An uncommon malignant neoplasm characterized by rapidly proliferating, extensively infiltrating anaplastic cells derived from blood vessels and lining irregular blood-filled spaces.
Affects a wide range of malignant endothelial vascular neoplasms that involve a variety of sites.
Aggressive lesions that tend to recur locally, spread widely, and have a high rate of lymph node and systemic metastases.
Rate of tumor-related death is high.
These tumors generally appear red and hemorrhagic.
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.
Approximately 50% of angiosarcomas occur in the head and neck.
Account for less than 0.1% of head and neck malignancies.
Surveillance, Epidemiology, and End Results finds 4.1% of angiosarcomas were diagnosed in the 26,758 cases of soft-tissue sarcoma from 1978-2001.
Age-adjusted incidence rate for soft-tissue sarcoma was 3.1 per 100,000 population per year in the 2000-2004 period.
Tend to be aggressive and are often multicentric.
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, 50% of patients had metastasis, and a significant number (20%) had local recurrences.
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.
Have a reported 5-year survival rate around 20%.
Advanced stage at presentation and lack of extensive excision are associated with higher recurrence, higher distant metastasis rates, and worsened survival.
Cutaneous angiosarcoma is more frequent in males, with a male-to-female ratio of 2:1.
Bone and soft tissue angiosarcoma are also reported to be more frequent in males.
Has a peak incidence in the seventh decade of life.
A wide age range of patients (5-97 y) can be affected.
Bone angiosarcoma appears most often in adults.
Cutaneous angiosarcoma of the head and neck tends to occur in the elderly population.
African Americans are rarely affected by cutaneous angiosarcoma.
Most patients do not have risk factors which include: exposure to radiation therapy or other carcinogens, 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.
Etiology of most cases of angiosarcoma is unknown.
May develop as a complication of a preexisting condition:
Preexisting benign lesions such as bone infarct, pagetoid bone, chronic osteomyelitis
Chronic lymphedema is the most widely recognized risk factor, especially in angiosarcomas of the skin and soft tissue.
Usually, lymphedema-associated angiosarcomas occur in women who have undergone radical mastectomy for breast carcinoma and have had chronic lymphedema for many years, known as Stewart-Treves syndrome, or in the leg of patients as a consequence of radical inguinal lymphadenectomy for metastases from malignant melanoma known as Kettles syndrome.
Chronic lymphedema as a congenital, idiopathic, traumatic, or infectious etiology also predisposes to angiosarcoma.
Radiation-induced angiosarcomas can 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 increase with increasing dosage.
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.
Some angiosarcomas are associated with foreign material introduced in the body including; Dacron
Plastic graft material
Fowler solution (1% potassium arsenite)
Exposure to arsenic may increase the risk of angiosarcoma of the liver.
Angiosarcoma of bone can affect any portion of the skeleton.
Angiosarcoma of bone occurs in the axial skeleton 33% of the time, In the long tubular bones 33% of the time and the rest in the small bones of the hands and feet.
Bone angiosarcoma tumors can be multifocal, or multicentric, and 10% of patients have pathological fractures.
Cutaneous angiosarcoma variants include:
Angiosarcoma of the scalp and face
Angiosarcoma in the context of lymphedema known as Stewart-Treves syndrome
Angiosarcoma of the scalp and face is the most common form, and is primarily located on the head and neck.
Angiosarcoma of the scalp and face usually occurs in elderly persons; it is also known as Wilson-Jones angiosarcoma, senile angiosarcoma, or malignant angioendothelioma.
Most patients present with a bruise, a blue-black nodule, or an unhealed ulceration.
Initially, lesions can be confused with cellulitis, edema, bruising, or infection, leading to a delay in diagnosis.
May be associated with bleeding and pain.
Lesions may appear nodular, diffuse, or ulcerated.
Lymphedema -associated angiosarcoma (LAS) reported from postmastectomy lymphedema, after axillary node dissection, in the context of congenital lymphedema, filarial lymphedema, and chronic idiopathic lymphedema.
The risk for developing lymphedema associated angiosarcoma 5 years after mastectomy is approximately 5%.
Lymphedema associated angiosarcoma presents as a violaceous plaque or nodule superimposed on brawny, nonpitting edema.
Radiation-induced angiosarcoma 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 lead many years later to liver angiosarcoma.
The differential diagnosis includes the following:
Spindle-cell malignant melanoma
Metastatic Cancer With Unknown Primary Site
For lesions of the extremities, retroperitoneum, or abdominal wall, m
Magnetic resonance imaging (MRI) provides more accurate evaluation of the extent of local disease than computed tomography (CT).
Bone angiosarcoma is characterized by a solitary lesion on 60% of cases with multi centric involvement is present in 40% of cases.
Bone angiosarcoma frequently extends up and down the bone.
Tumor cells contain vimentin, occasional keratin and pinocytotic vesicles in their cytoplasm.
Weibel-Palade bodies, a marker of endothelial differentiation, may be seen.
Most lesions express vimentin and focally factor VIII–related antigen.
Lesions may express CD34, BNH9 and cytokeratins, and actin.
Epithelial membrane antigen, and S100 protein and gp, both melanocytic markers are not expressed.
Anti-CD31 antibodies are one of the most specific endothelial cell markers.
The American Joint Committee on Cancer (AJCC) staging uses T,N,M classification.
The T, N, and M are further divided into Tx, T0, T1, T2, T3, T4; Nx, N0, N1, N2, N3; and Mx, M0, and M1.
Stage IV indicates the presence of metastases.
Stage I: Localized and resectable tumor is found at one site and could be treated surgically.
Stage II: Localized and possibly resectable primary tumor is found at one or more locations in the organ and may be treated surgically.
Stage III: Advanced cancer has spread to more than one location in the organ and/or to other parts of the body.
In advanced disease surgical resection does not provide benefit to the patient.
Stage IV: Disseminated cancer involves multiple sites throughout the body.
Stage IV: frequently, surgery is not indicated, and chemotherapy is the best option.
The stages of the disease are as follows:
Ia – Low grade, intracompartmental G1/T1/M0
Ib – Low grade, extracompartmental G1/T2/M0
IIa – High grade, intracompartmental G2/T1/M0
IIb – High grade, extracompartmental G2/T2/M0
IIIa – Low or high grade, intracompartmental G1-G2/T1/M1 with metastases
IIIb – Low or high grade, extracompartmental G1-2/T2/M1 with metastases
Early detection by biopsy offers the only realistic chance of a cure.
Core-needle biopsies and fine-needle aspiration (FNA) are accurate tools, but larger samples of tissue may be necessary to determine grade and histologic type.
Randomized studies using doxorubicin-based chemotherapy fail to show a survival benefit from neoadjuvant chemotherapy, although meta-analysis suggests improved local control and disease-free survival with chemotherapy.
Preoperative chemotherapy is reserved for patients with high-grade lesions.
Response to neoadjuvant chemotherapy does not always correlate with radiographic response.
The use of irradiation in conjunction with surgery results in 80% of local control and excellent functional and cosmetic outcome.
Because 50% of angiosarcomas have distant metastases, irradiation does not improve survival.
Intraoperative radiation, brachytherapy, or more external beam therapy can complement preoperative external beam radiotherapy.
The disadvantage of preoperative radiation is that a higher wound complication rate may delay surgery.
The advantages of preoperative radiation are as follows:
Optimization for surgery
Smaller volume of external beam fields
Less hypoxic tissue
Potential to reduce the chance of intraoperative implantation
Potential improvement in local control in advanced tumors
Surgical treatment of angiosarcoma of the soft tissue, retroperitoneum, and abdomen includes wide surgical margins, with at least 2 cm of unaffected tissue surrounding the tumor.
The resection should include skin when applicable and the soft tissue around the angiosarcoma.
Resection of large lesions sometimes requires amputation for local control.
Local control does not prevent distant relapse.
Free surgical margins sometimes have anatomic constraints.
Surgical treatment of angiosarcoma of bone is as follows:
Surgical resection and radiation therapy are the standard treatment for localized angiosarcoma of the bone.
The number of lesions in a limb may make limb salvage impossible, and amputation may be indicated.
Surgical treatment of cutaneous angiosarcoma.:contraindicated in tumors extending into vital structures, in those of massive size, or in those with multicentricity.
Cutaneous lesion may be solitary or multicentric and frequently extend laterally throughout the dermis, making gross assessment of surgical margins difficult and necessitating multiple biopsies of the surrounding tissues.
In the primary treatment of angiosarcomas of the scalp the excision of the scalp should be full-thickness, including the pericranium, and the margins should be at least 5 cm on all sides.
80% of soft-tissue and bone angiosarcomas that recur do so within 2 years of the resection.
Surveillance chest radiographs every 6 months is required.
MRI is the most accurate technique for detecting locally recurrent or residual sarcoma.
Baseline postoperative MRI examinations serve as a technique for detecting locally recurrent or residual sarcoma.
After the first 2 years, schedule visits every 6 months for the next 3 years, and after 5 years, patients are seen annually.
The differential diagnosis for signal abnormality on a postoperative MRI includes:
Residual or recurrent neoplasm
For cutaneous angiosarcoma clinical examination every 3 months is required to detect possible recurrences.
Imaging surveillance studies include CT scan and MRI of the head and neck and plain chest radiograph and CT chest scans every 3 months for 1 year, every 6 months for 2 more years, and then annually.
Distant metastasis can occur late.
With larger higher-grade soft-tissue angiosarcomas, adjuvant radiotherapy is effective in reducing local recurrence.
Adjuvant radiotherapy can be delivered intraoperatively, by brachytherapy, or by external beam.
Brachytherapy is often the technique of choice in angiosarcomas near joints or gonads.
In bone angiosarcoma use of combinations of radiation therapy and chemotherapy as adjuvant methods of treatment.
In cutaneous angiosarcoma, postoperative radiotherapy is warranted in cases with unsatisfactory margins, large tumor size, deep extension, and multicentricity.
High-field electron beam therapy shows promise in prolonging survival of patients with localized lesions.
Older patient age, retroperitoneal tumor location, and larger tumor size are unfavorable prognostic factors.
Approximately 66% of retroperitoneal angiosarcomas recur locally.
Retropertoneal angiosarcomas can recur diffusely throughout the peritoneal cavity.
High-grade bone angiosarcomas exhibit extremely aggressive behavior with rapid local growth and early disseminated metastasis.
Prognosis depends on the histologic grade.
For bone angiosarcomas disease-free survival rate reported as 95% in grade 1 tumors, 62% in grade 2, and 20% in grade 3.
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 lymph nodes are common.
The lung is the most common site of distant metastasis, followed by the liver and bone.
Unlike other sarcomas, grade is not useful in predicting survival, and no correlation exists between appearance of the lesion and survival or local recurrence.
Favorable prognostic importance appear to be related to a tumor size of less than 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.
Propranolol has been reported to be highly effective in patients with non resectable disease.