Angiosarcomas are malignant tumours derived from endothelial cells and comprise <2% of all soft tissue sarcomas.3
In adults approximately 25% of primary cardiac tumours are malignant and one third of these are angiosarcomas. This cardiac tumour has been seen slightly more often in men in most series, and arises predominantly during the fourth to fifth decades of life.4
It usually affects the right side of the heart, mainly the atrium. Cardiac manifestations vary depending upon the size and position of the tumour, and are non-specific. Most angiosarcomas are metastasised at the time of clinical presentation, but cutaneous metastasis are infrequent.2
We described the case of a 72-year-old man who presented with cutaneous metastasis on both hands. To our knowledge only two comparable cases have been reported. Pomper et al
depicted a 43-year-old man whose tumour manifested as soft tissue and cutaneous metastasis.5
CT scan disclosed a mass in the right atrium and the biopsy of the mass showed a high grade angiosarcoma. Val-Bernal et al
reported on a 51-year-old patient in whom multiple cutaneous metastasis were the initial presentation of the disease.6
The initial skin biopsy was diagnosed as metastatic undifferentiated sarcoma. The finding of a left atrial mass occurred only at autopsy. Immunohistochemical study of the tumour tissue revealed a pure epithelioid angiosarcoma.
One of the problems in the diagnosis of angiosarcoma is histopathologic recognition. The microscopic findings typically demonstrate irregular anastomising vascular channels lined by swollen atypical and proliferative endothelial cells.4
An epithelioid cytomorphology of tumour cells may be seen focally, but purely epithelioid angiosarcomas are rare.6
Immunohistochemical findings include reactivity for endothelial markers such as CD31, CD34 or Fli-1 as well as for factor VIII related antigen. Epithelioid variants may exhibit positive staining with cytokeratin epithelial markers. Panels of antibodies are therefore mandatory to avoid misdiagnosis.
The radiological diagnosis of the cardiac tumour is based on the recognition of an intracavitary mass or filling defect within the heart. Transthoracic echocardiography can help in the diagnosis but has a limited sensitivity. Transoesophageal echocardiography, CT and MRI appear to be more sensitive. In addition to tumour location, CT can assess the extent of the tumour and evaluate for possible metastasis. PET may be useful to help stage the disease accurately.
The treatment protocols for cardiac angiosarcomas include surgery, chemotherapy, and radiation therapy, alone or in combination. Surgery remains the mainstay of management of cardiac tumours, although success is limited by early recurrence and spread.7
In patients with unresectable tumours and/or metastatic disease the treatment options are sometimes limited to palliative chemotherapy and radiation, generally with a poor response. Aoka and colleagues showed the potential value of carbon-ion radiotherapy in the control of a primary cardiac angiosarcoma.8
Interleukin-2 was found to be useful in the treatment of one patient.9
More recently, Nakamura-Horigome and colleagues demonstrated the effectiveness of combination therapy with docetaxel and radiotherapy.10
Cardiac transplantation may have a role in the future for patients with localised disease.11
Several chemotherapeutic drugs have been used in the treatment of angiosarcomas, mainly doxorubicin, ifosfamide, cyclophosphamide, vincristine, and dacarbazine. However, most of the published experience consists of case reports. There are no randomised trials in this context and the only available data consists of a few small series of angiosarcomas and primary cardiac sarcomas. In a series of 21 patients diagnosed with a primary cardiac sarcoma between 1964 and 1989, seven underwent surgical resection alone, one chemotherapy alone, and 13 surgery followed by doxorubicin based chemotherapy. Median survival was significantly longer in the 11 patients who could be completely resected (24 versus 10 months in all others). Two year survival was only 14% for the entire group.1
Skubitz and colleagues reported a small series of patients with angiosarcoma originating at several sites: eight treated with paclitaxel and six with pegylated liposomal doxorubicin. Five of the paclitaxel treated patients had major responses; the remaining three had progressive disease. Of the six doxorubicin treated patients, five showed clinical benefit: three had a partial response and two had stable disease; only one patient had progressive disease. This study is noteworthy for illustrating the activity of liposomal doxorubicin in angiosarcoma.12
Pegylated liposomal doxorubicin has demonstrated good results in soft tissue sarcomas in general and has been shown to be highly effective (with reduced toxicity) in patients with Kaposi sarcoma in particular, a tumour composed of abnormal endothelial cells with potential similarities with angiosarcoma.13–18
These aspects, taken together, are good indicators of the possible efficacy and safety of liposomal doxorubicin in angiosarcomas, and justified our choice of this drug. Knowing that the overall prognosis of this tumour is dismal, with a median survival time of only 9–12 months after diagnosis,19
we observed an excellent response to systemic chemotherapy with liposomal doxorubicin.
Our case is unusual in three main aspects:
- The diagnosis was revealed by cutaneous intravascular metastasis to the hands.
- The primary tumour, an uncommon epithelioid variant, was located in the left atrium, which is also infrequent.
- The response to systemic chemotherapy with liposomal doxorubicin was protracted, without noticeable toxicity.