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Pathology of the reactive, monocytic component has been well elucidated, whereas the populations of neoplastic cells and all the sources of CSF\u20101 overproduction are incompletely characterized. Podoplanin (PDPN), or gp38, is a cell surface glycoprotein that is expressed on fibroblast\u2010like synovial cells and upregulated in rheumatoid arthritis and many cancers; it governs cell mobility, epithelial\u2013mesenchymal transition, and other functions and is associated with lymphangiogenesis and poor prognosis in many solid tumors, which underscores its local and possible systemic effects. We found higher PDPN expression in TGCT than in internal controls of patients' healthy synovium. Flow cytometry partitioned PDPN<jats:sup>high<\/jats:sup> cells into PDPN<jats:sup>high<\/jats:sup>CD90<jats:sup>+<\/jats:sup> and PDPN<jats:sup>high<\/jats:sup>CD14<jats:sup>+<\/jats:sup> populations. Quantitative real\u2010time polymerase chain reaction analysis of the PDPN<jats:sup>high<\/jats:sup>CD90<jats:sup>+<\/jats:sup> cells revealed that CSF\u20101 expression was 10\u2010fold higher than in PDPN<jats:sup>high<\/jats:sup>CD14<jats:sup>+<\/jats:sup> cells. Therefore, we conclude that the lining fibroblast\u2010like synovial cells, which express PDPN<jats:sup>high<\/jats:sup>CD90<jats:sup>+<\/jats:sup>, are responsible for the overproduction of CSF\u20101 and for driving tumor growth.<\/jats:p>","DOI":"10.1002\/jor.25216","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T15:30:01Z","timestamp":1638459001000},"page":"1918-1925","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Neoplastic synovial lining cells that coexpress podoplanin and CD90 overproduce CSF\u20101, driving tenosynovial giant cell tumor"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2527-0125","authenticated-orcid":false,"given":"Andrew C.","family":"Chandler","sequence":"first","affiliation":[{"name":"Department of Surgery, Orthopaedic Service Memorial Sloan Kettering Cancer Center New York New York USA"},{"name":"Touro College of Osteopathic Medicine New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"Yakoub","sequence":"additional","affiliation":[{"name":"Department of Surgery, Orthopaedic Service Memorial Sloan Kettering Cancer Center New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4257-9180","authenticated-orcid":false,"given":"Tomohiro","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Surgery, Orthopaedic Service Memorial Sloan Kettering Cancer Center New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura T.","family":"Donlin","sequence":"additional","affiliation":[{"name":"Hospital for Special Surgery New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul Edward","family":"Purdue","sequence":"additional","affiliation":[{"name":"Hospital for Special Surgery New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0802-1186","authenticated-orcid":false,"given":"John H.","family":"Healey","sequence":"additional","affiliation":[{"name":"Department of Surgery, Orthopaedic Service Memorial Sloan Kettering Cancer Center New York New York USA"},{"name":"Hospital for Special Surgery New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"WHO Classification of Tumours of Soft Tissue and Bone","author":"Fletcher CDM","year":"2013"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30100-7"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.160816"},{"issue":"11","key":"e_1_2_8_5_1","first-page":"20","article-title":"Management of tenosynovial giant cell tumor: a neoplastic and inflammatory disease","volume":"4","author":"Healey JHBN","year":"2020","journal-title":"J Am Acad Orthop Surg Glob Res Rev"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)30764-0"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0507321103"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3181a6d86f"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-018-0129-0"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22807"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31802b86f8"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0377-2_14"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-020-06936-9"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2019.04.007"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3274"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"e_1_2_8_17_1","unstructured":"Abcam. 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