Cell differentiation and matrix gene expression in mesenchymal chondrosarcomas

Mesenchymal chondrosarcomas are small-cell malignancies named as chondrosar comas due to the focal appearance of cartilage islands. In this study, the use of in situ detection techniques on a large series of mesenchymal chondr osarcoma specimens allowed the identification of tumor-cell differentiation pathways in these neoplasms. We mere able to trace all steps of chondrogen esis within mesenchymal chondrosarcoma by using characteristic marker genes of chondrocytic development. Starting from undifferentiated cells, which w ere negative for vimentin and any other mesenchymal marker, a substantial p ortion of the cellular (undifferentiated) tumor areas showed a chondroproge nitor phenotype with an onset of expression of vimentin and collagen type I IA. Cells in the chondroid areas showed the full expression panel of mature chondrocytes including type X collagen indicating focal hypertrophic diffe rentiation of the neoplastic chondrocytes. Finally, evidence was found for transdifferentiation of the neoplastic chondrocytes to osteoblast-like cell s in areas of neoplastic bone formation. These results establish mesenchyma l chondrosarcoma as the very neoplasm of differentiating premesenchymal cho ndroprogenitor cells. The potential of neoplastic bone formation in mesench ymal chondrosarcoma introduces a new concept of neoplastic (chondrocytic) o steogenesis in musculoskeletal malignant neoplasms,which qualifies the old dogma that neoplastic bone/osteoid formation automatically implies the diag nosis of osteosarcoma.