Extraskeletal Myxoid Chondrosarcoma

Extraskeletal myxoid chondrosarcoma is a very rare type of cancer that develops in soft tissues rather than bones, affecting only about 14 people each year in England. Despite its slow growth, this tumor can come back or spread years after initial treatment, requiring long-term monitoring and careful management.

Table of contents

• What is extraskeletal myxoid chondrosarcoma?
• Identification codes and classification
• Who gets this disease?
• Where does it occur in the body?
• Signs and symptoms
• How is it diagnosed?
• Genetic characteristics
• Treatment options
• Long-term outlook and survival

What is extraskeletal myxoid chondrosarcoma?

Extraskeletal myxoid chondrosarcoma, often shortened to EMC, is a very rare type of soft tissue sarcoma, which is a form of cancer that develops in the body’s connective tissues^[1]. Despite its name suggesting a connection to cartilage, EMC does not actually develop from cartilage cells. Instead, it grows from soft tissue cells, and scientists are still uncertain about its exact origin^[2].

EMC is classified as a mesenchymal neoplasm with uncertain differentiation, meaning doctors cannot determine exactly what type of normal tissue these cancer cells were supposed to become^[7]. The disease was first described in 1953, but the specific concept of EMC was established in 1972^[4].

This cancer makes up less than 3% of all soft tissue tumors and accounts for only 0.36% of all soft tissue sarcomas^[2]. In England, an average of only 14 cases are diagnosed each year^[2].

Identification codes and classification

C563195
C49.9
10073134

Who gets this disease?

EMC primarily affects adults in middle age. Most people are diagnosed when they are around 49 to 54 years old, though the disease can occur at any age^[1][4]. The disease is more common in men than in women, with about two men affected for every one woman^[1][2].

Scientists believe that EMC occurs when chromosomes in cells break apart and rejoin incorrectly^[2]. Researchers are still working to understand why this happens and whether these genetic changes directly cause the disease.

Where does it occur in the body?

About two-thirds of EMC tumors are found in the deep soft tissues of the arms and legs, particularly in areas close to the body such as the thigh and the back of the knee^[4]. The tumors typically develop beneath a layer of tissue called the fascia, which covers muscles^[4].

• Upper arms and shoulders
• Thighs
• Legs (especially the area behind the knee)
• Pelvis

Less commonly, EMC can occur in other locations including the hands and feet, the area alongside the spine, and the head and neck region. When it affects the head and neck, this happens in less than 5% of cases^[4]. There have even been rare cases reported in the gums^[6].

The average size of an EMC tumor is about 9.3 centimeters, but tumors can range from as small as 3.3 centimeters to as large as 18 centimeters^[4].

Signs and symptoms

EMC typically grows slowly, causing symptoms that may take months to develop^[4]. The symptoms you experience can vary depending on where the tumor is located and how large it is^[2].

The most common symptom is a lump or swelling. This lump is often found under the skin of the arms or legs and is frequently accompanied by pain and tenderness^[2][4]. Sometimes the lump can look like a bruise. If the tumor is located near a joint, it may restrict your movement^[2].

Other symptoms may include feeling unusually tired or experiencing unintentional weight loss^[1]. Some patients may develop numbness or tenderness in the affected area, particularly as the tumor grows larger^[6].

If you notice a lump that doesn’t go away within two weeks or if you feel constantly exhausted, you should talk to a healthcare provider^[1].

How is it diagnosed?

A specialist will diagnose EMC using several different tests. The process typically begins with a physical examination, where the doctor looks at and feels the lump^[2].

You will likely need imaging tests to take pictures of the inside of your body. These may include^[2][1]:

• Ultrasound
• X-rays
• CT (computed tomography) scans
• MRI (magnetic resonance imaging) scans
• PET (positron emission tomography) scans
• Bone scans

The most important test is a biopsy, where a doctor takes a small sample of the tumor tissue to examine under a microscope^[2]. The tissue sample can be obtained in different ways, and a specialist called a pathologist will look at it to see if it has the characteristics of EMC^[1].

Under the microscope, EMC tumors have a distinctive appearance. The tumor cells are typically round or slightly elongated and uniform in shape and size. They are surrounded by abundant myxoid matrix, which is a jelly-like substance^[6]. The tumor often has a multinodular pattern with fibrous tissue dividing it into sections^[6].

Special laboratory tests called immunohistochemistry may be performed on the biopsy sample. These tests look for specific proteins in the tumor cells. EMC tumor cells are typically positive for a protein called vimentin and may show variable staining for a protein called S-100^[4][6].

Genetic characteristics

One of the most important features that helps doctors confirm an EMC diagnosis is the presence of specific genetic changes. Most EMC tumors have a rearrangement of a gene called NR4A3^[4][7]. This means that pieces of DNA have broken and rejoined incorrectly.

Most commonly, the NR4A3 gene fuses with another gene called EWSR1. This particular genetic fusion, written as EWSR1-NR4A3, is found in the majority of EMC cases^[7]. Less commonly, NR4A3 can fuse with other genes such as TAF15^[4][7].

To detect these gene rearrangements, doctors use a special test called fluorescent in situ hybridization, or FISH. This test is very useful for distinguishing EMC from other types of tumors that may look similar under the microscope^[6][9].

Treatment options

Surgery

The main treatment for EMC is surgery to remove the tumor^[2][7]. When performing surgery, the surgeon will remove not only the tumor but also an area of normal tissue around it. This border of healthy tissue is sometimes called “taking a margin,” and it helps ensure that all cancer cells are removed^[2].

If your tumor is in your arms or legs, your surgeon will perform what’s called “limb-sparing surgery.” The goal is to remove the cancer while preserving the function of your limb^[2]. In very rare cases where the cancer has spread extensively, a surgeon may need to perform a partial or full amputation to stop the disease, though this is uncommon^[2].

Studies have shown that achieving a complete removal of the tumor with clear margins (called an R0 resection) is very important for preventing the cancer from coming back in the same location^[11].

Radiotherapy

Radiotherapy is a treatment that uses high-energy radiation to kill cancer cells^[2]. You might have radiotherapy before or after surgery. When used before surgery, it aims to shrink the tumor to make it easier to remove. When used after surgery, it aims to kill any cancer cells that might have been left behind^[2].

However, the effectiveness of radiotherapy for EMC is not entirely clear. Like conventional chondrosarcomas, EMC has long been thought to be resistant to radiation^[11]. Recent research suggests that the benefits of radiotherapy for controlling local recurrence may be limited^[11].

Chemotherapy

Chemotherapy is a treatment that uses medicines to kill cancer cells^[2]. It is sometimes used if you have a high risk of the cancer coming back or if the tumor has spread to other parts of the body, a situation known as metastasis^[2].

Unfortunately, the effectiveness of chemotherapy for EMC is unclear. Research studies have found limited benefits from chemotherapy for this disease. In one study of 21 patients who received chemotherapy, no significant responses were noted, and the disease typically progressed within about 5 months of starting treatment^[1]. Recent research has also shown no clear association between chemotherapy and improved survival rates^[11].

Some types of chemotherapy drugs have shown slightly better results than others, but overall, chemotherapy is not considered highly effective for EMC^[2]. As a result, you may be more likely to receive surgery with or without radiotherapy as your main treatment.

Targeted and experimental therapies

Researchers are currently learning more about newer treatments called targeted therapies and immunotherapies^[2]. Targeted therapies are drugs that specifically target certain features of cancer cells. One type of targeted therapy being studied for EMC is antiangiogenic agents, which are drugs that stop tumors from forming new blood vessels^[7].

These newer treatment approaches are still being researched in clinical trials to determine how well they work for EMC patients^[2].

Long-term outlook and survival

EMC is generally considered a slow-growing cancer, but it has a tendency to come back in the same location or spread to other parts of the body, even many years after initial treatment^[1][7]. This means that long-term follow-up is essential.

For patients who initially present without metastases, about 37% develop local recurrence after an average of 3.3 years, and about 26% develop distant metastases after an average of 3.2 years^[1]. Approximately 13% to 23% of patients have metastases when they are first diagnosed^[1][11].

The lungs are the most common site for metastases, though the disease can spread to other locations as well^[11]. Importantly, even when EMC spreads to distant sites, the progression is often gradual, and patients can survive for several years^[11][13].

Studies have reported survival rates at different time points^[1][9]:

• 5-year overall survival: 71% to 100%
• 10-year overall survival: 60% to 88%
• 15-year overall survival: 58%

The 5-year disease-specific survival (meaning death specifically from EMC) is approximately 83%, and the 10-year disease-specific survival is also around 83%^[9]. Patients who have distant metastases at the time of diagnosis tend to have shorter survival compared to those without metastases^[11].

Factors that may affect your outlook include the size of the tumor, its location (tumors in the trunk may have worse outcomes), and whether the surgeon was able to remove all of the cancer with clear margins^[11]. Some research has documented cases where patients with metastatic disease survived for many years without active treatment, suggesting that in some cases, close observation may be a reasonable approach^[13].

Because EMC can recur or spread many years after initial treatment, you will need regular follow-up appointments and imaging tests for an extended period, often for the rest of your life.