Angiosarcoma Non-Metastatic

Angiosarcoma is a rare and aggressive cancer that begins in the cells lining blood vessels or lymph vessels. When detected before it spreads to other parts of the body, it is called non-metastatic angiosarcoma. Understanding this condition, its symptoms, and treatment options can help patients make informed decisions about their care.

Table of contents

• What is Angiosarcoma?
• Where Angiosarcoma Occurs in the Body
• Risk Factors and Causes
• Symptoms of Angiosarcoma
• How Angiosarcoma is Diagnosed
• Understanding Stages and Non-Metastatic Disease
• Treatment Options for Non-Metastatic Angiosarcoma
• Prognosis and Survival

What is Angiosarcoma?

Angiosarcoma is a rare type of cancer that starts in the inner lining of blood vessels or lymph vessels, which are part of the body’s immune system^[1]. The lymph vessels collect bacteria, viruses, and waste products from the body and help dispose of them^[2].

This cancer is highly aggressive and makes up only about 1 to 2 percent of all soft tissue sarcomas, which are themselves rare tumors^[1][5]. Because it develops from cells that line blood vessels throughout the body, angiosarcoma can occur almost anywhere^[7].

All angiosarcomas are considered “high-grade” by definition, which means they behave aggressively and grow quickly^[1]. Each year, approximately one person in one million people in the United States is diagnosed with this disease^[4][7].

Where Angiosarcoma Occurs in the Body

While angiosarcoma can develop anywhere in the body, it most commonly affects certain areas. About 60 percent of cases are cutaneous angiosarcomas, meaning they occur on the skin, particularly on the head and neck region^[5]. The scalp is the most frequent site for skin angiosarcoma^[1][7].

Other common locations include the breast, especially in women who have received radiation therapy for breast cancer^[1][2]. Less frequently, angiosarcoma develops in internal organs such as the liver, spleen, heart, or bones^[2][7].

Angiosarcoma affects people of all ages, but it is more common in elderly individuals, with most cases occurring in people aged 60 and older^[7]. The disease affects men and women at similar rates, though primary angiosarcoma occurs slightly more often in men^[5][7].

• Skin (especially scalp, head, and neck)
• Breast
• Liver
• Spleen
• Heart
• Bones
• Deep soft tissues

Risk Factors and Causes

The exact cause of most angiosarcomas is unknown. However, researchers have identified several risk factors that may increase the likelihood of developing this cancer^[5].

Previous radiation therapy is one of the most significant risk factors. Angiosarcoma can develop several years—usually around 8 to 10 years—after a person receives radiation treatment for another type of cancer, most commonly breast cancer^[1][7]. This is called radiation-induced angiosarcoma or secondary angiosarcoma.

Chronic lymphedema, which is long-term swelling caused by a buildup of lymph fluid in tissues, is another known risk factor^[1][5]. This condition often occurs after surgery, such as radical mastectomy. When angiosarcoma develops in areas of chronic lymphedema, it is sometimes called Stewart-Treves syndrome^[1].

Exposure to certain chemicals has also been linked to angiosarcoma, particularly liver angiosarcoma. These chemicals include vinyl chloride, arsenic, thorium dioxide, and radium^[1][5][7]. Sometimes angiosarcomas do not appear until 10 to 40 years after chemical exposure^[7].

In rare cases, certain genetic syndromes and genetic mutations may be associated with angiosarcoma, including neurofibromatosis, Maffucci syndrome, and Klippel-Trenaunay syndrome, as well as mutations in DNA repair genes like BRCA1 and BRCA2^[1].

Symptoms of Angiosarcoma

The symptoms of angiosarcoma vary greatly depending on where the tumor is located in the body^[2][7].

When angiosarcoma occurs on the skin—particularly on the scalp, face, neck, or breast—it may appear as a raised area that looks like a bruise^[2]. This bruise-like lesion typically grows larger over time rather than healing^[2]. The area may bleed easily when scratched or bumped^[2][4]. Some people notice swelling in the skin around the lesion^[2].

Skin angiosarcomas often appear as reddish or blue small lumps that eventually spread and grow bigger^[7]. They may also look like a purplish area of skin that resembles a rash or bruise and may be raised^[7]. Sometimes the lesion appears as a sore that does not heal or that seems to grow^[7].

When angiosarcoma develops in internal organs, such as the liver or heart, symptoms may not be noticeable until the tumor grows large enough to affect how the organ works or creates pressure on nearby structures^[2][7]. Symptoms of angiosarcoma in organs may include pain near the affected area, unexplained fatigue, general discomfort, and unintended weight loss^[7].

Shortness of breath is the most common symptom of cardiac angiosarcoma (angiosarcoma of the heart)^[7]. For liver angiosarcoma, symptoms might include jaundice (yellowing of the skin and eyes) and persistent pain in the upper left part of the belly^[7].

How Angiosarcoma is Diagnosed

If angiosarcoma is suspected, doctors will use several tests to confirm the diagnosis and understand the extent of the disease.

The first step typically involves a physical examination, where the doctor looks at and feels any unusual lumps or areas^[5]. Angiosarcomas on the skin often look like a bruised, purple-ish area that may bleed easily when scratched or bumped^[4].

Imaging tests are crucial for diagnosis and evaluation. These may include ultrasound, which uses sound waves to create pictures of the inside of the body, CT scans (computed tomography), MRI scans (magnetic resonance imaging), or PET scans (positron emission tomography)^[4][5]. These imaging tests help doctors see the tumor’s size and location and determine whether it has spread to other parts of the body^[4].

To confirm that a tumor is angiosarcoma, doctors must perform a biopsy^[4][5]. During this procedure, a small sample of the affected tissue is removed, usually with a needle. A specialist called a pathologist then examines cells from the sample under a microscope to determine what kind of tumor it is^[4]. The biopsy also includes immunohistochemical testing to confirm the diagnosis^[5].

Understanding Stages and Non-Metastatic Disease

Like other cancers, angiosarcoma is classified into different stages based on the size of the tumor and whether it has spread to other parts of the body^[6].

Stage 1 angiosarcoma means the tumor is relatively small and contained within the area where it started^[6]. Stage 2 indicates the tumor is larger than in stage 1 but has not started to spread into surrounding tissue^[6]. Both stage 1 and stage 2 are considered low-grade tumors^[6].

Stage 3 means the tumor is larger and has started to spread into surrounding tissues^[6]. Stage 4 indicates the angiosarcoma has spread from where it started to other organs or sites in the body—this is called metastatic cancer^[6]. Stage 3 and stage 4 are considered high-grade tumors^[6].

Non-metastatic angiosarcoma refers to disease that has not spread to distant parts of the body. This typically includes stages 1, 2, and 3. Unfortunately, many angiosarcoma patients are not diagnosed until their cancer has already spread to other parts of the body, which often results in a worse prognosis^[4].

The reported rates of advanced or metastatic disease at the time of diagnosis vary from 16 to 44 percent^[5]. Angiosarcoma is an easily infiltrative tumor with a high rate of local recurrence and spread to distant sites^[5].

Treatment Options for Non-Metastatic Angiosarcoma

Treatment for non-metastatic angiosarcoma typically involves a combination of approaches, with surgery being the cornerstone of care^[1][4].

Surgery

Surgical removal of the tumor is the most effective method to cure angiosarcoma when the disease is localized^[1][5]. The goal is to achieve complete removal with negative margins, meaning the surgeon removes the tumor along with a rim of normal tissue around it to ensure all cancer cells are eliminated^[1].

For angiosarcoma of the breast, particularly when it occurs after radiation therapy for breast cancer, treatment usually involves removal of the entire breast (mastectomy)^[9]. A study comparing treatment approaches found that both breast-conserving surgery and mastectomy can be effective if complete tumor removal is achieved^[9].

For angiosarcoma affecting the arms or legs, surgeons perform limb-sparing surgery whenever possible to preserve function^[9]. In very rare cases where cancer has spread throughout the limb, amputation may be necessary^[9].

Radiation Therapy

Radiation therapy uses high-energy beams to destroy cancer cells^[4][5]. For non-metastatic angiosarcoma, radiation therapy may be used before or after surgery to reduce the risk of the tumor coming back^[4].

Studies have shown that combining radiation therapy with weekly paclitaxel (a chemotherapy drug) has produced durable responses for cutaneous angiosarcoma^[1]. However, radiation treatment must be used cautiously, especially in cases of secondary angiosarcoma that developed after previous radiation therapy, as there is concern about additional side effects and complications^[9].

A large study found that routine radiation in unselected breast angiosarcoma patients should be approached with caution, as there was no survival benefit in primary angiosarcoma and it appeared to be associated with worse survival in secondary angiosarcoma^[9].

Chemotherapy

Chemotherapy uses medications to kill cancer cells or slow their growth^[4]. For non-metastatic angiosarcoma, chemotherapy may be given before surgery (called neoadjuvant chemotherapy) or after surgery (called adjuvant chemotherapy).

The most commonly used chemotherapy drugs for angiosarcoma include^[1][5]:

• Paclitaxel and docetaxel (taxanes)
• Doxorubicin and epirubicin (anthracyclines)
• Gemcitabine
• Ifosfamide
• Dacarbazine

Paclitaxel is particularly effective for angiosarcoma and is often given weekly^[11]. Angiosarcoma is highly sensitive to taxanes, and paclitaxel has proven to be well tolerated and active even in patients who have received previous treatment^[11].

Combination Approaches

The best outcomes for patients with non-metastatic angiosarcoma are often achieved through a multidisciplinary approach, where a team of specialists works together to develop a treatment plan^[1]. This team typically includes surgeons, medical oncologists, radiation oncologists, and other specialists.

For early-stage disease that can be completely removed with surgery, the best chance for cure comes from achieving negative surgical margins^[1]. Some patients may benefit from receiving chemotherapy or radiation therapy before surgery to shrink the tumor, making it easier to remove completely.

Prognosis and Survival

The prognosis for angiosarcoma depends on several factors, including the size and location of the tumor, the stage at diagnosis, how much of the tumor can be removed during surgery, and whether the cancer has spread to other parts of the body^[4].

For non-metastatic angiosarcoma, the prognosis is significantly better than for metastatic disease. One study found that the median overall survival for non-metastatic primary breast angiosarcoma was 93 months (nearly 8 years), compared to only 32 months for secondary breast angiosarcoma^[9]. The difference was largely due to older age and more aggressive tumor characteristics in secondary angiosarcoma patients^[9].

People with low-grade breast angiosarcoma survive longer than people with other types of this cancer^[4]. Patients who have early-discovered, small tumors that are removed with large surgical margins have much better results^[1].

The five-year survival rate for non-metastatic angiosarcoma is reported to be approximately 35 percent^[5]. However, angiosarcoma has a high rate of recurrence, with the majority of relapses (75 percent) occurring within 24 months of local treatment^[5].

Several factors are associated with poor survival outcomes, including older age, higher tumor grade, and tumor spread^[9]. The prognosis is particularly poor when diagnosis is delayed, as the tumor may have already spread by the time treatment begins^[4].

Despite the aggressive nature of this disease, some patients with non-metastatic angiosarcoma have achieved extended survival with comprehensive treatment approaches^[15]. Regular follow-up care and monitoring are essential after treatment to detect any recurrence as early as possible.