ANGIOSARCOMA
Angiosarcoma
is a rare, aggressive, malignant tumor of vascular or lymphatic vessels. These
tumors can be seen as a solitary finding or secondary to long-standing
lymphedema, such as after radiation therapy or an axillary or inguinal lymph
node dissection. This latter form tends to occur years after the radiation or
surgical procedure. Soft tissue sarcomas are very rare and make up a small
percentage of all malignancies reported.
Clinical Findings: Angiosarcomas are most common in the older male
population. They have no race predilection. The tumors most commonly arise in
the head and neck region and can manifest in many fashions. They often appear
as a red to purple plaque with ill-defined borders. They can often look like a
bruise, and the diagnosis can be delayed. The tumor continues to expand, forms
satellite foci of involvement, and eventually ulcerates and bleeds. For some
reason, the scalp and face of older men are most commonly involved. The tumor
has a propensity to involve sun-exposed areas of the face and scalp. The tumors
typically show an aggressive growth pattern and have a tendency to metastasize
early in the course of disease.
Angiosarcomas can also arise in
regions of previous long-standing lymphedema caused by radiation exposure or
surgical procedures. Any procedure that can result in abnormal lymphatic
drainage can lead to chronic lymphedema. It is believed that long-standing
lymphedema can result in the development of angiosarcoma. Common surgical
procedures that cause chronic lymphedema are radical mastectomies and lymph
node dissections of the axilla or groin after a diagnosis of lymph node
involvement by breast cancer or mela- noma. Angiosarcomas arising in areas of
chronic lymphedema were first described by Stewart and Treves and have been
given the eponym Stewart-Treves syndrome. This type of angiosarcoma is
highly aggressive and portends a poor outcome. The Stewart-Treves type of
angiosarcoma has been reported most commonly in women who have undergone
radical mastectomy or lymph node dissection for treatment of breast cancer.
After years of chronic lymphedema in the ipsilateral limb, the patient may
develop a reddish, bruise-like area on the limb. This area slowly enlarges and
develops plaque-like areas or nodules within the affected region. At this
point, the diagnosis is often entertained, and the diagnosis is made with a
skin biopsy. These tumors tend to be large at diagnosis, which most likely
accounts for the poor prognosis.
Radiation-induced angiosarcomas may
occur at the site of the radiation therapy or as a result of long-standing
chronic lymphedema if the radiation therapy interrupts the lymphatic drainage.
These tumors also tend to be diagnosed after they have become quite large, and
this portends a poor prognosis. These tumors tend to occur 4 to 10 years after
the initial radiation therapy.
Pathogenesis: Angiosarcomas are soft tissue tumors that are
derived from the endothelial lining of small blood or lymphatic vessels. Some
tumors are found to have elevated levels of vascular endothelial growth factor
(VEGF), which is critical in the regulation of vessel growth. Other potential
players in the pathogenesis of this tumor are mast cells, which cause an
increase in stem cell factor; Fas and Fas ligand expression; and lack of the
vascular endothelial cadherin protein. All of these factors may interact in an
unknown way to induce tumorigenesis. The exact mechanism of formation of
angiosarcoma is unknown. Radiation-induced angiosarcoma may result from a
direct mutagenic effect of the radiation on the endothelial DNA. No relation
with human herpesvirus-8 infection has been proven.
Histology: All angiosarcomas share the same pathological
features. The tumor lobules are poorly circumscribed and have an infiltrative
growth pattern. They contain large amounts of vascular tissue in a disorganized
arrangement. The lining of the vascular spaces contains atypical-appearing
endothelial cells. Mitoses are frequently encountered, as are intracytoplasmic lumina.
The same tumor can contain well and poorly differentiated regions.
Treatment: The standard treatment is wide local excision with
the goal of obtaining clear margins. This is usually followed by postoperative
radiation therapy. The 5-year survival rate is low (15%-20%). Tumors that are
metastatic or nonoperable can be treated palliatively with various chemotherapeutic
regimens. The median survival time in these cases is 3 to 6 months.
