Well-differentiated liposarcomas are low-grade, slow-growing, locally aggressive malignant mesenchymal neoplasms which are usually diagnosed after the fifth decade of life1 and are the second most frequent malignant soft tumor among all soft tissue tumors. They primarily occur in the retroperitoneum, buttocks, vulva, neck, and mediastinum, usually recur locally and rarely metastasize to distant sites including the heart and pericardium.2 The incidence of primary cardiac liposarcomas is extremely low as well.3 The diagnosis of cardiac involvement is seldom made antemortem because small lesions are usually silent as in not helpful in achieving a diagnosis. 3 If they remain undiagnosed, they may lead to sudden death, due to congestive heart failure or cardiac tamponade.
MATERIAL AND METHOD
Only 1 case of an undiagnosed primary cardiac liposarcoma has been recorded in the previous 10 years (2001–2011) in the archives of the Laboratory of Anatomic Pathology of National and Kapodistrian University of Athens.
A 67-year-old man was found dead on the floor of his residence by his wife. According to her, he had not complained recently of chest pain, dyspnea, or other symptoms arising from the heart. In his medical history, no disease or medical treatment was reported, although 2 decades before he had undergone a routine surgery for gallbladder removal.
A complete autopsy was performed the day after his death. The external examination of the body revealed congestion of the head and neck and cyanosis of the lips. No injuries or other remarkable pathological findings were reported. The examination of the thoracic cavity revealed an enlarged heart. After the removal of the pericardium, a yellowish-white, firm and not encapsulated tumor 15 cm in diameter was found on the anterolateral surface of the left ventricle. The heart weighed 760 g, all cavities seemed enlarged and the walls of the ventricles were thickened. The longitudinal axis was 20 cm and the transverse was 17 cm. The thickness of the right ventricle was 0.8 cm, of the left ventricle 2.4 cm, and of the intraventricular septum 1.8 cm. The coronary arteries did not present any histopathological deterioration and all cardiac valves were normal. The dissections of the ventricles showed expanded infiltration of the tumorous mass of the anterolateral wall of the left ventricle and the epicardium, as well as two thirds of the wall of the intraventricular septum (Fig. 1).
The lungs seemed congested, edematous, and free of metastatic lesions. From the macroscopic examination of the rest of the internal organs, no other remarkable pathological changes were reported. Mediastinal lymph nodes were negative for metastatic infiltration. Sections from all organs were taken for histological examination, whereas biological fluids such as blood, urine, bile, and vitreous fluid were collected for toxicological analysis.
The microscopic examination of the tumor showed fat cells mixed with fibrous tissue and lipoblasts (Fig. 2). Immunohistochemically, adipocytes and lipoblasts reacted positively for vimentin and S-100 protein, whereas desmin and CD34 were negative. We concluded that the tumor consisted of a well-differentiated primary liposarcoma of the epicardium, with extension into the underlying myocardium.
Careful examination of soft tissues did not reveal any other primary lipomatous tumor. Toxicological analysis was negative for alcohol or drug abuse.
Liposarcoma is the second most common soft tissue sarcoma after malignant fibrous histiocytoma, contributing to 16% to 18% of all soft tissue sarcomas.2,4 Primary cardiac liposarcoma is an extremely rare tumor which is found in only approximately 1% of primary malignant cardiac tumors.5,6 Primary cardiac tumors have an autopsy frequency of 0.001% to 0.28%.7 The frequency of primary heart mesenchymal tumors found during autopsies is estimated as high as 0.0017% to 0.28% and most of them (approximately 75%) are benign—myxomas, rhabdomyomas, lipomas, and fibromas. Among malignant nonepithelial neoplasms of the heart, the most frequent are teratomas, rhabdomyosarcomas, and fibrosarcomas in children up to 16 years old and angiosarcomas in adults. By contrast, metastatic involvement of the heart and pericardium is far more common (20–40 times),4 occurring in 1.5% to 21% of all autopsies performed on patients.7 The most common tumors that metastasize to the heart are of bronchial and breast origin.2
Atypical lipomatous tumors/well-differentiated liposarcomas are composed entirely or in part of an adipocytic proliferation (both lipoblasts and fat cells), showing significant variation in cell size, and at least focal nuclear atypia in both adipocytes and stromal cells.1,2 Liposarcoma has been classified by Enzinger and Winslow into 4 pathological subtypes as follows: well differentiated, myxoid, round cell, and pleomorphic.3 Liposarcomas malignant potential varies greatly according to its different histologic classes.8 The well-differentiated form accounts for approximately 40% to 50% of all tumors, and its malignant potential is usually low.9 The tumor described in the case presented consists of a well-differentiated liposarcoma as well. The myxoid variety is characterized by a slow growth and consists of proliferating lipoblasts in varying stages of differentiation, a delicate plexiform capillary pattern, and myxoid matrix.5 It is usually found in the lower extremities, particularly the thigh and less frequently in the retroperitoneum.3 Round cell and pleomorphic liposarcomas are aggressive tumors that are characterized by infiltrative growth, early metastasis to the lungs, and frequent local recurrence after surgical resection.10
Differential diagnosis of other cardiac entities includes arrhythmogenic right ventricular dysplasia, which also belongs to fat-containing cardiac lesions, and computed tomography-based diagnosis should be coestimated with results from other examinations. It should be kept in mind that liposarcoma belongs to tumors characterized by weak dispersion of cells, so the diagnosis based on cytological examination of neoplastic cells in body cavity effusions may be delayed.6
When primary cardiac liposarcoma is reported in the literature, it is usually described as arising from the right chambers of the heart, particularly the right atrium5 less frequently from the mitral valve, the pulmonary veins, or the aortic root.3 However, when secondary involvement of the heart by liposarcoma has been described, it seems to infiltrate the right ventricle.2 Although metastatic lesions of extracardiac liposarcoma are more common than the development of primary cardiac liposarcoma, the rate of such metastasis to the heart remain extremely low.11 Enterline et al12 studied 53 cases of liposarcoma and listed metastases, in order of frequency, to lung, liver, lymph nodes, brain, peritoneum, and skeletal system. Metastases to the heart did not occur in this series. Myxoid liposarcoma seems to metastasize most frequently to the lungs and bones, as well as to the extra pulmonary tissue, such as the retroperitoneum, abdominal wall, pleura, diaphragm, breast, colon, and rarely to the mediastinum.10 When cardiac metastasis occurs, the time interval between the first presentation and the pericardial metastasis ranges from 7 to 25 years.10
Noncardiac tumors, including liposarcoma, may invade the heart and pericardium by means of lymphatic or hematogenous dissemination, local extension, or a transvenous route. The predominant route is retrograde spread through lymphatic channels in the mediastinum to the heart, producing small tumor implants on the epicardial surface of the heart. Hematogenous metastases to the myocardium and epicardium occur via the coronary arteries or, less commonly, by implantation of cancer fragments carried through the vena cava. The transvenous route of tumor spread relies on extension of tumor thrombus into the right atrium via the superior or inferior vena cava or a central mass extending into the left atrium via the pulmonary veins. Finally, direct extension of tumors into the heart and pericardium almost never include liposarcoma. In any case, metastatic involvement of the heart and pericardium may go unrecognized until autopsy.13
Similar to other tumors of the heart, most cardiac liposarcomas remain undiagnosed until symptoms of cardiac constriction develop.3 Symptoms are related to the location and size of the tumor. Pericardial effusion may cause impairment of cardiac function which occurs in approximately 30% of patients. Symptoms of pericarditis attributed to pericardial infiltration can include dyspnea, arrhythmia, signs of congestive heart failure, and arterial embolism.5,12 Murmurs, as observed with atrial myxomas, may also occur.14 There have also been a few reports of cardiac tamponade and compression of the right atrium.9 In our case, death occurred because of congestive cardiomyopathy due to huge epicardial liposarcoma.
When the tumor involves only the endocardium, symptoms and signs are usually lacking except for congestive heart failure due to mechanical disturbance. However, heart failure and ventricle gallop occur earlier if the myocardium is involved, with or without outlet obstruction. This can occur along with arrhythmias13 or even cardiac rupture9 and when the mass involves the left ventricle, anginal pain and dyspnea can occur.4 Cardiac lipomas sometimes also grow into the atrial septum, causing lipomatous hypertrophy, disturbed venous return, or vulvar regurgitation.9
Diagnosis using advanced imaging methods is necessary when symptoms are observed, because a routine x-ray graphic examination of the chest does not allow visualization of the metastatic tumor unless it is so bulky as to alter the size and configuration of the heart. Two-dimensional echocardiography is the first choice of modality for diagnosis of cardiac tumors, whereas computed tomographic scanning and magnetic resonance imaging are useful adjuncts, revealing possible mediastinal extension.14
Although surgical intervention is rarely beneficial for malignant cardiac tumors, in selected patients whose primary tumor is well controlled and progressing slowly, and who display with no evidence of widespread disease, partial surgical resection of the tumor is the preferred treatment.2 The mortality rate, however, remains high (12%–40%).10 Chemotherapy and radiotherapy are only adjunctive therapies and are not established as standard treatments.5
Primary cardiac liposarcomas are extremely rare tumors. If they go undiagnosed, they provoke symptoms such as congestive heart failure, tamponade, or even sudden death. When they arise, patients should undergo all possible examinations to evaluate differential diagnosis and apply the appropriate treatment according to contemporary trends.
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