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Angiosarcoma Clinical Presentation

  • Author: Belen Carsi, MD, PhD, FRCS; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Jun 20, 2016
 

History

Angiosarcomas are insidious, and they may not produce symptoms until the disease is well advanced.[13] History should focus on identifying risk factors; however, most patients do not have these factors.

Risk factors are as follows:

  • 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 the clinical manifestations they cause are associated with the amount of organ tissue replaced, as follows:

  • 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
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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[14, 11] :

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

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).

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 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[15] suggests that although an increased risk of angiosarcoma in cancer patients is evident, especially with breast[16] and gynecologic 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 Mackillop[17] 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.[18]

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.

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Physical Examination

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

Angiosarcoma of soft tissue

Patients with soft-tissue angiosarcomas[6, 12] usually present with a moderately paced growing mass in the extremities; the rapid progression of the disease is sometimes the clue to the diagnosis. Soft-tissue angiosarcomas may also develop in the retroperitoneum or abdominal wall.

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; the incidence rate of node metastasis is as high as 45%

Angiosarcoma of bone

Angiosarcoma of bone[19] 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

Four variants of cutaneous angiosarcoma are currently recognized, as follows[20, 14] :

  • Angiosarcoma of the scalp and face
  • Angiosarcoma in the context of lymphedema (Stewart-Treves syndrome)
  • Radiation-induced angiosarcoma
  • Epithelioid angiosarcoma

Angiosarcoma of the scalp and face

This is the most common form of angiosarcoma. The disease is primarily located on the head and neck, and usually occurs in elderly persons; it 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 in six 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

These lesions occur in the radiation field 4-40 years after irradiation. Exposure to Thorotrast (a radioactive radiographic contrast agent used in the United States until the 1950s) may lead many years later to liver angiosarcoma.

Epithelioid angiosarcoma

This is a rare, recently described variant with an aggressive course. Death occurs 2-3 years after presentation.

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Contributor Information and Disclosures
Author

Belen Carsi, MD, PhD, FRCS Consultant, Department of Pediatric Orthopedics, University Hospital Southampton, UK

Disclosure: Nothing to disclose.

Coauthor(s)

Franklin Sim, MD 

Franklin Sim, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Orthopaedic Surgeons, American Association of Tissue Banks, American College of Sports Medicine, American Medical Association, American Orthopaedic Association, American Orthopaedic Society for Sports Medicine, International Skeletal Society, Mid-America Orthopaedic Association, Minnesota Medical Association, Sigma Xi

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Benjamin Movsas, MD 

Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, American Society for Radiation Oncology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Sanjiv S Agarwala, MD Chief of Oncology and Hematology, St Luke's Cancer Center, St Luke's Hospital and Health Network; Professor, Temple University Shool of Medicine

Sanjiv S Agarwala, MD is a member of the following medical societies: American Association for Cancer Research, American Head and Neck Society, European Society for Medical Oncology, American Society of Clinical Oncology, Eastern Cooperative Oncology Group

Disclosure: Received honoraria from BMS for speaking and teaching; Received consulting fee from Novartis for consulting; Received consulting fee from Merck for consulting.

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This is a classic example of angiosarcoma associated with chronic lymphedema after lymphadenectomy and radiotherapy. The patient is a 33-year-old woman who presented with a recurrent grade 2 angiosarcoma of the soft tissue after an attempt at wide excision and skin graft. Two weeks following this procedure, she developed multiple subcutaneous erythematous nodules involving the back and overlying the right scapula region, the supraclavicular fossa, the right breast, and arm. The window shows a microphotograph of the tissue obtained from the biopsy (hematoxylin and eosin stain, original magnification X160). Histologic preparation reveals neoplastic endothelial cells showing a solid pattern with occasional mitotic figures and sporadic protruding growth into the vascular lumens.
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.
This radiograph is from a 27-year-old woman who had preexisting mild pain in her left clavicle for a couple of weeks. She woke up one morning with severe pain. Radiographs showed a pathological fracture through a lytic lesion. The permanent section of the needle biopsy is shown in the window and was read as a grade 1 angiosarcoma. The cell morphology varied from epithelioid to spindle-shaped with indistinct borders. Most nuclei were large and vesicular, containing irregular large eosinophilic nucleoli and frequent mitoses. Physicians also found anastomosing vascular channels lined by pleomorphic malignant cells.
CT scan, MRI, and bone scan from a 27-year-old woman with grade 1 angiosarcoma who presented with a pathological fracture through a lytic lesion on her left clavicle. Note the expansile lytic lesion in the left clavicle accompanied by a soft tissue mass visible on the MRI. No other lesions are identifiable. Regional lymph nodes are visible by MRI, and they do not appear involved. Lungs are clear. She was treated with wide resection of the clavicle, leaving both bony ends. No further reconstruction was attempted. Eighteen months after surgery, she is free of disease and has a full range of motion in the left shoulder. The residual aesthetic deformity is minimal.
This 71-year-old man presented with a dark lesion on his scalp. The lesion was first treated with an excisional biopsy performed by his local physician; the lesion recurred quickly. He was treated with wide excision and adjuvant radiation therapy. The specimen (hematoxylin and eosin, original magnification X12.5) shows a well-differentiated cutaneous angiosarcoma composed of irregular vascular channels.
This young woman presented with multicentric angiosarcoma. The images show several bones of the right foot, the right distal femur, and the right patella affected with the process. The microphotograph of the specimen revealed a grade 2 angiosarcoma (hematoxylin and eosin, original magnification X100). Most bone tumors are solitary lesions with a very low incidence of multicentricity. Vascular tumors are an exception and may involve multiple bones. Angiosarcoma presents in this case as multiple lytic lesions in the same extremity.
This is a soft tissue angiosarcoma presenting as a rapidly growing mass in the calf. This 69-year-old woman was treated with wide resection of the mass followed by external beam radiotherapy. The full-thickness graft obtained from the ipsilateral thigh at the moment of surgery aided in the closure and prevented further wound complications during the adjuvant radiotherapy. The rapid growth of soft tissue angiosarcomas explains why they are often misdiagnosed as abscesses and tentatively treated with drainage. The drainage is sanguinous, with blood clots, and hemostasis may be challenging. To avoid this problem, fine-needle aspiration should precede any attempt at incisional or excisional biopsy of a soft tissue mass.
This 45-year-old man presented with progressive pain in his left hip. Activity-related at first, the pain turned constant. The patient described it as a dull ache and a boring sensation, with occasional stubbing episodes. The pelvic bone involvement was extensive. The patient was treated with an external hemipelvectomy. The patient survived for 1.5 years.
 
 
 
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