Ann Thorac Surg 2001;71:1438-1441
© 2001 The Society of Thoracic Surgeons
Original article: cardiovascular
Total orthotopic heart transplantation for primary cardiac rhabdomyosarcoma: factors influencing long-term survival
Daniel Grandmougin, MDa,*,
Georges Fayad, MDa,
Christophe Decoene, MDa,
Annie Pol, MDa,
Henri Warembourg, MDa
a Department of Cardiovascular Surgery, Anesthesiology, Cardiologique Hospital, Lille; and Department of Pathology, Calmette Hospital, University of Lille, Lille, France
Accepted for publication January 5, 2001.
* Address reprint requests to Dr Grandmougin, Service de Chirurgie Cardiovasculaire, 5ème étage, Hôpital Cardiologique, Bd Pr Leclercq, 59 037 Lille-cedex, France (Email: d-grandmougin{at}chru-lille.fr).
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Abstract
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Background. Primary cardiac sarcomas are uncommon and rare, with an unequal distribution in the population. A dismal prognosis is usually admitted that is related to a high propensity to develop distant metastasis with survival rarely exceeding 2 years. We report a case of a patient with a primary cardiac rhabdomyosarcoma characterized by an exceptional long-term survival after surgical treatment by a total orthotopic heart transplantation. From this limited experience, we reviewed factors that may influence survival to optimize therapeutic strategy.
Methods. A 33-year-old man was found to have a 10-cm primary cardiac rhabdomyosarcoma located in the right atrium and extending to the atrioventricular groove; therefore, resection was not possible. Since no metastases were detected, the patient was scheduled for urgent cardiac transplantation, which was performed after adjuvant radiotherapy.
Results. Postoperative outcome was uneventful and the patient is still alive, with regular follow-up, at 102 months.
Conclusions. In a case of primary rhabdomyosarcoma, heart transplantation, despite immunosuppressive therapy, can provide long-term survival and can be considered for selected patients after rigorous analysis of predictors of survival.
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Introduction
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Although described for the first time in the 16th century [1], primary cardiac tumors still remain a rare clinical entity, characterized by a low incidence varying, according to different autopsies series, from 0.0017% to 0.28% [2–4]. Of these, sarcomas of the heart are uncommon with an incidence accounting for 4% of all cardiac tumors in children and 18% in adults [5]. The most frequent histologic subtypes, in order, are sarcomas without any differenciation, angiosarcomas, leiomyosarcomas, and finally rhabdomyosarcomas [4]. Despite the therapeutic measures available, the survival of patients with cardiac sarcomas is limited and ranges from 6 months to 2 years [3, 5, 6]. We present the case of a 33-year-old man with exceptional long-term survival reaching 102 months. He was diagnosed with a primary cardiac rhabdomyosarcoma with local pleural and pericardial extension, and was successfully treated by heart transplantation after adjuvant radiotherapy for tumoral reduction. This clinical experience retrospectively led us to analyze predictive patterns of relapse and survival.
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Patient and methods
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In November 1990, a 33-year-old man was referred to our department for the surgical management of a right atrial tumoral mass. The patient was otherwise healthy and had no medical history except a recent increasing dyspnea related to pericarditis. On admission, physical examination was normal, heart sounds were not muffled, and no low voltage QRS complexes in the electrocardiogram (ECG) were present. Chest roentgenogram showed a marked enlargement of the cardiac silhouette exclusively located in the right inferior border without any increased pulmonary vasculature or cardiac calcifications (Fig 1). Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) confirmed the presence of a moderate pericardial effusion and disclosed a 10 x 7 cm noncapsulated mass located in the right atrium, almost filling all the cavity, partially extending to the superior vena cava, widely to the atrioventricular groove, and irregularly protruding through the tricuspid valve. Computed tomography (CT) showed a 10 cm right atrial located mass extending to the low portion of the superior vena cava and the atrioventricular groove and probably infiltrating the right ventricular wall. A right anterolateral pericardial extension was also suspected. Structure of the mass after contrast administration strongly evoked a central tumoral necrosis. Neither visceral metastasis nor retroperitoneal adenopathy was observed. A radionuclide bone scan was normal. Creatine kinase MB concentrations were within normal limits.
With the diagnosis of a strong presumption of primary cardiac tumor, a standard initial study was performed by cardiac-gated magnetic resonance imaging (MRI). Spin-echo sequences were used with T1-weighted axial, coronal, and sagittal sections along the thorax. T1-weighted spin echo (SE) images confirmed the presence of an heterogenous nonpediculated tumor infiltrating the wall of the right atrium toward the superior vena cava junction and widely to the atrioventricular groove. The invasion of the right ventricle and tricuspid valve could not be excluded although valve motion was echographically normal. The mass of solid characteristics was well delineated both in the axial and sagittal sections. Its signal intensity was intermediate and similar to that of the adjacent myocardial tissue. T2-weighted sequences showed an enhancement of the lesion. Neither mediastinal infiltration nor vascular compromise was demonstrated (Fig 2). All previous imaging elements were strongly suggestive of a malignant tumoral process as a primary cardiac rhabdomyosarcoma.
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Fig 2. Parasagittal section of the left hemithorax obtained by magnetic resonance imaging (T1-weighted spin echo image). Anteriorly the lesion protrudes into the pericardial space (arrows). The invasion of the right ventricle cannot be excluded.
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Because of the well-established poor prognosis and no other detected tumoral locations, an attempt at surgical resection was made through a median sternotomy. Pericardium was found particularly thickened with close adhesions on the right atrium and the anterior side of the right ventricle. The tumoral mass was easily located widely filling the right atrial cavity with parietal retraction, meaning an infiltration, with an obvious extension toward the superior vena cava, the atrioventricular groove, and also the initial portion of the right ventricle; therefore resection was not possible. Histologic diagnosis of rhabdomyosarcoma was made by biopsies with immunohistochemistry studies, showing a poor mitosis index and a moderate cellular differenciation resulting in a low-grade aggressive tumoral process (Fig 3). The tumoral cells were positive for vimentin, desmin, myoglobin, and α-actin and negative for smooth muscle actin, S-100 protein, keratin, factor VIII (von Willebrand), and EMA (epithelial membrane antigen). Pericardial and pleural biopsies adjacent to the right cavities were positive for a local extension.
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Fig 3. Histologic appearance. Tumoral cells (Tu) diffusely infiltrate the myocardium and extend (arrows) toward the right coronary artery (RCA). (Hematoxylin and eosin, original magnification x 20.)
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Results
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Postoperative outcome was uneventful, and the patient was transferred in January 1991 to the department of oncology for discussion about a therapeutic alternative between chemotherapy and surgery combined with adjuvant radiotherapy. Because of no disclosed metastasis, two surgical options were considered: local resection depending on significant tumoral reduction and heart transplantation according to donor availability and obviously related to lack of tumoral progression. Thus as the first step in our approach, adjuvant radiotherapy was delivered as 45 Gy targeted on the tumor enhanced with additional reduced-beam 10 Gy. Tolerance was excellent and degree of response was quantified with regular MRI examinations. The patient was then regularly followed up for 1 year, within which time a moderate mass reduction (9 cm) was observed with no intracavitary progression, as was emphasized by normal ECG tricuspid motion.
The patient remained healthy without any cardiac manifestations. Detection of metastases and adenopathies was negative, leading us to decide in favor of a heart transplant as a potential but also uncertain curative solution. Therefore, the patient was scheduled as an urgent recipient on a waiting list, and finally underwent in March 1992 a successful total orthotopic heart transplantation involving a high section of the superior vena cava. Because of previous positive biopsies, a large right-side pleural and pericardial resection including the right phrenic nerve was added (Fig 4). Closure of the pericardial window was performed with a patch of Gore-Tex (W. L. Gore and Associates, Flagstaff, AZ) to prevent a cardiac luxation in the right pleural cavity. Hospital outcome was free of events and the patient was discharged 21 days postoperatively. He is still alive, healthy, and free of disease with regular follow-up at 102 months.
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Fig 4. Macroscopic view of the heart showing tumor (Tu) filling the right atrium, surrounding the right coronary artery (black arrows) and extending toward the atrioventricular groove (AGr). Tumoral necrosis areas (white arrows) are obviously seen.
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Comment
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Tumors of the heart remain a rare clinical entity [2–4] and primary cardiac sarcoma is rare, accounting for 8% of all primary cardiac tumors resected [7]. The most frequent primary cardiac sarcomas, in order, are sarcomas without any differenciation, angiosarcomas, leiomyosarcomas, and finally rhabdomyosarcomas [7]. Rhabdomyosarcoma is most common in infancy and early childhood with a second peak in the sixth and seventh decades [5]. It has no predilection for a specific cavity, and multiple locations are frequent (60%). However, it seems that the chamber of origin is associated with the histologic subtype: cardiac angiosarcomas tend to arise in the right cavities, thus delaying symptoms; in contrast, nonvascular cardiac, sarcomas (leiomyosarcoma, rhabdomyosarcoma, liposarcoma, synovialsarcoma, malignant fibrous histiocytoma) tend to develop in the left chambers [8]. Our case contradicts these previous data as it was a nonvascular sarcoma located in the right cavity and occurring in the third decade.
Because of a low incidence and nontypical various symptoms, diagnosis of primary cardiac rhabdomyosarcoma was typically missed before cardiac imaging, surgery, or autopsy. Clinical manifestations vary considerably depending upon the histologic type, size, and location of the tumor, the degree of involvement of the myocardium, and eventual metastatic sites. It is remarkable, however, to observe that whatever the malignant tumor, pericardium is involved in 50% of patients, usually by direct tumoral extension, frequently leading to pericardial effusion [9], which was the single observed sign in our case. Paraneoplasic symptoms have been reported to be associated with cardiac rhabdomyosarcoma including hypertrophic osteoarthropathy, polyarthritis, amyloidis, neurofibromatosis, eosinophilia, and bilateral mammopathy [10]. Isotalo and colleagues [11] have related an interest in detection of increased serum creatine kinase MB and cardiac troponin T concentrations as the result of release of metastatic locations.
Primary cardiac rhabdomyosarcoma with nonspecific clinical manifestations and telemetry findings may often remain undetected for a long time, especially in cases of low evolution subtypes, and diagnosis is often made at autopsy [3]. At present, information obtained by ECG, CT, and MRI are considered sufficient for surgical planning. Even if echocardiography (TTE or TEE) has become the most frequent imaging method for the diagnosis of cardiac tumors, important limitations are presented, such as the difficulty of evaluating tumoral extension in adjacent mediastinal structures, and propagation into extracardiac structures through the pericardium, resulting in difficulty in distinguishing between a primary cardiac tumor and a mediastinal tumor infiltrating the heart. Furthermore, the acoustic impedance of an intracavitary mass may be similar to that of the blood and differentiation between a tumor and a thrombus may be difficult. CT scans routinely performed usually provide sufficient information by optimizing echographic data, but nevertheless require contrast administration and exposure to ionizing radiations. In contrast, MRI as a noninvasive technique offers several undeniable advantages, including discrimination of signal intensity of the blood with respect to other tissues and optimal delineation of the vessel walls and cardiac chambers, helping to determine whether the patient is a potential candidate. In the same way, precisely evaluating the regression of tumoral volume in response to alternative or adjuvant treatments to surgery may contribute to modifying the chemotherapy or radiotherapy protocols and also permits the possibility of discussing surgical treatment (resection/heart transplantation) [12] of a tumor for which surgery had initially been rejected. In our experience, this latter possibility was the determining factor in deciding to perform heart transplantation, as tumoral regression without any local progression or metastatic locations was definitively assessed by successive MRI scans. Because of the different behavior of the tissues according to the values of the proton concentration and relaxation times, MRI may provide, in a few cases, information about histologic nature, as in lipomatous tumors, but with no ability to distinguish between malignancy and benignity. T2-weighted sequences, in our case, provided serious arguments in favor of a malignant process with an enhancement meaning heterogenous structures related to tumoral necrosis [7]
The etiology of cardiac rhabdomyosarcoma remains elusive, and the rare occurrence of such tumors may explain the almost complete absence of etiologic studies. Finally, whatever the genesis of the tumor, diagnosis of cardiac rhabdomyosarcoma is certified by histologic and immunohistochemistry studies. Myoglobin and actin striated muscular fiber stainings specific to striated muscle differentiation are very helpful in cases of rhabdomyosarcoma. Importance must be given to prognostic factors such as the histologic tumoral subtype, for vascular cardiac sarcomas carry a poor prognosis compounded by the high frequency of distant metastasis at diagnosis, irrespective of primary sites and histologic grade [5, 13]. Several authors have also demonstrated a relationship between histologic features such as high mitotic activity, tumor necrosis, degree of cellular differentiation, extensive myocardial and pericardial extension and a dismal outcome [3, 13]. A retrospective analysis of 1,100 patients with resected sarcoma reported an overall survival of 14% at 5 years for angiosarcoma as opposed to 70% for patients with myxoid liposarcoma [3].
Therapeutic management must mainly integrate histologic subtypes and involves chemotherapy, radiotherapy, and surgery. Angiosarcomas are usually characterized by a high propensity to develop local relapse and distant metastases and are often resistant to conventional cytotoxic agents contributing to a poor prognosis, justifying the use of anthracyclin. However, even if polychemotherapies may optimize the rate of therapeutic response, they do not increase the survival rate. When metastatic locations are certified, doxorubicin must be electively chosen [14]. In contrast, nonvascular cardiac sarcomas are definitely known to be quite less aggressive, meaning a larger therapeutic scale. Survival prognosis is better, probably depending on the optimal possibility of resection and emphasized by the usual potential for local progression, the main source of relapse. Thus, several therapeutic strategies can be evoked. Surgical resection is often possible and neoadjuvant chemotherapy can be efficiently incorporated in that configuration [15]. However, adjuvant radiotherapy is commonly mandatory to preclude local relapse. The optimal dose usually reaches 50 Gy targeted on the tumor. When the limit of surgical resection is not histologicaly well delineated, this previous dose is currently enhanced with an additional 10 Gy delivered according to a reduced beam. Moreover, radiotherapy is also an adjuvant option when tumoral regression is expected, allowing an optimal secondary surgical resection.
Actually, the best option for very carefully selected patients theoretically remains an orthotopic cardiac transplant. It must integate the resulting immunosuppressive therapy as a prognostic factor of local relapse and distant metastases. Thus, lack of metastases must be confirmed. In contrast, local extension such as pericardial location may not exclude the possibility of transplantation. Although long-term survivors are known to be extremely rare [16], our limited experience represents an exceptional long-term survival and demonstrates that heart transplantation including, in that specific case, a local pericardial and pleural resection, is consistent with long-term immunosuppressive therapy without any relapse.
In conclusion, despite usually an admittedly dismal prognosis related to the development of local or distant relapses, cardiac transplantation can be mainly proposed for selected patients with no vascular cardiac sarcoma and no obvious distant metastases. Local and limited extracardiac extension may not be considered as a definitive contraindication but requires mandatory surgical resection to preclude relapse.
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Top
Abstract
Introduction
