Co-expression of Podoplanin and CD90 Identifies Synovial Neoplastic Cells Overproducing CSF-1 That Drive Tenosynovial Giant Cell Tumor

Tenosynovial Giant Cell Tumor (TCGT) is a rare neoplasm affecting the synovium of joints, bursae, and tendon sheaths. The overproduction of CSF1 by a minority of the tumor population, works in an autocrine and paracrine fashion to drive tumor growth. Pathology of the reactive, monocytic component has been well elucidated, while understanding of the true neoplastic cells and the sources of CSF-1 overproduction remain relatively unknown. Podoplanin (PDPN, gp38) is a cell surface glycoprotein that is expressed on fibroblast-like synoviocytes, is upregulated in rheumatoid arthritis and many cancers, governing cell mobility, epithelial-mesenchymal transition and other functions, while being associated with prognosis in many solid tumors. We showed the expression of PDPN increased in TGCT compared to patient-controlled healthy synovium. Flow cytometry partitioned PDPNhigh cells into PDPNhigh/CD90+ or PDPNhigh/CD14+ populations. Quantitative real-time polymerase chain reaction analysis of the PDPNhigh/CD90+ cells revealed a 10-fold increase in CSF1 expression. Therefore, we conclude that the fibroblast-like synoviocytes are characterized by the expression of both PDPN and CD90, drive tumor progression, and play an essential role in the pathophysiology of TGCT.