{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T11:35:13Z","timestamp":1775129713070,"version":"3.50.1"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":20,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive tumor originating in the synovial lining of the joint, bursa, and tendon sheath. TGCT typically affects individuals between 20 and 50 years of age and pediatric cases are considered ultra-rare. Research and clinical trials thus far have been largely focused on the adult TGCT population. Therefore, data are needed to understand the impact of TGCT on pediatric patients\u2019 quality of life and any differences between adults. Here we report the result of the pediatric TGCT population enrolled in an observational patient registry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>\n                      A total of 122 pediatric patients (9.5%) were included in this exploratory, cross-sectional analysis of a longitudinal 1,278-patient registry from October 06, 2022 to November 26, 2024. Among pediatric patients, 73.0% had diffuse TGCT (D-TGCT;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200989), 16.4% had localized TGCT (L-TGCT;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200920), and 10.6% had unspecified TGCT (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200913). Pediatric patients had a median age at diagnosis of 14.5 years.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      More than half of pediatric patients were initially misdiagnosed and were more likely to be misdiagnosed than adults (62.3% vs. 49.9%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) and received joint aspirations significantly more frequently than adult patients (47.5% [\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200958] vs. 22.5% [\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009112],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Most pediatric patients were diagnosed by orthopedic surgeons (\n                      <jats:italic>n<\/jats:italic>\n                      = 79, 64.8%), and 52.5% of pediatric patients were diagnosed\u2009\u2265\u20091 years after symptom onset. Pediatric patients with D-TGCT underwent an average of 3.4 surgeries, compared to 1.8 surgeries for those with L-TGCT. Recurrence rates were similar among adults and pediatric patients with 66.3% of pediatric patients with D-TGCT having\u2009\u2265\u20091 post-operative recurrence compared to 15.0% of L-TGCT pediatric patients, respectively. Despite no approved systemic therapies for pediatric use, pediatric and adult patients consulted medical oncologists in similar rates and systemic therapies were prescribed similarly but infrequently overall (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200921, 17.2% in pediatric patients and\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200995, 19.1% in adults).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Pediatric patients had significant disease burden, as compared to adults with TGCT, which severely affected their quality of life. The reliance on surgical treatment and underuse of multidisciplinary care emphasizes the unmet need for provider education and treatment advancements tailored to this population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>This study was an analysis of an observational patient registry and therefore was not registered as a clinical trial; no trial registration number is available. The study protocol was approved by Advarra (protocol reference number: Pro00077310). Patient enrollment for this analysis occurred from October 6, 2022, to November 26, 2024.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-026-04231-7","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T03:53:38Z","timestamp":1769745218000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pediatric patients with tenosynovial giant cell tumor: real-world evidence from an observational registry"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1479-605X","authenticated-orcid":false,"given":"Sydney","family":"Stern","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick F.","family":"McKenzie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giacomo G.","family":"Baldi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Scharschmidt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Palmerini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Rothschild","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"4231_CR1","unstructured":"De Saint Aubain Somerhausen N, van de Rijn M. World Health Organization classification of soft tissue and bone tumours. 5th ed. Lyon: International Agency for Research on Cancer (IARC); 2020."},{"key":"4231_CR2","doi-asserted-by":"publisher","first-page":"102491","DOI":"10.1016\/j.ctrv.2022.102491","volume":"112","author":"S Stacchiotti","year":"2023","unstructured":"Stacchiotti S, D\u00fcrr HR, Schaefer I-M, Woertler K, Haas R, Trama A, et al. Best clinical management of tenosynovial giant cell tumour (TGCT): A consensus paper from the community of experts. Cancer Treat Rev. 2023;112:102491. https:\/\/doi.org\/10.1016\/j.ctrv.2022.102491.","journal-title":"Cancer Treat Rev"},{"key":"4231_CR3","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.3899\/jrheum.160816","volume":"44","author":"V Ehrenstein","year":"2017","unstructured":"Ehrenstein V, Andersen SL, Qazi I, Sankar N, Pedersen AB, Sikorski R, et al. Tenosynovial giant cell tumor: Incidence, Prevalence, patient Characteristics, and Recurrence. A Registry-based cohort study in Denmark. J Rheumatol. 2017;44:1476\u201383. https:\/\/doi.org\/10.3899\/jrheum.160816.","journal-title":"J Rheumatol"},{"key":"4231_CR4","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1080\/14796694.2025.2488635","volume":"21","author":"S Stern","year":"2025","unstructured":"Stern S, McKenzie PF, Bernthal N, O\u2019Neill S, Palmerini E, Randall RL, et al. Localized and diffuse tenosynovial giant cell tumor: real-world results from a patient observational registry. Future Oncol. 2025;21:1501\u201310. https:\/\/doi.org\/10.1080\/14796694.2025.2488635.","journal-title":"Future Oncol"},{"key":"4231_CR5","doi-asserted-by":"crossref","unstructured":"Curtin WA, Lahoti OP, Fogarty EE, Dowling FE, Regan BF. Pigmented villonodular synovitis arising from the sheath of the extensor hallucis longus in an eight-month-old infant. Clin Orthop Relat Res. 1993:282\u20134.","DOI":"10.1097\/00003086-199307000-00037"},{"key":"4231_CR6","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1007\/s11999.0000000000000102","volume":"476","author":"MJL Mastboom","year":"2018","unstructured":"Mastboom MJL, Verspoor FGM, Uittenbogaard D, Schaap GR, Jutte PC, Schreuder HWB, et al. Tenosynovial giant cell tumors in children: A similar entity compared with adults. Clin Orthop. 2018;476:1803\u201312. https:\/\/doi.org\/10.1007\/s11999.0000000000000102.","journal-title":"Clin Orthop"},{"key":"4231_CR7","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1186\/s13023-021-01820-6","volume":"16","author":"NM Bernthal","year":"2021","unstructured":"TOPP Study Group, Bernthal NM, Spierenburg G, Healey JH, Palmerini E, Bauer S, et al. The diffuse-type tenosynovial giant cell tumor (dt-TGCT) patient journey: a prospective multicenter study. Orphanet J Rare Dis. 2021;16:191. https:\/\/doi.org\/10.1186\/s13023-021-01820-6.","journal-title":"Orphanet J Rare Dis"},{"key":"4231_CR8","doi-asserted-by":"publisher","first-page":"100458","DOI":"10.1016\/j.jorep.2024.100458","volume":"4","author":"B McCarthy","year":"2025","unstructured":"McCarthy B, Romano J, Yu J, Maslow JI. Pediatric giant cell tumor of tendon sheath: A case report. J Orthop Rep. 2025;4:100458. https:\/\/doi.org\/10.1016\/j.jorep.2024.100458.","journal-title":"J Orthop Rep"},{"key":"4231_CR9","doi-asserted-by":"publisher","first-page":"233","DOI":"10.4103\/jpgm.JPGM_305_19","volume":"65","author":"S Turkucar","year":"2019","unstructured":"Turkucar S, Makay B, Tatari H, Unsal E. Pigmented villonodular synovitis: four pediatric cases and brief review of literature. J Postgrad Med. 2019;65:233\u20136. https:\/\/doi.org\/10.4103\/jpgm.JPGM_305_19.","journal-title":"J Postgrad Med"},{"key":"4231_CR10","doi-asserted-by":"publisher","first-page":"e482","DOI":"10.1097\/BPO.0000000000001213","volume":"38","author":"SC Willimon","year":"2018","unstructured":"Willimon SC, Busch MT, Perkins CA. Pigmented villonodular synovitis of the knee: an underappreciated source of pain in children and adolescents. J Pediatr Orthop. 2018;38:e482\u20135. https:\/\/doi.org\/10.1097\/BPO.0000000000001213.","journal-title":"J Pediatr Orthop"},{"key":"4231_CR11","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/s11832-009-0236-z","volume":"4","author":"E Baroni","year":"2010","unstructured":"Baroni E, Russo BD, Masquijo JJ, Bassini O, Miscione H. Pigmented villonodular synovitis of the knee in skeletally immature patients. J Child Orthop. 2010;4:123\u20137. https:\/\/doi.org\/10.1007\/s11832-009-0236-z.","journal-title":"J Child Orthop"},{"key":"4231_CR12","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1097\/01.bpo.0000242380.95348.8b","volume":"27","author":"PA Gholve","year":"2007","unstructured":"Gholve PA, Hosalkar HS, Kreiger PA, Dormans JP. Giant cell tumor of tendon sheath: largest single series in children. J Pediatr Orthop. 2007;27:67\u201374. https:\/\/doi.org\/10.1097\/01.bpo.0000242380.95348.8b.","journal-title":"J Pediatr Orthop"},{"key":"4231_CR13","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1097\/PAS.0b013e31802b86f8","volume":"31","author":"JS Cupp","year":"2007","unstructured":"Cupp JS, Miller MA, Montgomery KD, Nielsen TO, O\u2019Connell JX, Huntsman D, et al. Translocation and expression of CSF1 in pigmented villonodular Synovitis, tenosynovial giant cell Tumor, rheumatoid arthritis and other reactive synovitides. Am J Surg Pathol. 2007;31:970\u20136. https:\/\/doi.org\/10.1097\/PAS.0b013e31802b86f8.","journal-title":"Am J Surg Pathol"},{"key":"4231_CR14","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1093\/annonc\/mdy129","volume":"29","author":"M Brahmi","year":"2018","unstructured":"Brahmi M, Alberti L, Tirode F, Karanian M, Eberst L, Pissaloux D, et al. Complete response to CSF1R inhibitor in a translocation variant of teno-synovial giant cell tumor without genomic alteration of the CSF1 gene. Ann Oncol. 2018;29:1488\u20139. https:\/\/doi.org\/10.1093\/annonc\/mdy129.","journal-title":"Ann Oncol"},{"key":"4231_CR15","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1002\/gcc.22807","volume":"59","author":"J Ho","year":"2020","unstructured":"Ho J, Peters T, Dickson BC, Swanson D, Fernandez A, Frova-Seguin A, et al. Detection of CSF1 rearrangements deleting the 3\u2032 UTR in tenosynovial giant cell tumors. Genes Chromosomes Cancer. 2020;59:96\u2013105. https:\/\/doi.org\/10.1002\/gcc.22807.","journal-title":"Genes Chromosomes Cancer"},{"key":"4231_CR16","doi-asserted-by":"publisher","first-page":"1805","DOI":"10.1007\/s40265-019-01210-0","volume":"79","author":"YN Lamb","year":"2019","unstructured":"Lamb YN, Pexidartinib. First Approval Drugs. 2019;79:1805\u201312. https:\/\/doi.org\/10.1007\/s40265-019-01210-0.","journal-title":"First Approval Drugs"},{"key":"4231_CR17","doi-asserted-by":"publisher","first-page":"2709","DOI":"10.1016\/S0140-6736(24)00885-7","volume":"403","author":"H Gelderblom","year":"2024","unstructured":"Gelderblom H, Bhadri V, Stacchiotti S, Bauer S, Wagner AJ, Van De Sande M, et al. Vimseltinib versus placebo for tenosynovial giant cell tumour (MOTION): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024;403:2709\u201319. https:\/\/doi.org\/10.1016\/S0140-6736(24)00885-7.","journal-title":"Lancet"},{"key":"4231_CR18","unstructured":"Press Release. Pimicotinib Approved as Systemic Treatment in China for Tenosynovial Giant Cell Tumor. 2025. https:\/\/www.emdgroup.com\/en\/news\/pimicotinib-china-approval-22-12-2025.html."},{"key":"4231_CR19","unstructured":"European Medicines Agency. Romvimza [Internet]. 2025. Available from: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/romvimza."},{"key":"4231_CR20","unstructured":"Food and Drug Administration. Pediatric Drug Development: Regulatory Considerations \u2014 Complying With the Pediatric Research Equity Act and Qualifying for Pediatric Exclusivity Under the Best Pharmaceuticals for Children Ac. 2023."},{"key":"4231_CR21","doi-asserted-by":"publisher","first-page":"95","DOI":"10.2176\/nmc.53.95","volume":"53","author":"M Ganau","year":"2013","unstructured":"Ganau M, Ennas F, Bellisano G, Ganau L, Ambu R, Faa G, et al. Synovial cysts of the lumbar spine: \u2014Pathological considerations and surgical Strategy\u2014. Neurol Med Chir (Tokyo). 2013;53:95\u2013102. https:\/\/doi.org\/10.2176\/nmc.53.95.","journal-title":"Neurol Med Chir (Tokyo)"},{"key":"4231_CR22","doi-asserted-by":"publisher","first-page":"327","DOI":"10.4103\/ams.ams_161_18","volume":"8","author":"S Shetty","year":"2018","unstructured":"Shetty S, Hegde U, Agarwal G, Sreeshyla H. Chondroid tenosynovial giant cell tumor of temporomandibular joint. Ann Maxillofac Surg. 2018;8:327. https:\/\/doi.org\/10.4103\/ams.ams_161_18.","journal-title":"Ann Maxillofac Surg"},{"key":"4231_CR23","doi-asserted-by":"publisher","unstructured":"Li Z, Feng H, Chen L, Yao J, Wang H. Uncommon localization of tenosynovial giant cell tumor in the coracoclavicular ligament: diagnostic challenges. Am J Case Rep. 2025;26. https:\/\/doi.org\/10.12659\/AJCR.949269.","DOI":"10.12659\/AJCR.949269"},{"key":"4231_CR24","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1016\/S1470-2045(19)30100-7","volume":"20","author":"MJL Mastboom","year":"2019","unstructured":"Mastboom MJL, Palmerini E, Verspoor FGM, Rueten-Budde AJ, Stacchiotti S, Staals EL, et al. Surgical outcomes of patients with diffuse-type tenosynovial giant-cell tumours: an international, retrospective, cohort study. Lancet Oncol. 2019;20:877\u201386. https:\/\/doi.org\/10.1016\/S1470-2045(19)30100-7.","journal-title":"Lancet Oncol"},{"key":"4231_CR25","doi-asserted-by":"publisher","first-page":"6112","DOI":"10.1158\/1078-0432.CCR-20-1696","volume":"26","author":"LH Boal","year":"2020","unstructured":"Boal LH, Glod J, Spencer M, Kasai M, Derdak J, Dombi E, et al. Pediatric PK\/PD phase I trial of pexidartinib in relapsed and refractory leukemias and solid tumors including neurofibromatosis type I\u2013Related plexiform neurofibromas. Clin Cancer Res. 2020;26:6112\u201321. https:\/\/doi.org\/10.1158\/1078-0432.CCR-20-1696.","journal-title":"Clin Cancer Res"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-026-04231-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-026-04231-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-026-04231-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T01:05:52Z","timestamp":1771549552000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13023-026-04231-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,30]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4231"],"URL":"https:\/\/doi.org\/10.1186\/s13023-026-04231-7","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,30]]},"assertion":[{"value":"17 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This analysis was approved by an institutional review board, Advarra (Columbia, Maryland) and the approved protocol reference number is Pro00077310. Written informed consent was obtained from each patient who participated in the registry.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Patients provided written consent to the collection and analysis of their information. No data from individual patients is shown.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Sydney Stern, Patrick McKenzie, and Sara Rothschild have no conflicts of interest to declare. Emanuela Palmerini has served on advisory boards for Daiichi Sankyo, Inc., Deciphera, EUSA Pharma, and SynOx Therapeutics. Giacomo Giulio Baldi, outside the submitted work: advisory role for Pharmamar, Eli Lilly, Glaxo Smith Kline, Merck Sharp & Dome, Deciphera. Consulting fees: Eli Lilly, Pharmamar. Honoraria: Pharmamar, Eli Lilly, Glaxo Smith Kline, Merck Sharp & Dome, IstitutoGentili. Travel grants: Istituto Gentili, Pharmamar, Eli Lilly. Thomas Scharschmidt has served as a consultant for Stryker, Onkos, AmMax Bio, Daichii Sankyo. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}],"article-number":"68"}}