Updated: Aug 18, 2022
  • Author: Maria Belén Carsi, MD, PhD, FRCS; Chief Editor: Edwin Choy, MD, PhD  more...
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Practice Essentials

An angiosarcoma (AS) is an uncommon malignant neoplasm characterized by rapidly proliferating, extensively infiltrating anaplastic cells derived from blood vessels and lining irregular blood-filled spaces. Specialists apply the term angiosarcoma to a wide range of malignant endothelial vascular neoplasms that affect a variety of sites. Angiosarcomas are aggressive and tend to recur locally, spread widely, and have a high rate of lymph node and systemic metastases. The rate of tumor-related death is high. See the images below.

This is a gross specimen from a proximal humerus b This is a gross specimen from a proximal humerus bone angiosarcoma. These tumors generally are red and hemorrhagic. Although the tumor has not extended into the adjacent soft tissues, cortical erosion is evident. The patient was treated with wide excision and reconstruction with a humeral spacer. The patient's next oncologic recheck showed multiple lesions, including a large destructive lesion in the right ilium extending to the sacroiliac joint and the right sacral ala. Also noted was an upper thoracic vertebral lesion, multiple indeterminate pulmonary nodules, extensive hepatic metastases most marked in the left lobe, and an indeterminate left adnexal mass.


Angiosarcomas arising at different sites and in different organs have some distinct features. Angiosarcomas may occur in any region of the body but are more frequent in skin and soft tissue. Angiosarcomas also can originate in the liver, breast, spleen, bone, or heart. [1, 2, 3, 4]

The Angiosarcoma Project performed whole-exome sequencing of 47 tumors and found recurrent mutations of genes including KDR, TP53, and PIK3CA. PIK3CA-activating mutations were observed predominantly in primary breast angiosarcoma, while angiosarcoma of the head, neck, face, and scalp was associated with a high tumor mutation burden and a dominant ultraviolet damage mutational signature, suggesting that ultraviolet damage may be a causative factor and that immune checkpoint inhibition may be beneficial. [5]



The etiology of most cases of angiosarcoma is unknown. The tumors may develop as a complication of a preexisting condition. The following factors may be associated with tumor development [6, 7] :

  • Radical mastectomy
  • Radiotherapy
  • Foreign materials
  • Environmental carcinogens
  • Preexisting benign lesions (eg, bone infarct, pagetoid bone, chronic osteomyelitis)
  • Genetic disorders

Radical mastectomy

Chronic lymphedema is the most widely recognized risk factor, especially in angiosarcomas of the skin and soft tissue. Typically, lymphedema-associated angiosarcomas occur in women who have undergone radical mastectomy for breast carcinoma and have had chronic lymphedema for many years (Stewart-Treves syndrome) or in the leg of patients as a consequence of radical inguinal lymphadenectomy for metastases from malignant melanoma (Kettles syndrome). [2]

Chronic lymphedema occurring on a congenital, idiopathic, traumatic, or infectious basis also predisposes to angiosarcoma. The rationale for this association is the immunologic privilege of a lymphedematous region.


Radiation-induced angiosarcomas occur in the absence of chronic lymphedema after radiotherapy for carcinoma of the cervixovaryendometrium, or breast and Hodgkin lymphoma.

The lesion arises in the area of previous radiation, with an interval between irradiation and the development of the new tumor of approximately 10 years. The risk of postradiotherapy sarcomas appears to augment with increasing dosage.

The diagnosis mandates that the lesion must have proven histologic differences from the primary neoplasm (carcinomas, lymphomas). Angiosarcomas of bone arising in a previously radiated bone are third in frequency after osteosarcoma and fibrosarcoma. Angiosarcoma of soft tissue is the first diagnosis in soft tissue sarcomas arising within the field of radiation, followed by malignant fibrous histiocytoma (MFH).

The Finnish Cancer registry [8]  suggests that although an increased risk of angiosarcoma in cancer patients is evident, especially with breast [9]  and gynecologic cancer, the excess does not appear to be strongly related to radiotherapy. Contrary to this finding, other researchers suggest that adjuvant radiotherapy increases the risk of breast angiosarcoma 9-fold. Regardless, radiation-associated angiosarcoma of the breast is rare, occurring in approximately 0.9 of 1,000 cases. Reported onset is as late as 23 years following radiotherapy. [10]

Foreign materials

Some angiosarcomas are associated with foreign material introduced in the body, either iatrogenically or accidentally. This association is described with the following materials:

  • Dacron
  • Shrapnel
  • Steel
  • Plastic graft material
  • Surgical sponges
  • Bone wax

Environmental carcinogens

Vintners who spray vines against mildew and patients with psoriases given prolonged treatment with Fowler solution (1% potassium arsenite) are at risk. Exposure to arsenic may increase the risk of angiosarcoma of the liver.

Dioxin, a contaminant of industrial processes, is a controversial risk factor associated with the development of soft tissue sarcomas. Likewise, exposure to vinyl chloride used in polymerization in the plastic industry can lead to angiosarcomas of liver and soft tissue.

Genetic disorders

Approximately 3% of primary angiosarcomas are associated with hereditary diseases, such as the following [11] :

  • Congenital retinoblastoma
  • Neurofibromatosis type 1
  • Ollier disease
  • Maffuci disease
  • Xeroderma pigmentosum


Angiosarcomas are rare neoplasms. Approximately 50% of angiosarcomas occur in the head and neck, but they account for less than 0.1% of head and neck malignancies. [12]

Around 2% of soft tissue sarcomas in general and 5.4% of cutaneous soft tissue sarcomas are angiosarcomas [1] . This is in contrast with the classic report of 1%. [13] The incidence of soft tissue sarcomas from 1973 to 2006 was 5.9 per 100,000 persons. [14]

Worldwide incidence is also low; in the United Kingdom, for example, the National Cancer Intelligence  Network (NCIN) reported that angiosarcomas represent 3.3% of all soft tissue sarcomas, with an incidence rate of 1.5 per million. [15]

Demographic variation includes the following:

  • African Americans in the United States are rarely affected by cutaneous angiosarcoma. [12]
  • Cutaneous angiosarcoma is more frequent in males than in females, with a male-to-female ratio of 2:1.
  • Bone and soft tissue angiosarcoma have a similar sex distribution. [1, 16, 17]
  • Bone angiosarcoma appears most often in adults (second to seventh decades of life).
  • Cutaneous angiosarcoma of the head and neck tends to occur in the elderly population. [12]


All angiosarcomas tend to be aggressive and are often multicentric. These tumors have high rates of local recurrence and metastasis because of their intrinsic biologic properties and because they are often misdiagnosed, leading to a poor prognosis and a high mortality rate. Malignant vascular tumors are clinically aggressive, difficult to treat, and have a reported 5-year survival rate around 20-35%. [3, 18, 16]  Advanced stage at presentation and lack of radical or wide excision are associated with higher recurrence rates, higher distant metastasis rates, and worsened survival. This is in contrast to the 5-year survival for all types of soft tissue sarcomas, which is around 65%. [7]  

Angiosarcoma of the viscera (particularly liver and heart) and retroperitoneal disease are especially associated with poor outcome. [1]  In a study of 346 primary hepatic angiosarcoma (PHA) patients, the median survival was 1.9 months.  Those who underwent surgical resection had a higher median survival rate of 7.7 months. Chemotherapy treatment also increased median survival to 5.1 months. [19]

More than 50% of patients develop metastatic disease, with the lung the primary organ involved. [18, 16]

Soft tissue angiosarcoma

Angiosarcoma of the soft tissue is a high-grade sarcoma with a high rate of death and short survival time. A large number of patients, 50% in some series, also had metastasis, and a significant number (20%) had local recurrences. [3, 18, 16]

Older patient age, retroperitoneum location, and larger tumor size are unfavorable prognostic factors. Approximately 66% of retroperitoneal angiosarcomas recur locally in the tumor bed and can recur diffusely throughout the peritoneal cavity (angiosarcomatosis).

Bone angiosarcoma

High-grade angiosarcomas exhibit extremely aggressive behavior with rapid local growth and early disseminated metastasis. Prognosis depends on the histologic grade, with the disease-free survival rate reported as 95% in grade 1 tumors, 62% in grade 2, and 20% in grade 3. Multicentricity does not affect prognosis.

Cutaneous angiosarcoma

Despite aggressive treatment, prognosis is poor. The median survival ranges from 15-24 months, with a 5-year survival rate of 12-33%. Local failure and metastases to local cervical lymph nodes are common. The lung is the most common site of distant metastasis, followed by the liver and bone, although these tend to occur late.

Unlike other sarcomas, grade is not useful in predicting survival. No correlation exists between appearance (eg, ulcerated, nodular, diffuse) and survival or local recurrence.

Findings of significantly favorable prognostic importance appear to be smaller tumor size (< 5 cm), complete surgical resection, and a moderate or marked lymphoid infiltrate in and around the tumor.

Unresectable lesions and metastatic disease at diagnosis suggest a dismal prognosis. Death can occur either from local extension or metastasis. Delayed diagnosis and treatment explain, in part, the poor prognosis of cutaneous angiosarcomas.