSC-2 at chromosome 16p13.3. The TSC-1 gene encodes hamartin, and TSC-2 tuberin, proteins involved in tumour suppression. Loss of heterozygosity is often found at these loci in tumours from patients with tuberous sclerosis. The precise roles of TSC-1 and TSC-2 in the development of cardiac tumours and regulation of embryonic and neonatal cardiomyocyte growth remain to be elucidated.

Rhabdomyomas have a natural history of spontaneous regression. Surgery is recommended if there is significant outflow obstruction or if medical antiarrhythmic treatment is not successful.

Haemangioma

Haemangiomas are incidental lesions discovered at chest radiogram or surgery for other purposes, or they may cause arrhythmias, pericardial effusions, congestive heart failure or outflow tract obstruction, and rarely sudden death. Cardiac haemangiomas are of two basic pathologic types.18 Circumscribed ones are histologically uniform and composed of cavernous vascular spaces, often with a myxoid background. They may be easily shelled out at surgery, are often endocardial based masses that project into the lumen, but may occur in the pericardium. Infiltrating cardiac haemangiomas, in contrast to their circumscribed counterparts, are more likely to cause symptoms than circumscribed haemangiomas, and often result in cardiac arrhythmias because of their intramural location.18 Cardiac haemangiomas are generally cured by surgical resection, occasionally requiring synthetic graft placement.18

Cardiac lymphoma

Cardiac lymphomas are usually part of disseminated disease; up to 20% of patients with disseminated non-Hodgkin lymphoma will have evidence of cardiac involvement at autopsy. Because of the rise in immunocompromised patients, due both to HIV–AIDS and allograft recipients, an increasing proportion—although still a small minority—of patients with cardiac lymphoma are in this category.

Primary cardiac lymphoma in immunocompetent patients is an uncommon malignancy, accounting for 1.3% of primary cardiac tumours and 0.5% of extranodal lymphomas.19 In a literature review of 40 patients, presenting symptoms included dyspnoea, oedema, arrhythmia and pericardial effusion. Tumours were found in the following locations, listed in order of frequency: right atrium, pericardium, right ventricle, left atrium, left ventricle, and other sites. Ante-mortem diagnosis was obtained in only 37 of the 40 patients.

Cardiac lymphomas comprise <5% of all lymphomas arising in patients with AIDS and organ transplants, and location of the tumour in the donor heart is the exception rather than the rule in heart transplant patients.

Lymphomas manifest as an ill-defined, infiltrative mass, in which case they are typically best depicted with MRI because of its superior soft tissue contrast.7 Atrial location is typical, with infiltration of atrial or ventricular walls. Lymphomas may have high or low signal on MRI, may have similar attenuation as muscle or lower attenuation than muscle on CT, and may show increased or decreased contrast enhancement. In addition to echocardiography, MRI and CT, nuclear medicine techniques may be useful procedures for the non-invasive assessment of cardiac lymphomas.

Cardiac lymphomas span the spectrum of B cell proliferations, and include follicular centre cell lymphomas, immunoblastic lymphomas, diffuse large cell lymphomas, and Burkitt lymphoma. Unlike other heart tumours, treatment is not primarily surgical, but includes anthracycline-based chemotherapy, and anti-CD20 treatment. Chemotherapy has been used alone or combined with radiotherapy. Palliative surgery has been performed, mainly for tumour debulking. Multimodality treatment may include autologous stem cell transplantation.

Metastatic cardiac tumours

In a series of 133 surgically resected cardiac tumours, 14% were metastases.20 Surgically resected lesions are usually right sided, and represent either cavoatrial extensions from abdominal tumours, such as renal cell carcinomas or hepatocellular carcinomas, or haematogenous metastases, that may present months or years after initial tumour excision. Intracardiac masses are often unusual tumours, such as sarcomas and melanomas or germ cell tumours. Occasionally, metastases of slow growing sarcomas may present years after initial presentation and resection of the primary tumour.