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Clinical Presentation of Left Atrial Cardiac Myxoma

2001; Wolters Kluwer; Volume: 80; Issue: 3 Linguagem: Inglês

10.1097/00005792-200105000-00002

1536-5964

L. Pinède, P. Duhaut, R Loire,

Peptidase Inhibition and Analysis

Introduction Cardiac myxoma is the most frequent “benign” tumor of the heart and presents an important diagnostic challenge (4,43,47). Myxomas may resemble many cardiovascular or systemic diseases, and can arise in any of the cardiac chambers, although 75% occur in the left atrium. Most cases of atrial myxomas are now diagnosed in living patients, allowing successful surgical extirpation (1,3,30,44,53). Before the introduction of angiocardiography in 1951, cardiac myxoma diagnosis was made only at autopsy (22). The first successful surgical removal of an atrial myxoma was performed in 1954 (35,47). In 1959, the first M-mode echocardiogram of a left atrial myxoma was reported (16). Indeed, the introduction of echocardiography has provided an important noninvasive means of diagnosis for cardiac myxomas (55). Thus, the diagnosis of small myxomas (less than 5 cm in size and asymptomatic) is becoming easier. We report here the experience of a French cardiovascular center in the clinical presentation of left atrial myxomas. The large number of patients in this series allowed us to perform an analytic, clinicopathologic study. Patients and Methods We reviewed the 112 cases of left atrial myxoma seen at 1 institution (Hôpital Louis Pradel, Lyons, France) over a 40-year period (1959–1998). In all cases the diagnosis was established before surgical removal. The patients’ medical records were reviewed, and data concerning clinical presentation, diagnostic methods, and postoperative course were collected. Histopathologic slides were reviewed for all cases by the same pathologist (RL). Other locations where cardiac myxoma occurred during that time period were the right atrium (15 cases), left ventricle (2 cases), and right ventricle (1 case). Follow-up information was obtained by contacting either the patients or the attending physicians, and a standardized questionnaire was completed for each case. Statistical analysis A chi-square test, or the Fisher exact test when required, was performed for all qualitative variables, and odds ratios (OR) with 95% confidence intervals (95% CI) were computed. For ordinal variables a Wilcoxon rank sum test was used. Data analysis was performed using SAS (Statistical Analysis System, SAS Institute Inc., Cary, NC). The variables studied in the statistical analysis were 1) sex and age, period of diagnosis (before or after echocardiography was available), delay to diagnosis (delay between the first symptoms and diagnosis), possible systematic (serendipitous) discovery; 2) size of the tumor (> or < 5 cm), tumor surface appearance (smooth or villous); 3) the main symptoms: cardiac (cardiac failure, malaise or syncope, chest pain or palpitations), embolic (cerebral, coronary, or peripheral artery), systemic (fever, weight loss, or pseudo-connective tissue disease signs), or neurologic (stroke, vertigo, epilepsy, coma, or other signs); 4) cardiac auscultation modifications (pseudo-mitral signs, “tumor plop”, nonspecific other signs); 5) possible chest X-ray abnormalities (left cardiac failure signs, cardiomegaly, pleural effusion, left atrium enlargement, visible myxoma when calcified), electrocardiogram (ECG) alterations (arrhythmias or conduction disturbances, ST-segment and T-wave shifts, left atrial hypertrophy, and nonspecific signs), or serologic test abnormalities (elevated erythrocyte sedimentation rate [ESR], anemia). Results Patient characteristics The study group included 72 women, (64% of the whole sample; median age, 53 yr; range, 23–84 yr) and 40 men (36% of the sample; median age, 58 yr, range, 5–77 yr). Forty-six patients (41% of the sample, 31 women, 15 men) were less than 50 years old, 47 (42%, 31 women, 16 men) were between 50 and 70 years, and 19 (17%, 10 women, 9 men) were older than 70. Age distribution was homogenous in men, but most female patients were between 40 and 60 years old (Figure 1).Fig. 1: Age distribution of 112 patients with left atrial myxoma.The clinical and laboratory features of left atrial myxoma in our series are presented in Table 1. The different frequencies of clinical and laboratory signs according to sex and age are detailed in Table 2. Male patients were more at risk than females for embolic complications and for neurologic symptoms; females were more at risk than males to develop systemic symptoms such as fever; younger patients (age 50 yr).TABLE 1: Clinical and laboratory features of left atrial myxoma (112 cases)TABLE 2: Frequencies of clinical and laboratory signs by sex and age*We divided the patients into 2 groups according to the pre-and post-echocardiography periods: 1) between 1959 and 1977, when the only diagnostic methods were angiocardiography and cardiac cathe-terization, only 14 patients (12.5%) underwent surgery; 2) since 1977, with 2-dimensional echocardiography use (transthoracic, then transesophageal), about 5 patients per year have undergone surgery for left atrial myxoma (98 patients, 87.5%). The sex ratio and age ranges are similar in these 2 patient groups, but other differences can be identified (Table 3). Before 1977, most patients were diagnosed on the basis of serologic or blood test abnormalities (particularly elevated ESR) and radiologic abnormalities; chest X-ray evidence of cardiac failure or left atrium enlargement was particularly prevalent in patients diagnosed before 1977 compared with those diagnosed after 1977 (p = 0.006 and p = 0.02, respectively).TABLE 3: Symptoms by year of diagnosis*Delay before surgery In our series, the time interval between symptoms onset and diagnosis (surgical removal) varied from 0 to 126 months (median, 4 mo). The median delay before surgery was 5.5 months before 1977, and 3 months after 1977; the difference is not significant. The median delay to diagnosis increased significantly when cardiac symptoms were present; there was no significant difference for the other symptoms (Table 4).TABLE 4: Delay to diagnosis by year and by principal clinical symptoms*Initial symptoms ( Figure 2) For 11 patients, the left atrial myxoma diagnosis was a mere chance, or serendipitous, discovery (“systematic findings” in Figure 2). Among these patients, in 9 cases echocardiography (8 cases) or computed tomography (CT) (1 case) was performed for another indication and allowed a diagnosis of myxoma. For 2 patients, echocardiography had been systematically performed during follow-up for surgery on a right atrial myxoma.Fig. 2: Initial symptoms of left atrial myxoma (112 cases).The most common initial symptoms of left atrial myxoma in our series were related to mitral valve obstruction: dizziness and occasionally syncope, palpitations, dyspnea, cough, pulmonary edema, or congestive heart failure were observed in 58 patients. Eight patients showed atypical paroxysmal clinical manifestations: chest pain, hemoptysis, limb claudication, thoracic noise, shortness of breath, or syncope when reclining. Embolic manifestations suggested myxoma in 18 patients. Constitutional or general systemic signs appeared as initial manifestations for 17 patients: myalgia, muscle weakness, arthralgia, fever, weight loss, fatigue, and Raynaud syndrome. Clinical features at diagnosis All patients presented with at least 1 or more symptoms of the classic triad: 1) obstructive cardiac signs; 2) embolic signs; and 3) constitutional or systemic manifestations (See Table 1). 1) Intracardiac obstruction signs occurred in 75 patients. Pulmonary edema or progressive congestive cardiac failure (dyspnea, orthopnea) were the most common symptoms (n = 48). Malaise or syncope occurred in 16 cases. Two patients experienced cardiac arrest before surgery and fully recovered after resuscitation. Other nonspecific cardiac symptoms were present in 34 patients: cough, thoracic pain, palpi-tations, myocardial infarction due to coronary embolism. Malaise, palpitations, or thoracic pain could vary with body postural changes. 2) Signs of embolism were present in 33 patients, either with 1 (n = 25) or several (n = 8) locations. Embolic locations were the central nervous system (n = 24), in 1 case in the retinal artery, the upper and lower extremities (n = 15), and the coronary arteries (n = 4). 3) Thirty-eight patients presented with systemic or constitutional symptoms. These symptoms were obviously nonspecific, including fever (n = 22), weight loss or fatigue (n = 20), and immunologic diseases mimicking symptoms such as myalgia, muscle weakness, arthralgia, or Raynaud syndrome (n = 6). 4) Other clinical presentations 4.1) Twenty-nine patients had neurologic symptoms, particularly transient or permanent motor or sensory neurologic deficiencies (n = 23), when cerebral emboli were present (stroke). Three of these patients developed multiple cerebral aneurysms, induced by cerebral emboli. Three patients had epileptic fits, or multilocular sclerosis mimicking symptoms. Six patients also suffered from other neurologic manifestations, such as vertigo or coma. One patient with streptococcal meningitis underwent surgery for a supposed antibiotic-resistant endocarditis suggested by echocardiographic findings, but surgery uncovered an incidental noninfected myxoma. 4.2) One patient had fever and positive blood cultures for Streptococcus viridans. 4.3) Three patients were investigated for liver abnormalities connected in fact with right cardiac failure. 4.4) For 3 patients, the main symptoms were abdominal pain or hemoptysis. Physical examination (cardiac auscultation) On cardiac auscultation 72 patients (64%) had abnormal findings, 18 (16%) of them with postural changes or with time examination modifications. These murmurs looked like significant mitral stenosis findings: apical diastolic or presystolic murmur (n = 60, 53%). A tumor plop was heard in 17 patients (15%), all before 1989. Other auscultatory features were changes in preexisting murmurs, gallops, or modification of the first (split) or second heart sound (n = 12, 11%). A significant association was observed between cardiac auscultation abnormalities and 1) systemic symptoms (fever, weight loss or fatigue); and 2) cardiac symptoms and signs (cardiac failure, etc.) (Table 5). Conversely, no association between auscultatory signs and embolic or neurologic symptoms was significant.TABLE 5: Correlations between various clinical abnormalities*Laboratory tests The most frequent laboratory finding was ESR (Westergren method) >20 mm/hr, found in 36 patients (see Table 1). Anemia (hemoglobin <12 g/dL in men, 10,000/mm3) or thrombocythemia (platelet counts >500,000/mm3) was present in 6 patients. The association between these serologic abnormalities and systemic manifestations was significant (see Table 5). However, there was no significant association between serologic signs and cardiac, embolic, or neurologic symptoms. Electrocardiogram abnormalities Two-thirds of the patients (n = 69) had abnormal electrocardiographic findings (see Table 1). Left atrial hypertrophy was the most frequent ECG sign (n = 39). Atrial arrhythmias (atrial fibrillation or flutter) or conduction disturbances were rare. Other electrocardiographic findings were ST-segment abnormalities (n = 24) or nonspecific ECG abnormalities (n = 27): ventricular hypertrophy, micro-voltage, extrasystoles. The association of ECG abnormalities with systemic manifestations and cardiac signs was significant (see Table 5). There was no significant association with embolic or neurologic symptoms. Chest X-rays Chest X-rays were abnormal in 56 patients (see Table 1). Nonspecific findings included pulmonary interstitial markings or congestive heart failure signs (n = 30), and nonspecific cardiomegaly (n = 35). Left atrial enlargement (n = 12), calcifications that made the tumor visible (n = 10), and pleural effusion were unusual (n = 8). The association of radiologic abnormalities with systemic and cardiac manifestations was significant (see Table 5). Chest X-ray abnormalities were significantly less frequent in patients with embolic or neurologic signs. Diagnostic methods Before 1977, all cases were diagnosed by angiocardiography with left heart catheterization (n = 14, 12.5%). After 1977, echocardiography was the usual diagnostic method (n = 96, 85.7%). Initially, only transthoracic M-mode echocardiography was available (Figure 3). Later, 2-dimensional imaging and particularly transesophageal echocardiography became the preferred methods in many cases. For 2 patients (1.8%), the diagnosis was established by CT or magnetic resonance imaging (MRI).Fig. 3: Transthoracic parasternal long-axis echocardiogram: A round myxoma is seen in the left atrium.Anatomic findings The pathologic diagnosis of myxoma was obtained after surgical tumor resection for all cases. On gross pathologic examination, the tumor diameter ranged from 1 cm to 15 cm. The precise size was available for 104 cases: it was greater than 5 cm in 62 myxomas, and smaller in 42 (in some cases tumors had been fragmented during surgery). The weight of the tumors ranged from 15 g to 180 g (mean, 37 g). In our series 85% of the myxomas were pedunculated with a short stalk (<1 cm), and 15% were sessile. Of the left atrial myxomas in our series, 80% arose around the septal fossa ovalis margin and 5% from the posterior left atrial wall, with only a few other locations: external wall (3%), superior wall (3%), infero-medial wall (3%), left auricle base (3%), posterior commissure (2%), and small mitral valve (1%). The myxoma surface was studied in 96 cases: it was friable or villous in 34% of these (n = 33) and smooth (Figure 4) in the other cases (n = 63, 66%). The less common villous or papillary (Figure 5) myxomas had a surface that consisted of multiple fine or very fine villous, gelatinous, and fragile extensions, with a tendency to fragment spontaneously (Figure 6).Fig. 4: Smooth-surface left atrial myxoma after formalin fixation.Fig. 5: Villous-surface left atrial myxoma..Fig. 6: Fine-surface villous fringe (magnification × 400).The histopathologic findings were based on the presence of characteristic myxoma cells embedded in an amorphous myxoid matrix, composed of an acid-mucopolysaccharide-rich stroma. The myxoma cells had a spindle or stellate shape, an ovoid nucleus, and a pink eosinophilic cytoplasm; they were scattered throughout the matrix. The surface of the tumor was covered by a single layer of flat endothelial-like cells. Calcification was observed in 9% of the cases. We differentiated histologic “active myxoma,” with a dense myxoma cell population, from “inactive myxoma,” with a sparse cell infiltrate and sometimes calcification or even ossification. Also, we distinguished different levels of histologic differentiation: 1) “normal differentiation” (Figure 7), with numerous rudimentary or well-formed vessels surrounded successively by cells then by condensed matrix; 2) “poor differentiation” (Figure 8), with many isolated, dispersed cells or lepidic cells gathered in short chains throughout the matrix. Sixty-four percent of the cases were “active” left atrial myxomas, half of them with poor and half with normal differentiation; 36% were “inactive” myxomas (two-thirds with poor differentiation). All recurrences were observed in patients with active myxoma and poor differentiation.Fig. 7: Left atrial myxoma with normal differentiation: Abundant extracellular matrix with myxoma cells grouping in rudimentary vascular formations.Fig. 8: Left atrial myxoma with poor differentiation: Dispersed or lepidic myxoma cells gathered in short chains.No significant association could be found between myxoma size (< or > 5 cm) and diagnosis circumstances (asymptomatic or symptomatic cases); villous surface; or presence of embolic, neurologic, systemic, or serologic symptoms or signs (Table 6). However, a myxoma size >5 cm was significantly associated with cardiac symptoms, auscultatory signs, and ECG and chest X-ray abnormalities. Diagnosis of larger myxomas paradoxically appeared to be more difficult, and the delay to diagnosis was shorter for small tumors than for large tumors (see Table 6).TABLE 6: Relationship of various clinical features to myxoma size (104 patients)*Villosity was associated significantly with neurologic symptoms, embolic complications, and cardiac auscultation abnormalities. However, there was no significant association between villosity and cardiac, systemic, serologic, ECG, or X-ray signs or symptoms; serendipitous discovery; or delay in diagnosis (Table 7).TABLE 7: Relationship of various clinical features to myxoma surface (96 patients)*Postoperative course All patients had surgery. Four patients (3.5%) died during the perioperative period: 1 patient died in 1967 during a second surgical intervention for a recurrence of myxoma 6 years after the first surgical removal; a 66-year-old woman, operated on in 1965 with severe cardiac insufficiency and instable hemodynamic function, died on the second postoperative day from acute renal insufficiency; a 5-year-old boy died in 1978 from acute mitral insufficiency by a mitral annulus rupture; and a 73-year-old man died in 1996 from bacterial meningitis concomitant with the myxoma, whereas the incidental tumor had been removed successfully. Only 1 patient needed a prosthetic mitral valve replacement: bacterial endocarditis was associated with the myxoma. The most frequent postoperative complication was transient arrhythmias (supraventricular arrhythmia or atrial fibrillation) in 29 patients (26%). A permanent cardiac pacemaker implantation for persistent bradycardia was necessary for only 2 patients. Follow-up During the postoperative course, 13 patients (11.5%) were lost to follow-up: foreign patients who returned alive to their native country and did not answer our questionnaire. Among the other 99 patients, 4 died and 95 (96%) were alive during the follow-up period. Patients who presented with peripheral arterial embolization fully recovered. The longest follow-up for patients alive with multiple cerebral aneurysms is 14 years (a woman suffering a stable cerebellum syndrome). In the present series, survivors were followed for a median of 3 years (range, 1 mo-17 yr). Recurrence Six patients (5%) had a recurrence of myxoma. Three patients with sporadic myxoma relapsed in the left atrium, (2.5, 8, and 17 years later, respectively). Three other patients had Carney complex. One of them suffered 2 recurrences in the left atrium, 16 and 26 months later, respectively. The other 2 patients with Carney complex had an initial myxoma in the right atrium; for 1 of them the recurrence was localized in the left atrium 3 years later, and for the other the recurrences were multiple in the left atrium (0.5 and 3.5 years later, respectively) and then in the right atrium 6.5 years later. Discussion We report here the largest series of patients with left atrial myxoma consecutively diagnosed in a single institution, to our knowledge. The patients presented over a 40-year period. Our 2:1 female-to-male ratio is consistent with other studies, in which this ratio varies from 2:1 to 3:1 (35,47,55). Myxomas can occur in all age-groups but are most frequent between the third and sixth decades of life (13,30,44,47). They occur predominantly in adult women (70%), although currently there is no explanation for this female predominance (perhaps due in part to hormonal influence). In our series, younger age is significantly associated with neurologic signs or cardiac auscultation abnormalities, and gender is associated with neurologic or embolic symptoms in men and systemic symptoms in women. Clinical features The clinical features of these tumors are determined by their location, size, and mobility; there are no pathognomonic signs and symptoms that suggest the presence of a myxoma (35,47,55). In a minority of cases, there are no symptoms at all (47) (10% in our series). However, there is no significant association between the size of the tumor (< or > 5 cm) and the circumstances of discovery (symptomatic or asymptomatic). Left atrial myxomas become symptomatic when they obstruct the mitral valve, embolize peripherally, or cause systemic effects: 1) Obstructive symptoms (valvular ball-valve obstruction) occur in 54%–95% of patients (35,55), 67% in our series. Many cases masquerade as mitral valve disease, but, conversely in mitral stenosis, atrial fibrillation and history of rheumatic fever are uncommon (47); only 9% of patients had arrhythmias in our study. Cardiac obstruction can be revealed by unusual, rapidly progressive congestive cardiac failure (dyspnea on exertion or orthopnea), or by malaise, syncope, or sudden death (due to complete mitral valve obstruction by the myxoma or coronary arteries embolism). The extent of valvular obstruction may vary with body position, and these symptoms’ postural changes are particularly suggestive of myxoma (35,47). Cardiac failure remains the most frequent manifestation (43% in our series). In our study, the presence of cardiac signs paradoxically increased the diagnosis delay, probably because one tends to believe that clinical symptoms are explained by another more common disease (myocardiopathy due to hypertension, ischemic processes, etc.). 2) Systemic emboli are the second arm of the classic triad, occurring in 10%–45% of myxoma patients (4,35,55), 29% in our study. More than two-thirds of myxomatous emboli migrate to the central nervous system (28,50) (24/33 in our series), but any arterial bed may be affected, leading to a great variety of symptoms and signs. Recorded cases document emboli in the upper and lower extremities, aortic saddle, coronary arteries, kidneys, liver, spleen, eye, skin, and more (47). Cerebral emboli may lead to numerous fusiform aneurysms, described as typical of cardiac myxomas (48), as in 3 patients in our study, whose long-term outcome was good (follow-up: 14, 12, 8 yr, respectively). We demonstrate that the presence of an irregular or friable (villous) surface is significantly associated with cerebral and peripheral embolisms. 3) Constitutional signs are the third arm of the classic triad (8,47,55). While these symptoms are rarely prominent, they may occur in up to 90% of cases (35). The prevalence is lower in our series (34%), perhaps because we studied a population at a cardiovascular institute. These signs and symptoms include myalgia, muscle weakness, arthralgia, fever, weight loss, and fatigue. They are obviously nonspecific and may occur in a variety of infectious (endocarditis or rheumatic fever), malignant, or immunologic diseases (rheumatoid arthritis, vasculitis, connective tissue diseases). Nonspecific cutaneous manifestations have also been reported in myxoma patients (18,31). Cardiac auscultation Cardiac auscultatory findings may vary between examinations, and may depend on body position. Apical presystolic or diastolic murmurs, suggesting significant mitral stenosis, may be heard in more than half of the patients (47,55), 54% in our series. The specific auscultatory finding of myxoma is called “tumor plop”: it is a protodiastolic heart sound of low frequency heard 0.08–0.15 seconds after the second heart sound (21,35). It may be confused with a third heart sound or a mitral opening snap. The tumor plop is uncommon, found in only 15% of patients in our series. We established a significant association between cardiac auscultation abnormalities and cardiac or systemic symptoms. Laboratory tests Serologic and hematologic tests are abnormal in only one-third of the patients (47,55), usually those presenting with systemic symptoms (a significant association was found in our study). The main but nonspecific laboratory abnormalities are anemia and elevated ESR, serum C-reactive protein, or globulin level. Anemia is generally normochromic or hypo-chromic; hemolytic anemia may occur by erythrocytes mechanical destruction on the tumor; polycythemia has also been reported. Less common findings are leukocytosis and thrombocythemia. Recent findings suggest that the production and release of a cytokine by the tumor itself may be responsible for systemic inflammatory and autoimmune manifestations (27). Interleukin-6 (IL6) has been implicated, with high serum levels of IL6 in patients with myxoma that return to normal after surgical removal (51). A correlation between the size of the tumor and the serum level of IL6 has also been suggested (54). Increased IL6 mRNA levels have also been found in myxoma tissue (52), probably explaining myxoma tissue infiltration in some cases by lymphocytes and plasma cells. Electrocardiogram findings ECG findings are nonspecific (35,47,55) but frequently observed (62% in our series). Left atrial hypertrophy occurs in one-third of patients, reflecting the hemodynamic alterations caused by the tumor. Atrial fibrillation is uncommon (less than 10% of cases) in contrast to the findings in mitral valve disease. We observed a significant association between ECG signs and the presence of cardiac or systemic symptoms. Chest X-rays Chest X-rays also reveal nonspecific features in half the patients (35,47,55) and are not helpful for diagnosis, except when the tumor is heavily calcified (9% in our study). Otherwise, a left atrium enlargement and signs of pulmonary congestion may be revealed. In our series, chest X-ray abnormalities were significantly associated with cardiac or systemic symptoms, but there were fewer radiologic signs when the myxoma was revealed by embolic or neurologic manifestations. In fact, cardiac signs or symptoms are more prevalent with large tumors, and one may hypothesize that friable, embolic tumors becoming symptomatic are diagnosed before the reach the size (about 5 cm) that leads to cardiac and radiologic signs. Our data suggest a positive association between small tumor size and embolic frequency (see Table 6). Diagnostic methods Echocardiography is the screening and diagnostic method of choice (36,47,55). It is accurate, reliable, noninvasive, and it does not entail any risk of tumor fragmentation and embolization (unlike angiography and cardiac catheterization). Transthoracic examination may be extended by the transesophageal approach (17,59). Transthoracic echocardiography is less invasive, with an excellent sensitivity, up to 95%(41,42), but transesophageal echocardiography sensitivity reaches 100%(17,39). Currently, the decision for surgery is generally based only on echocardiographic evidence of the disease; in our series angiocardiography has not been used since 1977. However, coronary arteriography in patients over 40 years old is usually required in order to rule out concomitant coronary artery disease (47). Other potential diagnostic methods include CT (40) and MRI (20,45). The advantage of CT and MRI over echocardiography is that they provide sectional views of mediastinal, pulmonary, and thoracic structures. They are also more accurate in assessing tumor attachment, endocardial site localization, and tumor stalk presence and size (45). Anatomic findings Anatomic data indicate that most left atrial myxomas arise from the atrial septum, usually near or around the fossa ovalis margin (14,19,55). Tumor mobility depends on the extent of attachment and on the stalk length. Gross appearance is generally white, gray-white, yellowish, or brownish with a polypoid, round or oval tumor, pedunculated or sessile. Tumor consistency is gelatinous (7), and the surface is either smooth or villous (66% and 34%, respectively, in our study). Smooth-surfaced myxomas usually appear with constitutional symptoms, while friable, irregular, or villous tumors usually embolize (30). In the literature (7,30), histologic findings such as fibrosis, calcification, and smooth surface are seen in older people, suggesting that they represent degenerative phenomena. In our series, there was no significant association between villosity and age. The size and weight of myxomas vary, but in our study, the mean duration of symptoms was paradoxically longer in patients with larger tumors. When, based on histologic appearance, we could distinguish active or inactive myxomas and normally or poorly differentiated myxomas according to the aspect of the cell infiltrate (33), we found that all recurrences actually occurred in patients with “active and poorly differentiated” myxomas. Many hypotheses regarding the origin of cardiac myxomas have been proposed (5,14,19). The current opinion of most authors is that myxomas are benign neoplasms of endocardial origin (24,32). It is no longer believed that myxomas are organized thrombi. Some myxomas may have a complex of pleomorphic cells that at first view may be considered malignant. However, the rare presence of multiple surface cell layers or mitotic activity is not associated with recurrence or any particular mode of presentation, and it is important not to predict an aggressive behavior on the basis of these atypical cells (7). Conversely, “myxoid imitators,” which are true cardiac sarcomas, must not be confused with myxomas (2). The cells giving rise to the tumor are considered to be multipotential mesenchymal cells, and immunohistochemical analysis (5,7) has shown that myxoma cells express endothelial markers (60) as tumor vessel cells (QBEnd = CD34 and factor VIII-related antigen). Tumor cells are vimentin-positive, and some may be smooth-muscle-actin positive. Positivity for S-100 protein and cytokeratin (scarce cases with glandular structures) is rarely observed, as is the histocytic marker KP-1 (7,24). Burke (7) showed that endothelial differentiation was best demonstrated by CD34 positivity, which is also a sensitive endothelial marker for Kaposi sarcoma. This corroborates the concept that myxomas arise from primitive stromal cells having the capacity to