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(American Journal of Pathology. 2000;156:1327-1335.)
© 2000 American Society for Investigative Pathology

Regular Articles

Cell Differentiation and Matrix Gene Expression in Mesenchymal Chondrosarcomas

Thomas Aigner^*, Stefan Loos^*, Susanna Müller^*, Linda J. Sandell, K. Krishnan Unni and Thomas Kirchner^*

From the Institute of Pathology,^*
the University of Erlangen-Nürnberg, Erlangen, Germany; the Department of Orthopaedic Surgery,
Washington School of Medicine, St. Louis, Missouri; and the Department of Pathology and Laboratory Medicine,
the Mayo Foundation, Rochester, Minnesota

Mesenchymal chondrosarcomas are small-cell malignancies named as chondrosarcomas due to the focal appearance of cartilage islands. In this study, the use of in situ detection techniques on a large series of mesenchymal chondrosarcoma specimens allowed the identification of tumor-cell differentiation pathways in these neoplasms. We were able to trace all steps of chondrogenesis within mesenchymal chondrosarcoma by using characteristic marker genes of chondrocytic development. Starting from undifferentiated cells, which were negative for vimentin and any other mesenchymal marker, a substantial portion of the cellular (undifferentiated) tumor areas showed a chondroprogenitor phenotype with an onset of expression of vimentin and collagen type IIA. Cells in the chondroid areas showed the full expression panel of mature chondrocytes including type X collagen indicating focal hypertrophic differentiation of the neoplastic chondrocytes. Finally, evidence was found for transdifferentiation of the neoplastic chondrocytes to osteoblast-like cells in areas of neoplastic bone formation. These results establish mesenchymal chondrosarcoma as the very neoplasm of differentiating premesenchymal chondroprogenitor cells. The potential of neoplastic bone formation in mesenchymal chondrosarcoma introduces a new concept of neoplastic (chondrocytic) osteogenesis in musculoskeletal malignant neoplasms, which qualifies the old dogma that neoplastic bone/osteoid formation automatically implies the diagnosis of osteosarcoma.

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