Excerpt from Stewart-Treves Syndrome

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Background

Stewart-Treves syndrome is a rare, deadly cutaneous angiosarcoma that develops in long-standing chronic lymphedema. Most commonly, this tumor is a result of lymphedema induced by radical mastectomy to treat breast cancer. Unfortunately, although the breast cancer may be cured with such radical surgery, this second primary cancer may be responsible for the patient's worsening course. The term Stewart-Treves syndrome is broadly applied to an angiosarcoma that arises in a chronically lymphedematous region due to any cause, including congenital lymphedema and other causes of secondary lymphedema unassociated with mastectomy. As reported by Durr et al in 2004, this lymphangiosarcoma occurs as a rare complication. Lymphangiosarcoma is a misnomer because this malignancy seems to arise from blood vessels instead of lymphatic vessels. A more appropriate name is hemangiosarcoma.

In 1906, Lowenstein first described angiosarcoma in a patient's arm that had been affected by severe posttraumatic lymphedema for 5 years. In 1948, Stewart and Treves reported this rare secondary malignancy in 6 cases of angiosarcoma in postmastectomy lymphedema. They recognized that an edematous arm after radical mastectomy for breast cancer may suggest recurrent breast cancer, but that long-standing chronic edema without recurrent cancer may occasionally produce "a heretofore unrecognized and unreported sequel ... long after the malignant breast neoplasm has apparently been arrested ... a new specific tumor." Stewart and Treves suggested that these angiosarcomas were probably not observed previously because they were mistaken for recurrent, inoperable, cutaneous manifestations of breast cancer.

Lymphangiosarcoma has been described in Milroy disease and in idiopathic, congenital, traumatic, or filarial lymphedema.

A case of lymphangiosarcoma in hereditary lymphedema of the lower extremity has been reported in a 36-year-old woman. Despite of chemotherapy, local hyperthermia, and later amputation of the extremity, the patient died of progressive disease due to pulmonary metastasis. In respect to this case, the different therapeutic concepts, as reported in the literature, and their results are presented and discussed.

Pathophysiology

The pathogenic mechanism by which lymphedema may induce angiosarcoma has been the subject of controversy. Stewart and Treves found a high incidence of third malignancies in patients with postmastectomy angiosarcoma. Thus, they speculated that a systemic carcinogenic factor was the main causative factor in the pathogenesis of lymphangiosarcomas.

In 1979, Schreiber and others postulated the concept of local immunodeficiency in the presence of lymphedema. This theory is supported by experimental evidence. In 1960, Stark and associates demonstrated that homograft skin transplanted to lymphedematous arms survive much longer than those transplanted to healthy arms. Therefore, lymphedema may cause some degree of local immunodeficiency and lead to oncogenesis.

The possibility that radiation therapy has an important role in the induction of lymphangiosarcoma is also postulated. Sternby et al reported that, in their study, the patient with the shortest interval between radical mastectomy and the onset of the tumor (8 mo) received both preoperative radiation therapy of the breast and involved axillary lymph nodes followed by fractionated radiation. Others suggest that irradiation is not an essential factor in the pathogenesis of this tumor. Finally, irradiation may be an indirect cause of lymphangiosarcomas because it may cause axillary node sclerosis and thereby accelerate and aggravate the edema.

Frequency

International

Currently, approximately 400 cases are reported in the world literature. In 1962, Schirger calculated that the incidence of this disease is 0.45% in patients who survive at least 5 years after radical mastectomy. Others have noted a much lower incidence of 0.07% in patients after mastectomy.

Mortality/Morbidity

Lymphangiosarcomas are extremely aggressive tumors with a high local recurrence rate and a tendency to metastasize early to many areas. Long-term survivors are the exceptions.

• Metastatic angiosarcoma to the lungs and chest wall are the most common cause of death in patients with Stewart-Treves syndrome.
• Metastases to the liver and bones can also occur.
• Lymphangiomas are associated with a high rate of local recurrence and metastasis, even after aggressive surgical treatment.

Race

No racial predominance exists.

Sex

Most patients with Stewart-Treves syndrome are women with a history of breast cancer that has been treated with radical mastectomy, which causes chronic lymphedema.

Age

Stewart-Treves syndrome usually occurs in middle-aged or elderly women, a few years or many years after mastectomy.

• In 1981, Sordillo and associates reported a peak incidence in persons aged 65-70 years.
• In 1972, Woodward et al described a series of 23 patients in a review of 163 cases of Stewart-Treves syndrome from the literature. They recorded an average patient age of 68.8 years at the onset of lymphangiosarcoma; the youngest patient was aged 44 years and the oldest, 84 years.

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