Realdo Columbus first identified the presence of a heart tumor in 1559. However, it was not until 1934 that the first clinical diagnosis of a primary heart sarcoma was reported. Primary cardiac neoplasms are extremely rare. The autopsy incidence is around 1 in every 500 cardiovascular surgical cases. The majority of tumours are benign (75%). Of the remaining 25% of tumours that are identified as being malignant, cardiac sarcomas comprise 95% of cases. While surgery is the primary method of treatment, combination with chemotherapy and radiation is usually preferred. Casha reported a case of primary cardiac angiosarcoma with familial incidence. The report described a 24-year-old woman with primary cardiac angiosarcoma who had a father that died at the age of 31 with the same tumor; histological and immunohistochemical features were identical.
There have been 4 known reports of familial cardiac angiosarcomas since then. The patients had a mean survival time of 4 months compared to a 5-year survival rate of 14% in patients with sporadic angiosarcoma. Angiosarcoma is most commonly found in the right atrium and frequently interferes with neighbouring structures, resulting in congestive heart failure, pericardial effusion, and cardiac tamponade. The rarity of this diagnosis has made it difficult to standardize therapy, but surgical treatment is usually preferred. The exact benefits of chemotherapy and radiation are still being investigated.
Anatomy and Histology
Primary cardiac angiosarcoma is an endothelial cell tumor. Nearly 90% of tumours occur in the right atrium as a multicentric mass. It is characterized by an aggressive and permeating growth within the surrounding myocardial wall, but can project into or fill the atrial chamber and invade the vena cava and tricuspid valve. Less than 5% occur in the left atrium or ventricles. Though the pericardium is commonly involved in right-sided angiosarcoma.
Histologically, angiosarcomas consist of highly variable endothelium-lined channels. Common characteristics include anastomosing vascular channels, which vary in size based on frequency of mitoses, solid spindle cell areas with minimal or no apparent vascular spaces, foci of endothelial tufting, and lack of calcification. Cardiac angiosarcomas have well differentiated vascular channels mixed with poorly differentiated solid areas of epithelioid cells and spindle cells. Tumours have been reported to have spindle cell proliferation that resembles Kaposi’s sarcoma. The tumor cells have hyperchromatic, pleomorphic nuclei with frequent mitoses. There are 3 patterns seen histologically: a vascular area with anatomizing channels, a solid high-grade epithelioid area, and a spindle cell Kaposi-like area sarcoma.
Early diagnosis of primary cardiac angiosarcoma remains elusive. Generalized symptoms and rarity of the disease often prevent clinicians from including this disease in an initial differential diagnosis. However, with new imaging technology, early detection of cardiac neoplasms has improved. The rate of ante mortem tissue diagnosis has improved from only 4 of 41 cases in a 1968 review, to 50% in 1986, 70% in 1992, and 82% in 2000. Physical examination, ECG, and cardiac catheterization are all used in evaluation.
Imaging studies like CT, nuclear magnetic resonance, ultrasound, and echocardiography have emerged as preferred methods. Metastases are often widespread at the time of diagnosis. The lungs are the most common site of metastatic disease, but the liver, lymph nodes, bone, adrenal glands, and spleen may also be involved. They postulated that the higher incidence may be due to greater dissemination of malignant cells into the systemic circulation with tumor dissection. In addition to echocardiography, CT should be used to gain a better understanding of the cardiac tumor anatomy and to check for systemic metastasis.
Cardiac MRI is better than CT in characterizing the soft tissue and distinguishing between different abnormalities specific to the myocardium. Cardiac MRI can help distinguish between thrombi and tumours in the cardiac cavity. This results in localized nodular areas of increased signal intensity, dispersed among areas of low to intermediate signal intensity, to produce a cauliflower-like appearance. The second pattern is based on diffuse pericardial infiltration, in which linear contrast material enhancement along vascular pools demonstrates a sunray appearance. Pericardiocentesis and tissue biopsy are also used for diagnosis. Pericardial fluid cytology is unreliable and should not be used. Malignant cells are very rarely found in the bloody fluid, even when the tumor has invaded the pericardium.
The prognosis for primary cardiac angiosarcoma is poor, with a mean survival of 3.8±2.5 months without surgical resection. There have been no clear prognostic factors. Tumor grade, mitotic rate, age, sex, growth pattern, margin status, and proliferation rate have not shown any consistent pattern regarding prognosis. However, the study was limited by its small sample size. Therapy is not standardized and the exact benefit of adjunctive chemotherapy and/or radiation is still unknown.
The challenges lie in the rarity of this disease, the commonly advanced stage at diagnosis, and its aggressive course. However, given the tumor’s high fatality rate, an aggressive approach utilizing a multimodality regimen seems to be favored. Thus, a number of different treatment combinations have been utilized, with varying results. There have been reports of survival times ranging from 12 to 30 months in patients with various combinations of surgery, chemotherapy, radiation, and/or transplantation. Wide resection has been universally accepted as the main treatment modality. Wide resection provides a definitive histological diagnosis and relieves severe mechanical obstruction of cardiac output.
Studies have reported difficulty in achieving complete resection of tumours with negative margins. In cases in which complete resection is possible, patients commonly experience local recurrence. Although it appears that most angiosarcomas are resistant to chemotherapy and radiation, aggressive treatment does seem to contribute to reducing tumor size. Chemotherapy and radiation are important in treatment of angiosarcomas because of the high probability of metastases. Cisplatin, cyclophosphamide, dacarbazine, doxorubicin, ifosfamide, mitomycin-C, paclitaxel, and vincristine are commonly prescribed agents in standard chemotherapy.
Due to their aggressive and invasive behavior, early diagnosis is imperative for prolonged survival. Unfortunately, this tumor is often overlooked due to its minimal incidence and broad-spectrum of clinical manifestations. If there is any degree of suspicion, clinicians should not discount cardiac angiosarcoma in the initial differential diagnosis. Early diagnosis can prevent tumor progression and metastasis, and can also provide an opportunity to assess different therapeutic combinations and modalities and develop a more standardized treatment regimen for cure or long-term palliative care.
For now, surgical resection seems to provide the best chance for prolonging survival. Further investigation of endothelial angiosarcoma markers may provide insight into the etiology of tumor genesis at its site of primary origin and may also provide a more clear and precise profile of angiosarcoma. Until then, a broad-spectrum immunohistochemistry panel should be used and results should be assessed and combined with other diagnostic modalities to aid in the diagnosis and treatment of angiosarcoma.