eMedicine Specialties > Dermatology > Malignant Neoplasms

Stewart-Treves Syndrome

Author: Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Coauthor(s): Geover Fernandez, MD, FAAD, Staff Physician, Department of Dermatology, University of Medicine and Dentistry New Jersey, New Jersey Medical School
Contributor Information and Disclosures

Updated: Nov 13, 2009

Introduction

Background

Stewart-Treves syndrome is a rare, deadly cutaneous angiosarcoma that develops in long-standing chronic lymphedema.¹ 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.² 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.³ In 1948, Stewart and Treves reported this rare secondary malignancy in 6 cases of angiosarcoma in postmastectomy lymphedema.⁴ 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.^5,6

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.⁷ 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.⁸ 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.⁹ 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 of Stewart-Treves syndrome 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.¹⁰ 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 for Stewart-Treves syndrome.

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.¹¹
• In 1972, Woodward et al described a series of 23 patients in a review of 163 cases of Stewart-Treves syndrome from the literature.¹² 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.

Clinical

History

Lymphangiosarcoma typically develops in patients many years after mastectomy, more commonly 5-15 years after surgery.

• In their original series, Stewart and Treves reported that the earliest angiosarcoma appeared 6 years after radical mastectomy, the longest interval being 24 years (average, 12.5 y).
• In 1988, Tomita and associates demonstrated that the most common interval between radical mastectomy and the onset of lymphangiosarcoma was 5-14 years.¹³
• In 1981, Yap et al reported a series of 22 patients in whom the median interval from mastectomy to the onset of angiosarcoma was 11 years (range, 5-16 y).¹⁴

Physical

• As Stewart and Treves described, edema occurs first.
  • Severe chronic edema of an upper extremity usually occurs in patients with Stewart-Treves syndrome.
  • In patients who undergo radical mastectomy, edema first appears on the arm on the side operated on.
  • The occurrence of edema is not associated with complications such as postoperative infection or thrombosis.
  • The edematous area gradually extends from arm to forearm and dorsal aspect of the hand and fingers.
  • Initially, pain is absent, although skin distention may produce local discomfort.
  • In the areas of long-standing chronic edema, recurrent erysipelas may occur, just as they do in patients with congenital lymphedema.
• The skin in patients with Stewart-Treves syndrome tends to become atrophic and eventually pachydermatous, with prominent wrinkle lines. At times, hyperkeratoses and telangiectasias can be observed.
• After an interval of 1-30 years, a purplish patch appears that then develops into a plaque or nodule in the area of chronic lymphedema.
• Other initial lesions of Stewart-Treves syndrome may include a palpable subcutaneous mass or a poorly healing eschar with recurrent bleeding and oozing.
• The lesions of Stewart-Treves syndrome typically appear as multiple reddish blue macules or nodules that may become polypoid.
  • Around these nodules, small satellite areas can develop and become confluent, forming an enlarging lesion.
  • Sometimes, a bullous component may be seen.
• As the angiosarcoma continues to grow and expand, the overlying atrophic epidermis may ulcerate, producing recurrent episodes of bleeding and infection.
• Necrosis may be evident in advanced cutaneous tumors.
• Ultimately, extensive cutaneous nodules and systemic metastases appear. These nodules most commonly occur in the lungs and cause the patient's death.
• Not every tumor in an area of lymphedema is an angiosarcoma.

Causes

• The most important single causative agent in Stewart-Treves syndrome is prolonged chronic lymphedema.
  • Although Stewart-Treves syndrome develops after radical mastectomy in most patients, lymphangiosarcoma also develops in other forms of acquired lymphedema and in congenital lymphedema.
  • Causes for such secondary lymphedema may include trauma, surgical invasion of the groin for the treatment of penile or cervical cancer, filariasis, idiopathic acquired lymphedema, vascular stasis, and morbid obesity.
• Edema secondary to cardiac or renal disease is not associated with this malignancy. Thus, edema alone is not sufficient to cause lymphangiosarcoma. Perhaps additional factors such as a genetic predisposition are required.

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