Recurrence of benign tumors is unusual. Myxoma is the most common benign tumor (represents almost 50%) of the heart; though benign, recurrence has been observed in 2%-3% of patients.1 Recurrence or metastasis of myxomas is not rare and can lead to malignancy and they are therefore considered as latent malignant tumor;2,3 the recurrent rate has been estimated as 1%-3% in patients with sporadic myxomas and 12% in patients with familial myxomas.4 But the mechanism of recurrent myxoma has not been clearly understood yet. Once recurs, the re-operation for recurrent myxoma is more difficult and more effort is warranted for treatment. So comprehensive diagnosis and complete surgical resection are necessary to prevent recurrence and alleviate patients' suffering. Up to now five patients with recurrent cardiac myxoma have been treated in the Department of Cardiothoracic Surgery, Changhai Hospital. Here in this paper we described these recurrent myxoma cases in details and analyzed the possible risk factors, diagnosis and therapy for the recurrence, so as to prevent recurrent cardiac myxoma and advocate a new clinical classification of the recurrent tumors.
From October 1994 to December 2008, a total of 107 patients with cardiac myxoma underwent surgery in our center. During a follow-up of 1-15 years, the recurrence was observed in 5 cases, with the recurrence rate being 4.67%. Among the 5 cases, four were females and one was male; they had an age range of 33-50 years old. The time interval from initial operation to tumor recurrence varied from 5 months to 6 years.
A 33-year-old female represented with “sudden extremity numbness and left radial pulse disappearance” on November 7, 2004. Magnetic resonance imaging (MRI) revealed multiple intracranial infarctions; echocardiography revealed left atrial myxoma. The operation was subsequently performed through the median stenotomy via a biatrial approach. During the operation the tumor looked like grapes, attaching to the lower interatrial septum and invading part of the posterior fibrous ring of mitral valve. Excision of the tumor was complete and postoperative recovery was uneventful; echocardiography revealed no residual tumor. Histologically, the myxoma was confirmed to have a benign character (Figure 1). One year later (on November 16, 2005), echocardiography revealed a mass in the left atrium, suggesting a recurrence of the left ventricle myxoma. Reoperation was performed and the tumor had a size of 3 cm × 4 cm × 3 cm, protruding into the posterior papillary muscle. To achieve a complete resection, excision was accomplished including the mitral valve and involved subvalvular tissues. The mitral valve was replaced with bioprosthetic valve. Histology examination confirmed the diagnosis of myxoma. Regular postoperative follow-up review was performed. Four years later (on January 1, 2009), echocardiography showed recurred myxoma in the right ventricle. Three-dimensional reconstruction of blood vessels indicated an occlusion in the right common carotid artery and focal stenosis in the right common iliac artery. Reoperation was performed to remove the right ventricular myxoma. The recurrent tumor, with a size of 2 cm × 1 cm, was located in the trabecular carneae (pectinate muscle) of the right ventricle, adjacent to which three 0.2 cm diametric satellite lesions were noted, and a globular tumor with a 0.2 cm diameter attached to the right atrial appendage was found. Histology confirmed the suspected recurrence of myxoma (Figure 2). The postoperative period was uneventful, and the tumor has not recurred to date at 2 years' follow-up.
A 42-year-old female represented with palpitation and progressive chest tightness. Echocardiography examination revealed left atrial myxoma; excision of the tumor was then performed. Two masses were found in the left atrium during operation; both were originated from the posterior wall of the left atrium between the opening of left pulmonary vein and the left atrial appendage, measuring 8.0 cm ×5.5 cm × 5.0 cm and 1.0 cm × 0.5 cm × 0.3 cm. Frozen section confirmed a diagnosis of myxoma. Six years later, the patient developed “chest tightness and shortness of breath”. Echocardiography suggested recurrent left atrium myxoma. Re-operation was done and a cluster of tumors were found located on the anterior and posterior atrial surface, with the largest one measuring 4 cm × 3 cm × 2 cm. The tumors were firm, sessile and closely adhered to atrial tissues. So both the tumor and the adjacent endocardium were excised together. The mass was extirpated completely, and pathologic examination showed low grade malignant myofibroblast. The patient died of heart function failure at 1 year after re-operation.
A 48-year-old male complaining “chest tightness, cough and shortness of breath for a month” was admitted to our department (on July 17, 2007). Echocardiography showed bi-atrial myxoma. Cardiac myxoma excision was performed through biatrial approach. At operation, a giant mass with the size of 9.5 cm × 8.0 cm × 5.0 cm was found in the left atrium (Figure 3), with the base located in the lower part of the interatrial septum, close to the left posterior atrial wall. The other round tumor measuring 1.5 cm × 1.5 cm × 1.0 cm was found in the right atrium, with the base located in the center of the interatrial septum. The interatrial septum was therefore removed and then repaired with autologous pericardium. Histology examination revealed benign cardiac myxoma (Figure 4). Echocardiography on the second postoperative year (on March 6, 2009) revealed recurrent cardiac myxoma in the left atrium. Reoperation was performed subsequently. The mass was observed with a size of 3 cm × 2 cm × 2 cm, with the bases of the tumor located in the lower part of the interatrial septum in the left atrial surface. Postoperative pathological results indicated left atrial myxoma (Figure 5). A family history of such myxoma was noted. Follow-up examination found no residual mass. He had an unremarkable postoperative course 2 years after operation.
A 46-year-old female presented with exertional chest tightness associated with dyspnea, palpitation. A right atrial myxoma was diagnosed by echocardiography. The operation was performed through right atrium excision. A7 cm × 8 cm × 5 cm ovals mass was found in the left atrium, the base of which was in the interatrial septum, adjacent to the fossa ovalis. Frozen section revealed a myxoma. Echocardiography at 2-year postoperative follow-up revealed a recurrent myxoma in right atrial. Reoperation was performed and the tumor was noted with a size of 4.5 cm × 4.5 cm × 3.0 cm, the base of which was at the bottom of the interatrial septum. Postoperative pathological results revealed myxoma. No history of myxoma was noted. The postoperative course was unremarkable.
A 43-year-old female presented with palpitation and chest tightness; echocardiography showed “a giant left atrial myxoma”. The operation was done through biatrial approach and a 7 cm × 3 cm tumor was found at the posterior wall of the left atrium. Histology showed left atrium myxoma. Six months later, the patient became aware of chest tightness and shortness of breath again. Echocardiography indicated a recurrent left atrial myxoma with the size of 7.6 cm × 2.3 cm in the left atrium, moving into the left ventricle via the mitral orifice during diastole. Full-body bone emission computed tomography (ECT) and cranial CT scan were performed in case of malignancy, and no obvious abnormalities were observed. The suspected recurrent tumor was confirmed and excised completely through biatrial approach. The tumor, measuring 10 cm × 6 cm × 4 cm, was covered by smooth intact envelope, occupying 70% of the left atrium, which had a wider attachment to the left atrial posterior wall between the left veins and right ones. The tumor and partial left atrial posterior wall were excised, and the left atrial defect was reconstructed by autologous pericardium patch. The recovery of the patients was satisfactory. Postoperative pathological results revealed a low grade fibromyxoid sarcoma in the left atrium. The patient remains well and free of tumor recurrence.
Myxoma is by far the most frequently found primary cardiac tumor. A greater percentage (75%) is located in the left atrium.5, 6 Of these, 90% originate from an area in the atrial septum near the fossa ovalis.1,7 Right atrial myxomas are uncommon, being 3-4 times less frequent than those in the left atria.1,6 Biatrial tumors are present in approximately 2.5% of the total cases.6,7 Cardiac myxomas arising from two different heart chambers are extremely rare, being more common in the familial cases.8,9 To understand the risk factors of recurrent myxoma is vital to improve the therapy, decrease recurrence, and ameliorate prognosis. Atypical primary sites, insufficiency excision, metastasis, multicentricity and familial inheritance are all risk factors of recurrent myxoma after surgery.10
It is summarized that the following 5 characters are the risk factors for the recurrence of cardiac myxoma: (1) Atypical primary site: the primary sites of the 5 cases were not from the typical predilection site (near left atrium, atrial septum, fossa ovalis), instead they were from the lower atrial septum, right atrium, posterior wall of the left atrium, and both atriums, suggesting that the primary sites of myxoma have a correlation with the recurrence. (2) Specificity primary forms: it is believed that the myxoma is ellipse, single site and pedicel; while our cases presented multiple sites, pedicels, and even grape-like appearance. Cardiac myxoma is jelly-like, soft and frangible, disintegrates and falls off with systole and blood ablation. (3) Familial inheritance: our study suggests an association of familial history and recurrent myxoma, with one case having a complex familial myxoma which is associated with lesion of skin, pituitary, adrenal gland or lacteal gland. The recurrent rate of complex familial myxoma is reportedly 22%.1 One case in our group exhibited obvious familial inheritance without genetics confirmation. (4) Malignant feature: though cardiac myxoma belongs to benign tumor, the recurrent cardiac myxomas have a certain malignant potential. Two cases in our group had recurrence and had malignant transfer, so did in Kusumi's study.11 Which type of myxoma is liable to become malignant is not clear yet. (5) Early distant metastasis and plant: one patient in our group metastasized to the brain before surgery, and then recurred in the left ventricle, which we considered caused by metastasis and plant or fall off during surgery; and then a second recurrent tumor was found in the right ventricle, which may be caused by the implantation after blood flowing from the left ventricle to the right ventricle. Previous studies have also reported patients with recurrent myxoma complicated with distant metastasis to the intracalvarium, liver and splanchnocoele; the definite mechanism is not clear.
Based on the above five points, we advocate a clinical classification of “typical” and “atypical” cardiac myxoma. The typical myxoma refers to the tumors located at the left atria with single pedicle, rooted at or around the fossa ovalis, and without abnormal genetic factor; the atypical myxomas originate from multiple chambers or atypical primary sites, with familial inheritance, associated with clear gene mutation, or with malignant tendency.
The clinical managements of primary and recurrent myxomas require detailed pre-operation diagnosis, intra-operative exploration, and radical resection.
Preoperative imaging diagnosis must be detailed. The development of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE) has facilitated the diagnosis of myxomas, avoiding the need for invasive techniques. TOE and TTE can display the location, origin, size, shape, attachment, mobility, valve compromise and hemodynamic consequences of the tumor.5 TOE and TTE are valuable for diagnosis of myxomas, but it is difficult for both of them to distinguish myxomas from valvular vegetation or left atrial thrombus, and the small masses are often missed. Real-time three-dimensional (3D) TEE is increasingly used in general clinical practice. Both Tolstrup et al12 and Culp et al13 reported that 3D TEE accurately identified cardiac myxomas and provided detailed morphologic description and location of the tumors. MRI is another important non-invasive diagnostic tool that provides detailed information on tissue characterization, metastasis, and degree of invasion, which can help the differential diagnosis of these masses. In addition to imaging diagnosis, genetic testing for atypical myxoma may prove to be the best predictor of the likelihood of recurrence and close postoperative follow-up is necessary.14
Surgical excision is the only effective way to treat cardiac tumor and must be done as soon as possible after diagnosis for preventing recurrence, which grows faster and falls off easily due to obstruction or embolization. The mortality reached 8% in delayed surgery cases.15 Atypical myxoma should be excised completely with a large range and inspected carefully of all heart chambers during surgery, so as to prevent missed diagnosis and its recurrence. It is generally believed that myxoma originates from subendocardial mesenchymal tissue and develops into the chamber, but sometimes it can infiltrate the myocardium, making it impossible for complete excision and leading to recurrence in situ.
The decision of incision should take the location, size, number and involved structures into consideration. The tumor in privileged site (pulmonary vein opening, entrance of the superior or inferior vena cava) should be excised completely and fulgurized to eliminate the infiltration cells. The excision should be with a large scope and the defect should be repaired with autologous pericardium or prosthesis patch.16 The replacement of mitral valve or palliative resection is necessary for tumors in the valve and difficulties in redevelopment. Centofanti et al17 believe surgery is essential since it can identify the property of the tumors, remove the mechanical obstruction, and prolong life of patients. Anand et al18 excised the thyroidea, peripheral lymph nodes, metastatic tumor of the right ventricle and conducted 131I radiotherapy for a patient with right ventricle metastatic thyroid follicular, who recovered totally and without recurrence during 1 year follow-up. The endoscope-assisted surgery is becoming an exciting technique for mitral valve repair and tumor resection;19,20 more cases with recurrent cardiac myxoma have received this novel strategies and gained satisfactory outcomes.21,22
In summary, recurrence of cardiac myxoma is commonly seen, and it is important to eliminate the possible causes of recurrence, which may guide the diagnosis and treatment for recurrent cardiac myxomas. Surgical resection is the most important therapy for recurrent myxomas. Postoperative follow-up is of vital importance in cases of atypical myxomas.
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