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BMJ Case Rep. 2010; 2010: bcr08.2009.2157.
Published online Feb 19, 2010. doi:  10.1136/bcr.08.2009.2157
PMCID: PMC3027499
Unexpected outcome (positive or negative) including adverse drug reactions
Extended remission of metastatic epithelioid angiosarcoma of the heart with liposomal doxorubicin
Carlos Marques Candeias,1 Inês Luís,2 Joana Ribeiro,2 Luís Costa,2 Luís Soares de Almeida,3 Manuel Marques Gomes,3 Luísa Barreto,1 Luís Brito-Avô,1 and José Luís Ducla-Soares1
1Santa Maria Hospital, Medicine, Avenida Professor Egas Moniz, Lisbon, 1649-035, Portugal
2Santa Maria Hospital, Oncology, Avenida Professor Egas Moniz Lisbon, Lisbon, 1649-035, Portugal
3Santa Maria Hospital, Dermatology, Avenida Professor Egas Moniz, Lisbon, 1649-035, Portugal
Correspondence to Carlos Marques Candeias, carlosmarquescandeias/at/
Angiosarcoma is the most common primary malignant tumour of the heart. It is a rare and aggressive neoplasm that almost always has a short and fatal evolution. By the time it produces symptoms it has usually progressed to a mass causing haemodynamic compromise. Initial presentation with metastatic disease is unusual. We report the case of a 72-year-old man who presented with painful skin lesions on both hands. The skin biopsy was diagnosed as intravascular metastasis of epithelioid angiosarcoma. Body computed tomography scan disclosed a solid mass in the left atrium. The tumour was judged unresectable and the patient was treated with systemic chemotherapy, consisting of liposomal doxorubicin, which resulted in a complete clinical response. The patient remains free of disease after 48 months of follow-up. The excellent clinical evolution of our patient verifies that liposomal doxorubicin may be effective in the treatment of these tumours and significantly prolong patients’ lifespan.
Angiosarcoma is the most common primary cardiac malignancy. It is a rare tumour associated with a very poor prognosis.1 Most patients present with symptoms and signs related to the primary tumour. Initial manifestation as metastatic disease is uncommon.2 We describe the case of a patient with primary cardiac epithelioid angiosarcoma who presented with cutaneous intravascular metastasis to the hands and had an outstanding response to chemotherapy.
A 72-year-old white man presented with a 3 month history of painful erythematous and nodular skin lesions on both hands. Past medical history was relevant for cigarette smoking (30 pack-years) and arterial hypertension clinically under control. One year before the patient had undergone resection of a pulmonary nodule; pathology disclosed bronchiectasis with no evidence of neoplastic tissue. Physical examination revealed multiple erythematous cutaneous papules and nodules (<0.5 cm) on the palmar surface of the hands. The fingers showed swelling, with increased local temperature, and were tender (fig 1). The remaining physical examination was normal. Initial diagnostic work-up, including laboratory tests, vascular Doppler ultrasound of the arms, transthoracic echocardiogram, and body computed tomography (CT) scan, showed no abnormalities.
Figure 1
Figure 1
Right hand of patient reveals multiple erythematous cutaneous papules and nodules. The fingers showed swelling, with increased local temperature, and were tender.
Because of the unclear nature of the disease process, one of the cutaneous nodules was biopsied. Microscopic examination revealed superficial dermal vessels obliterated by thrombi composed of large epithelioid cells (fig 2). Immunohistochemically, the cells were positive for the endothelial markers CD31 and Fli-1 (fig 3), and pan-cytokeratin as well as cytokeratin 8/18 (CAM 5·2); and were negative for CD20, CD 79a, CK5/6, LYVE-1 (lymphatic endothelial cell marker). The skin biopsy was thus diagnosed as intravascular metastasis of epithelioid angiosarcoma.
Figure 2
Figure 2
Haematoxylin and eosin stain showing superficial dermal vessels obliterated by thrombi composed of large epithelioid cells (×100 and ×400).
Figure 3
Figure 3
Sections showing positive staining for CD31 and Fli-1, respectively, in the neoplastic cells, indicative of the vascular origin of the tumour.
The body CT scan was repeated and revealed a solid intracavitary left atrial mass (18.6×15.6 mm) arising from the lateral atrial wall adjacent to the mitral valve. Transoesophageal echocardiography further delineated that the mass protruded slightly into the lumen of the left atrium, not causing any obstruction to the flow across the mitral valve. Other cardiac structures were free of abnormalities. A positron emission tomography (PET) scan revealed no evidence of distant metastasis other than to the hands.
The cardiac tumour was considered unresectable and, given the patient’s haemodynamic stability and extent of the disease, the decision was made to proceed with systemic chemotherapy, consisting of liposomal doxorubicin 50 mg/m2 every 4 weeks, in a total of 11 cycles. The patient had a complete clinical response to chemotherapy. Magnetic resonance imaging (MRI) of the heart showed a striking shrinkage or the tumour mass. In the last scans only a residual image remains, which could be interpreted as fibrosis (fig 4). After 48 months of follow-up the patient remains free of disease.
Figure 4
Figure 4
Magnetic resonance images of the heart demonstrating shrinkage of the tumour mass with chemotherapy (scans obtained 2 and 45 months after diagnosis, respectively).
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.1318 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.
Learning points
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.
Competing interests: None.
Patient consent: Patient/guardian consent was obtained for publication.
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