What is Epithelioid Sarcoma?

Epithelioid sarcoma is a rare and aggressive type of cancer that affects the soft tissues in the body. It’s characterized by having characteristics of both epithelial and mesenchymal cells. This condition mainly affects young adults and it often appears as a painless but slowly growing mass, usually found on the hands or feet. The cancer has the potential to locally invade the surrounding areas and often spreads to the nearby lymph nodes and other parts of the body.

Doctors diagnose epithelioid sarcoma by taking a sample of the tissue (known as a biopsy), and imaging studies like X-rays or scans are crucial for determining how far the primary tumor has spread and if it has reached other parts of the body.

If the disease is detected early enough, completely removing the tumor through surgery can cure it. However, the cancer can recur locally or spread to distant parts in the body at a later stage, which is why long-term monitoring is necessary. Radiation therapy may be used to help with treatment, and can also help ease symptoms in cases where the disease can’t be cured.

The good news is, newer treatment options have become available with the development of targeted therapies. These new treatments specifically focus on the cancer cells and aim to improve life expectancy and quality of life for patients.

What Causes Epithelioid Sarcoma?

Epithelioid sarcomas are a type of cancer that starts in cells that can change into cells lining organs (a process called epithelial cell differentiation). In up to 90% of cases, these cancers lose what’s called integrase interactor-1 (or INI-1) expression.[3]

INI-1 is a component of something called the SWI/SNF chromatin remodeling complex, and it’s found in all normal cells that have a nucleus. This complex plays an important role in our bodies because it adjusts the structure of DNA to allow for DNA transcription, which is a process that’s key for making new proteins and cells.

The gene for INI-1, which is also called SMARCB1, is found on a specific location on chromosome 22 known as the 22q11 band. A variety of gene deletions and rearrangements in this location, including the swapping of genetic material between chromosomes (called translocation), can cause cancers in cells that are deficient in INI-1 or epithelioid sarcomas.[4]

Interestingly, some people have had prior injuries at the location where the tumor is found, noted in up to 27% of occurrences.[5] Nonetheless, injuries to the distal extremity or ends of limbs are quite common, so it’s difficult to definitively say if these injuries actually triggered the cancer.

Risk Factors and Frequency for Epithelioid Sarcoma

Epithelioid sarcomas are uncommon, making up less than 1% of soft tissue sarcomas. These primarily affect men, with twice as many cases in men as in women. The majority of these tumours are found in young males between the ages of 10 and 45. However, it can occur in anyone between the ages of 4 and 90, with the most common age being 27.

Signs and Symptoms of Epithelioid Sarcoma

Epithelioid sarcoma is identified by a slowly growing bump or lesion, often found on the upper extremities like the fingers, hands, and forearm. These nodules are typically painless and grow at a gradual pace, often creating a cluster-like appearance. It’s common for these lesions to break the skin’s surface or spread into nearby areas. They can appear in several layers of the skin, including the dermis, subcutis, or deep fascia.

Essential information for diagnosing this condition includes the history of the lesion’s appearance, the rate at which it has grown, any previous injuries to the area, symptoms relating to nerve or blood vessel deficits, and any symptoms that might suggest the disease has spread to the lungs – like a new cough or spitting up blood.

This type of sarcoma often moves along fascial planes and tendons, potentially affecting a larger area than what is visible. Another variant of this sarcoma, the proximal variant, usually appears in the areas around the pubic region, genitals, or trunk of the body. These can become quite large, up to 20 cm, particularly in the proximal variant. However, they often measure less than 5 cm across.

During a physical exam, doctors will focus on the size of the tumor, how close it is to surrounding structures, if it has invaded surrounding structures, and any changes in the overlying skin. Since this type of sarcoma frequently spreads to lymph nodes – a rarity for soft tissue sarcomas – all surrounding lymph node areas should be checked. A general physical evaluation will include a whole-body skin examination, lung sound check, and examination of other potential metastatic disease sites.

Testing for Epithelioid Sarcoma

If you have a soft tissue swelling, your doctor will likely need to perform a biopsy to figure out the cause. A biopsy is a procedure where a small sample of tissue is removed and examined under a microscope. The most common type of biopsy used for this purpose is a core needle biopsy. Additionally, if any of your lymph nodes (small, bean-shaped organs that produce and store cells that fight infection and disease) look suspicious, your doctor might take samples from there as well.

Magnetic Resonance Imaging (MRI) is usually the best tool for diagnosing soft-tissue sarcomas, a type of cancer that begins in the body’s connective tissues. An MRI provides detail-oriented images showing if and how much the tumor has spread into the surrounding tissues. For larger, more complex lesions, your doctor may recommend an image-guided biopsy to ensure they’re sampling the most active areas of the tumor. In some cases, larger incisional (a small cut is made and a portion of the tumor is removed) or excisional (the entire tumor is removed) biopsies might be necessary. If a surgical biopsy is performed, it will be planned in such a way that the biopsy can be included in any later surgeries to remove the tumor.

If you’re diagnosed with epithelioid sarcoma, a specific type of soft-tissue sarcoma, there’s a chance the cancer could spread to other parts of your body. Some recent studies suggest that this might happen in up to half of cases. The most common places this cancer spreads to are the lungs, lymph nodes, and skin. Due to this risk, your doctor will want to create a “map” of the cancer and may perform a chest Computed Tomography (CT) scan, which offers detailed pictures of the structures inside your chest. More extensive imaging like fluorodeoxyglucose-positron emission tomography (FDG-PET) scans or additional CT scans might also be necessary, depending upon the properties of the original tumor.

Treatment Options for Epithelioid Sarcoma

The first course of action in treating a non-spreading epithelioid sarcoma, a rare type of soft tissue cancer, is a procedure called a wide excision. This involves the removal of the tumor and some normal tissue around it. The margins or the size of normal tissue cut away can range from 2 to 5 cm, depending on the individual case. The goal is to strive for a balance between removing as much of the tumor as possible and maintaining the functionality of the affected limb.

Even though this disease tends to spread or metastasize, doctors do not usually recommend checking sentinel lymph nodes (the first lymph nodes where cancer is likely to spread) in patients who do not appear to have cancer in the lymph nodes. However, removal of the lymph nodes in the immediate area is advised if cancer is detected in these nodes.

There’s differing opinions and limited data on the best surgical approach for managing the disease when it has spread within the same region (solitary in-transit metastases) or to the lungs (isolated pulmonary metastases). In some situations, the removal of these metastasis, a procedure called metastasectomy, might be recommended.

Radiation therapy is often added to the treatment plan to lessen the chance of the disease coming back in the same area. That being said, the decision to use radiation therapy is typically made on a case-by-case basis. It’s often suggested for patients where the cancer was not completely removed during surgery, if the disease comes back, or to ease symptoms in patients with large tumors. Recently, a new drug called Tazemetostat, which inhibits a protein called EZH2, has been approved for use in patients who have unresectable (unable to be removed with surgery) or metastatic epithelioid sarcoma.

The chances of the disease returning in the same area after treatment is unfortunately quite high – between 40% to 60%. This usually happens within 1 to 2 years after the initial surgery, but can occur as late as 20 years later. Due to this risk, it’s crucial for patients to undergo frequent check-ups with imaging tests to monitor the original site of the disease and the lungs, typically every 6 months to 1 year.

Epithelioid sarcoma diagnosis can often be complicated. It shares features with many other conditions, making it difficult to identify based merely on its physical characteristics. Doctors usually use a type of labelling test, immunohistochemical staining, to confirm the diagnosis. However, these tests too can sometimes be misleading as other common conditions can present the same results. Therefore, the clinical context, such as a young male with a soft tissue mass in the extremity, is also very important in diagnosis. The labelling test serves as additional supportive evidence for the diagnosis.

The conditions that can be confused with epithelioid sarcoma based on their appearance include benign conditions such as:

Granulomatous diseases
Nodular fasciitis
Fibrohistiocytic lesions
Fibromatosis
Tenosynovial giant cell tumors

It can also resemble malignant conditions like:

Metastatic carcinoma
Melanoma
Synovial sarcoma
Vascular neoplasms
Spindle cell squamous cell carcinoma
Malignant peripheral nerve sheath tumor (MPNST)
Extrarenal rhabdoid tumor

The immunohistochemical stains used to help diagnose epithelioid sarcoma generally have the following results:

CD34: Positive in about half cases of epithelioid sarcoma
Vimentin: Tested positive in epithelioid sarcoma patients
INI-1: Generally poorly expressed in cases of epithelioid sarcoma
CK7: Usually not seen in epithelioid sarcoma
CK5/6 and p63: Generally negative in epithelioid sarcoma cases
S100: Not seen in epithelioid sarcoma
CD31: Rarely seen in epithelioid sarcoma, except in one documented case
SALL4: Mostly not present in epithelioid sarcoma

Epithelioid sarcoma tests also show varying levels of positivity for ERG, and have demonstrated the presence of markers like ERG, FLI1, and D240.

What to expect with Epithelioid Sarcoma

The outlook or prognosis of epithelioid sarcoma, like most types of cancer, greatly depends on how advanced the disease is at the time of diagnosis. Factors influencing the prognosis include the size of the tumor, whether the cancer has spread to blood vessels (vascular invasion), whether the tumor can be completely removed (resectability), and whether the disease has spread to other parts of the body (metastases). Large tumors and early spread of the disease generally lead to worse outcomes.

There are two types of epithelioid sarcoma: proximal and usual. The proximal type is generally seen as more aggressive, but a study found no significant difference in survival rates between the two types.

Many factors can impact the prognosis. These include the patient’s gender, age at diagnosis, location of the tumor, size of the tumor, and certain microscopic characteristics of the tumour. For instance, females and younger patients generally have better outcomes. Similarly, tumors that are located further away from the center of the body (distal lesions) tend to have better outcomes compared to those closer to the center (proximal lesions).

On the other hand, tumors larger than 2 cm in diameter, as well as those showing death of tissue (necrosis) and vascular invasion, are associated with worse outcomes. Typically, the 5-year survival rate for this disease ranges from 60% to 75%.

Possible Complications When Diagnosed with Epithelioid Sarcoma

The complications connected to epithelioid sarcoma are mainly divided into
problems linked to the primary illness, those due to the treatments, and
complications resulting from the cancer spread to distant body parts. When the
tumor spreads locally, it can harm nearby tissues, nerves, blood vessels, and bones, causing damage to the skin, underlying soft tissues, and bones. The spread of the cancer to the lymph nodes, lungs, and skin can result in local symptoms. In addition, depending on where the original tumor is, surgery to remove it or radiation treatment can cause complications.

Common Complications Include:

Damage to nearby tissues, nerves, blood vessels, and bones
Destruction of skin, soft tissues under the skin, and skeletal structure
Spread of the cancer to lymph nodes, lungs, and skin
Local symptoms based on the site of the tumor
Complications resulting from surgical removal of the tumor
Complications due to radiation treatment

Preventing Epithelioid Sarcoma

Epithelioid sarcoma is a slow-growing tumor often found in the soft tissues, especially in the arms and hands. It is more common in young men. Sometimes, the condition may not show any symptoms, which is why it’s important to get any unusual growths checked by a doctor.

Once diagnosed, it’s crucial that the patient is fully informed about all the treatment options available, along with their potential risks and benefits. Patients should also be made aware of any complications that might occur after treatment and any troubling symptoms. If any of these symptoms show up, the patient should immediately let their doctor know.

Doctors should also talk to their patients about what to expect in terms of the disease’s progression. Patients should understand that this kind of tumor can sometimes come back years after the first treatment, making it necessary to frequently monitor the condition long-term.

While there are currently no known ways to prevent Epithelioid sarcoma, patients should understand the importance of regular check-ups and adhering to follow-up appointments for image scans. These steps are critical in managing the condition and ensuring potential issues are dealt with promptly.