What is chondrosarcoma?
Chondrosarcoma is a spectrum of tumors that, by definition, forms cartilage tissue and which usually arises either in or on the surface of bone. Rarely, it can occur in soft-tissues as well. Most chondrosarcomas are low grade and grow very slowly. These are often managed as benign cartilage tumors, as they pose a low risk of spreading beyond their original location. However, rarely chondrosarcomas present as high-grade tumors, which are true cancers, and which have a much higher likelihood of metastasizing. High-grade chondrosarcoma can arise in any bone, with the pelvis, hip, knee and shoulder being the most common locations. It is more common in adults over the age of 50, and extremely rare in the pediatric and young adult population.
Chondrosarcoma subtypes include:
· Conventional chondrosarcoma
· Clear cell chondrosarcoma
· Myxoid chondrosarcoma
· Mesenchymal chondrosarcoma
· Dedifferentiated chondrosarcoma
What causes it?
Several specific genetic mutations have been linked to chondrosarcoma. These mutations include EXT1 or EXT2 which are linked to the development of solitary and multiple osteochondromas, from which a secondary chondrosarcoma can rarely develop. Mutations in the isocitrate dehydrogenase (IDH1 and IDH2) genes are often found in hereditary conditions such as Ollier’s disease and Maffucci syndrome, both of which exhibit high risks of malignant transformation of benign cartilage tumors into high-grade chondrosarcomas. Other genes and pathways have been implicated as well, including tumor suppressor pathways such as p53 and Rb. There is no evidence that environmental, social, dietary or other external factors contribute to its development.
What are the symptoms?
Low grade lesions may result in pain, though often they are incidentally identified on an x-ray obtained for other reasons, such as mild trauma. Sometimes, the bone is weakened enough to result in pain, a fracture or both. Higher-grade lesions often result in a painful swollen area. When in an extremity, this may be more visible. If located in the pelvis or spine, it may be harder to visualize, and pain may be the main symptom. Patients may report varying degrees of discomfort even while sitting or at rest. They may experience pain that wakes them from sleep. Pain may prevent normal range of motion and patients may report stiffness, weakness, or other subjective senses of discomfort.
How is it diagnosed?
Chondrosarcoma is diagnosed using imaging studies, such as plain x-rays and MRI. A CT scan of the chest and either a PET scan or a bone scan is often obtained as well to detect the extent of the disease. Ultimately, a biopsy is required to sample the tumor and review its microscopic appearance.
How is chondrosarcoma treated?
• Chondrosarcoma requires a comprehensive team approach, including the multi-disciplinary expertise of orthopaedic oncologists, pediatric oncologists, medical oncologists, radiation oncologists, musculoskeletal radiologists, bone and soft-tissue pathologists, nuclear medicine specialists, surgical oncologists, plastic and reconstructive surgeons among others.
• Treatment for low-grade lesions generally involves removing the tumor, while sparing or maintaining as much normal anatomy as possible. Bone grafting or an equivalent procedure is often needed as well. Treatment is generally limited to surgery alone.
• Treatment for high-grade lesions also involves surgery. However, these tumors demand much more complex procedures, designed to remove the entire tumor, including all microscopic disease. To do so, a more comprehensive surgery is required, after which reconstruction of the involved bone or joint is usually necessary. Again, surgery is the mainstay of treatment in most cases.
• Rarely, cytotoxic chemotherapy can be administered. This may be more relevant in specific settings, such as in the case of mesenchymal chondrosarcoma. Generally, however, conventional chemotherapy and radiation are not effective against chondrosarcoma.
• Novel therapies are being explored, often within the context of ongoing clinical trials. These include IDH inhibitors, mTOR inhibitors, tyrosine kinase inhibitors, histone deacetylase (HDAC) inhibitors angiogenesis inhibitors and a variety of other targeted agents designed to affect a very specific pathway.
• Following the completion of treatment, patients treated for high-grade chondrosarcomas will require close surveillance for a period of 5 years. This includes physical examinations and periodic imaging studies. Many patients continue to follow up even after 5 years, albeit at a reduced frequency. Some tumors, such as clear cell chondrosarcoma, has been reported to recur many years later, and on occasion, there is rationale for longer more extended surveillance.