{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T20:07:04Z","timestamp":1793131624191,"version":"4.5.0"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T00:00:00Z","timestamp":1645401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to joint destruction and bone erosion. Even if many treatments were developed with success in the last decades, some patients fail to respond, and disease chronicity is still a burden. Mechanisms involved in such resistance may include molecular changes in stromal cells. Other explanations can come from observations of tenosynovial giant cell tumor (TGCT), first considered as an inflammatory arthritis, but with unusual neoplastic features. TGCT leads to synovium hypertrophy and hyperplasia with hemosiderin deposition. It affects young adults, resulting in secondary osteoarthritis and increased morbidity. TGCT shows clinical, histological and genetic similarities with RA but affecting a single joint. However, the monoclonality of some synoviocytes, the presence of translocations and rare metastases also suggest a neoplastic disease, with some features common with sarcoma. TGCT is more probably in an intermediate situation between an inflammatory and a neoplastic process, with a main involvement of the proinflammatory cytokine CSF-1\/CSF1R signaling axis. The key treatment option is surgery. New treatments, derived from the RA and sarcoma fields, are emerging. The tyrosine kinase inhibitor pexidartinib was recently FDA-approved as the first drug for severe TGCT where surgery is not an option. Options directly targeting the excessive proliferation of synoviocytes are at a preclinical stage.<\/jats:p>","DOI":"10.3389\/fimmu.2022.820046","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T00:06:38Z","timestamp":1645401998000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":44,"title":["Update on Tenosynovial Giant Cell Tumor, an Inflammatory Arthritis With Neoplastic Features"],"prefix":"10.3389","volume":"13","author":[{"given":"Marie","family":"Robert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Farese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Miossec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01661","article-title":"Evolving Concepts of Rheumatoid Arthritis","volume":"423","author":"Firestein","year":"2003","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"18001","DOI":"10.1038\/nrdp.2018.1","article-title":"Rheumatoid Arthritis","volume":"4","author":"Smolen","year":"2018","journal-title":"Nat Rev Dis Primers"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-021-00665-4","article-title":"Importance of Lymphocyte-Stromal Cell Interactions in Autoimmune and Inflammatory Rheumatic Diseases","volume":"17","author":"Noack","year":"2021","journal-title":"Nat Rev Rheumatol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.ocl.2005.08.002","article-title":"Pigmented Villonodular Synovitis","volume":"37","author":"Ofluoglu","year":"2006","journal-title":"Orthop Clin North Am"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1148\/rg.285085134","article-title":"Pigmented Villonodular Synovitis: Radiologic-Pathologic Correlation","volume":"28","author":"Murphey","year":"2008","journal-title":"Radiographics"},{"key":"B6","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1053\/hupa.2003.52","article-title":"Cell Characterization of Mononuclear and Giant Cells Constituting Pigmented Villonodular Synovitis","volume":"34","author":"Yoshida","year":"2003","journal-title":"Hum Pathol"},{"key":"B7","article-title":"Multinucleated Cells in Pigmented Villonodular Synovitis and Giant Cell Tumor of Tendon Sheath Express Features of Osteoclasts","volume":"150","author":"Darling","year":"1997","journal-title":"Am J Pathol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.crad.2003.11.013","article-title":"Pigmented Villonodular Synovitis","volume":"59","author":"Al-Nakshabandi","year":"2004","journal-title":"Clin Radiol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2005.01959.x","article-title":"Rheumatoid Arthritis and Pigmented Villonodular Synovitis: Comparative Analysis of Cell Polyploidy, Cell Cycle Phases and Expression of Macrophage and Fibroblast Markers in Proliferating Synovial Cells","volume":"46","author":"Berger","year":"2005","journal-title":"Histopathology"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0507321103","article-title":"A Landscape Effect in Tenosynovial Giant-Cell Tumor From Activation of CSF1 Expression by a Translocation in a Minority of Tumor Cells","volume":"103","author":"West","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.2870060404","article-title":"Chromosome Aberrations in Tenosynovial Giant Cell Tumors and Nontumorous Synovial Tissue","volume":"6","author":"Mertens","year":"1993","journal-title":"Genes Chromosomes Cancer"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2010.07.005","article-title":"Pigmented Villonodular Synovitis: A Retrospective Single-Center Study of 122 Cases and Review of the Literature","volume":"40","author":"Ottaviani","year":"2011","journal-title":"Semin Arthritis Rheumatol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199110000-00030","article-title":"Localized Pigmented Villonodular Synovitis of the Knee. 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