{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T07:51:23Z","timestamp":1773733883565,"version":"3.50.1"},"reference-count":123,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T00:00:00Z","timestamp":1773532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000692","name":"Royal College of Surgeons of Edinburgh","doi-asserted-by":"crossref","award":["2024"],"award-info":[{"award-number":["2024"]}],"id":[{"id":"10.13039\/501100000692","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Leicester Hospitals Charity Sarcoma Fund","award":["APP8971"],"award-info":[{"award-number":["APP8971"]}]},{"DOI":"10.13039\/501100020013","name":"NIHR Leicester Biomedical Research Centre","doi-asserted-by":"crossref","award":["NIHR203327"],"award-info":[{"award-number":["NIHR203327"]}],"id":[{"id":"10.13039\/501100020013","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Tenosynovial giant cell tumours (TGCT) are a group of mesenchymal tumours involving the synovium, bursae, and tendon sheaths, comprising two subtypes: nodular and diffuse. Although predominantly benign, diffuse forms can be locally aggressive, resulting in bone destruction. The pathogenesis of TGCTs is still poorly understood. The aim of this study was to systematically review the current literature on the factors, mechanisms, and markers involved in TGCT disease, focussing on their potential role in bone destruction. Methods: This systematic review was conducted using the PRISMA guidelines. A search was performed using PubMed, Scopus, and Cochrane Library, and all original scientific research into mechanisms\/pathways\/signalling involving TGCTs was included. Results: After the review process, 51 studies were included for data extraction. Extracted data included authorship, publication year, patient numbers and aetiology (nTGCT\/dTGCT), demographics, investigative methods, and studied biological factors, mechanisms, and markers. Cross-tabulation of reported elements revealed 159 unique factors, with most appearing only once. Eight elements were reported five or more times: CSF1, CD68, Ki-67, MMP9, CD163, TRAP, TNF-\u03b1, and IL-1\u03b2. Although representing just 5% of all identified factors, these appeared in 69% of the included studies, highlighting their prominence in the literature. Conclusions: Apart from the well-known osteoclastogenesis factor CSF1, inflammatory cytokines (TNF-\u03b1 and IL-1\u03b2) and monocyte\u2013macrophage lineage makers (CD68, CD163) are signalling pathways key to TGCT disease progression and associated bone destruction.<\/jats:p>","DOI":"10.3390\/jcm15062238","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T08:41:26Z","timestamp":1773650486000},"page":"2238","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Expression of Molecular Markers Associated with Tenosynovial Giant Cell Tumours and Bone Destruction: A Systematic Review"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9527-4324","authenticated-orcid":false,"given":"Thomas R. W.","family":"Ward","sequence":"first","affiliation":[{"name":"Orthopaedic Department, University Hospitals of Leicester NHS Trust, Leicester LE1 5WW, UK"},{"name":"Leicester Cancer Research Centre, School of Medical Sciences, University of Leicester, Leicester LE1 5WW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9235-0750","authenticated-orcid":false,"given":"Feier","family":"Zeng","sequence":"additional","affiliation":[{"name":"Leicester Cancer Research Centre, School of Medical Sciences, University of Leicester, Leicester LE1 5WW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8246-2334","authenticated-orcid":false,"given":"Robert U.","family":"Ashford","sequence":"additional","affiliation":[{"name":"Orthopaedic Department, University Hospitals of Leicester NHS Trust, Leicester LE1 5WW, UK"},{"name":"Leicester Cancer Research Centre, School of Medical Sciences, University of Leicester, Leicester LE1 5WW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas C.","family":"Eastley","sequence":"additional","affiliation":[{"name":"Orthopaedic Department, University Hospitals of Leicester NHS Trust, Leicester LE1 5WW, UK"},{"name":"Leicester Cancer Research Centre, School of Medical Sciences, University of Leicester, Leicester LE1 5WW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2663-7515","authenticated-orcid":false,"given":"Ning","family":"Wang","sequence":"additional","affiliation":[{"name":"Leicester Cancer Research Centre, School of Medical Sciences, University of Leicester, Leicester LE1 5WW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S1058-2746(98)90185-9","article-title":"Pigmented villonodular synovitis of the elbow","volume":"7","author":"Pimpalnerkar","year":"1998","journal-title":"J. Shoulder Elb. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.fuspru.2023.03.001","article-title":"Tenosynovial giant cell tumour of the foot and ankle: The orthopaedic tumour surgeon\u2019s perspective","volume":"21","author":"Riedel","year":"2023","journal-title":"Fu\u00df Sprunggelenk"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"122","DOI":"10.2106\/00004623-196749010-00010","article-title":"Localized pigmented villonodular synovitis of the knee. Report of five cases","volume":"49","author":"Granowitz","year":"1967","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_4","unstructured":"World Health Organization, Fletcher, C., Bridge, J., Hogendoorn, P., and Mertens, F. (2013). WHO Classification of Tumours of Soft Tissue and Bone: WHO Classification of Tumours, World Health Organization. [4th ed.]."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S91","DOI":"10.1016\/j.otsr.2016.11.002","article-title":"Localized and diffuse forms of tenosynovial giant cell tumor (formerly giant cell tumor of the tendon sheath and pigmented villonodular synovitis)","volume":"103","author":"Gouin","year":"2017","journal-title":"Orthop. Traumatol. Surg. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Siegel, M., Bode, L., S\u00fcdkamp, N., K\u00fchle, J., Zwingmann, J., Schmal, H., and Herget, G.W. (2021). Treatment, recurrence rates and follow-up of Tenosynovial Giant Cell Tumor (TGCT) of the foot and ankle-A systematic review and meta-analysis. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0260795"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1007\/s00247-025-06338-8","article-title":"Tenosynovial giant cell tumor and its differential diagnosis in children","volume":"55","author":"Barber","year":"2025","journal-title":"Pediatr. Radiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"102491","DOI":"10.1016\/j.ctrv.2022.102491","article-title":"Best clinical management of tenosynovial giant cell tumour (TGCT): A consensus paper from the community of experts","volume":"112","author":"Stacchiotti","year":"2023","journal-title":"Cancer Treat. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.3899\/jrheum.160816","article-title":"Tenosynovial Giant Cell Tumor: Incidence, Prevalence, Patient Characteristics, and Recurrence. A Registry-based Cohort Study in Denmark","volume":"44","author":"Ehrenstein","year":"2017","journal-title":"J. Rheumatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1080\/17453674.2017.1361126","article-title":"Higher incidence rates than previously known in tenosynovial giant cell tumors","volume":"88","author":"Mastboom","year":"2017","journal-title":"Acta Orthop."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"28","DOI":"10.25259\/JMSR_246_2024","article-title":"Giant cell tumor of the tendon sheath: A critical review of current diagnostic and therapeutic approaches with treatment recommendations for hand and foot lesions","volume":"9","author":"Jerome","year":"2025","journal-title":"J. Musculoskelet. Surg. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1002\/(SICI)1096-9098(199806)68:2<100::AID-JSO5>3.0.CO;2-A","article-title":"Giant cell tumor of the tendon sheath: A retrospective study of 28 cases","volume":"68","author":"Rodrigues","year":"1998","journal-title":"J. Surg. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13","DOI":"10.4103\/2156-7514.152343","article-title":"Malignant tenosynovial giant cell tumor of the leg: A radiologic-pathologic correlation and review of the literature","volume":"5","author":"Richman","year":"2015","journal-title":"J. Clin. Imaging Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Nakayama, R., Jagannathan, J.P., Ramaiya, N., Ferrone, M.L., Raut, C.P., Ready, J.E., Hornick, J.L., and Wagner, A.J. (2018). Clinical characteristics and treatment outcomes in six cases of malignant tenosynovial giant cell tumor: Initial experience of molecularly targeted therapy. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-5188-6"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.clinthera.2016.03.008","article-title":"Patient-reported Symptoms of Tenosynovial Giant Cell Tumors","volume":"38","author":"Gelhorn","year":"2016","journal-title":"Clin. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.knee.2025.06.006","article-title":"Current management of Tenosynovial Giant Cell Tumours of the knee in the United Kingdom","volume":"56","author":"Ward","year":"2025","journal-title":"Knee"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature01658","article-title":"Osteoclast differentiation and activation","volume":"423","author":"Boyle","year":"2003","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"427","DOI":"10.2353\/ajpath.2007.060834","article-title":"Osteoclasts: What do they do and how do they do it?","volume":"170","author":"Teitelbaum","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1189\/jlb.3RU0316-144R","article-title":"Biological role of granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on cells of the myeloid lineage","volume":"100","author":"Ushach","year":"2016","journal-title":"J. Leukoc. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"690","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. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/labinvest.2014.1","article-title":"Colony-stimulating factor 1 potentiates lung cancer bone metastasis","volume":"94","author":"Hung","year":"2014","journal-title":"Lab. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zhang, T., Zeng, B., Liu, K., Zeng, Q., Wang, N., Peng, L., Qiu, H., Chen, X., and Wang, L. (2024). Exploration of the molecular biological mechanisms and review of postoperative radiotherapy cases in tenosynovial giant cell tumors. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1331815"},{"key":"ref_23","first-page":"285","article-title":"The Mixed Methods Appraisal Tool (MMAT) version 2018 for information professionals and researchers","volume":"34","author":"Hong","year":"2018","journal-title":"Educ. Inf."},{"key":"ref_24","first-page":"448","article-title":"Recurrent and non-recurrent pigmented villonodular synovitis 1","volume":"22","author":"Adem","year":"2002","journal-title":"Ann. Pathol."},{"key":"ref_25","first-page":"327","article-title":"Iron deposits, cell populations and proliferative activity in pigmented villonodular synovitis of the knee joint","volume":"82","author":"Aigner","year":"1998","journal-title":"Verh. Dtsch. Ges. Pathol."},{"key":"ref_26","first-page":"332","article-title":"Expression of CD60 on multiple cell lineages in inflammatory synovitis","volume":"73","author":"Carr","year":"1995","journal-title":"Lab. Investig. J. Tech. Methods Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/gcc.2870040312","article-title":"Trisomy 5 and trisomy 7 are nonrandom aberrations in pigmented villonodular synovitis: Confirmation of trisomy 7 in uncultured cells","volume":"4","author":"Fletcher","year":"1992","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_28","first-page":"155","article-title":"Fibroma and giant cell tumor of tendon sheath: A comparative histological and immunohistological study","volume":"8","author":"Maluf","year":"1995","journal-title":"Mod. Pathol."},{"key":"ref_29","first-page":"463","article-title":"Cell populations involved in pigmented villonodular synovitis of the knee","volume":"27","author":"Oehler","year":"2000","journal-title":"J. Rheumatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/j.1440-1827.1995.tb03435.x","article-title":"Giant cell tumors of tendon sheath: A single and multiple immunostaining analysis","volume":"45","author":"Tashiro","year":"1995","journal-title":"Pathol. Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"262","DOI":"10.5958\/0976-5506.2016.00167.4","article-title":"Clinicopathological and Biological Behaviour of Malignant Pigmented Villonodular Synovitis-A Retrospective Analysis of 10 Cases","volume":"7","author":"Vijay","year":"2016","journal-title":"Indian J. Public Health Res. Dev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"102904","DOI":"10.1016\/j.ctrv.2025.102904","article-title":"Therapeutic advances in Tenosynovial giant cell Tumor: Targeting the CSF1\/CSF1R axis","volume":"134","author":"Assi","year":"2025","journal-title":"Cancer Treat. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1080\/03009740410009823","article-title":"Strong expression of Bcl-2 in pigmented villonodular synovitis of the knee with aggressive clinical behaviour","volume":"34","author":"Berger","year":"2005","journal-title":"Scand. J. Rheumatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"197","DOI":"10.3892\/or.2015.4350","article-title":"Imatinib mesylate induces mitochondria-dependent apoptosis and inhibits invasion of human pigmented villonodular synovitis fibroblast-like synovial cells","volume":"35","author":"Chen","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/modpathol.2008.29","article-title":"Giant cell tumor of bone express p63","volume":"21","author":"Dickson","year":"2008","journal-title":"Mod. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3832","DOI":"10.1038\/s41598-022-07745-9","article-title":"Synoviocytes from pigmented villonodular synovitis are less sensitive to cadmium-induced cell death than synoviocytes from rheumatoid arthritis","volume":"12","author":"Farese","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.autrev.2010.07.001","article-title":"Molecular pathways involved in synovial cell inflammation and tumoral proliferation in diffuse pigmented villonodular synovitis","volume":"9","author":"Fiocco","year":"2010","journal-title":"Autoimmun. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1177\/1066896910381899","article-title":"Chondroid tenosynovial giant cell tumor: A clinicopathological and immunohistochemical analysis of 5 new cases","volume":"19","author":"Hoch","year":"2011","journal-title":"Int. J. Surg. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.cytogfr.2025.10.007","article-title":"Targeting the colony-stimulating factor 1 axis for the treatment of Tenosynovial Giant Cell Tumors","volume":"86","author":"Humbert","year":"2025","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_40","first-page":"2182","article-title":"Identification of potential biomarkers of pigmented villonodular synovitis by transcriptome analysis","volume":"27","author":"Liu","year":"2023","journal-title":"Chin. J. Tissue Eng. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1136\/jcp.50.7.605","article-title":"Giant cells in pigmented villo nodular synovitis express an osteoclast phenotype","volume":"50","author":"Neale","year":"1997","journal-title":"J. Clin. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"174528","DOI":"10.1155\/2010\/174528","article-title":"Therapeutic Antibodies Targeting CSF1 Impede Macrophage Recruitment in a Xenograft Model of Tenosynovial Giant Cell Tumor","volume":"2010","author":"Cheng","year":"2010","journal-title":"Sarcoma"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1007\/s13577-020-00425-8","article-title":"Establishment and characterization of a novel cell line, NCC-TGCT1-C1, derived from a patient with tenosynovial giant cell tumor","volume":"34","author":"Noguchi","year":"2021","journal-title":"Hum. Cell"},{"key":"ref_44","first-page":"161","article-title":"Value of clusterin expression in pathologic diagnosis and histogenesis of giant cell tumor of tendon sheath","volume":"41","author":"Tang","year":"2012","journal-title":"Zhonghua Bing Li Xue Za Zhi"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"239","DOI":"10.3233\/TUB-220005","article-title":"Role of colony-stimulating factor 1 in the neoplastic process of tenosynovial giant cell tumor","volume":"44","author":"Tap","year":"2022","journal-title":"Tumour Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1158\/1078-0432.CCR-21-2007","article-title":"Results from Phase I Extension Study Assessing Pexidartinib Treatment in Six Cohorts with Solid Tumors including TGCT, and Abnormal CSF1 Transcripts in TGCT","volume":"28","author":"Tap","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/0046-8177(92)90340-9","article-title":"Diffuse and localized tenosynovial giant cell tumor and pigmented villonodular synovitis: A clinicopathologic and flow cytometric DNA analysis","volume":"23","author":"Joyce","year":"1992","journal-title":"Hum. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1080\/01913120600689707","article-title":"Similarities between giant cell tumor of bone, giant cell tumor of tendon sheath, and pigmented villonodular synovitis concerning ultrastructural cytochemical features of multinucleated giant cells and mononuclear stromal cells","volume":"30","author":"Anazawa","year":"2006","journal-title":"Ultrastruct. Pathol."},{"key":"ref_49","first-page":"11","article-title":"Apoptosis resistance in pigmented villonodular synovitis","volume":"20","author":"Berger","year":"2005","journal-title":"Histol. Histopathol."},{"key":"ref_50","first-page":"687","article-title":"Comparative analysis of cell populations involved in the proliferative and inflammatory processes in diffuse and localised pigmented villonodular synovitis","volume":"19","author":"Berger","year":"2004","journal-title":"Histol. Histopathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"490","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":"ref_52","doi-asserted-by":"crossref","first-page":"10573","DOI":"10.7150\/thno.48666","article-title":"Cadherin-11 cooperates with inflammatory factors to promote the migration and invasion of fibroblast-like synoviocytes in pigmented villonodular synovitis","volume":"10","author":"Cao","year":"2020","journal-title":"Theranostics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"461","DOI":"10.21873\/cgp.20272","article-title":"\u03b2-Arrestin2 Inhibits the Apoptosis and Facilitates the Proliferation of Fibroblast-like Synoviocytes in Diffuse-type Tenosynovial Giant Cell Tumor","volume":"18","author":"Cao","year":"2021","journal-title":"Cancer Genom. Proteom."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1002\/jor.25216","article-title":"Neoplastic synovial lining cells that coexpress podoplanin and CD90 overproduce CSF-1, driving tenosynovial giant cell tumor","volume":"40","author":"Chandler","year":"2022","journal-title":"J. Orthop. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1186\/s13018-023-04279-2","article-title":"Identification of potential diagnostic biomarkers for tenosynovial giant cell tumour by integrating microarray and single-cell RNA sequencing data","volume":"18","author":"Chen","year":"2023","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/jor.23031","article-title":"Multi-lineage differentiation and angiogenesis potentials of pigmented villonodular synovitis derived mesenchymal stem cells--pathological implication","volume":"34","author":"Chiang","year":"2016","journal-title":"J. Orthop. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1097\/PAS.0b013e31802b86f8","article-title":"Translocation and expression of CSF1 in pigmented villonodular synovitis, tenosynovial giant cell tumor, rheumatoid arthritis and other reactive synovitides","volume":"31","author":"Cupp","year":"2007","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0165-4608(01)00488-5","article-title":"Analysis of the distribution and frequency of trisomy 7 in vivo in synovia from patients with osteoarthritis and pigmented villonodular synovitis","volume":"131","author":"Broberg","year":"2001","journal-title":"Cancer Genet. Cytogenet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/0046-8177(94)90254-2","article-title":"Expression of metalloproteinases in pigmented villonodular synovitis","volume":"25","author":"Darling","year":"1994","journal-title":"Hum. Pathol."},{"key":"ref_60","first-page":"1383","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":"ref_61","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s10735-021-09961-5","article-title":"cIAP2 expression and clinical significance in pigmented villonodular synovitis","volume":"52","author":"Ding","year":"2021","journal-title":"J. Mol. Histol."},{"key":"ref_62","first-page":"e60377","article-title":"Cytoplasmic PPAR\u03b3 Significantly Correlates With P53 Immunohistochemical Expression and Tumor Size in Localized Tenosynovial Giant Cell Tumor","volume":"16","author":"Elkhamisy","year":"2024","journal-title":"Cureus"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1002\/art.21641","article-title":"Analysis of pigmented villonodular synovitis with genome-wide complementary DNA microarray and tissue array technology reveals insight into potential novel therapeutic approaches","volume":"54","author":"Finis","year":"2006","journal-title":"Arthritis Rheum."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Gauduchon, T., Vanacker, H., Pissaloux, D., Cassier, P., Dufresne, A., Karanian, M., Meurgey, A., Bouhamama, A., Gouin, F., and Ray-Coquard, I. (2022). Expanding the molecular spectrum of tenosynovial giant cell tumors. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1012527"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.canlet.2007.05.003","article-title":"High expression level of bone degrading proteins as a possible inducer of osteolytic features in pigmented villonodular synovitis","volume":"255","author":"Geldyyev","year":"2007","journal-title":"Cancer Lett."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Ge, M., Yang, R., Xu, B., Fan, L., Xu, M., Xu, T., Li, J., Li, Y., Gong, M., and Fu, W. (2025). Proteomics and metabolomics studies in pigmented villonodular synovitis uncover the regulation of monocyte differentiation by the ADGRE5-NF-\u03baB pathway. BMC Med., 23.","DOI":"10.1186\/s12916-025-04358-7"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1002\/gcc.22807","article-title":"Detection of CSF1 rearrangements deleting the 3\u2019 UTR in tenosynovial giant cell tumors","volume":"59","author":"Ho","year":"2020","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1136\/ard.2004.025445","article-title":"Increased expression of humanin peptide in diffuse-type pigmented villonodular synovitis: Implication of its mitochondrial abnormality","volume":"64","author":"Ijiri","year":"2005","journal-title":"Ann. Rheum. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"17129","DOI":"10.2147\/JIR.S549953","article-title":"Mechanistic Study of CD90-Positive Synovial Fibroblasts in the Invasion and Recurrence of Pigmented Villonodular Synovitis","volume":"18","author":"Kong","year":"2025","journal-title":"J. Inflamm. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5","DOI":"10.17816\/PTORS635368","article-title":"Diagnostic value of synovial calprotectin (S100A8\/A9) in differential diagnosis of juvenile idiopathic arthritis and pigmented villonodular synovitis in children: Preliminary results of a single-center study","volume":"13","author":"Kozhevnikov","year":"2025","journal-title":"Pediatr. Traumatol. Orthop. Reconstr. Surg."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1002\/art.42946","article-title":"Mapping and Analysis of Protein and Gene Profile Identification of the Important Role of Transforming Growth Factor Beta in Synovial Invasion in Patients With Pigmented Villonodular Synovitis","volume":"76","author":"Li","year":"2024","journal-title":"Arthritis Rheumatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1136\/jcp.2009.070342","article-title":"Immunophenotypic distinction between pigmented villonodular synovitis and haemosiderotic synovitis","volume":"63","author":"Mahendra","year":"2010","journal-title":"J. Clin. Pathol."},{"key":"ref_73","first-page":"547","article-title":"Synovial colony-stimulating factor-1 mRNA expression in diffuse pigmented villonodular synovitis","volume":"29","author":"Molena","year":"2011","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1002\/gcc.20501","article-title":"Molecular identification of COL6A3-CSF1 fusion transcripts in tenosynovial giant cell tumors","volume":"47","author":"Mandahl","year":"2008","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1002\/(SICI)1096-9896(199609)180:1<80::AID-PATH617>3.0.CO;2-A","article-title":"Expression of parathyroid hormone (PTH)-related peptide (PTHrP) and PTH\/PTHrP receptor in giant cell tumour of tendon sheath","volume":"180","author":"Nakashima","year":"1996","journal-title":"J. Pathol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s00428-015-1874-9","article-title":"Tenosynovial giant cell tumour (pigmented villonodular synovitis-)-like changes in periprosthetic interface membranes","volume":"468","author":"Sesselmann","year":"2016","journal-title":"Virchows Arch."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s00428-002-0640-y","article-title":"Molecular cytogenetic mapping of recurrent chromosomal breakpoints in tenosynovial giant cell tumors","volume":"441","author":"Nilsson","year":"2002","journal-title":"Virchows Arch."},{"key":"ref_78","first-page":"26","article-title":"Cytokine and matrix metalloproteinase expression in pigmented villonodular synovitis may mediate bone and cartilage destruction","volume":"18","author":"Rosier","year":"1998","journal-title":"Iowa Orthop. J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"5361","DOI":"10.1007\/s13277-015-3197-5","article-title":"Expression of colony-stimulating factor 1 is associated with occurrence of osteochondral change in pigmented villonodular synovitis","volume":"36","author":"Ota","year":"2015","journal-title":"Tumour Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1038\/modpathol.3800211","article-title":"Immunohistochemical evaluation of microphthalmia-associated transcription factor expression in giant cell lesions","volume":"17","author":"Seethala","year":"2004","journal-title":"Mod. Pathol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1097\/00000478-200004000-00002","article-title":"Diffuse-type giant cell tumor: Clinicopathologic and immunohistochemical analysis of 50 cases with extraarticular disease","volume":"24","author":"Somerhausen","year":"2000","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"6453","DOI":"10.1245\/s10434-021-09836-9","article-title":"Patient-Derived Tumor Xenografts Plus Ex Vivo Models Enable Drug Validation for Tenosynovial Giant Cell Tumors","volume":"28","author":"Tang","year":"2021","journal-title":"Ann. Surg. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/path.2937","article-title":"Osteoclast formation and function in pigmented villonodular synovitis","volume":"225","author":"Taylor","year":"2011","journal-title":"J. Pathol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.humpath.2021.05.010","article-title":"RNAscope CSF1 chromogenic in situ hybridization: A potentially useful tool in the differential diagnosis of tenosynovial giant cell tumors","volume":"115","author":"Thangaiah","year":"2021","journal-title":"Hum. Pathol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1007\/s13577-022-00823-0","article-title":"Novel CSF1R-positive tenosynovial giant cell tumor cell lines and their pexidartinib (PLX3397) and sotuletinib (BLZ945)-induced apoptosis","volume":"36","author":"Thongchot","year":"2023","journal-title":"Hum. Cell."},{"key":"ref_86","first-page":"110","article-title":"Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in pigmented villonodular synovitis suggests their potential role for joint destruction","volume":"31","author":"Uchibori","year":"2004","journal-title":"J. Rheumatol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4934","DOI":"10.1158\/1078-0432.CCR-22-1898","article-title":"Interactions in CSF1-Driven Tenosynovial Giant Cell Tumors","volume":"28","author":"Matusiak","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Vougiouklakis, T., Shen, G., Feng, X., Hoda, S.T., and Jour, G. (2019). Molecular Profiling of Atypical Tenosynovial Giant Cell Tumors Reveals Novel Non-CSF1 Fusions. Cancers, 12.","DOI":"10.3390\/cancers12010100"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.ijom.2019.10.022","article-title":"Clinical and immunohistochemical analysis of diffuse tenosynovial giant cell tumour of the temporomandibular joint","volume":"49","author":"Wang","year":"2020","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.canlet.2004.01.013","article-title":"Expression of cell cycle-related gene products in different forms of primary versus recurrent PVNS","volume":"210","author":"Weckauf","year":"2004","journal-title":"Cancer Lett."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e2415835","DOI":"10.1002\/advs.202415835","article-title":"Single-Cell Analysis Clarifies Pathological Heterogeneity in Tenosynovial Giant Cell Tumor and Identifies Biomarkers for Predicting Disease Recurrence","volume":"12","author":"Xie","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1620\/tjem.248.87","article-title":"Expression Profiling of Receptor-Activator of Nuclear Factor-Kappa B Ligand in Soft Tissue Tumors","volume":"248","author":"Yamagishi","year":"2019","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_93","doi-asserted-by":"crossref","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":"ref_94","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1002\/1529-0131(199904)42:4<669::AID-ANR9>3.0.CO;2-V","article-title":"Different mechanisms of synovial hyperplasia in rheumatoid arthritis and pigmented villonodular synovitis: The role of telomerase activity in synovial proliferation","volume":"42","author":"Yudoh","year":"1999","journal-title":"Arthritis Rheum."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Zenginkinet, T., Faruq, A.U., Toksoz Yildirim, A.N., Iyetin, Y., Ozturan, B., Okay, E., Celik, A., Ozkan, K., and Akyurek, M. (2022). PD-L1 Status in Tenosynovial Giant Cell Tumors. Medicina, 58.","DOI":"10.3390\/medicina58091270"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"8708692","DOI":"10.1155\/2022\/8708692","article-title":"Immune Cell Infiltration Characteristics of Pigmented Villous Nodular Synovitis and Prediction of Potential Diagnostic Markers Based on Bioinformatics","volume":"2022","author":"Zhang","year":"2022","journal-title":"Biomed. Res. Int."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Lv, J., Zhang, H., Xie, J., Dai, H., and Zhang, X. (2021). Gene Expression Profiles Analyzed Using Integrating RNA Sequencing, and Microarray Reveals Increased Inflammatory Response, Proliferation, and Osteoclastogenesis in Pigmented Villonodular Synovitis. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.665442"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"dev199908","DOI":"10.1242\/dev.199908","article-title":"The origins and roles of osteoclasts in bone development, homeostasis and repair","volume":"149","author":"Yahara","year":"2022","journal-title":"Development"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1182\/blood.V98.8.2544","article-title":"Bifurcation of osteoclasts and dendritic cells from common progenitors","volume":"98","author":"Miyamoto","year":"2001","journal-title":"Blood"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.bbrc.2005.07.092","article-title":"The hematopoietic transcription factor PU.1 regulates RANK gene expression in myeloid progenitors","volume":"335","author":"Kwon","year":"2005","journal-title":"Biochem. Biophys Res. Commun."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/S0140-6736(19)30764-0","article-title":"Pexidartinib versus placebo for advanced tenosynovial giant cell tumour (ENLIVEN): A randomised phase 3 trial","volume":"394","author":"Tap","year":"2019","journal-title":"Lancet"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"593","DOI":"10.2217\/fon-2023-0238","article-title":"The MOTION study: A randomized, phase III study of vimseltinib for the treatment of tenosynovial giant cell tumor","volume":"20","author":"Tap","year":"2024","journal-title":"Future Oncol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1016\/S0140-6736(24)00885-7","article-title":"Vimseltinib versus placebo for tenosynovial giant cell tumour (MOTION): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trial","volume":"403","author":"Gelderblom","year":"2024","journal-title":"Lancet"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"14551","DOI":"10.1038\/s41598-019-51211-y","article-title":"Long-term efficacy of imatinib mesylate in patients with advanced Tenosynovial Giant Cell Tumor","volume":"9","author":"Verspoor","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.suronc.2020.08.030","article-title":"The effect of Imatinib Mesylate in diffuse-type Tenosynovial Giant Cell Tumours on MR imaging and PET-CT","volume":"35","author":"Mastboom","year":"2020","journal-title":"Surg. Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1080\/14796694.2024.2396227","article-title":"MANEUVER: A Phase III study of pimicotinib to assess efficacy and safety in tenosynovial giant cell tumor patients","volume":"22","author":"Niu","year":"2026","journal-title":"Future Oncol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"TPS11584","DOI":"10.1200\/JCO.2025.43.16_suppl.TPS11584","article-title":"A phase 3, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of emactuzumab in patients with tenosynovial giant cell tumor (TANGENT)","volume":"43","author":"Gelderblom","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"TPS11585","DOI":"10.1200\/JCO.2023.41.16_suppl.TPS11585","article-title":"A phase 2, open-label, adaptive, dose-ranging study with long-term extension to evaluate the safety, tolerability, efficacy, and pharmacokinetics of intra-articular AMB-05X injections in patients with tenosynovial giant cell tumor","volume":"41","author":"Gelderblom","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_109","unstructured":"Ganjoo, K.N. (2026, January 26). A Phase 1\/2 Study of Cabiralizumab, an Anti-CSF1 Receptor Antibody, in Patients With Pigmented Villonodular Synovitis (PVNS)\/Diffuse Type Tenosynovial Giant Cell Tumor (Dt-TGCT). Available online: https:\/\/clinicaltrials.stanford.edu\/trials\/s\/NCT02471716.html."},{"key":"ref_110","first-page":"1","article-title":"Inhibition of Integrin \u03b1","volume":"17","author":"Huang","year":"2023","journal-title":"Cell Adh. Migr."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"235","DOI":"10.7150\/ijbs.13814","article-title":"Selective Regulation of MAPK Signaling Mediates RANKL-dependent Osteoclast Differentiation","volume":"12","author":"Lee","year":"2016","journal-title":"Int. J. Biol. Sci."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Dania, V., Stavropoulos, N.A., Gavriil, P., Trikoupis, I., Koulouvaris, P., Savvidou, O.D., Mavrogenis, A.F., and Papagelopoulos, P.J. (2024). Treatment Modalities for Refractory-Recurrent Tenosynovial Giant Cell Tumor (TGCT): An Update. Medicina, 60.","DOI":"10.3390\/medicina60101675"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1186\/ar594","article-title":"Is juvenile rheumatoid arthritis\/juvenile idiopathic arthritis different from rheumatoid arthritis?","volume":"4","author":"Prahalad","year":"2002","journal-title":"Arthritis Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1172\/JCI0215582","article-title":"Osteoclasts are essential for TNF-alpha-mediated joint destruction","volume":"110","author":"Redlich","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Ashley, J.W., Shi, Z., Zhao, H., Li, X., Kesterson, R.A., and Feng, X. (2011). Genetic ablation of CD68 results in mice with increased bone and dysfunctional osteoclasts. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025838"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"8183","DOI":"10.4049\/jimmunol.178.12.8183","article-title":"A previously unrecognized protein-protein interaction between TWEAK and CD163: Potential biological implications","volume":"178","author":"Bover","year":"2007","journal-title":"J. Immunol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.ajpath.2013.05.027","article-title":"TWEAK promotes osteoclastogenesis in rheumatoid arthritis","volume":"183","author":"Park","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.jot.2024.09.002","article-title":"The CD163\/TWEAK\/Fn14 axis: A potential therapeutic target for alleviating inflammatory bone loss","volume":"49","author":"Qian","year":"2024","journal-title":"J. Orthop. Translat."},{"key":"ref_119","first-page":"655","article-title":"Association of Ki-67 Level on Bone Destruction in Chronic Suppurative Otitis Media Patients with Cholesteatoma","volume":"12","author":"Lasminingrum","year":"2021","journal-title":"Syst. Rev. Pharm."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.3892\/mmr.2014.2914","article-title":"Ki67 is a promising molecular target in the diagnosis of cancer (review)","volume":"11","author":"Li","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1007\/s12094-017-1774-3","article-title":"Ki67 targeted strategies for cancer therapy","volume":"20","author":"Yang","year":"2018","journal-title":"Clin. Transl. Oncol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"22907","DOI":"10.1074\/jbc.274.33.22907","article-title":"Intracellular fragmentation of bone resorption products by reactive oxygen species generated by osteoclastic tartrate-resistant acid phosphatase","volume":"274","author":"Halleen","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1093\/jbmr\/zjae023","article-title":"Temporal patterns of osteoclast formation and activity following withdrawal of RANKL inhibition","volume":"39","author":"Kim","year":"2024","journal-title":"J. Bone Miner. Res."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/6\/2238\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T05:27:14Z","timestamp":1773725234000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/6\/2238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,15]]},"references-count":123,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["jcm15062238"],"URL":"https:\/\/doi.org\/10.3390\/jcm15062238","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,15]]}}}