Skeletal and Extraskeletal Myxoid Chondrosarcoma: a Comparative Clinicopathologic, Ultrastructural, and Molecular Study

Background: Skeletal myxoid chondrosarcoma (SMC) is considered to be either a typical chondrosarcoma with prominent myxoid alterations or an altogether unique malignant cartilage tumor. Extraskeletal myxoid chondrosarcoma (EMC) is a relatively rare but well-recognized neoplasm. It was initially thought to be a low grade sarcoma of cartilage derivation and was recently found, in most cases, to contain a reciprocal t(9;22), resulting in a fusion of the EWS and CHN genes. Are SMC and EMC the same entity arising in two different locations, or are they two separate entities? To the authors' knowledge, this study represents the first systematic attempt to answer this question.

Methods: Forty consecutive cases of EMC (20 cases) and SMC (20 cases) were compared by light and electron microscopy, immunohistochemistry, and molecular analysis. The mean clinical follow-up for both groups was 55 months. Histologic criteria for SMC consisted of 95% myxoid matrix, with only minimal hyaline cartilage formation.

Results: The gender distribution was identical in both groups (13 males and 7 females). The mean age was 55 years for EMC patients and 45 years for SMC patients. The EMC tumors were predominantly located in the deep soft tissues of the lower extremity (60%) and buttock (20%), and the mean tumor size was 13 cm. SMC was most commonly located in the bones around the hip joint (pelvis 35%; proximal femur 20%) and shoulder (20%); the mean size was 9 cm. Histologic grade in the EMC group correlated with survival (82% of the high grade tumors metastasized). Electron microscopy performed in 8 EMC cases revealed intracisternal microtubules in 3 cases and prominent mitochondria in 5, whereas in 5 SMC cases it revealed only inconspicuous organelles. Molecular analysis for the EWS-CHN fusion RNA resulting from the t(9;22) was performed in 15 cases (9 EMC and 6 SMC) and was detected in 7 of 9 EMC cases and 0 of 6 SMC cases. In one case, the molecular structure of the EWS-CHN fusion RNA was novel. The probability of metastasis was significantly higher (P=0.004) for the EMC group than for the SMC group.

Conclusions: Although similar light microscopic features are noted in EMC and SMC, fundamental differences are noted at the ultrastructural and molecular levels, suggesting that EMC and SMC represent two distinct entities in the chondrosarcoma family of tumors.