Lymphangiosarcoma

Lymphangiosarcoma is a rare and aggressive cancer that develops in people with long-standing swelling of the lymph nodes, most commonly affecting the arms. This serious condition requires prompt diagnosis and treatment, though its rarity means it is less well-known than many other cancers.

Table of contents

• What is Lymphangiosarcoma?
• Alternative Names
• Causes and Risk Factors
• Signs and Symptoms
• Associated Anatomy
• Diagnosis
• Treatment Options
• Prognosis and Outlook

What is Lymphangiosarcoma?

Lymphangiosarcoma is a rare type of cancer that occurs in people who have had chronic swelling of the lymph nodes, a condition called lymphedema, for a long time^[1]. The swelling usually affects the arms or legs, but the cancer develops most commonly in the arms^[1].

Despite its name suggesting it comes from lymphatic vessels, this cancer is believed to arise from endothelial cells (cells that line blood vessels), which is why it may be more accurately called angiosarcoma^[1]. This is an aggressive cancer that spreads quickly to other parts of the body^[1].

Lymphangiosarcoma belongs to a group of cancers called soft tissue sarcomas, which account for less than 1% of all cancers^[4]. This particular type is extremely rare, with only around 300 cases reported worldwide^[7].

Alternative Names

Lymphatic vessel tumors, angiosarcomas, lymphangioendothelioma, hemangiosarcomas

Causes and Risk Factors

The main cause of lymphangiosarcoma is long-standing, chronic lymphedema^[1]. In the past, this cancer was a relatively common complication following a surgical procedure called the classical Halstedian radical mastectomy, which was used to treat breast cancer^[1]. This surgery involved removing lymph nodes and lymphatic channels from the armpit, which led to massive swelling of the arm in many patients.

When lymphangiosarcoma develops following a mastectomy, it is known as Stewart-Treves syndrome^[1]. This condition was first described in 1948 by doctors Fred Stewart and Norman Treves, who reported six cases of this cancer in patients with chronic swelling after mastectomy^[4]. The cancer typically develops five to fifteen years after the surgery^[3].

The classical radical mastectomy was abandoned in most parts of the world in the late 1960s to early 1970s and replaced with more conservative surgical procedures^[1]. Because of this change in medical practice, swelling after breast cancer treatment is now rare, and lymphangiosarcoma following mastectomy is now extremely uncommon^[1].

The reported chance of developing angiosarcoma in patients who survived at least five years after radical mastectomy ranges from 0.07% to 0.45%^[4]. Around 90% of cases of lymphangiosarcoma occur in people with long-standing lymphedema^[3].

The exact way that lymphedema leads to cancer is not fully understood. Several theories have been proposed^[1]. Stewart and Treves suggested that a cancer-causing agent might be present in swollen limbs. Another theory, proposed by Schreiber and colleagues, suggests that the swelling causes local immunodeficiency (weakening of the immune system in that area), creating an “immunologically privileged site” where the cancer can develop more easily^[1].

Risk factors for lymphangiosarcoma include a history of primary or secondary lymphedema, having had a classical radical mastectomy, or having received radiation or chronic infections in a limb with lymphedema^[3]. Women are affected more often than men^[3].

Signs and Symptoms

Lymphangiosarcoma may first appear as a purple discoloration or a tender lump in the skin of the affected limb, typically on the front surface^[1]. This area may look bruised or purplish^[3]. Around 60% of cases occur on the skin of the arms or legs, especially the forearm and elbow^[3].

The cancer then progresses to form an open sore with crusting that develops into an extensive area of dead tissue involving the skin and the tissue underneath^[1]. This mass or nodule can become painful^[12]. The tumor spreads rapidly to other parts of the body^[1], most commonly to the lungs^[3].

In patients who have had a mastectomy, lymphangiosarcoma is associated with cancerous degeneration, especially in patients who have survived five or more years and who have severe lymphedema^[1]. The cancer most commonly occurs in the upper arm, forearm, elbow, and front of the chest wall^[1].

Associated Anatomy

• Lymphatic vessels
• Blood vessels (endothelial cells)
• Upper arm
• Forearm
• Elbow
• Anterior chest wall
• Skin and subcutaneous tissue

Diagnosis

The appearance of purplish, bruised-looking areas on the limbs of a person with long-standing lymphedema is an indication for further evaluation^[3]. When concerning skin changes are identified, diagnosis is made through examination of tissue taken from the affected area^[3].

Diagnostic imaging techniques such as ultrasound, CT scan, MRI, and PET scan can be used to detect the location, size, and extent of the tumor^[12]. A biopsy (removal of a small sample of tissue) is performed, and the tissue is examined under a microscope in a process called histological examination^[3]. This examination helps to confirm the diagnosis and rule out other conditions such as recurrent breast cancer or other types of sarcoma^[3].

Unfortunately, delays in diagnosis are common because lymphangiosarcomas can appear as relatively harmless-looking lesions at first^[4].

Treatment Options

The most successful treatment for lymphangiosarcoma is amputation of the affected limb if possible^[1]. This approach provides the best chance of long-term survival^[9]. Alternatively, wide surgical removal of the tumor may be performed^[9].

Chemotherapy (treatment using anti-cancer drugs) may be given if there is evidence or suspicion that the cancer has spread to other parts of the body^[1]. Evidence supporting the effectiveness of chemotherapy is often unclear due to the wide variety of factors affecting outcomes and small numbers of patients^[1].

However, there is some evidence to suggest that certain drugs exhibit anti-tumor activity. These include paclitaxel, doxorubicin, ifosfamide, and gemcitabine^[1]. Chemotherapy and radiation therapy continue to be evaluated as additions to surgery, but currently these treatment options offer limited benefit^[9].

Even with early surgical treatment, the outlook is disappointing, with a high rate of the cancer returning in the same area and spreading to other parts of the body^[9]. There is no standard treatment for lymphangiosarcoma^[11].

Prognosis and Outlook

Lymphangiosarcoma has a poor prognosis, meaning the expected outcome is generally not favorable^[4]. The rate of the cancer coming back is high, and the long-term survival rate is poor, largely because the tumor spreads rapidly to the chest wall, liver, and bones^[3].

Most people survive for around 2.5 years following diagnosis^[3]. The five-year survival rate is less than 5% even with multi-treatment approaches^[7].

The most efficient way to avoid this highly lethal disease is by preventing or treating long-standing lymphedema, which predisposes individuals to this cancer years later^[9]. Early biopsy of any suspicious lesion should be performed because early diagnosis and surgical treatment offers the highest rate of long-term survival^[9].