Dedifferentiated chondrosarcoma is known to have a poor prognosis. Median survival has been as short as 6 months, and 5-year survival rates may be as low as 10% to 13%. Patients rarely survive for more than 2 years[3, 4]. Consistent with the reported unfavorable prognosis, all current cases died of lung metastases, with a median survival time of only 10 months (range, 3.4 to 18.8 months). In two very recent reports, the median survival time was 7.5 months and 1.4 year, and the overall 5-year survival rate was 7.1% and 24%, respectively. The prognosis of dedifferentiated chondrosarcoma has shown a slow improvement trend over time, presumably due to earlier diagnosis and improved staging and treatment.
Metastasis, especially to the lung, is the most important treatment problem in patients with dedifferentiated chondrosarcoma[5–7]. In the current study, the presence of metastases at diagnosis was a significant unfavorable prognostic factor. Chemotherapy is an option for control of metastatic lesions. However, the value of chemotherapy for cases with dedifferentiated chondrosarcoma has not been supported[2, 4]. In addition to the lack of convincing evidence of the benefit of chemotherapy, the toxicity of chemotherapy experienced by older patients with dedifferentiated chondrosarcoma generally rules it out as a standard treatment. However, in a previous report, 2 out of 13 patients with dedifferentiated chondrosarcoma experienced a good response to chemotherapy, demonstrating more than 90% necrosis. These results suggest a possible benefit of chemotherapy for some patients with dedifferentiated chondrosarcoma.
The prognosis of patients with dedifferentiated chondrosarcoma can be improved by an accurate preoperative diagnosis. Characteristically on plain radiographs, a combined pattern composed of the aggressive parts of dedifferentiated chondrosarcoma components and the less aggressive parts of well-differentiated chondrosarcoma components suggests dedifferentiated chondrosarcoma[8, 9]. Reflecting the aggressive nature of dedifferentiated chondrosarcoma, osteolytic lesions associated with cortical destruction have been reported in the majority of cases on plain radiographs. In the current study, bone destruction was present in about half of the cases on plain radiographs, and all of these cases demonstrated extraskeletal extension on MRI. The presence of matrix mineralization, indicative of a cartilaginous tumor, accompanied by bone destruction of an aggressive nature may suggest a diagnosis of dedifferentiated chondrosarcoma based on plain radiographs.
It is important to distinguish between conventional chondrosarcoma and dedifferentiated chondrosarcoma, considering the greatly different prognosis. A pathological diagnosis would be inaccurate if the biopsy sample contained just one component of dedifferentiated chondrosarcoma. Therefore, a carefully planned biopsy based upon MRI, assessing each component of dedifferentiated chondrosarcoma, is essential. Even if only one component—either a conventional chondrosarcoma component or a dedifferentiated component—is detected in the pathological sample, possible dedifferentiated chondrosarcoma should be considered in cases in whom plain radiographs show matrix mineralization with a destructive aggressive feature.
Local control by surgery does not appear to be related to prognosis[5–7]. This observation seems to emphasize the importance of not only local control, but also control regarding metastasis, which is directly associated with the prognosis. However, surgical treatment for local control is still an important procedure for dedifferentiated chondrosarcoma. Local recurrence has been reported in up to 50% of cases after excision, with much better local control when there is adequate, or wide, resection[3–5]. In the current study, local recurrence was seen in 2 out of 6 cases treated with wide resection, including 1 case in the tibia and 1 case in the humerus. Since the tibia and humerus are close to essential vessels, the creation of an adequate surgical margin intended to prevent local control may be difficult.
Regarding the pathogenesis of dedifferentiated chondrosarcoma, no structural or numerical chromosomal aberrations that are highly specific for dedifferentiated chondrosarcomas have been identified. However, some evidence has suggested clustering of breakpoints in specific regions of 6q13-22 and 9p21-24 in dedifferentiated chondrosarcoma. High-grade dedifferentiated components have been shown to have a higher malignant potential than low-grade chondrosarcoma components, with increased proliferation as demonstrated by expression of Ki-67 and proliferating cell nuclear antigen. The plasminogen activator system is a key regulator of invasion and tumor angiogenesis. Plasminogen activator inhibitor 1 (PAI-1) acts as an inhibitor of tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). In dedifferentiated chondrosarcoma, high-grade dedifferentiated components display diffuse coexpression of t-PA, u-PA, and PAI-1. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are principally involved in the breakdown of the extracellular matrix, as well as in tumor angiogenesis. Upregulation of MMP2 and MT1-MMP has been reported in high-grade malignant cartilaginous tumors, as well as in the high-grade dedifferentiated component of dedifferentiated chondrosarcoma.