Introduction:
Extraskeletal myxoid chondrosarcoma (EMC) is a type of cancer that arises in the soft tissues of the body and is characterized by the presence of a gelatinous substance, a specific cell arrangement, and a rearrangement in the NR4A3 gene. The tumor has a unique structure with lobes, and the cells are evenly organized in cord-like patterns, clusters, and networks. Despite these distinct features, the exact origin and nature of the tumor cells remain uncertain.
What Are the Essential Features of Extraskeletal Myxoid Chondrosarcoma?
- Tumor cells have simple features like being plain-looking with a pinkish cytoplasm.
- Nuclei are round to oval, with even chromatin distribution and a subtle nucleolus.
- Cells in the tumor are interconnected, forming cords, small groups, and complex patterns.
- Despite the name, there is no indication that the tumor cells are becoming cartilage.
- The NR4A3 gene is rearranged in these cells.
What Are the Common Sites Involved in Extraskeletal Myxoid Chondrosarcoma?
- A specific type of cancer called extraskeletal myxoid chondrosarcoma usually appears in the arms or legs. It can occur at any age but tends to happen around 50.
- Most of these tumors develop in the deep soft tissues of the upper limbs and thigh area, with the thigh being the most common location.
- Another type, extraskeletal mesenchymal chondrosarcoma, is more common in young adults. It can show up in the thigh but prefers the head and neck, including areas like the brain covering (meninges), eye socket (orbit), and even in the brain itself.
- They can also occur in less common areas such as the pelvis, the space in the jaw where chewing muscles are, bones, lungs, the protective layer around the brain (dura), the area behind the abdomen (retroperitoneum), and the membrane around the lungs (pleura).
- Chondrosarcomas, in general, have been reported in various body parts, although less frequently. This includes the brain and spinal cord covering (meninges), lower limbs (especially the thigh), soft tissues of the head and neck, eye socket (orbit), voice box (larynx), nasal cavity, and even in the lungs as a very rare occurrence. In some cases, they can also be found in solid organs like the pancreas.
What Are the Clinical Features of Extraskeletal Myxoid Chondrosarcoma?
- The tumor grows slowly and usually appears as a painless lump in the soft tissues.
- About 87 percent of people initially have the tumor only in one place (localized), while 13 % already have it spreading to other parts of the body (metastases).
- When it does spread, the first place it usually goes to is the lungs in 80 % of cases.
What Is the Diagnosis of Extraskeletal Myxoid Chondrosarcoma?
- The most reliable way to confirm the diagnosis is by taking a sample of the tissue.
- The presence of changes in the NR4A3 gene is a key feature that helps identify this condition.
What Are the Radiological Features of Extraskeletal Myxoid Chondrosarcoma?
- CT and MRI scans images reveal a lumpy mass with a lower signal on one type of sequence (T1) and a higher signal on another type (T2).
- After injecting a contrast agent called gadolinium, the scans show increased brightness within the mass and internal partitions becoming more noticeable.
What Are the Prognostic Factors of Extraskeletal Myxoid Chondrosarcoma?
- The illness tends to progress slowly over a long time.
- Survival rates at 5, 10, and 15 years are estimated to be around 82 % to 90 %, 65 % to 70 %, and 58 % to 60 %, respectively.
- Factors like older age, larger tumor size (over 10 cm), and location in certain areas are linked to a less favorable outlook.
- Some studies suggest that certain features in the tumor cells, like high cell density or abnormal appearances, increased cell division, and specific proteins, may indicate a higher chance of the disease spreading or lower overall survival.
- Tumors with certain genetic changes tend to have more aggressive characteristics and a less positive outcome compared to others.
What Is the Treatment Of Extraskeletal Myxoid Chondrosarcoma?
- When the disease is limited to one area, the usual treatment involves surgery, sometimes with additional radiation therapy. This approach can lead to long-lasting survival, although there's a roughly 50 percent chance of cancer coming back.
- In more advanced cases, along with the standard chemotherapy for soft tissue tumors, new medications that target blood vessel growth have shown promise in recent studies.
What Is the Differential Diagnosis of Extraskeletal Myxoid Chondrosarcoma?
- Soft Tissue Myoepithelioma: A combination of tests using certain proteins can help identify myoepithelial differentiation in most cases.
- Ossifying Fibromyxoid Tumor: Typically, there is a surrounding layer of bone in most cases. Desmin, a muscle-related protein, is present in 70 % of cases. Genetic changes involving the PHF1 gene are common, with fusion to EP400 observed in many cases. Specific gene fusions are more common in this tumor's malignant and S100-negative types.
- Soft Tissue Chordoma: Detection of a specific protein called brachyury is an indicator.
- Myxofibrosarcoma, Epithelioid Variant: Overproduction of the MET protein is observed.
- Myxoid Leiomyosarcoma: Expressing certain proteins like HMGA2, h-caldesmon, and desmin is typical. In all these cases, there is no evidence of rearrangement in the NR4A3 gene.
What Are the Current Research and Future Perspectives on Extraskeletal Myxoid Chondrosarcoma?
- EMC exhibits unique patterns of immune activity, but the effectiveness of PD1/PDL1 inhibitors is not well-established.
- A recent trial combining Sunitinib and Nivolumab showed positive responses in some EMC patients, but it is unclear how much each drug contributed to the effect.
- Tazemetostat, a drug approved for another cancer type, is showing promise in early tests for EMC cases without a specific gene (INI-1).
- Patients facing distant relapses have limited treatment options, and the prognosis is challenging.
- Ongoing research identifies potential treatment targets, but there is a critical need to understand factors predicting outcomes and develop effective strategies for initial treatment and relapse.
- Collaboration and discussions with regulators are crucial for advancing research and drug development for these rare tumors.
Conclusion:
Since Extraskeletal Myxoid Chondrosarcoma (EMC) is so rare, it is tough to study. However, a small collaborative using Pazopanib shows that research is possible even in ultra-rare cases. Research on an extremely rare soft tissue, sarcoma, provides valuable information, drawing from one of the largest groups of cases. The quality of surgery for the main tumor did not show a clear impact, but it was found that more extensive surgery relates to lower rates of cancer coming back locally or spreading. Also, the location of the initial tumor and having only one lung metastasis can predict better survival. Traditional chemotherapy using anthracyclines did not improve outcomes, but a drug called Trabectedin showed decent control over the disease. Findings suggest that taking breaks from medication is safe when treating the disease that has spread. More research is needed to find more effective treatments and identify factors to help decide if some patients can delay or even skip systemic (whole-body) treatment for the spreading.
