Cardiac Tumors

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Cardiac tumors - UpToDate

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Official reprint from UpToDate® www.uptodate.com ©2019 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Cardiac tumors Authors: William H Gaasch, MD, Thomas J Vander Salm, MD Section Editor: Wilson S Colucci, MD Deputy Editors: Sadhna R Vora, MD, Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jan 2019. | This topic last updated: Jan 17, 2019.

INTRODUCTION Primary cardiac tumors are extremely rare [1]. As an example, in one series of over 12,000 autopsies, only seven were identified, for an incidence of less than 0.1 percent [2]. By comparison, metastatic involvement of the heart is over 20 times more common and has been reported in autopsy series in up to one in five patients dying of cancer [2-5]. Cardiac tumors may be symptomatic or found incidentally during evaluation for a seemingly unrelated problem or physical finding. In symptomatic patients, a mass can virtually always be detected by echocardiography, magnetic resonance imaging, and/or computed tomography. Because symptoms may mimic other cardiac conditions, the clinical challenge is to consider the possibility of a cardiac tumor so that the appropriate diagnostic test(s) can be conducted.

CLINICAL MANIFESTATIONS The specific signs and symptoms of cardiac tumors generally are determined by the location of the tumor in the heart and not by its histopathology [6]. Mechanisms of symptom production — Cardiac tumors may cause symptoms through a variety of mechanisms: ●

Embolization, which is usually systemic but can be pulmonic. Aortic valve and left atrial

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tumors were associated with greatest risk of embolization [7]. ●

Obstruction of the circulation through the heart or heart valves, producing symptoms of heart failure.



Interference with the heart valves, causing regurgitation.



Direct invasion of the myocardium, resulting in impaired left ventricular function, arrhythmias, heart block, or pericardial effusion with or without tamponade.



Invasion of the adjacent lung may cause pulmonary symptoms and may mimic bronchogenic carcinoma [8].



Constitutional or systemic symptoms.

Left atrial tumors — Tumors arising in the left atrium tend to grow into the atrial lumen and cause symptoms by obstructing blood flow or creating mitral regurgitation. Left atrial tumors thus may simulate mitral valve disease and produce heart failure and/or secondary pulmonary hypertension. (See "Clinical manifestations and diagnosis of rheumatic mitral stenosis" and "Classification and prognosis of pulmonary hypertension in adults".) Commonly observed symptoms and signs include dyspnea, orthopnea, paroxysmal nocturnal dyspnea, pulmonary edema, cough, hemoptysis, edema, and fatigue. Symptoms may be worse in certain body positions due to motion of the tumor within the atrium. On physical examination, a characteristic "tumor plop" may be heard early in diastole. (See "Auscultation of cardiac murmurs in adults".) In addition to interfering with the circulation, left atrial tumors may release tumor fragments or thrombi into the systemic circulation. The most serious complications of such embolization are neurologic. This was illustrated by a series of 74 consecutive patients with atrial myxomas from the Mayo Clinic [9]. Central nervous system complications were identified in nine patients (12 percent), and in seven of these the neurologic symptoms were the initial manifestation of the myxoma. Two of these nine patients had evidence of systemic myxomatous tumor embolization in addition to their neurologic symptoms. Benign myxomas are the most common tumors arising in the left atrium (see 'Myxomas' below). However, other benign and malignant tumors can simulate myxomas and should be considered in the differential diagnosis [10].

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Right atrial tumors — Tumors arising in the right atrium grow into the atrial lumen and obstruct blood flow, producing hemodynamic changes that are similar to those seen with tricuspid stenosis. Typical cardiovascular signs and symptoms are those of right heart failure (ie, fatigue, peripheral edema, hepatomegaly, ascites, and prominent "a waves" in the jugular veins). On physical examination, a diastolic murmur has been described, which is similar to the "tumor plop" heard with left atrial myxomas. (See "Tricuspid stenosis".) In addition to obstructing circulation through the right side of the heart, tumor fragments may be released into the pulmonary circulation, causing symptoms consistent with pulmonary emboli [11]. Right atrial hypertension can result in shunting of venous blood into the systemic circulation if a patent foramen ovale (or atrial septal defect) is present, resulting in hypoxemia or systemic emboli [12,13]. Myxomas are the most common tumors of the right atrium. However, sarcomas and, in particular, angiosarcomas, have been reported to arise in the right atrium. Right ventricular tumors — Lesions arising in the right ventricle most commonly interfere with filling and/or outflow from the right ventricle, resulting in right-sided heart failure. Typical signs and symptoms may include peripheral edema, hepatomegaly, ascites, shortness of breath, syncope, and sudden death. Tumors arising in the right ventricle can be misdiagnosed as pulmonic stenosis, restrictive cardiomyopathy, or tricuspid regurgitation. (See "Clinical manifestations and diagnosis of pulmonic stenosis in adults" and "Idiopathic restrictive cardiomyopathy", section on 'Clinical presentation'.) Left ventricular tumors — Tumors arising in the left ventricle may be intramural and present with arrhythmias or conduction defects. Alternately, left ventricular tumors may be intracavitary and present with systemic embolization or outflow obstruction. Syncope or left ventricular failure may be observed. (See "Clinical manifestations and diagnosis of aortic stenosis in adults".)

DIAGNOSTIC EVALUATION The goals of the initial evaluation are to ascertain whether or not a cardiac tumor is present, the location of the lesion within the heart, and, to the extent possible, whether a tumor is benign or malignant. This information is vital in planning further evaluation and management. https://www.uptodate.com/contents/cardiac-tumors/print?search=fet…rch_result&selectedTitle=1~150&usage_type=default&display_rank=1

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Echocardiography, cardiac magnetic resonance imaging (MRI), and ultrafast computed tomography (CT) provide complementary information to address these questions. Most adults having heart operations of any kind will have coronary angiography as part of the routine preoperative evaluation. For those with epicardial tumors, coronary angiography is specifically required to assess the location of the tumor's nutrient vessels and any that are parasitized by the tumor. Echocardiography — Echocardiography is widely available and provides a simple, noninvasive technique for the initial evaluation. Echocardiography images both the myocardium and the cardiac chambers and can usually identify the presence of a mass and its mobility. In addition, echocardiography may provide information about any obstruction to the circulation, as well as the likelihood that the tumor could be a source of emboli. (See "Echocardiographic evaluation of the atria and appendages", section on 'Left atrial masses and tumors'.) Although transthoracic echocardiography is simpler and usually can identify a tumor, transesophageal echocardiography (TEE) may be more informative. The superior diagnostic utility of TEE is due to the proximity of the esophagus to the heart, the lack of intervening lung and bone, and the ability to use high-frequency imaging transducers that afford superior spatial resolution [14]. (See "Transesophageal echocardiography: Indications, complications, and normal views".) Cardiac MRI and CT — Although both cardiac magnetic resonance imaging (MRI) [15-18] and ultrafast computed tomography (CT) [19,20] provide noninvasive, high-resolution images of the heart, MRI generally is preferred. In addition to furnishing detailed anatomic images, the T1and T2-weighted sequences reflect the chemical microenvironment within a tumor, thereby offering clues as to the type of tumor that is present [6,17,18,21,22]. However, CT scanning is still useful when MRI is not immediately available or is contraindicated. An excellent pictorial review of many cardiac tumors and comparison of MRI and CT scanning has been published [23]. (See "Clinical utility of cardiovascular magnetic resonance imaging" and "Noninvasive coronary imaging with cardiac computed tomography and cardiovascular magnetic resonance".) The utility of information derived from echocardiography, MRI, and/or CT is illustrated by several examples: ●

The location of myxomas within the atrial lumen facilitates their diagnosis by echocardiography (movie 1 and movie 2 and movie 3 and movie 4 and movie 5 and movie 6). In most cases, TEE provides better visualization of the tumor (image 1A-B).

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In four series totaling 130 patients, characteristic radiographic appearances and tissue densities accurately facilitated the diagnosis of myxomas, other benign tumors, and sarcomas [17,24-26].



Papillary fibroelastomas, the second most common benign cardiac tumors, characteristically are pedunculated and mobile and flutter or prolapse with cardiac motion when imaged by echocardiography [27,28]. (See 'Papillary fibroelastomas' below.)



Benign lesions such as fibromas and lipomas also have distinctive appearances on echocardiography, CT, and MRI [29].



The combination of echocardiography plus cardiac MRI or CT may be useful in differentiating thrombus from tumor in lesions appearing to arise on a heart valve [30].

PET scan — Positron emission tomography (PET) has been useful in identifying cardiac involvement in patients with metastatic tumors [31-34], atrial myxoma [35], or lipomatous septal hypertrophy [36]. Coronary angiography — Mapping the blood supply of tumors arising from the epicardial surfaces must be performed with coronary angiography [6]. This information is vital to the success of excising such tumors. Significant involvement of coronary arteries with tumor may require resection and grafting of such arteries. Transvenous biopsy — Limited data are available on the risks and benefits of transvenous biopsy of suspected cardiac tumors. Because myxomas may embolize, transvenous biopsy is not generally warranted if the appearance is typical on noninvasive imaging. Biopsy is considered reasonable for other cardiac tumors if potential benefits are deemed sufficient to outweigh potential risks. (See "Endomyocardial biopsy".) Summary — The information obtained from echocardiography and cardiac MRI or CT can confirm the presence of a cardiac tumor and its location within the heart and may provide an initial indication of the type of tumor. Transvenous biopsy may be helpful in certain situations. In general, the information from noninvasive imaging is sufficient to make a decision regarding the need for surgery, where a definitive histologic diagnosis can be established.

BENIGN TUMORS

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Over 75 percent of primary cardiac tumors are benign [37-42]. In adults, the majority of benign lesions are myxomas; other common benign lesions include papillary fibroelastomas and lipomas. In children, rhabdomyomas and fibromas are the most common; malignant tumors are very rare [43]. Myxomas — Myxomas are the most common primary cardiac neoplasm. Histologically, these tumors are composed of scattered cells within a mucopolysaccharide stroma. The cells originate from a multipotent mesenchyme that is capable of neural and endothelial differentiation [44]. Myxomas produce vascular endothelial growth factor, which probably contributes to the induction of angiogenesis and the early stages of tumor growth [45,46]. Macroscopically, typical myxomas are pedunculated and gelatinous in consistency; the surface may be smooth, villous, or friable. Tumors vary widely in size, ranging from 1 to 15 cm in diameter, and weigh between 15 and 180 g [47]. Approximately 35 percent of myxomas are friable or villous, and these tend to present with emboli. Larger tumors are more likely to have a smooth surface and to be associated with cardiovascular symptoms. Clinical manifestations — The cardiovascular manifestations depend upon the anatomic location of the tumor. Approximately 80 percent of myxomas originate in the left atrium and most of the remainder are found in the right atrium [6,11,48-50]. (See 'Left atrial tumors' above and 'Right atrial tumors' above.) In addition to their cardiovascular effects, patients with myxomas frequently have constitutional symptoms (eg, weight loss, fever) and laboratory abnormalities that suggest the presence of a connective tissue disease [51]. Although the etiology of these symptoms is not fully understood, the production of various cytokines and growth factors by the tumor may contribute to these clinical and laboratory abnormalities [46,52]. The relative frequencies of different signs and symptoms associated with left atrial myxomas are illustrated by a series of 112 patients, 72 of whom were women [47]: ●

Cardiovascular symptoms were present in 67 percent. Most commonly, these resembled symptoms of mitral valve obstruction and were frequently associated with electrocardiographic evidence of left atrial hypertrophy. Although auscultatory abnormalities were found in 64 percent, the classic "tumor plop" was identified in only 15 percent. (See 'Left atrial tumors' above.)



Evidence of systemic embolization was present in 29 percent of patients, and 20 percent

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had neurologic deficits. Despite the greater frequency of myxomas in women, men were more likely to have evidence of embolization. With myxomas, the incidence of embolization is associated with smaller size (≤4.5 cm) and softer tumors [53]. ●

Constitutional symptoms (eg, fever, weight loss) were seen in 34 percent of patients. Laboratory abnormalities (eg, anemia and elevations in the erythrocyte sedimentation rate, C-reactive protein, or globulin level) were present in 37 percent, usually those with systemic symptoms.

Other large series of patients with myxomas have also included a predominance of women (60 to 70 percent) and have reported similar incidences of cardiovascular, embolic, and constitutional symptoms [11,49,50,54,55]. Carney complex — The Carney complex is an inherited, autosomal dominant disorder characterized by multiple tumors, including atrial and extracardiac myxomas, schwannomas, and various endocrine tumors. The cardiac myxomas generally are diagnosed at an earlier age than sporadic myxomas and have a higher tendency to recur [56]. Patients with Carney complex also have a variety of pigmentation abnormalities, including pigmented lentigines and blue nevi on the face, neck, and trunk. The Carney complex is discussed elsewhere. (See "Cushing's syndrome due to primary pigmented nodular adrenocortical disease", section on 'Carney complex (CNC)'.) The Carney complex must be distinguished from other syndromes associated with Carney with which it may be confused. These include the Carney Stratakis syndrome and the Carney triad, neither of which include cardiac tumors [57]. (See "Epidemiology, classification, clinical presentation, prognostic features, and diagnostic work-up of gastrointestinal stromal tumors (GIST)", section on 'Pediatric GIST'.) Treatment and prognosis — Once a presumptive diagnosis of myxoma has been made on imaging studies, prompt resection is required because of the risk of embolization or cardiovascular complications, including sudden death [49,55,58]. The results of surgical resection are generally very good, with most series reporting an operative mortality rate under 5 percent [47,49,50,54,55,59,60]. Cardiac autotransplantation (with atrial reconstruction) or transplantation are potential options for treatment of recurrent atrial myxoma [61,62]. Postoperative recovery is generally rapid. However, atrial arrhythmias or atrioventricular conduction abnormalities were present postoperatively in 26 percent of patients in one series https://www.uptodate.com/contents/cardiac-tumors/print?search=fet…arch_result&selectedTitle=1~150&usage_type=default&display_rank=1

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[47]. In addition, patients are at risk for recurrence of the myxoma, which may occur in 2 to 5 percent of cases, or the development of additional lesions [47,63]. Recurrence is more common in patients whose primary tumor was multicentric [53]. Development of a second primary myxoma may be more common in patients with a family history of myxoma [59]. Papillary fibroelastomas — Papillary fibroelastomas are the second most common primary cardiac tumor in adults [64]. Their appearance is often compared to sea anemones, with frondlike arms emanating from a stalked central core (picture 1). The clinical spectrum of fibroelastomas can be illustrated by two reports combining information from 887 patients [28,64]: ●

Demographics – Fifty-five percent of patients were male. The mean age at detection was 60 years, and 29 percent were 70 years of age or older.



Size, location, and number – Tumors varied from 2 to 70 mm in size with a mean of 9 mm. Over 80 percent of fibroelastomas were found on the heart valves, usually on the left side of the heart (aortic 36 percent, mitral 29 percent, tricuspid 11 percent, and pulmonic 7 percent), while the remaining lesions were scattered throughout the atria and ventricles. Multiple tumors were present in 9 percent of patients.



Clinical features – Symptoms usually were caused by embolization, either of the tumor itself or thrombus. The most common clinical presentation was stroke or transient ischemic attack, followed by angina, myocardial infarction, sudden death, heart failure, syncope or presyncope, and systemic or pulmonary embolic events.

Approximately 30 percent of papillary fibroelastomas were asymptomatic and diagnosed incidentally, either by echocardiography at cardiac surgery or at autopsy [28,64]. Treatment — A presumptive diagnosis of papillary fibroelastoma can usually be made on echocardiography (generally transesophageal echocardiography). While some recommend surgery for all patients because of the risk of embolization and associated morbidity [65-69], others have suggested that careful observation is an acceptable option for asymptomatic patients as long as the tumor remains small and nonmobile [28]. Surgery is recommended for patients who have had embolic events or complications directly related to tumor mobility (eg, coronary ostial occlusion) and those with highly mobile or large (≥1 cm) tumors [28,64]. Recurrence of cardiac papillary fibroelastoma following surgical https://www.uptodate.com/contents/cardiac-tumors/print?search=fet…rch_result&selectedTitle=1~150&usage_type=default&display_rank=1

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resection has not been reported. Rhabdomyomas — Rhabdomyomas develop almost exclusively in children, mostly before the age of one year, and approximately 80 to 90 percent are associated with tuberous sclerosis [7072]. With increasing use of ultrasound and improvements in technique and magnetic resonance imaging (MRI), these tumors are being detected with increasing frequency, even in the prenatal period [70,72-75]. Rhabdomyomas are usually found in the ventricular walls or on the atrioventricular valves. (See "Tuberous sclerosis complex: Genetics, clinical features, and diagnosis", section on 'Clinical features'.) Most rhabdomyomas regress spontaneously, and resection is usually not required unless a child is symptomatic [71,75-78]. Symptoms, if present, are caused by obstruction of blood flow through the heart or consist of rhythm disturbances such as heart block of ventricular tachycardia [71,77]. Fibromas — Although uncommon, fibromas are nevertheless the second most common pediatric cardiac tumor and can also occur in adults [48,79-81]. Histologically, these are similar to fibromas arising elsewhere in the body. Fibromas usually arise in the ventricular muscle and may become quite large. Unlike rhabdomyomas, fibromas do not regress spontaneously. They arise approximately five times more frequently in the left ventricle than the right ventricle [48]. Heart failure is the most common symptom due to obstruction of blood flow or interference with valvular function. Myocardial dysfunction and conduction disturbances also occur. Echocardiography supplemented with computed tomography scans or MRI confirms the diagnosis. Symptomatic tumors should be resected. Complete resection of very large tumors may require cardiac transplantation. Teratoma — Teratomas are tumors of embryonic origin derived from two or three germinal layers. Cardiac teratoma is a rare, generally benign tumor with most reported cases presenting as fetal or neonatal tumors; in adults they are estimated to constitute less than 1 percent of cardiac tumors [82]. Nearly all cardiac teratomas arise within the pericardium, with the remainder in the myocardium [83-88]. Fetal and neonatal intrapericardial teratoma — Although these tumors are generally benign, they tend to grow rapidly (ie, significant growth over a few weeks) and can have serious mechanical consequences either by causing tamponade or through direct pressure on the heart with consequent reduced cardiac output, fetal hydrops, and death. Intrapericardial teratomas https://www.uptodate.com/contents/cardiac-tumors/print?search=fet…rch_result&selectedTitle=1~150&usage_type=default&display_rank=1

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are typically located in the region of the pericardial reflection at the junction of the ascending aorta and right atrial appendage, which leads to compression of the right side of the heart as the teratoma grows [89]. Thus, there is a risk of death in utero or immediately after birth. Treatment therefore requires timely detection and resection [89]. When a small suspected teratoma is detected, frequent serial assessment is required to detect changes in tumor size and cardiac output prior to the onset of hydrops. An increase in tumor size and a declining or abnormally low cardiac output are indications for tumor resection, ideally prior to development of signs of hydrops. The tumor can be removed by fetal tumor excision, an ex utero intrapartum therapy approach (which involves uterine hysterotomy, continued uteroplacental support during surgical tumor excision, followed immediately by delivery), or by early postnatal surgery, with timing dictated by tumor size and the patient's hemodynamic condition [85,87,89,90]. Because teratomas usually have a single blood supply, are well encapsulated, and are not invasive, properly timed tumor surgery is typically straightforward and successful. By contrast, other approaches may not be therapeutic. For example, drainage of the cystic component of a teratoma may not relieve tamponade and will not stop tumor growth. Pericardiocentesis may not relieve tamponade if tumor mass is not removed. Other cardiac teratomas — Scant reports are available on adult cases of benign cardiac teratoma, which are predominantly pericardial [82,91]. In adults, cardiac teratoma may grow slowly and may be detected as an incidental finding in an asymptomatic patient. Symptoms such as chest pain or dyspnea may develop due to associated pericardial effusion. Intramyocardial teratomas have been rarely diagnosed in newborns, children, and adults. These tumors may cause heart failure or an arrhythmia [91]. The primary treatment for benign cardiac teratoma is surgical excision [82,92]. Purkinje cell tumors/hamartomas — These tumors consist of small, flat sheets of cells most frequently located in the left ventricle and on the endocardial and epicardial surfaces [93,94]. As such, they are undetectable by echocardiographic or radiologic techniques. These are usually tumors of young children and present with incessant ventricular tachycardia [94]. Electrocardiograms often demonstrate a bundle branch pattern (right bundle branch block when the tumor is in the left ventricle). Electrophysiologic studies can localize the tumors, facilitating surgical excision. Lipomas — Lipomas and fibrolipomas are characterized by a predominance of benign fatty https://www.uptodate.com/contents/cardiac-tumors/print?search=fet…rch_result&selectedTitle=1~150&usage_type=default&display_rank=1

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cells. Approximately half of these tumors occur in the subendocardial region with the remainder evenly divided between the myocardial and subepicardial regions. They may also occur on valves [95,96]. Although most are no more than a few centimeters in size, lipomas as large as 4.8 kg have been reported [97]. Symptoms, when present, are generally related to local tissue encroachment (arrhythmias, conduction block, sudden death), although valvular tumors can cause insufficiency and symptoms of heart failure [98]. The diagnosis can be made with echocardiography and the distinctive fat pattern seen on MRI. Because of the symptoms they cause and their progressive growth, myocardial lipomas require resection. Pericardial lipomas are typically an incidental finding and clinically insignificant. Rarely, a pericardial lipoma can assume gigantic proportions and its appearance on a chest radiograph may be mistaken for a huge pericardial effusion or massive cardiomegaly (image 2 and image 3). Benign pericardial lipomas can infiltrate the myocardium. If the ventricular septum is invaded, communication between the pericardial space and the right ventricular cavity may result. Lipomatous hypertrophy of the interatrial septum — Lipomatous hypertrophy of the interatrial septum is an exaggerated growth of normal fat existing within the septum and is not a true tumor. Rather, it is a developmental disorder caused by expansion of adipose tissue trapped in the interatrial septum during embryogenesis [99]. The septal hypertrophy may be as large as 2 cm in thickness and is seen primarily in older patients and in those who are obese [100,101]. It has been suggested that this disorder is associated with the presence of coronary artery disease in proportion to the degree of atrial septal thickness [102]. Lipomatous hypertrophy of the interatrial septum is indistinguishable from lipoma except that the former occurs in the atrial septum with a typical distribution (generally sparing the fossa ovalis). In the absence of symptoms of atrial arrhythmias, heart block, or rare vena caval obstruction, they do not require resection [103]. Other pseudoneoplasms — There are other pseudoneoplasms (like lipomatous hypertrophy) as well [99]. These include inflammatory myofibroblastic tumor, hamartoma of mature cardiac myocytes, calcified amorphous tumor [104], and mesothelial/monocytic incidental cardiac excrescences. But unlike lipomatous hypertrophy, these four tumors require resection to distinguish them from neoplasms or to prevent embolization or obstruction of blood flow [99]. This is also true of the rare intracardiac blood cyst [105]. https://www.uptodate.com/contents/cardiac-tumors/print?search=fet…rch_result&selectedTitle=1~150&usage_type=default&display_rank=1

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TUMORS THAT MAY BE EITHER BENIGN OR MALIGNANT Paragangliomas — Paragangliomas are neuroendocrine tumors that can be either benign or malignant and can be hormonally active or inactive. In tumors not producing catecholamines, symptoms are due to cardiac compression or tamponade. By contrast, cardiac paragangliomas that are hormonally active primarily produce norepinephrine and may cause systemic symptoms (eg, headache, sweating, tachycardia, hypertension) [106]. (See "Paragangliomas: Epidemiology, clinical presentation, diagnosis, and histology".) Paragangliomas do not occur commonly in the chest, but when they do, the hormonally inactive tumors are more frequent in the pericardium, while hormonally active tumors (pheochromocytomas) more frequently arise elsewhere in the thorax [107]. Paragangliomas may be localized with echocardiography. Their extreme vascularity creates a characteristic magnetic resonance imaging (MRI) appearance [90,108]. Coronary angiography is required to plan the operative resection. (See 'Coronary angiography' above.) Both benign and malignant paragangliomas occurring within the pericardium parasitize the cardiac blood supply and are, as a consequence, very difficult to excise [108-110]. All intrapericardial paragangliomas require resection. Complete resection may be difficult but is usually possible. Cardiopulmonary bypass and even circulatory arrest may be required because of the high degree of vascularity or to moderate the extreme hypertension possible from tumor manipulation or hormonally active tumors [110,111]. If complete resection is not possible, cardiac transplantation may be required [112]. As is true of all pheochromocytoma resections, preoperative and intraoperative adrenergic blockade must be employed. (See "Paragangliomas: Treatment of locoregional disease" and "Paraganglioma and pheochromocytoma: Management of malignant disease".) Mesothelioma — Although most mesotheliomas arise in the pleura, these tumors can also arise from the pericardium, where they are usually malignant [113-117]. Although a causal relationship between asbestos exposure and pleural mesotheliomas is well established, the relationship between asbestos exposure and pericardial mesothelioma is less certain. Mesotheliomas arising in the pericardium produce tamponade and constriction [113-116]. These tumors will be seen with echocardiography, computed tomography scan, MRI, and sometimes by chest radiograph [113-115]. Pericardiocentesis may yield a cytologic diagnosis [114].

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More rarely, mesotheliomas may arise as benign tumors of the atrioventricular (AV) node where they may produce heart block [118,119]. Diagnosis of the AV nodal tumors causing heart block can be confirmed with echocardiography. Resection is the treatment of choice for mesothelioma, but the prognosis with malignant pericardial mesotheliomas is very poor [114,115]. The addition of radiation and/or chemotherapy has been attempted but has not been shown to be of value.

PRIMARY MALIGNANT TUMORS Malignant tumors constitute approximately 15 percent of primary cardiac tumors [38]. Sarcomas are the most common, although other tumor types have been reported. Sarcomas — Virtually all types of sarcomas have been reported in the heart [6,120-125]. Cardiac sarcomas are extremely rare, and for most types, only isolated case reports have been described. As with benign lesions, the clinical presentation is largely determined by the location of the tumor rather than its histopathology. The diagnostic approach relies upon echocardiography, magnetic resonance imaging, and computed tomography to define the presence of a tumor and its anatomic relationship to normal structures (movie 7). The most frequently described sarcomas include (see "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'Histopathology'): ●

Angiosarcomas – Angiosarcomas are composed of malignant cells that form vascular channels. The pathology of angiosarcomas may overlap with Kaposi sarcoma, which can also involve the myocardium [126]. Angiosarcomas arise predominantly in the right atrium [126,127]. Epithelioid hemangioendothelioma, another sarcoma of vascular origin, has also been reported [128]. Of sarcomas, 40 percent are angiosarcomas, and 10 percent are spindle sarcomas [129].



Rhabdomyosarcomas – Rhabdomyosarcomas constitute as many as 20 percent of all primary cardiac sarcomas [130]. These tumors are most commonly found in adults, although they have also been described in children. Multiple sites of myocardial involvement are common, and there is no predominant localization within any area of the heart.

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Fibrosarcomas and undifferentiated sarcomas – Fibrosarcomas and undifferentiated/unclassified soft tissue sarcomas (which were formerly included in a broad category termed malignant fibrous histiocytomas or high-grade pleomorphic sarcomas [131]) are white, fleshy ("fish flesh") tumors that are composed of spindle cells and may have extensive areas of necrosis and hemorrhage [132,133]. These tumors tend to extensively infiltrate the myocardium.



Leiomyosarcomas – Leiomyosarcomas are spindle-celled, high-grade tumors that arise more frequently in the left atrium [134]. These sarcomas have both a high rate of local recurrence and systemic spread.



Other types include liposarcoma and synovial sarcoma [124,135].

Treatment and prognosis — In general, sarcomas proliferate rapidly and cause death through widespread infiltration of the myocardium, obstruction of blood flow through the heart, and/or distant metastases. Although complete resection is the treatment of choice, most patients develop recurrent disease and die of their malignancy even if their tumor can be completely resected [54,60,129,136,137]. The median survival is typically 6 to 12 months [120,124], although long-term survival has been reported with complete resection [120,123,138,139], and patients with low-grade sarcomas may have a better prognosis [123]. Neoadjuvant or adjuvant chemotherapy has been used in an effort to improve on the poor results with resection alone. However, most of the published experience consists of anecdotal case reports or retrospective reviews [38,138,140-149], and no randomized trials have been conducted. Rhabdomyosarcomas may have a better outcome with chemotherapy. (See "Rhabdomyosarcoma in childhood, adolescence, and adulthood: Treatment".) Alternative strategies such as cardiac transplantation and cardiac autotransplantation are being explored. Radiation has been used infrequently and primarily as a treatment of metastases [135]. Studies illustrating the prognosis of these sarcomas are discussed below: ●

In a 95-patient series of malignant primary cardiac tumors, all of whom had surgical treatment with 60 percent having preoperative adjunctive chemotherapy, only two patients lived beyond five years [129]. In a 40-year study of over 500 primary malignant cardiac tumors, the overall survival rates at one, three, and five years were 46, 22, and 17 percent, whereas with sarcomas the survival rates were 47, 16, and 11 percent, respectively [150].

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In a 34-patient series treated at the Mayo Clinic over a 32-year period [122], the median survival was significantly longer when a complete surgical resection was possible (17 versus 6 months when complete resection was not possible). Similarly, the median survival was longer in those who did not have metastases on presentation (15 versus 5 months in those with detectable metastases at diagnosis). Larger series of 95 patients and over 500 patients have shown similar and very poor long-term survival [129,150].

The poor results with surgical resection have led to occasional attempts to treat patients with cardiac transplantation if extracardiac disease is not present [145,151-155]. Most of these patients have undergone chemotherapy and radiation prior to transplantation. In the largest series, results of cardiac transplantation in patients with malignant tumors (most of which were sarcomas) were evaluated in a review of 21 cases [151]. Although mean survival was only 12 months, seven patients were free of recurrent malignancy at a mean follow-up of 27 months. An alternative treatment, cardiac autotransplantation, has shown promise. In these cases, the heart is excised, the tumor is resected ex vivo, and the heart is reconstructed before being reimplanted. The advantage of this procedure is the increased ease with which major resection and reconstruction can be performed, while at the same time avoiding the need for antirejection treatment [156,157]. Another promising adjunct in operative therapy is to plan the complex operative strategy (in a Schwannoma) by creating a three-dimensional printer reproduction of the heart and tumor [158]. Other primary cardiac tumors — Primary lymphomas arising in the myocardium have been reported. In a review of 40 cases identified from the literature between 1995 and 2002, the outlook was generally poor [159]. However, 38 percent of cases achieved a complete response with systemic therapy. At least some of these responses may be durable [159-161]. Other tumors may also arise in the heart, including paragangliomas [162,163] and extramedullary plasmacytomas [164-166].

SECONDARY CARDIAC TUMORS In contrast to primary malignant cardiac tumors, metastatic involvement of the heart is relatively common. As an example, in one of the largest autopsy series of over 1900 patients dying of https://www.uptodate.com/contents/cardiac-tumors/print?search=fet…rch_result&selectedTitle=1~150&usage_type=default&display_rank=1

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cancer, 8 percent had metastatic disease involving the heart [5]. Cardiac involvement may arise from hematogenous metastases, direct invasion from the mediastinum, or tumor growth into the vena cava and extension into the right atrium [167]. Malignant melanomas are particularly likely to metastasize to the heart [126,164,168,169]. Other solid tumors commonly associated with cardiac involvement include lung cancer, breast cancer, soft tissue sarcomas, renal carcinoma, esophageal cancer, hepatocellular carcinoma, and thyroid cancer [170]. There is also a high prevalence of secondary cardiac involvement with leukemia and lymphoma. Cardiac or pericardial metastasis should be considered whenever a patient with known malignancy develops a pericardial effusion; any cardiovascular symptom; or signs such as a new or changing heart murmur, electrocardiographic conduction delay, or arrhythmia. The development of cardiomegaly on chest radiograph should suggest pericardial effusion. Emboli thought to originate in the heart should also raise the possibility of cardiac involvement with tumor. Cardiac metastases rarely may be the first manifestation of malignant disease [171]. The specific symptoms will reflect the site of cardiac involvement in a manner analogous to primary cardiac tumors. The diagnostic evaluation is the same as that for primary cardiac tumors and relies upon echocardiography, magnetic resonance imaging, and computed tomography to ascertain the extent of cardiac involvement. In very carefully selected patients, resection of cardiac metastases has been used to provide symptom palliation and prolong life [126,172,173]. Other causes of cardiac symptoms must also be considered. In particular, metastatic disease must be distinguished from the cardiotoxicity that may be associated with chemotherapeutic agents, particularly anthracyclines. (See "Clinical manifestations, monitoring, and diagnosis of anthracycline-induced cardiotoxicity".)

SUMMARY ●

Tumors involving the heart may cause symptoms by obstruction of circulation, interference with heart valves, direct invasion of the myocardium, invasion of adjacent lung, or embolization. Constitutional or flu-like symptoms may be present. Except for tumors with constitutional symptoms, the signs and symptoms of a cardiac tumor are generally determined by the location of the tumor in the heart rather than by its histopathology. (See

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'Clinical manifestations' above.) ●

If a cardiac tumor is suspected, imaging procedures are used to determine whether or not a mass is present and where the tumor is located within the heart. Echocardiography is the simplest technique for such evaluation; cardiac magnetic resonance imaging and ultrafast computed tomography provide more detailed information. Tumors that occur from or invade the epicardial surface of the heart require coronary angiography preoperatively to define distortion of the coronary arteries and determine coronary blood supply of the tumor. (See 'Diagnostic evaluation' above.)



Over 75 percent of cardiac tumors are benign, and the majority of these are myxomas. Approximately 80 percent of myxomas arise in the left atrium and most of the remainder are found in the right atrium. Myxomas are managed with prompt surgical resection because of the risk of embolization or other cardiovascular complications. A number of other benign lesions may also occur. (See 'Myxomas' above and 'Benign tumors' above.)



Primary malignant tumors of the heart are rare; most of these are sarcomas. Primary sarcomas arising in the heart generally are rapidly progressive and cause death through infiltration of the myocardium, by obstructing circulation, or by distant metastases. When feasible, treatment is surgical, although most of these tumors recur relatively rapidly. (See 'Sarcomas' above.)



Metastatic involvement of the heart is relatively frequent and may result from hematogenous spread, direct invasion, or tumor growth through the vena cava into the right atrium. Cardiac or pericardial metastases should be considered whenever a patient with known malignancy develops cardiovascular symptoms. As with primary cardiac tumors, specific signs and symptoms reflect the site of cardiac involvement. (See 'Secondary cardiac tumors' above.)

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Sarcomas: Review of a Single-Institution Experience. Ann Thorac Surg 2016; 101:698. 130. Castorino F, Masiello P, Quattrocchi E, Di Benedetto G. Primary cardiac rhabdomyosarcoma of the left atrium: an unusual presentation. Tex Heart Inst J 2000; 27:206. 131. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F. World Health Organization Classi fication of tumours of soft tissue and bone, 4th ed, IARC Press, Lyon 2013. 132. Schena S, Caniglia A, Agnino A, et al. Survival following treatment of a cardiac malignant fibrous histiocytoma. Chest 2000; 118:271. 133. Okamoto K, Kato S, Katsuki S, et al. Malignant fibrous histiocytoma of the heart: case report and review of 46 cases in the literature. Intern Med 2001; 40:1222. 134. Pins MR, Ferrell MA, Madsen JC, et al. Epithelioid and spindle-celled leiomyosarcoma of the heart. Report of 2 cases and review of the literature. Arch Pathol Lab Med 1999; 123:782. 135. Bakaeen FG, Jaroszewski DE, Rice DC, et al. Outcomes after surgical resection of cardiac sarcoma in the multimodality treatment era. J Thorac Cardiovasc Surg 2009; 137:1454. 136. Kosuga T, Fukunaga S, Kawara T, et al. Surgery for primary cardiac tumors. Clinical experience and surgical results in 60 patients. J Cardiovasc Surg (Torino) 2002; 43:581. 137. Raaf HN, Raaf JH. Sarcomas related to the heart and vasculature. Semin Surg Oncol 1994; 10:374. 138. Putnam JB Jr, Sweeney MS, Colon R, et al. Primary cardiac sarcomas. Ann Thorac Surg 1991; 51:906. 139. Shapira OM, Korach A, Izhar U, et al. Radical multidisciplinary approach to primary cardiac sarcomas. Eur J Cardiothorac Surg 2013; 44:330. 140. Llombart-Cussac A, Pivot X, Contesso G, et al. Adjuvant chemotherapy for primary cardiac sarcomas: the IGR experience. Br J Cancer 1998; 78:1624. 141. Antunes MJ, Vanderdonck KM, Andrade CM, Rebelo LS. Primary cardiac

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leiomyosarcomas. Ann Thorac Surg 1991; 51:999. 142. Kakizaki S, Takagi H, Hosaka Y. Cardiac angiosarcoma responding to multidisciplinary treatment. Int J Cardiol 1997; 62:273. 143. Pessotto R, Silvestre G, Luciani GB, et al. Primary cardiac leiomyosarcoma: seven-year survival with combined surgical and adjuvant therapy. Int J Cardiol 1997; 60:91. 144. Landolsi-Ben Ammou A, Ben Fatma L, Kallel L, et al. [Primary cardiac sarcoma: report of 3 cases and review of the literature]. Ann Cardiol Angeiol (Paris) 2003; 52:370. 145. Fahn W, Schlemmer M, Issels R, et al. [Leiomyosarcoma of the heart--interdisciplinary therapeutic approach of systemic chemotherapy and subsequent heart transplantation]. Dtsch Med Wochenschr 2003; 128:2005. 146. Mery GM, Reardon MJ, Haas J, et al. A combined modality approach to recurrent cardiac sarcoma resulting in a prolonged remission: a case report. Chest 2003; 123:1766. 147. Nakamichi T, Fukuda T, Suzuki T, et al. Primary cardiac angiosarcoma: 53 months' survival after multidisciplinary therapy. Ann Thorac Surg 1997; 63:1160. 148. Mayer F, Aebert H, Rudert M, et al. Primary malignant sarcomas of the heart and great vessels in adult patients--a single-center experience. Oncologist 2007; 12:1134. 149. Abu Saleh WK, Ramlawi B, Shapira OM, et al. Improved Outcomes With the Evolution of a Neoadjuvant Chemotherapy Approach to Right Heart Sarcoma. Ann Thorac Surg 2017; 104:90. 150. Oliveira GH, Al-Kindi SG, Hoimes C, Park SJ. Characteristics and Survival of Malignant Cardiac Tumors: A 40-Year Analysis of >500 Patients. Circulation 2015; 132:2395. 151. Gowdamarajan A, Michler RE. Therapy for primary cardiac tumors: is there a role for heart transplantation? Curr Opin Cardiol 2000; 15:121. 152. Uberfuhr P, Meiser B, Fuchs A, et al. Heart transplantation: an approach to treating primary cardiac sarcoma? J Heart Lung Transplant 2002; 21:1135. 153. Talbot SM, Taub RN, Keohan ML, et al. Combined heart and lung transplantation for unresectable primary cardiac sarcoma. J Thorac Cardiovasc Surg 2002; 124:1145.

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154. Baay P, Karwande SV, Kushner JP, et al. Successful treatment of a cardiac angiosarcoma with combined modality therapy. J Heart Lung Transplant 1994; 13:923. 155. Grandmougin D, Fayad G, Decoene C, et al. Total orthotopic heart transplantation for primary cardiac rhabdomyosarcoma: factors influencing long-term survival. Ann Thorac Surg 2001; 71:1438. 156. Reardon MJ, Malaisrie SC, Walkes JC, et al. Cardiac autotransplantation for primary cardiac tumors. Ann Thorac Surg 2006; 82:645. 157. Blackmon SH, Reardon MJ. Surgical treatment of primary cardiac sarcomas. Tex Heart Inst J 2009; 36:451. 158. Son KH, Kim KW, Ahn CB, et al. Surgical Planning by 3D Printing for Primary Cardiac Schwannoma Resection. Yonsei Med J 2015; 56:1735. 159. Ikeda H, Nakamura S, Nishimaki H, et al. Primary lymphoma of the heart: case report and literature review. Pathol Int 2004; 54:187. 160. Anghel G, Zoli V, Petti N, et al. Primary cardiac lymphoma: report of two cases occurring in immunocompetent subjects. Leuk Lymphoma 2004; 45:781. 161. Nakagawa Y, Ikeda U, Hirose M, et al. Successful treatment of primary cardiac lymphoma with monoclonal CD20 antibody (rituximab). Circ J 2004; 68:172. 162. Moorjani N, Kuo J, Wilkins D. Left atrial phaeochromocytoma. Heart 2004; 90:e64. 163. Lupinski RW, Shankar S, Agasthian T, et al. Primary cardiac paraganglioma. Ann Thorac Surg 2004; 78:e43. 164. Keung YK, Lau S, Gill P. Extramedullary plasmacytoma of the heart presenting as cardiac emergency. Review of literature. Am J Clin Oncol 1994; 17:427. 165. Khankirawatana B, Ginete WL. Primary extramedullary plasmacytoma of the heart. Clin Cardiol 2004; 27:368. 166. Fernandez LA, Couban S, Sy R, Miller R. An unusual presentation of extramedullary plasmacytoma occurring sequentially in the testis, subcutaneous tissue, and heart. Am J Hematol 2001; 67:194.

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167. Longo R, Mocini D, Santini M, et al. Unusual sites of metastatic malignancy: case 1. Cardiac metastasis in hepatocellular carcinoma. J Clin Oncol 2004; 22:5012. 168. Savoia P, Fierro MT, Zaccagna A, Bernengo MG. Metastatic melanoma of the heart. J Surg Oncol 2000; 75:203. 169. Reynen K, Köckeritz U, Strasser RH. Metastases to the heart. Ann Oncol 2004; 15:375. 170. Goldberg AD, Blankstein R, Padera RF. Tumors metastatic to the heart. Circulation 2013; 128:1790. 171. Sosinska-Mielcarek K, Senkus-Konefka E, Jassem J, et al. Cardiac involvement at presentation of non-small-cell lung cancer. J Clin Oncol 2008; 26:1010. 172. Messner G, Harting MT, Russo P, et al. Surgical management of metastatic melanoma to the ventricle. Tex Heart Inst J 2003; 30:218. 173. Labib SB, Schick EC Jr, Isner JM. Obstruction of right ventricular outflow tract caused by intracavitary metastatic disease: analysis of 14 cases. J Am Coll Cardiol 1992; 19:1664.

Topic 4881 Version 26.0

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GRAPHICS Left atrial myxoma on transthoracic and transesophageal echocardiography

A four chamber view from a transthoracic echocardiography (panel A) suggests a well encapsulated mass within the left atrium (arrow). The consistence is fairly uniform although there may be a few rarefactions. Transesophageal echocardiography (panel B) shows the details of the tumor attachment to the lower limbus of the foraminal portion of the interatrial septum. The implied irregularity on transthoracic echocardiography are clearly seen cysts that are also typical of these tumors. Graphic 60232 Version 2.0

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Left atrial myxoma

The long axis precordial view from a transthoracic echocardiography shows the tumor as a vague mass just behind the aortic root (panel A). The apical four chamber view (panel B) shows the mass attached to the interatrial septum. A transesophageal echocardiography (panels C and D) reveals that the myxoma is highly mobile and at surgery, the tumor had the consistency of jelly and fragmented easily. Graphic 68725 Version 3.0

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Papillary fibroelastoma of mitral valve

Gross and microscopic pathology of a papillary fibroelastoma of the mitral valve. The gross specimen (left) reveals multiple frond-like structures when photographed underwater. Low (right, top) and high power (right, bottom) microscopic features include dense elastin (black) at the core of each frond coated with collagen (red pink) and lined by flat endocardial cells. Reprinted from Journal of the American College of Cardiology, volume 30, Klarich, KW, Enriquez-Sarano, M, Gura, GM, et al. Papillary fibroelastoma: Echocardiographic characteristics for diagnosis and pathogenesis correlation, p.784, Copyright 1997, with permission from the American College of Cardiology.

http://www.elsevier.com/locate/jacc http://www.sciencedirect.com Graphic 76001 Version 2.0

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Pericardial lipoma on chest x-ray

A P-A chest x-ray (A) shows the border of the left ventricle (arrowhead) surrounded by a lower density border of a pericardial lipoma (arrow). A lateral view (B) shows the posteriorly positioned lowdensity lipoma of the pericardium (arrow). P-A: posteroanterior. Graphic 89414 Version 1.0

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Pericardial lipoma on CT scan

A CT scan through the mid-chest shows a large low-density pericardial lipoma (arrow in panel A). A CT reformatted in the sagittal plane shows a lipoma posterior to the heart (arrow) and pressing against the esophagus (arrowhead). CT: computed tomography. Graphic 89413 Version 1.0

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Contributor Disclosures William H Gaasch, MD Nothing to disclose Thomas J Vander Salm, MD Nothing to disclose Wilson S Colucci, MD Consultant/Advisory Boards: Novartis [Heart failure (Valsartan, sacubitril/valsartan)], Merck [Heart failure (Enalapril)]. Sadhna R Vora, MD Nothing to disclose Susan B Yeon, MD, JD, FACC Nothing to disclose Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy

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