Epithelioid Sarcoma

Epithelioid sarcoma is a rare and aggressive type of soft tissue cancer that often starts as a small, painless lump, usually on the hands, arms, legs, or feet. Though it grows slowly, this cancer is known for being difficult to treat and has a high chance of returning after treatment.

Table of contents

• What is Epithelioid Sarcoma?
• Types of Epithelioid Sarcoma
• Signs and Symptoms
• Causes and Risk Factors
• How Doctors Diagnose Epithelioid Sarcoma
• Understanding Cancer Stages
• Treatment Options
• Outlook and Survival

What is Epithelioid Sarcoma?

Epithelioid sarcoma is a very rare type of cancer that starts in the soft tissue, which includes muscles, tendons, fat, and other tissues that connect and support the body^[1]. This cancer accounts for less than 1% of all soft tissue sarcomas, making it extremely uncommon^[2]. In England, an average of only 19 cases are diagnosed each year^[7].

The disease most commonly affects young adults, particularly those between ages 20 and 40, and is slightly more common in men^[2][8]. However, it can occur at any age, including in teenagers and children^[1][4].

Epithelioid sarcoma typically appears in the arms, hands, fingers, legs, or feet, but it can develop anywhere in the body^[1][2]. Despite growing slowly, this cancer is considered aggressive because it often grows deeply into tissue and can spread to other parts of the body^[2]. About half the time, it comes back after surgery removes it^[2].

Because epithelioid sarcoma is so rare and can look like more common conditions such as warts, cysts, or skin infections, it is often misdiagnosed^[4][6]. This is why it is important for people with this condition to receive care from specialists who have experience in diagnosing and treating rare sarcomas^[2][4].

Types of Epithelioid Sarcoma

There are two main types of epithelioid sarcoma, and they differ in where they appear on the body^[2][7]:

Distal type is the most common form. It typically affects teenagers and young adults and appears under the skin in the lower parts of the arms and legs, such as the fingers, hands, forearms, feet, and lower legs^[2][7][8]. In some cases, the tumor may break through the skin and create an open sore or ulcer within a few months^[8].

Proximal type is less common and mainly affects adults. It forms in areas closer to the center of the body, such as the head, neck, chest, abdomen, pelvis, groin, shoulders, and thighs^[2][7][8]. These tumors are usually located more deeply and are larger in size than the distal type^[8].

Signs and Symptoms

Epithelioid sarcoma is a slow-growing and usually painless tumor, which often results in a long period of time between when the tumor first appears and when it is diagnosed^[6]. Because the cancer grows slowly, people may have symptoms for months or even years before noticing anything is wrong^[2][4]. On average, the time from when symptoms start to diagnosis is about 10 months, though one-third of patients have symptoms for more than two years^[8].

The most common symptom is a small, firm lump or swelling under the skin^[1][2][7]. This lump is usually hard and slow-growing, and it typically doesn’t hurt^[7][8]. Sometimes there is more than one lump^[1].

As the tumor grows, other symptoms may appear^[2]:

• A new, hard lump beneath the skin
• An existing lump that gets bigger
• Open wounds or sores on the skin above the lump, which may bleed and can be painful^[1][2][7]
• Pain, if the tumor puts pressure on muscles or nerves^[2]

These tumors often grow into tissue where they cannot be seen, which is why symptoms may not be noticed for a long time^[2]. The lumps most often appear on the fingers, hands, forearms, knees, or lower legs^[1][7].

Causes and Risk Factors

The exact cause of epithelioid sarcoma is not known^[1][4][7]. However, researchers have found that the disease is linked to a problem with a gene called SMARCB1 (sometimes also called INI-1)^[2][4][6].

The SMARCB1 gene is a tumor suppressor gene, which means it contains instructions that tell the body how to prevent tumors from forming^[2]. In epithelioid sarcoma, this gene changes or mutates. The mutation happens at some point during a person’s lifetime, so it is not something people are born with^[2]. Up to 90% of epithelioid sarcomas show a loss of function of the INI-1 protein^[3][6].

When the SMARCB1 gene doesn’t work properly, the cancer cells get changes in their DNA, which holds the instructions that tell cells what to do^[1]. In healthy cells, DNA gives instructions to grow and multiply at a set rate and to die at a set time. In cancer cells, the DNA changes give different instructions, telling the cells to grow out of control^[1].

Anyone can get epithelioid sarcoma, but certain factors may increase the risk^[2]:

• Being a young adult, especially between ages 20 and 40
• Being male (it is slightly more common in men)
• Having had radiation therapy for other cancers in the past

How Doctors Diagnose Epithelioid Sarcoma

Epithelioid sarcoma can be hard to diagnose because it looks like problems that are much more common, such as warts, cysts, or skin infections^[9]. Often, doctors consider those more common problems first^[9].

To diagnose epithelioid sarcoma, doctors use several tests^[2][4][9]:

Physical exam: The doctor will do a whole-body skin check to look for lumps and feel any areas of concern^[2][7]. This helps rule out skin conditions that may look like epithelioid sarcoma^[2].

Imaging tests: These tests take pictures of the inside of the body and can show the location and size of the tumor^[4][9]. They also help doctors see if the cancer has spread to other parts of the body, such as lymph nodes, lungs, or bones^[2][4]. Imaging tests may include:

• MRI (Magnetic Resonance Imaging): This helps find the tumor inside the body^[2][4]
• CT scans (Computed Tomography): These show if the cancer has spread^[2][4]
• Chest CT: This checks the lungs for cancer spread^[4]
• PET scan (Positron Emission Tomography): This measures important body functions and can show whether cancer has spread^[4][9]
• X-ray: This may also be used to look at the affected area^[9]

Biopsy: This is the only way for doctors to confirm a diagnosis of epithelioid sarcoma^[2][9]. A biopsy is a procedure where the doctor removes a small sample of tissue for testing in a lab^[9]. The tissue might be removed using a needle that is put through the skin and into the cancer^[9]. Sometimes surgery is needed to get the tissue sample^[9].

A specialist examines the tissue under a microscope to see if it is cancer and to check for the SMARCB1 or INI-1 marker^[4]. Other special tests give more details about the cancer cells^[9]. It is important that the doctor who performs the biopsy and the pathologist who evaluates it are experienced in bone and soft tissue tumors^[8].

Understanding Cancer Stages

Cancer staging helps doctors determine how advanced the cancer is^[2][4]. Staging of epithelioid sarcoma is based on the size of the tumor and whether it has spread to lymph nodes or distant sites in the body^[4].

Doctors assign numbers from 1 (I) to 4 (IV) based on things like tumor size, location, and whether it has spread^[2]. Stage I is the least advanced, or early-stage cancer. Stage IV is the most advanced, or cancer that has spread^[2].

Doctors may also use words like “localized” or “metastatic” to describe the cancer stage^[2][4]:

• Localized epithelioid sarcoma means the tumor has not spread and is only in one area. This is easier to treat^[2][4].
• Metastatic epithelioid sarcoma means the tumor has spread past nearby tissues to the lungs or other organs^[4].

Epithelioid sarcoma commonly spreads to regional lymph nodes and distant sites^[3]. In fact, at the time of initial diagnosis, about one-third of patients have lymph node metastases and about one-quarter have lung metastases^[8].

Treatment Options

The primary treatment for epithelioid sarcoma is complete surgical removal of the tumor^[3][7][8]. Sometimes other treatments may be used in addition to surgery^[9].

Surgery

Surgery is the most common and most important treatment for epithelioid sarcoma^[7][9]. The goal of surgery is to remove all of the cancer^[9].

During surgery, doctors perform a procedure called a wide resection with margins^[4][7]. This means the surgeon removes the tumor and some of the healthy tissue around it^[9]. Taking some healthy tissue, called “taking a margin,” helps make sure that all the cancer cells are removed^[7][9]. Getting all of the cancer cells lowers the risk that the cancer will come back^[9].

A tumor that is not removed cleanly with wide margins has a nearly 100% recurrence rate and is prone to spread to other parts of the body^[8]. For this reason, it is important that the surgeon performing the operation is an experienced specialist^[8].

If the doctor is concerned that cancer has also spread to nearby lymph nodes, they may also be removed^[4].

Because epithelioid sarcoma mostly affects the hands, arms, legs, and feet, surgeons try to do limb-sparing surgery so that the limb can continue to work well^[7]. However, in very rare cases, if the cancer has spread throughout the limb, surgeons may have to perform a partial or full amputation to stop the cancer^[7]. About half of recurrent tumors require amputation^[8].

Radiation Therapy

Radiation therapy uses powerful energy beams to kill cancer cells^[3][7][9]. It can be used either before or after surgery^[4][7].

When used before surgery, radiation therapy aims to shrink the tumor. This can make it more likely that all of the cancer will be removed during surgery^[4][9].

When used after surgery, radiation therapy aims to kill off any remaining cancer cells that have not been removed by surgery^[4][7][9].

Adding radiotherapy to surgical treatment before or after surgery reduces the chance of the tumor coming back^[8]. Therefore, surgery combined with radiotherapy is the standard of care^[8].

Chemotherapy

Chemotherapy uses anti-cancer drugs to destroy cancer cells^[7]. It is sometimes used in patients who have a high risk of the cancer coming back or if the cancer has spread to other parts of the body^[7].

In patients with epithelioid sarcoma, chemotherapy is recommended for locally advanced or metastatic cases^[8]. Drugs such as doxorubicin combined with ifosfamide, gemcitabine combined with docetaxel, and pazopanib are among the chemotherapy drugs used for this purpose^[8].

Targeted Therapy

Targeted therapy uses drugs that target specific changes in cancer cells^[9]. Recently, treatment options have evolved with the development of targeted therapies, which aim to improve patient outcomes^[3].

One such targeted therapy is tazemetostat, which has been developed for advanced cases of epithelioid sarcoma^[8].

Outlook and Survival

Epithelioid sarcoma has an aggressive course, which means there is a high risk of the cancer coming back after surgery and a high risk of spreading to other parts of the body, often to the lymph nodes and lungs^[8].

The average risk of the cancer coming back after surgery is reported to be 50%, though it can range from 30% to 70%^[8]. The risk of the cancer spreading to other parts of the body (metastasis) is about 40%^[8].

Because of the high likelihood of the cancer coming back or spreading, long-term monitoring is essential for managing the disease^[3].

The average 5-year survival rate of patients with epithelioid sarcoma is 70% for patients with local disease and 50% for patients with regional lymph node involvement^[8]. In patients with lung metastases, the one-year survival rate is 50%, and the five-year survival rate is unfortunately close to zero^[8].

Several factors are associated with a worse outcome^[8]:

• Tumor diameter greater than 5 centimeters
• Regional lymph node involvement
• Vascular invasion (cancer cells in blood vessels)
• Necrosis rate (dead tissue) greater than 30%
• Local symptoms
• Positive surgical margins (cancer cells at the edge of removed tissue)
• Metastases (cancer spread to other parts of the body)

Factors associated with a better outcome include younger age, being female rather than male, having the distal type rather than the proximal type, smaller tumor size, and negative margins upon tumor removal^[6].