Myxomas are composed of cells, primitive capillaries, and foci of extramedullary hematopoiesis within a myxoid matrix of acid mucopolysaccharide. The stroma contains variable numbers of reticulocytes and elastin fibers, smooth muscle cells, and collagen deposits. The matrix also contains polygonal cells with scant eosinophilic cytoplasm, either single and stellate or multinuclear and in small nests. At the periphery of the tumor, the cells form a monolayer with clustering in the crevices, thereby simulating primitive capillaries. The stalk has abundant large arteries and veins that communicate with the subendocardium; at this interface, lymphocytes and plasma cells are prominent. Microscopic foci of calcium and areas of metaplastic bone are found in 10% of myxomas. ^, The nucleus of the polygonal cells is typically irregular and slightly hyperchromatic, but mitoses are not seen. The cells contain fine parallel filaments similar to those in glomangioma and fibromyxosarcoma. These filaments are believed to be the contractile components of smooth muscle cells. Immunologically identifiable smooth muscle-type filaments are recognized in endocardial cells, which are more abundant in the left atrium, especially in the region of the fossa ovalis, than in other chambers.

The notion that myxomas are derived from thrombi has been thoroughly dispelled. Ferrans and Roberts believe the organelle content of myxoma cells does not provide sufficient information to determine the cell of origin. Although myxoma cells have a “vasoformative” tendency, in their view, the cytoarchitectural features of the variously differentiated blood vessel-like structures differ from those of normal blood vessels. Thus, myxomas are considered to arise from pluripotential mesenchymal cells capable of differentiating into various types of cells, a view supported by the finding of bone and bone marrow tissue in myxomas. Histologic examination of the atrial septum in 11 autopsied patients younger than age 4 months revealed myxomatous or myxofibrous tissue in the endocardium near the fossa ovalis, further supporting the concept that myxomas are derived from embryonal undifferentiated mesenchymal cells, perhaps during endothelial–mesenchymal transformation, leading to cardiac septation and valve formation.

Based on immunohistochemical identification of three neuroendocrine markers in 24 excised atrial myxomas, Krikler and colleagues have suggested that these tumors originate from endocardial sensory nerve tissue. Occasional association of cardiac myxomas with cutaneous leiomyomatosis and systemic findings such as fever, hypergammaglobulinemia, and weight loss resemble manifestations of other tumors of neural origin. Increasing numbers of reports document the malignant potential of myxomas. Extensive local invasion has been noted. Death attributable to metastatic spread of an atrial myxoma was once reported as a result of fatal brainstem compression from an expanding cerebellar mass with histologic features identical to those of a large, pedunculated left atrial myxoma also found at autopsy. There have been many reports of local recurrence and of distant metastases with invasion of vessel walls, aneurysmal change, and independent growth. ^, Transgression beyond a blood vessel has also been noted.

Most atrial myxomas, whether left or right, arise from the atrial septum, usually from the region of the limbus of the fossa ovalis. About 10% have other sites of origin, particularly the posterior and anterior atrial walls and the appendage (in order of frequency). Importantly, atrial masses thought to be myxomas but not originating from the intra-atrial septum may have more complex pathology. On the left atrial side, they may be extensions of hilar lung tumors such as mesothelioma, sarcoma, or carcinoma. On the right side, they may be intracaval extensions of renal or uterine tumors. Most myxomas—80% to 90%—are in the left atrium. Right atrial myxomas tend to be more solid and sessile than left atrial myxomas, with a wider attachment to the atrial wall or septum. ^, In one reported case, an atrial myxoma presenting in the right atrium arose from the inferior vena cava. Atrial myxomas may be multicentric (within a single chamber) or biatrial. The most common arrangement (75%) of biatrial tumors involves attachment of two stalks to opposite sides of the same area of the septum. Of 312 cases of right and left atrial myxomas reviewed by Newman and colleagues, only two were complicated by presence of an atrial septal defect ; Natarajan and colleagues reported four cases. Such cases may have right-to-left shunts.

Found commonly on the right ventricular free wall or ventricular septum, ventricular myxomas are sometimes described as infiltrating the ventricular myocardium. In about 15% of reported cases, right ventricular myxomas are associated with other cardiac myxomas. Left ventricular myxomas are rare. Both right and left ventricular myxomas can extend into the outflow tract and cause partial outflow tract obstruction.

Myxomas arising from the mitral, tricuspid, or pulmonary valves have been reported.

Myxomas may produce (1) symptoms of hemodynamic derangement from obstruction of flow within the cardiac chambers or deformation of a cardiac valve, (2) symptoms associated with embolization, and (3) constitutional symptoms, the least common manifestation. ^, In rare circumstances, atrial myxomas may become infected; only 2 of 12 reported cases were diagnosed before death. ^, Central nervous system embolism has been a constant association in this circumstance.

Nearly all solitary myxomas have a normal DNA ploidy and are nonfamilial. Nonfamilial (“sporadic”) cardiac myxomas are disorders primarily of middle-aged women. The tumors are usually single (94%) and in the left atrium (about 75%); they uncommonly have associated conditions, they rarely recur, and only about 20% have abnormal DNA ploidy.

Carney complex and its subsets LAMB syndrome and NAME syndrome are autosomal dominant conditions comprising myxomas of the heart and skin, hyperpigmentation of the skin (lentiginosis), and endocrine overactivity. The tumors are primarily disorders of young men and are less common in the left atrium (62%), are more often multiple (33%), and associated with unusual conditions in about 20% of patients. These conditions include Sertoli cell tumors of the testes, Cushing syndrome as a result of primary adrenocortical nodular dysplasia, pituitary tumors, centrofacial and labial lentiginosis (brown macules with regular edges, sometimes termed spotty pigmentation ), cutaneous myxomas, and multiple myxoid mammary fibroadenomas. ^{, ,} Familial myxomas have the same histologic appearance as nonfamilial myxomas and produce the same symptoms.

Carney complex is caused by inactivating mutations of the tumor suppressor gene PRKAR1A and there are no gross or histologic tumor features that distinguish syndromic and nonsyndromic myxomas. However, immunohistochemical staining of PRKAR1A may be useful to identify patients at increased risk of having syndromic disease. Lack of PRKAR1A staining is 100% sensitive for Carney complex myxoma but is only 68% specific because a small subset of nonsyndromic tumors may also have abnormal PRKAR1A expression.

Pitsava and colleagues reported the largest prospective series of patients with Carney complex that defined the risk of developing cardiac myxomas and their recurrence. The development and recurrence of cardiac myxomas is the predominant cause of death in Carney complex patients. These authors examined 318 patients with Carney complex from 1995 to 2020. Of the patient cohort, 136 patients developed myxomas (42.6%) during the study interval. The mean age at diagnosis was 28.7 ± 16.6 years in females and 25.0 ± 16.4 years in males. By age 30, 35% of females and 45% of males had at least one myxoma. Recurrences of cardiac myxoma occurred in 44% of patients, more commonly in females and typically within the first 10 years following resection. Familial cardiac myxomas are aneuploid in virtually all cases, supporting the concept that they are neoplasms.

Left atrial myxomas produce symptoms similar to those of mitral stenosis (see Chapter 11 ) in most patients, with dyspnea and hemoptysis predominating. ^, Symptoms are commonly of short duration, episodic, and associated with syncope. They may rapidly become severe and intractable and are associated with heart failure. Right atrial myxomas may also produce episodic symptoms, and these may progress rapidly. Abdominal protuberance from hepatomegaly and ascites and peripheral edema are frequent presenting complaints. In a review by Morrisey and colleagues, all 18 patients had right-sided heart failure, with a prominent a wave, increased venous pressure, hepatomegaly, ascites, and peripheral edema ; absence of orthopnea and paroxysmal nocturnal dyspnea was notable. Symptoms that result from embolization include neurologic deficits, coldness and pain in an extremity, angina or infarction from coronary embolization, and dyspnea from pulmonary embolization. Constitutional symptoms may be subtle or absent when the tumor is small, but occasionally constitute the entire symptomatology.

Diagnosis of atrial myxoma is sometimes made immediately after hospital admission by histologic examination of an embolus removed from a peripheral artery. However, absence of myxoma cells in the embolus does not rule out myxoma because thrombus forming on the neoplasm may be the cause of the embolism. Before the advent of echocardiography, interpretation of auscultatory findings for left atrial myxomas was aided by a combination of phonocardiographic and hemodynamic studies. ^, A loud first heart sound is prolonged by vibrations coinciding with the c wave of the left atrial pressure tracing and also with a characteristic notch in the left ventricular pressure curve; these vibrations occur after mitral valve closure when the tumor momentarily comes to rest in the left atrium. For mobile tumors moving from the left ventricle to the left atrium in early systole, a notch in the ascending limb of the left ventricular pressure tracing is attributed to a sudden increase in left atrial volume, which itself is manifested in the left atrial pressure pulse by a prominent c wave and subsequent dominant v wave. Accordingly, the first heart sound may be preceded by a loud ejection sound resulting from forceful ejection of the tumor from the left ventricle back into the left atrium.

When the tumor stays in the left atrium during the entire cardiac cycle, the diastolic murmur and pressure tracings may be indistinguishable from those of mitral stenosis (i.e., there is no notch in the ventricular pressure wave, and the y descent is relatively slow). The second heart sound is normally split, of low intensity, and followed by a third heart sound described as either an opening snap or a ventricular gallop. The opening snap occurs after the mitral valve opens and is thought to be due either to the tumor striking the heart wall or to the diastolic sound of mitral regurgitation caused by increased blood flow. Systolic murmurs have also been recorded and have been attributed to associated mitral regurgitation. ^,

With right atrial myxomas, a loud early systolic sound is heard, usually regarded as a widely split first heart sound, corresponding to expulsion of the tumor from the right ventricle. This sound is likely to correspond to a notch in the upstroke of the right ventricular pressure curve. A pulmonary ejection murmur with a delayed and accentuated pulmonic second sound and an early, late, or prolonged tricuspid diastolic murmur or rumble is heard. A systolic murmur is due to tricuspid regurgitation.

Ventricular myxomas are sufficiently rare that their auscultatory features are not fully known, but murmurs may suggest aortic or pulmonary stenosis. Occasionally, friction rubs are heard, presumably a result of physical contact of the tumor with the endocardium of one of the cardiac chambers. Rarely, patients presenting with constitutional manifestations exhibit cyanosis and clubbing of the fingers and toes, or a gallop rhythm and sinus tachycardia. ^{, , , ,}

Results of laboratory studies are usually normal. In rare instances of presentation with constitutional manifestations, some findings may be characteristic but not pathognomonic. Among them are anemia, thrombocytopenia, and findings associated with an immune response (see “ Constitutional Manifestations ” earlier in this section).

Electrocardiographic findings associated with myxomas are not specific but include arrhythmias and conduction disturbances, particularly atrial fibrillation and bundle branch block, and abnormal P waves.

Features on a plain chest radiograph are not specific. Generalized cardiomegaly or specific chamber enlargement may be evident, particularly in the case of large left atrial myxomas causing obstruction. Septal lines, especially at the base and in the midzone of the lung, are fairly common findings because of coexisting pulmonary venous hypertension.

Transthoracic echocardiography (TTE) supplemented by transesophageal echocardiography (TEE) has become the most appropriate screening and diagnostic imaging modality for myxomas (and most other cardiac tumors). ^, Mitral valve stenosis can be excluded, and tumor prolapse through the atrioventricular valve may be demonstrated. Tumor prolapse is characteristically evident if echoes are seen behind the anterior leaflet, particularly if they move into the left ventricle during diastole. Echocardiography is invaluable in identifying the precise origin of the myxoma ( Figs. 17.1 and 17.2 ). ^,

Transesophageal echocardiogram of large myxoma in left atrium with origin at intra-atrial septum.

Atrial myxomas and other cardiac tumors can also be identified with computed tomography (CT) or magnetic resonance imaging (MRI), either alone or in combination with echocardiography. Asymptomatic tumors are occasionally identified when CT or MRI scans are performed for other indications.

Unless other types of cardiac or coronary artery disease require assessment, catheterization and angiography no longer constitute the investigative method of choice. If invasive study is required for suspected left atrial tumors, a selective right-sided heart study is performed by injecting radiopaque media into the pulmonary artery and filming as the dye passes through the left atrium. This method usually gives a clear demonstration of the tumor, whereas selective left ventricular cineangiography often fails to delineate it. For right atrial myxomas, catheter placement into the right atrium is contraindicated, and injection is made into one of the venae cavae.

The approach is biatrial. For initial exploration and orientation, the usual incision is made in the left atrium posterior to the interatrial groove ( Fig. 17.3 A ). Blood is removed from the left atrium, and the point of attachment of the tumor to the atrium is determined by inspection ( Fig. 17.3 B ). Assuming it is attached to the atrial septum, which is usually the case, the tumor is not removed from the left atrium. Instead, an oblique right atriotomy is made and the interior of the right atrium examined to exclude the presence of a second tumor ( Fig. 17.3 C). As much as possible of the interior of the right ventricle is also inspected through the tricuspid valve. The atrial septum is then opened with a knife near the center of the fossa ovalis, and a sufficient amount of atrial septum is excised to include the tumor attachment and, if possible, uninvolved tissue 5 mm beyond it. The superior half of the fossa ovalis and adjacent limbus are, if possible, included in the excision, because cells thought to be the precursor of myxoma are more abundant in this area. The tumor is then removed from the heart through the left or right atriotomy, whichever is larger ( Fig. 17.3 D ). Very large tumors may have to be removed piecemeal, although every attempt is made to keep the tumor intact and to avoid tumor embolization. After the tumor is removed, the interior of the left atrium is copiously irrigated with saline solution to evacuate any residual tumor fragments. The defect in the atrial septum is closed either by direct suture or, if too large for this, with a pericardial or synthetic patch ( Fig. 17.3 E ).

Resection of left atrial myxoma. (A) Two atrial incisions are used. Tumor is explored via left atrial incision (dashed line) . Later, tumor will be removed from right atrial approach. (B) As for exposure of mitral valve, left atrium is opened and explored and attachment of myxoma to atrial septum identified. (Tumor may be isolated from pulmonary vein orifices at this point by small packing sponges.) (C) From opened right atrium, tumor attachment to atrial septum is usually apparent. A circular septal incision is made to surround the tumor origin (seen as a dimple). (D) Via its circumscribed septal attachment, myxoma is delivered into right atrium. (E) Atrial septal defect is closed using pericardial or synthetic patch. Ao, Aorta; IVC, inferior vena cava; PT, pulmonary trunk; RA, right atrium; RV, right ventricle; SVC, superior vena cava.

If the tumor is attached to the left atrial wall rather than the septum, the zone of attachment is excised, preferably with the full thickness of the adjacent wall, but if this is impracticable, with endocardium and some underlying muscle. The defect created in the atrial wall can be closed by direct suture or with a patch of autologous or bovine pericardium. The atria are closed and usual precautions against air embolization taken (see “ De-airing the Heart ” in Section III of Chapter 2 ). The rest of the procedure is completed in standard fashion.

Separate left and right atriotomies are not necessary unless there is preoperative evidence of an associated left atrial myxoma. Instead, only the right atrium is opened by the usual oblique incision, and after attachments of the tumor are defined, the tumor is excised with the adjacent portion of atrial septum in the manner described in the preceding text. The left atrium is then carefully inspected via the surgically created atrial septal defect. Only if a tumor is seen in the left atrium is that chamber opened by a separate incision. The atrial septal defect is closed as described in the preceding text, and the remainder of the procedure is completed as described.

Removal of ventricular myxomas does not require excision of full-thickness ventricular wall because such a procedure would increase risk and no recurrences have been recorded following less radical removal. Tumors in the left ventricular outflow tract can sometimes be removed via an aortic approach. Otherwise, the approach is through the right atrium for right ventricular tumors and left atrium for left ventricular tumors. ^, The ventricle is opened directly only when the atrial approach is inadequate for tumor removal. The procedure should include careful inspection of the interior of both right and left atria to exclude the presence of additional atrial tumors, which have been found in 15% of patients with right ventricular myxomas.

In those rare instances in which the tumor arises from an atrioventricular valve, the valve usually requires replacement. Also, valve replacement is occasionally required because of leaflet disruption or distortion from the “wrecking ball” action of the tumor (see Fig. 17.2 ). A markedly enlarged atrioventricular valve anulus may require anuloplasty to correct residual valve regurgitation. Such enlargement is particularly likely to occur in the tricuspid valve because the tricuspid anulus is more easily overstretched by a bulky tumor than is the mitral anulus.

Transthoracic echocardiogram of a large left atrial myxoma originating from the lower atrial septum, prolapsing through the mitral valve in diastole (A) and returning into the atrium in systole (B).

(From Konstantinov IE, Saxena P, Barrett T, Jenkins G. Resection and reconstruction of the roof of the coronary sinus for an unusually attached left atrial myxoma. J Thorac Cardiovasc Surg . 2009;137:1032-1034.)

What has been classified as recurrence can be due to (1) tumor implantation (seeding at the time of removal), (2) incomplete removal, or (3) growth from a new focus (multicentric origin). Recurrence of a “sporadic” myxoma is unusual, occurring in only about 1% to 3% of patients, and myxomas with a normal ploidy rarely recur. ^, In contrast, 30% to 75% of patients with familial myxomas experience recurrence. When the tumor exhibits an abnormal ploidy, 40% of patients experience recurrence. A first recurrence is often followed by a second, and recurrence may be in a cardiac chamber that was not the site of the original tumor. ^, Recurrences may become apparent as early as 6 months and as late as 11 years after excision, but the average is about 30 months after removal of the first myxoma. ^, At least one patient has experienced recurrence of a left ventricular myxoma; it involved the aortic valve and necessitated valve replacement.

Atrial arrhythmias are common after removal of atrial myxomas. Conduction disturbances are also reported and may be related to failure to limit resection to safe areas of the atrial septum or wall.

Living patients are generally in good health unless they have other disease processes or residual effects from a preoperative embolic event.