Stewart - Treves Syndrome

What Is Stewart-Treves Syndrome (STS)?

It is a rare cutaneous disorder characterized by angiosarcoma that develops from chronic lymphedema. Lymphedema is a condition in which lymph fluid gets accumulated in the tissue, which results in swelling of the affected area. This disorder most commonly affects upper limbs and is rare in lower limbs. It is an aggressive disorder that occurs post-breast surgery or mastectomy along with axillary lymph node excision.

According to Durr, 2004 it is considered a rare complication. Angiosarcoma, which occurred as a complication of post-traumatic lymphedema, was first described in 1906 by Lowenstein. Later in 1948, doctors Fred Stewart and Norman Treves described this rare disorder again as a complication of post-traumatic lymphedema. It is more appropriate to call this disorder hemangiosarcoma instead of lymphangiosarcoma because this rare malignancy develops in blood vessels and not lymphatic vessels.

Stewart and Treves explained that an edematous arm that is caused due to breast surgery might indicate recurrence of breast cancer. But in some cases, this long-standing lymphedema without any signs of breast cancer may later develop a complication, that is angiosarcoma.

What Is the Cause for Stewart-Treves Syndrome?

STS is a deadly cutaneous disorder. It is described as an association between chronic lymphedema and angiosarcoma. It is commonly found in women with a previous history of breast surgery or mastectomy along with axillary node excision. Some cases reported it as congenital lymphedema. When it was first reported in 1948 by Stewart and Treves, they called it “elephantiasis chirurgica.”

Another unique presentation of chronic lymphedema is “massive localized lymphedema (MLL).” The cause for the transformation of chronic lymphedema into angiosarcoma is still unclear and remains controversial. Some researchers have explained that long-standing lymphedema can cause local immunodeficiency, which in turn leads to regional abnormal cell proliferation and local oncogenesis. This affected area is altered by protein-rich interstitial fluid, thereby developing lymphangiogenesis. When local immunity is deficient, that area is predisposed to malignant transformation, such as Stewart-Treves syndrome. There are many other causes of STS.

They are listed as follows:

• Trauma.

• Infectious filariasis.

• Idiopathic acquired lymphoma.

• Venous stasis.

• Morbid obesity.

• Leg ulcerations.

• Lymphoma.

• Recurrent cellulitis.

• Surgery of the groin, legs, or pelvis.

• Prolonged use of systemic immunosuppressive drugs.

• Axillary radiation therapy.

• Acquired immunodeficiency syndrome.

• Chemotherapy.

• Besides acquired causes for STS, there are congenital causes that are postulated by a few scholars. They include genetic mutations of BRCA1 and BRCA2. Mutation of breast cancer gene (BRCA) 1 and 2 predisposes an individual to angiosarcoma after mastectomy along with axillary lymph node removal.

• Recent studies have explained that in a few cases, mutation of c Myc oncogene is responsible for Stewart-Treves syndrome. c Myc gene is a proto-oncogene that regulates cell proliferation, apoptosis, and transformation.

Who Is Most Affected by Stewart-Treves Syndrome?

Stewart-Treves syndrome occurs in one in 200 patients. It is a rare cutaneous disorder characterized by lymphangiosarcoma. When women have undergone treatment for breast cancer that includes mastectomy associated with lymph node removal may cause lymphedema. The mean duration between mastectomy and lymphangiosarcoma is 11 years. It is mostly found between the ages of 65 to 70 years. Few cases have been reported in patients with chronically edematous abdominal pannus and with renal transplants. Patients who are treated with segmental resection and anti-hormonal treatment have also been reported to develop Stewart-Treves syndrome.

What Are Signs and Symptoms of Stewart-Treves Syndrome?

• Chronic edema with pain and discomfort in the affected area.

• Spreading bruises.

• Raised papules.

• Palpable subcutaneous mass.

• Recurrent bleeding.

• Reddish blue macules or nodules.

• Polypoid formations of nodules.

• Small satellite areas form around the nodule that later join to form a larger lesion.

• Erysipelas (acute bacterial infection on skin with raised red patches).

• Overlying skin becomes atrophic and ulcerate.

• Non-healing eschar (dead tissue that falls off from healthy skin).

• Recurrent infection in the affected area.

• Necrosis (death of tissue to reduced or devoid blood flow).

How Is STS Diagnosed?

A biopsy is performed to obtain a tissue specimen from the affected area. A biopsy is performed under anesthesia. Fine needle aspiration is performed to obtain the specimen. Once the tissue sample is obtained, the doctor shall send it to the laboratory for further studies that help in the diagnosis of Stewart-Treves syndrome.

1. Ultrastructural And Immunohistological Studies:

• Staining positive for factor VIII-related antigens.

• Staining positive for the endothelial marker, Ulex europaeus- I.

• Staining positive for the vascular endothelial marker, CD34.

• Absence of keratin.

• Staining positive for laminin, CD31, collagen 4.

• Staining positive for vimentin.

2. Imaging Studies:

• Magnetic resonance imaging (MRI) helps in determining the size and extent of cancer. MRI may show low signal intensity on T2 weighting and also in short-tau inversion recovery (STIR) imaging due to dense cellular and less vascularity.

• Chest computed tomography (CT) helps to determine whether it has spread to the lungs and detect pulmonary effusion.

• Positron emission tomography (PET) helps to determine the extent of subcutaneous spread.

What Are the Phases of Stewart-Treves Syndrome?

There are three phases in the development of STS:

1. Phase 1 (Prolonged Lymphedema): Chronic lymphedema leads to extreme edema of the affected area that is associated with degeneration of fat and collagen. Lymphedema has a long-standing cause of local immunosuppression, thereby leading to oncogenesis.

2. Phase 2 (Angiomatosis): This phase involves the formation of foci of small vessels. Superficial areas appear as bruises or vesicles, and deeper areas are more like indurated and cause hemorrhage.

3. Phase 3 (Angiosarcoma): This phase includes an aggressive form of the disease that develops into premalignant angiomatosis.

What Are the Treatment Modalities for Stewart-Treves Syndrome?

• Surgical Therapy: Early amputation of the affected limb is the preferred treatment for early STS. Amputation is preferred over wide excision, even in the early stages. Surgical therapy can be used for symptomatic improvement. Chemotherapy, radiotherapy, and immunotherapy can be chosen as adjuvant treatments for lymphangiosarcoma.

• Medical Therapy: Chemotherapy and radiotherapy separately provide very little benefit. It is best used when they are used as adjuvants to surgical therapy. Hyperthermic limb perfusion with tumor necrosis factor-alpha and melphalan combined with radical dissection with large safety margins may improve survival chances. Medications like intra-arterial Mitoxantrone, Eribulin mesylate, and Paclitaxel are used, though the outcomes of these medicines are discouraging. Future et al. have demonstrated the use of immunotherapy as a beneficial modality of treatment. Targeted anti-lymphangiogenic therapy is used in a few cases.

What Is the Prognosis For Stewart-Treves Syndrome?

When it comes to the prognosis of STS, early detection is important. A recent study has found three-year and five-year survival of 55% and 35%, respectively. However, the prognosis of Stewart-Treves syndrome remains poor, with a median survival of five to seven months. Untreated patients succumbed to death soon enough, depending on severity. Even with aggressive therapy, medical survival time is 15 to 30 months.

Conclusion:

Stewart-Treves syndrome is a life-threatening aggressive condition that has a poor prognosis. It is a condition that is commonly found in females. There are many complications associated with STS. Early diagnosis may improve survival. Regular check-ups after mastectomy are suggested for early diagnosis and a better outcome.