Epithelioid sarcoma is a rare and aggressive type of soft tissue cancer that often begins as a small, painless lump under the skin. Though it grows slowly, this cancer has a high tendency to return after treatment and can spread to other parts of the body, making early detection and specialized care essential for better outcomes.
What Is Epithelioid Sarcoma?
Epithelioid sarcoma is an extremely rare form of cancer that develops in the soft tissues of the body. Soft tissue refers to the material that connects, supports, or surrounds other structures in the body, including muscles, fat, blood vessels, nerves, and tissues around joints. This particular type of cancer accounts for less than one percent of all soft tissue sarcomas, which themselves are already among the rarest types of cancer.[1][2]
What makes epithelioid sarcoma especially challenging is its appearance and behavior. The cancer typically presents as a small, firm growth called a nodule beneath the skin. These nodules are usually painless, which can delay people from seeking medical attention. Sometimes the nodule develops into a sore on the skin that refuses to heal, resembling a persistent wound or wart. This innocent appearance often leads to misdiagnosis, as doctors may initially mistake it for more common conditions like skin infections or benign cysts.[1][6]
Despite its slow growth pattern, epithelioid sarcoma is considered aggressive. It has a tendency to grow deeply into surrounding tissues and can spread to other areas of the body. The cancer most commonly returns after surgical removal, with approximately half of all cases experiencing recurrence, meaning the cancer comes back after treatment. About forty percent of patients develop metastasis, which is when cancer spreads from its original location to distant parts of the body, most often the lymph nodes, lungs, and bones.[2][8]
There are two main types of epithelioid sarcoma. The distal type is the most common form, typically affecting teenagers and young adults. This version usually develops in the lower portions of the arms and legs, particularly in the hands, fingers, forearms, feet, and lower legs. The proximal type is less common but more aggressive. It tends to affect adults and develops in areas closer to the center of the body, including the head, neck, chest, abdomen, pelvis, and genital regions. The proximal type tumors are often located more deeply within tissues and tend to be larger in size.[2][7]
How Common Is Epithelioid Sarcoma?
Epithelioid sarcoma is exceptionally rare. In England, an average of only nineteen cases are diagnosed each year. To put this in perspective, epithelioid sarcoma makes up just under half a percent of all soft tissue sarcomas, and approximately 0.01 percent of all cancers diagnosed. These numbers highlight just how uncommon this disease truly is.[7]
The disease can affect people of all ages, but it most commonly strikes young adults between the ages of twenty and forty. Men are slightly more likely to develop epithelioid sarcoma than women. While the cancer can theoretically develop anywhere in the body, the vast majority of cases occur in the extremities, particularly the arms and legs.[2][3]
Because the cancer grows slowly and is often painless, many patients experience symptoms for months or even years before receiving a proper diagnosis. On average, the time from when symptoms first appear to when the diagnosis is made ranges from nine to thirty months. About one-third of patients have symptoms for more than two years before discovering they have epithelioid sarcoma. This lengthy delay in diagnosis means that by the time patients first seek medical attention, approximately one-third already have cancer spread to nearby lymph nodes, and about one-quarter have lung metastases.[8]
What Causes Epithelioid Sarcoma?
The exact cause of epithelioid sarcoma remains unknown. Scientists have not identified what triggers the initial development of this cancer. However, research has revealed important clues about the genetic changes that occur in these tumors.[1]
Epithelioid sarcoma begins when cells in soft tissue undergo changes in their DNA, which is the genetic material that contains instructions for how cells should function. In healthy cells, DNA provides precise directions for growth, multiplication, and death at appropriate times. In cancer cells, DNA changes give different instructions. These altered commands tell cells to grow and multiply uncontrollably and to avoid dying when they should.[1]
The most significant genetic finding in epithelioid sarcoma involves a gene called SMARCB1, also known as INI-1. This is a tumor suppressor gene, meaning it normally contains instructions that help prevent tumors from forming. In eighty to ninety percent of epithelioid sarcoma cases, this gene either becomes inactivated or its protein product is lost. When the SMARCB1 gene doesn’t function properly, it becomes easier for tumors to develop and grow.[2][4][6]
Importantly, this genetic mutation is not something people are born with. Instead, it happens at some point during a person’s lifetime. The mutation is acquired rather than inherited, which means it develops in the tissue cells themselves rather than being passed down from parents. Researchers are still working to understand why these genetic errors occur and exactly how they lead to the development of epithelioid sarcoma.[2][7]
Who Is at Risk?
Anyone can potentially develop epithelioid sarcoma, regardless of age, gender, or background. However, certain characteristics appear more commonly among those diagnosed with this cancer. The disease shows a clear preference for young adults, with most cases occurring in people between twenty and forty years old. This age distribution is unusual for cancer, as many types of cancer are more common in older individuals.[2][3]
Gender plays a small role in risk, with males being slightly more likely to develop epithelioid sarcoma compared to females. However, this increased risk is modest, and the disease certainly affects both men and women.[2]
One identified risk factor is previous exposure to radiation therapy for other cancers. People who have undergone radiation therapy as treatment for a different type of cancer appear to have a slightly elevated risk of developing epithelioid sarcoma later in life. Radiation therapy uses high-energy beams to kill cancer cells, but in rare cases, it can damage healthy DNA in ways that later contribute to new cancers developing.[2]
It’s important to understand that having one or more risk factors doesn’t mean someone will definitely develop epithelioid sarcoma. Many people with these characteristics never develop the disease, and some people with no apparent risk factors do develop it. The rarity of this cancer means that even among those with risk factors, the absolute chance of developing epithelioid sarcoma remains very low.[2]
What Are the Symptoms?
The symptoms of epithelioid sarcoma can vary depending on where the tumor is located and how large it has grown. Many people have the disease for months or even years before noticing any symptoms at all. This happens because tumors often grow into deep tissue where they cannot be easily seen or felt from the outside.[2]
The most common symptom is discovering a new lump or area of swelling beneath the skin. This lump typically feels hard or firm to the touch. It is usually painless, which unfortunately means many people delay seeking medical attention because the lump doesn’t cause discomfort. The nodule may be small when first noticed but can gradually increase in size over time.[1][2]
In some cases, the skin over the lump may break down, creating open sores called ulcers. These sores don’t heal the way normal wounds do, even with time and standard care. The ulcers may bleed or develop areas of dead tissue called necrosis. When this happens, the condition might be mistaken for a skin infection, a poorly healing injury, or a persistent wart.[7][8]
Sometimes multiple nodules appear in the same area rather than just a single lump. About thirteen percent of patients present with multiple tumors at the time of diagnosis. The edges of these lumps may not feel clearly defined, and they can sometimes feel connected to deeper structures.[6]
Pain is not a typical early symptom of epithelioid sarcoma. However, if the tumor grows large enough to put pressure on nearby nerves or muscles, pain can develop. This type of pain usually feels deep and may worsen with movement or use of the affected limb.[2]
The location of symptoms most commonly involves the hands, fingers, forearms, feet, and lower legs for the distal type. For the proximal type, symptoms may appear around the shoulders, upper arms, thighs, groin, chest, back, or even the genital area.[2][7]
How Is Epithelioid Sarcoma Diagnosed?
Diagnosing epithelioid sarcoma can be challenging because it resembles many more common conditions. Healthcare providers often consider and rule out other possibilities before arriving at this rare diagnosis. The diagnostic process typically involves several steps and different types of tests.[9]
The process begins with a thorough physical examination. A doctor will carefully look at and feel any lumps or areas of concern. They will assess the size, texture, and location of the mass. A complete skin examination may be performed to look for additional lumps and to help rule out skin conditions that might appear similar to epithelioid sarcoma.[2]
Imaging tests are essential for seeing what’s happening inside the body. An MRI scan (magnetic resonance imaging) is particularly useful because it provides detailed pictures of soft tissues. It helps doctors determine the exact size and location of the tumor and whether it has grown into nearby structures like blood vessels, nerves, or bones. Sometimes the borders of epithelioid sarcoma appear unclear on MRI, and the tumor may seem to exist as multiple connected areas rather than one distinct mass.[4][8]
Additional imaging tests help determine if the cancer has spread beyond its original site. CT scans (computed tomography) of the chest, abdomen, and pelvis can reveal whether cancer has spread to internal organs, particularly the lungs, which are a common site of metastasis. PET scans (positron emission tomography) may also be used to identify cancer cells throughout the body. These scans work by detecting areas where cells are particularly active, which can indicate the presence of cancer.[4][9]
A biopsy is the only way to definitively confirm a diagnosis of epithelioid sarcoma. During a biopsy, a small sample of tissue is removed from the suspicious area and examined under a microscope by a specialist called a pathologist. The biopsy can be performed using a needle inserted through the skin, or sometimes a small surgical procedure is necessary to obtain an adequate sample. It’s important that the doctor performing the biopsy has experience with bone and soft tissue tumors, as the technique used can affect both diagnosis and future treatment.[4][8][9]
The tissue sample undergoes several special tests in the laboratory. Pathologists look at the structure and appearance of the cells. They also perform tests to detect the presence or absence of specific proteins. A key finding in epithelioid sarcoma is the loss of the INI-1 protein, which corresponds to the SMARCB1 gene mutation. This test helps distinguish epithelioid sarcoma from other types of tumors that may look similar under the microscope.[3][4]
Blood work is typically performed as part of the overall evaluation, though there is no specific blood test that can diagnose epithelioid sarcoma. Blood tests help assess general health and organ function, which is important for planning treatment.[4]
Because epithelioid sarcoma can spread to lymph nodes more often than other soft tissue sarcomas, doctors may examine the lymph nodes near the tumor. In some cases, a lymph node biopsy may be recommended if imaging suggests the cancer has spread to these areas.[8]
Prevention
There are no known specific methods to prevent epithelioid sarcoma. Because the exact cause of this cancer remains unclear and the genetic changes involved appear to happen spontaneously rather than being inherited, there are no lifestyle modifications, dietary changes, or supplements that have been proven to reduce the risk of developing this disease.[1][7]
Given the rarity of epithelioid sarcoma and the lack of identifiable preventable causes, general cancer prevention strategies don’t specifically apply. However, awareness of one’s body and prompt medical attention for concerning symptoms remain the best approaches for early detection. Being attentive to any new, persistent lumps, especially those that grow, change, or develop skin changes, allows for earlier medical evaluation and potentially earlier diagnosis if cancer is present.[2]
For people who have previously been treated for other cancers with radiation therapy, there is a slightly increased risk of developing epithelioid sarcoma. However, this risk is so small that it doesn’t outweigh the benefits of radiation therapy when it’s needed to treat other cancers. Regular follow-up care after cancer treatment can help detect any new problems early.[2]
How Epithelioid Sarcoma Affects the Body
Understanding what happens in the body when epithelioid sarcoma develops requires looking at both the cellular level and the broader impact on tissues and organs. Pathophysiology refers to the changes in normal body functions that occur because of disease.[3]
At the cellular level, epithelioid sarcoma represents an unusual type of cancer because it shows characteristics of both epithelial and mesenchymal cells. Epithelial cells normally form the lining of organs and skin, while mesenchymal cells make up connective tissues like bone, cartilage, and fat. This dual nature makes epithelioid sarcoma somewhat unique among cancers and contributes to its distinctive appearance under the microscope.[3]
When examined microscopically, epithelioid sarcoma typically shows a nodular or lobular pattern. The cancer cells often arrange themselves around areas of central necrosis, where tissue has died. The cells themselves appear epithelioid, meaning they look somewhat like epithelial cells with a polygonal shape and eosinophilic (pink-staining) cytoplasm. At the edges of the tumor, cells may appear more elongated or spindle-shaped.[3]
The tumor grows by invading surrounding tissues. Unlike some cancers that grow as well-defined masses that push nearby structures aside, epithelioid sarcoma tends to infiltrate into adjacent tissues. This infiltrative growth pattern makes it challenging to determine the exact boundaries of the tumor, which has important implications for surgical treatment. Complete removal requires taking out not just the visible tumor but also surrounding tissue to ensure no microscopic cancer cells remain.[3]
Epithelioid sarcoma has an unusual tendency to spread through the lymphatic system. Most soft tissue sarcomas spread primarily through the bloodstream, but epithelioid sarcoma behaves more like some epithelial cancers in its pattern of spread. Between twenty-two and forty-eight percent of cases show lymphatic spread, meaning cancer cells travel through lymph vessels to nearby lymph nodes. This is why examination and sometimes biopsy of regional lymph nodes is an important part of diagnosis and staging.[6]
The cancer can also spread through the bloodstream to distant organs. The lungs are the most common site of distant metastasis, followed by bones and less commonly the brain. When cancer spreads to these distant sites, it creates new tumors that consist of epithelioid sarcoma cells, not cells of the organ where the metastasis is located.[6]
On imaging studies, the tumor may show certain characteristic features. Calcification, which is the deposit of calcium salts, can sometimes be seen within the tumor. In larger tumors, areas of hemorrhage (bleeding) and necrosis are often present. The tumor may surround or encase nearby blood vessels, nerves, or even bone without necessarily invading these structures.[8]
The biological behavior of epithelioid sarcoma is characterized by its high rates of both local recurrence and distant metastasis. Even after what appears to be complete surgical removal, microscopic cancer cells may remain in the surrounding tissue or may have already spread through lymphatic or blood vessels before surgery. This is why many patients experience the cancer returning either at the original site or appearing in distant locations months or years after initial treatment.[3][8]