eMedicine Specialties > Oncology > Sarcomas of Soft Tissue and Bone

Angiosarcoma

Author: Belen Carsi, MD, PhD, FRCS, Consultant, Department of Orthopedics, University College Hospital London
Coauthor(s): Franklin Sim, MD, Chairman of Orthopedic Oncology, Professor, Department of Orthopedic Surgery, Mayo Medical School
Contributor Information and Disclosures

Updated: Jan 9, 2009

Introduction

Background

An angiosarcoma (AS) is an uncommon malignant neoplasms 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.

Pathophysiology

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.

Frequency

United States

• 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.¹
• Based on analyses of Surveillance, Epidemiology, and End Results program, 4.1% of angiosarcomas were diagnosed in the 26,758 cases of soft tissue sarcoma available for analysis from 1978-2001. This is in contrast with the classic report of 1%.² The age-adjusted incidence rate for soft tissue sarcoma was 3.1 per 100,000 men and women per year in the 2000-2004 period.³

International

Worldwide incidence is also low.

Mortality/Morbidity

All angiosarcomas tend to be aggressive and are often multicentric. These tumors have a high local recurrence rate 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%.^4,5 Advanced stage at presentation and lack of extensive excision are associated with higher recurrence, higher distant metastasis rates, and worsened survival.

The 5-year survival for soft tissue sarcomas is 67%.⁶ The mortality for soft tissue sarcomas was around 1.6 cases per 100,000 population in 2000.

Race

African Americans in the United States are rarely affected by cutaneous angiosarcoma.¹

Sex

• Cutaneous angiosarcoma is more frequent in males than in females, with a male-to-female ratio of 2:1.
• Bone and soft tissue angiosarcoma are also  reported to be more frequent in males.⁷

Age

• Soft tissue angiosarcoma has a peak incidence in the seventh decade of life, although a wide age range of patients (5-97 y) can be affected.⁷
• 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.

Clinical

History

Angiosarcomas are insidious, and they may not produce symptoms until the disease is well advanced. History should focus on identifying risk factors; however, most patients do not have these factors.

• Risk factors  
  • Toxic exposure or radiation therapy
  • Other carcinogens (eg, bone wax, Dacron, metal bodies)
  • Lymphedema
• Angiosarcomas arising at different sites and in different organs have some distinct features, but they cause symptoms associated with the amount of organ tissue replaced.  
  • Pathologic fractures, anemia, or hepatic dysfunction
  • Other intrinsic characteristics of a malignant vascular proliferation (eg, bleeding, thrombocytopenia, or intravascular disseminated coagulation)
  • Compression of adjacent neurovascular structures that causes pain

Physical

Physical examination findings often are unremarkable; however, subtle findings may provide clues to early detection.

• Angiosarcoma of soft tissue (extremities, retroperitoneum, abdominal wall)^2,7  
  • Patients with these angiosarcomas usually present with a moderately paced growing mass in the extremities. The rapid progression of the disease is sometimes the clue to the correct diagnosis.
  • Retroperitoneal angiosarcomas usually present as asymptomatic masses and generally grow to large sizes because the abdomen can accommodate tumors. Patients may present with neurologic symptoms from compression of lumbar or pelvic nerves.
  • Approximately 33% of patients have evidence of recent hemorrhage or coagulopathy, including anemia, persistent hematoma, hemothorax, hemorrhagic ascites, and gastrointestinal bleeding.
  • Frequently, the adjacent nodes are enlarged because the incidence rate of node metastasis is as high as 45% compared to other soft tissue sarcomas.
• Angiosarcoma of bone⁸
  • This type of tumor can affect any portion of the skeleton, although 33% of these tumors occur in the axial skeleton, 33% in long tubular bones, and the rest in the small bones of the hands and feet.
  • These tumors can be multifocal, affecting the same bone with multiple lesions, or multicentric, involving multiple bones of the same extremity. The patients do not present specific symptoms, although pain is common and the area is frequently tender.
  • Sometimes, swelling and increased size of the affected limb due to affectation of a superficial bone or to soft tissue extension characterize the presentation. Pathologic fractures occur in 10% of patients.
• Cutaneous angiosarcoma:^9,10 Four variants of cutaneous angiosarcoma are currently recognized, including angiosarcoma of the scalp and face, angiosarcoma in the context of lymphedema (Stewart-Treves syndrome), radiation-induced angiosarcoma, and epithelioid angiosarcoma.
  • Cutaneous angiosarcoma of the scalp and face: This is the most common form of angiosarcoma. The disease is primarily located on the head and neck of elderly persons and is also known as Wilson-Jones angiosarcoma, senile angiosarcoma or malignant angioendothelioma. Most patients present with an enlarging bruise, a blue-black nodule, or an unhealed ulceration. Initially, these lesions can be confused with cellulitis, edema, bruising, or infection, leading to a delay in diagnosis. Bleeding and pain may be present. The clinical pattern of the lesions may be nodular, diffuse, or ulcerated.
  • Cutaneous angiosarcoma associated with lymphedema: Lymphedema-associated angiosarcoma (LAS) was first reported by Stewart and in 6 patients with postmastectomy lymphedema. In each case, angiosarcoma developed in the ipsilateral arm and occurred several years after mastectomy. Subsequently, LAS was reported after axillary node dissection for melanoma and in the context of congenital lymphedema, filarial lymphedema, and chronic idiopathic lymphedema. The risk for developing LAS 5 years after mastectomy is approximately 5%. The most common site is the medial aspect of the upper arm. LAS presents as a violaceous plaque or nodule superimposed on brawny, nonpitting edema. Ulceration may develop rapidly.
  • Radiation induced angiosarcoma: Lesions occur in the radiation field 4-40 years after irradiation. Exposure to thorotrast may lead many years later to liver angiosarcoma.
  • Epithelioid angiosarcoma is a rare, recently described variant with an aggressive course. Death occurs 2-3 years after presentation.

Causes

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:^10,6

• Radical mastectomy 
  • Chronic lymphedema is the most widely recognized, 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).
  • Chronic lymphedema occurring on a congenital, idiopathic, traumatic, or infectious basis also predisposes to angiosarcoma. The rationale for this association is the status of immunologic privilege of a lymphedematous region.
• Radiotherapy 
  • Radiation-induced angiosarcomas occur in the absence of chronic lymphedema after radiotherapy for carcinoma of the cervix, ovary, endometrium, or breast and Hodgkin disease.
  • 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 patient 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 registry¹¹ suggests that although an increased risk of angiosarcoma among cancer patients is evident, especially with breast¹² and gynecological cancer, the excess does not appear to be strongly related to radiotherapy. Contrary to this finding, based on 135 soft tissue sarcomas identified in 194,798 women in the SEER database, Huang and Mackillop¹³ reported a 16-fold increased risk (95% CI, 6.6-38.0) of angiosarcoma (based on 27 cases) and a 2-fold increased risk (95% CI, 1.4-3.3) of other sarcomas in breast cancer patients who had received radiation therapy, compared to those who had not.¹⁴  
• Foreign materials 
  • Some angiosarcomas are associated with foreign material introduced in the body, either iatrogenically or accidentally.
  • This association is described with Dacron, shrapnel, steel, plastic graft material, surgical sponges, and bone wax.
• Angiosarcoma associated with 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.
• Angiosarcoma occurs with increased frequency in those with AIDS.
• Preexisting benign lesions: Angiosarcoma of bone may arise on a previous lesion as a bone infarct, a pagetoid bone, or chronic osteomyelitis.

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