Angiosarcoma is a rare and aggressive cancer that begins in the cells lining blood vessels or lymph vessels throughout the body. While it can appear anywhere, it most commonly affects the skin, particularly on the head, neck, and scalp. Understanding this disease and its effects can help patients and families navigate the journey ahead with more confidence and awareness.

Epidemiology

Angiosarcoma is an exceptionally rare disease. In the United States, only about one person per million is diagnosed with angiosarcoma each year. This makes it one of the rarest forms of cancer, accounting for just one to two percent of all soft tissue sarcomas, which themselves represent less than one percent of adult cancers. The rarity of angiosarcoma means that large studies on the disease are scarce, and much of what doctors know comes from smaller groups of patients and individual case reports.^[2][3]

This cancer does not discriminate by gender in most cases, affecting men and women at similar rates overall. However, when it comes to primary angiosarcoma that develops spontaneously, men tend to be diagnosed more frequently than women. The disease can strike at any age, from children to the elderly, but it shows a clear preference for older adults. Most patients receive their diagnosis between the ages of 60 and 70, with the median age at diagnosis being around 71 years old.^[2][7][13]

Geographically, angiosarcoma appears most commonly in elderly white men, particularly when it affects the skin of the head and neck region. The scalp alone accounts for approximately 50 percent of all angiosarcoma cases, though this still represents less than 0.1 percent of all head and neck tumors. In England, an average of 164 cases of angiosarcoma are diagnosed each year, making up about 4.16 percent of all soft tissue sarcomas and roughly 0.05 percent of all cancers diagnosed in that country.^[2][7][13]

The rate of angiosarcoma appears to be increasing in the United States, though the reasons for this trend are not entirely clear. This rise may be related to better detection methods, increased awareness among doctors, or changes in exposure to risk factors over time.^[2]

Causes

The exact cause of angiosarcoma remains unknown in most cases. Unlike some cancers where a single trigger can be identified, angiosarcoma appears to develop through complex changes in the endothelial cells, which are the cells that line the inner walls of blood vessels and lymph vessels. These cells normally form a protective barrier between the bloodstream and surrounding tissues. In angiosarcoma, something causes these cells to become malignant, meaning they start multiplying uncontrollably and forming abnormal blood vessels that eventually become tumors.^[1][10]

Scientists have recently identified genetic mutations in some adult patients with angiosarcoma. For example, people with changes in a gene called POT1 may be more likely to develop angiosarcoma of the heart, and this genetic change can be passed down through families. However, these hereditary cases are very rare. Researchers continue searching for therapies that target these specific genetic mutations, hoping to develop more effective treatments in the future.^[4][9]

While the disease can appear spontaneously without any identifiable cause, several risk factors have been clearly linked to its development. This means that although we cannot pinpoint one single cause, we do understand circumstances that make angiosarcoma more likely to occur. The disease is not contagious and cannot be transmitted from one person to another.^[2]

Risk Factors

Previous radiation therapy is one of the most significant risk factors for developing angiosarcoma. This type of angiosarcoma, called radiation-induced angiosarcoma, typically appears several years after a person has received radiation treatment for another cancer. Most commonly, it develops in breast cancer survivors who received radiation therapy to the chest wall, but it can occur in any area of the body that was previously irradiated. The latency period—the time between radiation exposure and cancer development—usually ranges from eight to ten years, though it can vary.^[1][2][14]

Chronic lymphedema represents another important risk factor. Lymphedema is persistent swelling caused by a buildup of lymphatic fluid, usually in the arms or legs. This condition can develop after cancer surgery, infection such as filariasis, or be present from birth (a condition called Milroy’s disease). When angiosarcoma develops in the context of chronic lymphedema, it is sometimes called Stewart-Treves syndrome. Approximately five percent of all angiosarcomas are linked to this form of chronic swelling.^[2][10][13]

Exposure to certain industrial chemicals has been associated with an increased risk of angiosarcoma, particularly in the liver. Vinyl chloride, used in plastics manufacturing, is one of the most well-documented chemical causes. Workers exposed to this substance have shown higher rates of hepatic angiosarcoma (liver angiosarcoma). Other chemicals linked to the disease include arsenic, thorium dioxide (a substance once used in medical imaging), and certain herbicides. The concerning aspect of chemical-related angiosarcoma is that it may not appear until ten to forty years after exposure, making the connection between cause and disease difficult to establish.^[2][10][13]

Several rare genetic syndromes also increase the risk of developing angiosarcoma. These include neurofibromatosis, Klippel-Trenaunay syndrome, and Maffucci syndrome. Additionally, some case reports suggest an association between angiosarcoma and mutations in DNA repair genes like BRCA1 and BRCA2, though this connection remains under investigation. Angiosarcomas have also been reported in association with long-standing foreign bodies in the body, and infrequently with breast implants.^[2][13]

Symptoms

The symptoms of angiosarcoma vary dramatically depending on where in the body the cancer develops. This variability can make early detection challenging, as the signs may be subtle or easily mistaken for other, less serious conditions.^[1][2]

When angiosarcoma affects the skin—the most common location—it typically appears as a raised area that looks like a bruise. This bruise-like lesion is usually purplish or reddish in color and does not fade over time like a normal bruise would. Instead, it grows larger and may spread to surrounding areas. The lesion might bleed easily when it is scratched or bumped, even with minor contact. In some cases, patients notice a soft lump that can be felt under the skin, or the area may become swollen and painful. On the scalp, where angiosarcoma frequently occurs, the lesion may be mistaken for a benign condition at first, leading to delays in diagnosis.^[1][7][8]

The skin around an angiosarcoma lesion may show additional changes. Swelling of the surrounding tissue is common, and the area might feel tender to the touch. The bruise-like appearance can sometimes be raised, giving it a distinct texture compared to the surrounding skin. Because these skin changes can look similar to other conditions, people often wait before seeking medical attention, not realizing the seriousness of what they are observing.^[7]

When angiosarcoma develops in deeper tissues or internal organs such as the liver, heart, or spleen, symptoms are often less obvious and may not appear until the tumor has grown quite large. The cancer may cause pain in the area where it is growing. If the tumor is in an organ, symptoms depend on which organ is affected and how the tumor interferes with its function. For example, cardiac angiosarcoma—angiosarcoma of the heart—commonly causes shortness of breath, chest pain, heart palpitations, fatigue, and sometimes fainting spells. In 80 percent of cases, this rare tumor develops in the right atrium (upper heart chamber).^[1][9][14]

Hepatic angiosarcoma, which affects the liver, may cause jaundice (yellowing of the skin and eyes), persistent pain in the upper left part of the abdomen, fatigue, and weight loss. As the tumor grows, a doctor may be able to feel an abnormal mass during a physical examination. Angiosarcoma in the breast may present as a rapidly growing lump, sometimes accompanied by skin changes over the affected area.^[14]

General symptoms that can occur with angiosarcoma regardless of location include unexplained fatigue, malaise (a general feeling of being unwell), and unintentional weight loss. These non-specific symptoms often appear when the disease is more advanced or has spread to other parts of the body. Some patients remain completely asymptomatic until the cancer is discovered incidentally during medical imaging or examination for another reason.^[2][14]

One of the most concerning aspects of angiosarcoma is its aggressive nature and high tendency to spread. By the time diagnosis occurs, the cancer has already spread to distant parts of the body in 16 to 44 percent of cases. The lungs, liver, and bones are common sites of metastasis, which is when cancer cells spread from their original location to other organs. This propensity for early spread contributes to the poor prognosis associated with this disease.^[2][10]

Prevention

Because the exact cause of most angiosarcomas remains unknown, there are no guaranteed ways to prevent the disease. However, understanding risk factors can help people take reasonable precautions to reduce their exposure to known triggers.^[2]

For individuals who have received radiation therapy in the past, particularly for breast cancer treatment, awareness of the risk is important. While the absolute risk of developing radiation-induced angiosarcoma remains low, patients should be vigilant about any new or changing lesions on their skin in the previously irradiated area. Regular self-examination of the skin and prompt reporting of any unusual findings to a healthcare provider can facilitate earlier detection. The benefits of radiation therapy in treating the original cancer typically far outweigh the small risk of developing angiosarcoma years later, so patients should not avoid necessary radiation treatment out of fear of this rare complication.^[14]

People with chronic lymphedema should work with their healthcare providers to manage the swelling as effectively as possible. Proper treatment of lymphedema may include compression garments, specialized massage techniques, elevation of the affected limb, and sometimes surgery. While managing lymphedema may not eliminate the risk of angiosarcoma entirely, maintaining good control of the swelling and monitoring the affected area for any suspicious changes is prudent.^[14]

Workplace safety measures are crucial for individuals who work with chemicals known to increase angiosarcoma risk. Workers in industries that use vinyl chloride, arsenic, or other implicated chemicals should follow all safety protocols, use proper protective equipment, and ensure adequate ventilation. Regulatory agencies in many countries have established exposure limits for these substances to protect workers. Long-term monitoring of workers in high-risk industries can help detect any problems early.^[13]

For individuals with genetic syndromes that increase angiosarcoma risk, regular medical follow-up and surveillance may be recommended. While this does not prevent the disease, it may allow for earlier detection if it does develop. Genetic counseling can help families understand their risk and make informed decisions about monitoring and care.^[4]

General cancer prevention strategies, such as maintaining a healthy lifestyle, avoiding tobacco, limiting alcohol consumption, and protecting skin from excessive sun exposure, are always advisable, though their specific impact on angiosarcoma risk is not well established. What remains most important is awareness of the disease and prompt medical evaluation of any persistent, unusual symptoms.^[2]

Pathophysiology

Understanding what happens in the body when angiosarcoma develops requires looking at how blood vessels normally function and what changes when this cancer takes hold. Pathophysiology refers to the changes in normal bodily functions that occur with disease.^[10]

Blood vessels are lined with a thin layer of specialized cells called endothelial cells. These cells form the interface between circulating blood and the tissues of the body. They serve many important functions: they regulate what passes in and out of the bloodstream, they help control blood clotting, and they can signal the body to create new blood vessels when needed (a process called angiogenesis). Lymphatic vessels, which are part of the immune system, are similarly lined with endothelial cells and help transport lymph fluid, bacteria, viruses, and waste products for disposal.^[1][10]

In angiosarcoma, these normally well-behaved endothelial cells undergo malignant transformation. The cells acquire genetic mutations or alterations that cause them to lose their normal growth controls. Instead of dividing in an orderly, regulated fashion, they multiply rapidly and uncontrollably. These cancerous endothelial cells form new, abnormal blood vessels that are disorganized and structurally unstable. Unlike normal blood vessels that have clear boundaries and organized walls, the vessels formed by angiosarcoma are chaotic and leak easily.^[10]

As the malignant cells continue to proliferate, they invade surrounding tissues. Angiosarcoma is described as having an infiltrative growth pattern, meaning it does not remain contained but instead sends extensions into nearby structures. This infiltrative nature makes it very difficult to determine the exact boundaries of the tumor during surgery, which is one reason why achieving complete surgical removal can be challenging and local recurrence rates are high.^[10]

One of the most dangerous characteristics of angiosarcoma is its high propensity for metastasis. Because the cancer cells originate from the lining of blood and lymphatic vessels, they have direct access to the circulatory and lymphatic systems. This makes it relatively easy for cancer cells to break off from the primary tumor, enter the bloodstream or lymphatic circulation, and travel to distant sites in the body. The liver and lungs are particularly common sites of metastasis, though the cancer can spread to virtually any organ including bones, brain, and other soft tissues.^[2][10]

When angiosarcoma develops in response to radiation therapy, the pathophysiology involves damage to endothelial cells from the radiation exposure. The radiation causes DNA damage and chronic inflammation in the irradiated area. Over time, this damage can accumulate and lead to malignant transformation of the endothelial cells. Similarly, chronic lymphedema creates an environment of persistent inflammation and impaired lymphatic drainage, which may contribute to the development of lymphangiosarcoma through mechanisms that are not fully understood but likely involve chronic tissue stress and altered immune surveillance.^[2]

At the microscopic level, angiosarcomas show certain characteristic features. The tumor cells are typically arranged in patterns that attempt to form vascular channels or spaces, reflecting their origin from blood vessel lining cells. However, these structures are highly abnormal compared to normal blood vessels. The cells themselves show features of malignancy including irregular shapes, large nuclei, and frequent cell division. Pathologists use special stains and immunohistochemical markers to confirm the diagnosis, looking for proteins that are specifically expressed by endothelial cells.^[10]

The aggressive biological behavior of angiosarcoma is reflected in its tendency for rapid growth, extensive local spread, high rates of recurrence after treatment, and frequent distant metastasis. Even with intensive treatment, many patients experience cancer returning at the original site or developing new tumors in distant organs. This aggressive nature is why angiosarcoma carries such a poor prognosis, with five-year survival rates ranging from 30 to 38 percent overall, and even lower for cardiac and hepatic forms of the disease.^[2][10]