Dedifferentiated Chondrosarcoma

Staging is according to bone sarcoma protocols (see TNM staging of tumors of bone). See also the information on staging in section Bone tumors: Introduction.

The finding of identical TP53 and IDH mutations in the conventional and dedifferentiated components indicates a common origin of the components. Potential genetic targets for treatment are under study and could be BCL2 family members and TGFB genes.

The cartilaginous and non-cartilaginous components of the tumor are grossly evident in varying proportions. The bluish-grey, lobulated cartilage component is usually located centrally, whereas the fleshy, pale-yellow or tan-brown high-grade sarcoma component is predominantly extraosseous or near the site of pathological fracture.

There is an abrupt transition between the conventional hyaline cartilage and high-grade sarcoma components of dedifferentiated chondrosarcoma. The cartilaginous portion can range from enchondroma-like appearance to grade 1 or grade 2 chondrosarcoma. The high-grade dedifferentiated component usually has the appearance of a high-grade undifferentiated pleomorphic sarcoma or osteosarcoma. Less frequently, it demonstrates features of a high-grade angiosarcoma, leiomyosarcoma, or rhabdomyosarcoma. Rare cases of dedifferentiated chondrosarcoma with epithelial differentiation, including squamous, epithelial, and adamantinoma-like, have been reported. The ratio of conventional to dedifferentiated is highly variable, and the percentage of dedifferentiated component ranges from 2% to 98% (median: 60%). Dedifferentiated chondrosarcomas usually show a poor histological response to preoperative chemotherapy.

Not clinically relevant

Patients with dedifferentiated chondrosarcoma have a dismal prognosis, most often as a result of widespread lung metastases. Overall 5-year survival rates of 7–24% have been reported. Treatment consists of surgery with wide or radical margins. Poor prognostic factors include size > 8 cm, presence of a pathological fracture, metastatic disease at diagnosis, pelvic location, and inadequate surgical margin or treatment without surgery. Chemotherapy and radiation therapy have not been shown to improve prognosis.

Dedifferentiated chondrosarcomas harbor complex karyotypes. About 50–87% of dedifferentiated chondrosarcomas carry mutations in IDH1 or IDH2, which can be found in both the conventional chondrosarcoma and the dedifferentiated component. Because the two components share identical genetic aberrations, including the early IDH mutation, a common precursor cell for the components is presumed. Additional genetic changes occur in the anaplastic component, indicating early diversion of the two components during the development of dedifferentiated chondrosarcoma. Mutations in TP53 are also frequently found.

Essential: conventional chondrosarcoma juxtaposed to a high-grade sarcoma, with a sharp interface.

Desirable: IDH mutations present.