Asian Cardiovasc Thorac Ann 2002;10:8-11
© 2002 Asia Publishing EXchange Pte Ltd
Cardiac Myxoma and Myxosarcoma: Clinical Experience and Immunohistochemistry
Liu Sha, MD,
Wang Zhe, MD1,
Chen An Qing, MD1,
Zhou Guang Hua, MD1,
Jiang Zhen Bin, MD1,
Xiao Ming Di, MD
Department of Cardiovascular Surgery Shanghai First People's Hospital Shanghai, People's Republic of China
1 Department of Cardiovascular Surgery Shanghai Institute of Cardiovascular Diseases Fudan University Zhongshan Hospital Shanghai, People's Republic of China
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Liu Sha, MD Tel: 86 21 6324 0090 Ext. 3031 Fax: 86 21 6324 0825 email: drliusha{at}yahoo.com Department of Cardiovascular Surgery, Shanghai First People's Hospital, 85 Wujin Road, Shanghai 200080, People's Republic of China.
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ABSTRACT
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From January 1978 to February 1999, 120 patients (42 males and 78 females) with cardiac myxoma (115) or myxosarcoma (5) underwent surgical excision or biopsy. There were 5 early postoperative deaths (mortality, 4.2%). Seventy-three survivors were followed up for 0.75 to 20.25 years (mean, 9.42 years); they comprised 4 myxosarcoma patients who all had recurrence or metastasis, and 69 myxoma patients who had no evidence of recurrence or metastasis. Neither familial myxoma nor Carney complex was found. The 5 cases of myxosarcoma and 18 randomly selected cases of myxoma were evaluated for proliferative activity, metastatic potential, and oncogene products by immunohistochemistry. The expression of p53 and Bcl-2 was similar in both groups. Overexpression of proliferating cell nuclear antigen and low expression of nm23 in myxosarcoma are consistent with the high rate of recurrence and metastasis of this tumor. Surgical resection of sporadic myxoma is a safe and effective treatment with satisfactory early and long-term results. However, the prognosis of myxosarcoma is still disappointing. Regular echocardiography and chest radiography or computed tomography are necessary for early detection of recurrence or metastasis of myxosarcoma.
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INTRODUCTION
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Primary cardiac tumors occur much less often than metastatic masses. The incidence of primary cardiac tumors is between 0.0017% and 0.03% based on autopsy series.1 The majority of these masses are benign, and myxoma is the most common. The results of surgical excision of cardiac myxoma are satisfactory, whereas recurrence and metastasis of cardiac myxosarcoma are frequent. Radical treatment of cardiac myxosarcoma is extremely difficult. This report summarizes our 20-year experience in 120 patients with a primary cardiac tumor.
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PATIENTS AND METHODS
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From January 1978 to February 1999, 115 patients with cardiac myxoma and 5 with cardiac myxosarcoma were operated on at Fudan University Zhongshan Hospital and Shanghai First People's Hospital. There were 42 (35%) males and 78 (65%) females; their mean age was 42.4 years (range, 8 to 68 years) at the time of operation. The locations of the tumors are summarized in Table 1
. None of the patients had a family history of myxoma. The majority had cardiac manifestations including congestive heart failure in 79 (66%), dyspnea and shortness of breath in 80 (67%), palpitations in 64 (53%), syncope in 22 (18%), and fever in 14 (12%); 5 patients were asymptomatic. Peripheral arterial embolization occurred in 5 patients (4%) and embolization of the central nervous system in 9 (8%). Most patients (92, 77%) had signs detected at cardiac examination, the most common abnormality being a diastolic murmur heard at the apex. In 68 cases (57%), there were abnormal but nonspecific electrocardiographic findings. Chest radiographs also demonstrated nonspecific changes such as cardiomegaly, specific chamber enlargement, or pulmonary edema, especially in patients with congestive heart failure. Pre-operative diagnosis was established by echocardiography. Postoperatively, formalin-fixed and paraffin-embedded specimens confirmed the diagnosis pathologically.
Surgical removal of the tumor was performed as soon as possible after the diagnosis had been established. Some patients needed an emergency operation because of the severity of their symptoms. The same surgical technique via a median sternotomy with cardiopulmonary bypass and hypothermia was used in all cases. To prevent embolization, the heart and the mass were manipulated with caution, as such masses are fragile. Radical resection of the tumor and its pedicle, along with an adjacent cuff of endocardium, was the basic principle of excision. The chamber where the tumor had originated was thoroughly explored for debris and additional tumors. The other chambers were explored if possible. As myxomas frequently originate from the atrial septum, the atrial septum was partially excised in some patients. The resulting atrial septal defect was closed by suturing or repaired with a Dacron or autologous pericardial patch. Irrigation of the chambers with cold saline solution was performed to eliminate any possible tumor fragments. The tumors ranged in size from l.5 x 1.0 x 0.5 cm to 13.5 x 5.5 x 7.5 cm and weighed from l.5 to 97.5 g. Postoperative pathologic examinations diagnosed myxoma in 115 patients and myxosarcoma in 5.
Five cases of myxosarcoma and 18 randomly selected cases of myxoma were evaluated for proliferative activity, metastatic potential, and oncogene products of p53 and Bcl-2 by immunohistochemistry. For this, 4-µm sections of paraffin-embedded specimens were stained with the following antibodies: proliferating cell nuclear antigen (PCNA), nm23, p53, and Bcl-2 (Dako Ltd., Glostrup, Denmark).
The survivors were followed up by means of question-naires and telephone calls during 1999. They underwent clinical examination, echocardiography, electrocardio-graphy, and chest radiography. Forty-two patients were lost to follow-up after discharge because of change of address; 73 survivors were contacted.
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RESULTS
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There were 5 early deaths (mortality, 4.2%) between the 1st and 4th postoperative days among patients with myxoma. The causes of death were arrhythmia (such as intractable ventricular fibrillation) in 3 and multiorgan failure in 2. Radical resection of the tumor was performed in 118 patients. Only 3 of the 5 patients with myxosarcoma had complete resection of their tumors, and the results after discharge were disappointing. Details of these 5 cases are listed in Table 2.
In contrast, the long-term results of myxoma resection were very good. Sixty-nine of the patients who survived myxoma resection were followed up for 0.75 to 20.25 years (mean, 9.42 years), of whom 30 had more than 10 years of follow-up. Neither metastases nor recurrence were found, even in 2 patients who had tumor cells remaining at the edge of the resection area, as noted on pathologic examination (echocardiography detected no intracardiac recurrence during 7.25 and 8.58 years of follow-up). Familial myxoma and Carney complex were not found in this series. During follow-up, 55 patients (80%) were in New York Heart Association functional class I, 8 (12%) were in class II, and 6 (9%) were in classes III to IV. The most common complication was arrhythmia in 26 patients, including atrial fibrillation and atrial flutter in 7 (1 had atrial fibrillation preoperatively, which persisted postoperatively), atrial or ventricular premature beats (7), bradycardia (4), supraventricular tachycardia (2), and ventricular tachycardia (1). Three patients underwent pacemaker insertion at the ages of 58, 62, and 78 years. There was one late death (at 17.8 years postoperatively) in the myxoma group. This patient died suddenly at the age of 66 years in a local hospital and her death was attributed to myocardial infarction. Her tumor resection procedure and recovery had been uneventful, and no evidence of tumor recurrence was found during hospitalization prior to her death.
The immunohistochemical staining results for PCNA and p53 were expressed as a positive cell percentage of the total cells, and the results with nm23 and Bcl-2 were expressed as grade minus to ++++ (Table 3). The positive cell percentage for PCNA in the myxosarcoma group (mean, 59%) was higher than that in the myxoma group (mean, 17.2%), and the expression of nm23 in myxosarcoma was significantly lower compared to myxoma, while the results of p53 and Bcl-2 staining in both groups showed no significant differences.
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DISCUSSION
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Cardiac myxoma is encountered in every age group and there is predominance of females. In this series, the female to male ratio was 1.875:1. The embolization rate was 11.7% (14/120); this is similar to the occurrence of embolization reported previously (10% to 20%).2–4 As neither recurrence nor metastasis occurred during the follow-up of patients in the myxoma group, both early and long-term results were considered satisfactory. The prognosis for these patients can be regarded as very favorable.
However, the presence of a tumor in the right atrium was generally associated with a poor prognosis. As Table 1
shows, 60% (3/5) of myxosarcomas originated from the right atrium (or both atria) while only 8% (9/115) of myxomas originated in the right heart. Analysis of 127 cases of primary cardiac tumor, including other types of tumor, during the same period, demonstrated that only 2% (2/109) of left heart tumors were malignant, whereas 33% (6/18) of right-sided or bilateral tumors were malignant (p < 0.01 by chi-squared test). Mean age at diagnosis in the myxosarcoma group was younger than that of the myxoma group (36.0 versus 42.6 years, p < 0.01 by Student's t test). Consequently, attention must be paid to younger patients and those with right heart tumors, in order to differentiate malignancies from myxoma before the operation and to detect recurrence and metastasis early postoperatively.
Echocardiography is the most important diagnostic modality. It allows preoperative diagnosis with a fair degree of accuracy regarding size, shape, attachment, and mobility. Preoperatively, 21 patients were diagnosed only as having a heart tumor, and 2 cases of myxosarcoma were misdiagnosed as myxoma. It is difficult to make a correct diagnosis preoperatively in cases of myxosarcoma. Surgical excision of the tumor must be carried out as soon as possible because of the high risk of valvular obstruction and systemic embolization. A bilateral approach together with removal of adequate margins has been advocated to exclude the presence of multifocal tumors, and thereby eliminate the potential for recurrence and minimize the risk of perioperative embolization.5,6 Nevertheless, we used a unilateral approach and encountered only one case of postoperative embolization. Bjessmo and Ivert7 reported a similar result; they performed surgical resection in 63 patients through a unilateral approach during a period of 40 years, and encountered no perioperative embolization.
Postoperative echocardiography has been recommended for detecting recurrent myxoma. Because of the rarity of recurrence of myxoma with the current resection technique, it may not be necessary to perform echocar-diography frequently thereafter, except in patients with multifocal or familial myxoma, or Carney complex. None of our patients had these conditions, which may explain the low recurrence and metastasis rate. However, for patients with myxosarcoma, echocardiography must be performed frequently because of the tendency to recur. Two of the 4 patients who underwent surgical resection in this series suffered a recurrence within 10 months; all 4 had metastasis. Our data suggest that myxosarcoma is prone to metastasize to the chest wall and lung. Since recurrence and metastasis were the causes of the patients' deaths, frequent postoperative chest radiography or computed tomography and echocardiography may be helpful for early detection and treatment. It can be seen from this study that surgical resection alone is un-satisfactory in cases of myxosarcoma. Perhaps combined therapy is needed.
PCNA has often been used to investigate cell proliferation.8,9 The high expression of PCNA indicates that myxosarcoma has high proliferative activity. Such results are in agreement with the microscopic findings in myxosarcoma, which show cellular pleomorphism and mitotic activity. Increasing evidence indicates that nm23 has anti-metastatic activity, suggesting that reduced expression of nm23 may be associated with metastasis.10,11 The low expression of nm23 in myxosarcoma is consistent with its high metastatic potential. Immunostaining results for p53 and Bcl-2 in 10 cases of myxoma reported by Suvarna and Royds12 are similar to ours. However, present data are not sufficient to determine the roles of p53 and Bcl-2 in the occurrence of cardiac myxoma and myxosarcoma.
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Acknowledgments
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We thank Dr. Wang Xiu Nan, Department of Pathology, Zhongshan Hospital, and Dr. Lu Hong Fen, Department of Pathology, Shanghai Cancer Hospital, for their technical assistance.
Presented at the 9th Annual Meeting of The Asian Society for Cardiovascular Surgery, Nagoya, Japan, March 28–30, 2001, and awarded the Travel Award.
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ABSTRACT
INTRODUCTION
