Orphanet Journal of Rare Diseases | Real-World Evidence Study of Pediatric Tenosynovial Giant Cell Tumor

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Based on the world's largest patient registry cohort, this study systematically characterizes the disease burden, diagnostic pathways, and treatment patterns of pediatric tenosynovial giant cell tumor (TGCT) for the first time, revealing high misdiagnosis rates, substantial surgical burden, and insufficient multidisciplinary management in children, providing crucial real-world evidence to improve diagnostic and therapeutic strategies for pediatric rare tumors.

 

Literature Overview

This article, 'Pediatric patients with tenosynovial giant cell tumor: real-world evidence from an observational registry,' published in the journal Orphanet Journal of Rare Diseases, reviews and summarizes cross-sectional analysis results from 122 pediatric patients in the global TGCT Support patient registry cohort. The study systematically describes the epidemiological characteristics, diagnostic journey, treatment patterns, recurrence rates, and quality of life impacts in pediatric TGCT patients, comparing them with adult patients. Results show that pediatric patients have significantly higher misdiagnosis rates than adults, undergo joint aspirations more frequently, and despite a high disease burden, experience low multidisciplinary team involvement and insufficient use of systemic therapies. The study underscores the urgent need to enhance clinicians' awareness of pediatric TGCT and calls for the development of treatment strategies tailored to pediatric populations. This research provides the most comprehensive real-world data to date for this ultra-rare disease in children.

Background Knowledge

Tenosynovial giant cell tumor (TGCT) is a locally invasive mesenchymal tumor arising from synovial membranes, bursae, or tendon sheaths, classified into diffuse-type (D-TGCT) and localized-type (L-TGCT). Its molecular mechanism is primarily driven by CSF1 gene rearrangements, leading to aberrant activation of the CSF1/CSF1R signaling pathway. TGCT most commonly affects adults aged 20–50, with pediatric cases being extremely rare. Currently, surgical resection is the primary treatment, but D-TGCT has a high local recurrence rate. In recent years, systemic therapies targeting CSF1R (e.g., pexidartinib, vimseltinib) have been approved in several countries for adult TGCT, significantly improving outcomes for patients who are inoperable or have recurrent disease. However, these drugs are not yet approved for patients under 18, and pharmacokinetic and safety data in children remain extremely limited. Due to the lack of pediatric-specific studies, pediatric TGCT management often follows adult protocols, but whether its natural course, treatment response, and long-term impacts are consistent with adults remains unclear. Additionally, nonspecific symptoms in children (e.g., joint pain, swelling) are easily misdiagnosed as growing pains or juvenile arthritis, leading to delayed diagnosis. This study fills critical gaps in patient-reported outcomes and real-world diagnostic and treatment pathways for pediatric TGCT, providing key evidence to optimize the management of pediatric rare tumors and highlighting the need to advance pediatric drug development and clinical awareness.

 

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Research Methods and Experiments

This study is a cross-sectional analysis based on the international TGCT Support patient registry cohort, including 122 patients diagnosed with TGCT who were under 18 years of age at enrollment, registered between October 6, 2022, and November 26, 2024. Data were collected via electronic questionnaires (REDCap platform), covering demographics, disease characteristics, diagnostic experiences, treatment history, symptom management, quality of life, and patient journeys. The primary analyses compared pediatric and adult TGCT patients in terms of misdiagnosis rates, time from diagnosis to treatment, treatment modalities, number of surgeries, and recurrence rates. Chi-square and t-tests were used for group comparisons, with conditional logistic and Poisson regression models adjusting for potential confounders. All analyses were conducted using SAS v9.4.

Key Conclusions and Insights

• Among 122 pediatric patients, 73.0% had diffuse-type TGCT (D-TGCT), with a median diagnosis age of 14.5 years, and 90% were adolescents at diagnosis
• Children with TGCT had a misdiagnosis rate as high as 62.3%, significantly higher than adults (49.9%), with the most common misdiagnoses being sports injuries, Baker’s cysts, and juvenile idiopathic arthritis
• 52.5% of pediatric patients experienced symptoms for over one year before diagnosis; despite high misdiagnosis rates, the time from symptom onset to diagnosis was similar to that of adults
• Surgery remains the primary treatment, with D-TGCT patients undergoing an average of 3.4 surgeries—significantly more than L-TGCT patients (1.8 surgeries)—and a postoperative local recurrence rate as high as 66.3% for D-TGCT
• Although no systemic therapy is approved for children, 17.2% of pediatric patients received systemic treatments (e.g., imatinib, pexidartinib), a rate comparable to adults (19.1%), though most use was off-label
• Pediatric patients underwent joint aspiration significantly more frequently than adults (47.5% vs. 22.5%), while involvement of orthopedic oncology specialists was much lower than in adults (36.9% vs. 61.6%), indicating suboptimal management

Research Significance and Outlook

This study represents the largest real-world evidence on pediatric TGCT to date, offering the first comprehensive patient-centered depiction of the disease's diagnostic and treatment journey. It reveals significant unmet medical needs in pediatric TGCT, including high misdiagnosis rates, disease burden from repeated surgeries, and lack of multidisciplinary management. These findings emphasize the importance of enhancing TGCT awareness among pediatricians and orthopedic surgeons to reduce misdiagnosis and delays. Furthermore, although systemic therapies are infrequently used in children, their off-label application reflects an existing clinical demand, underscoring the urgent need for pharmacokinetic and safety studies in pediatric populations to support drug approval. The findings support establishing multidisciplinary care models for pediatric TGCT, involving collaboration among pediatric oncology, orthopedic oncology, and rheumatology to optimize treatment decisions. Future research should further explore similarities and differences in molecular profiles and treatment responses between pediatric and adult TGCT, and advocate for including children in clinical trials of novel systemic therapies to develop more effective, less invasive strategies that fundamentally improve quality of life and long-term outcomes.

 

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Conclusion

This study analyzes the largest global pediatric TGCT patient registry cohort to date, systematically revealing the real-world diagnostic and treatment landscape of this rare disease in children. It finds that pediatric TGCT patients face high misdiagnosis rates, frequent repeat surgeries, and substantial disease burden. Despite symptoms similar to adults, they have less access to specialized oncology care, highlighting insufficient multidisciplinary management. Although no systemic therapy is currently approved for children, a notable proportion have received off-label treatments, reflecting an urgent clinical need for non-surgical options. The study emphasizes that pediatric TGCT is not simply a smaller version of the adult disease, and its unique diagnostic and therapeutic challenges require targeted solutions. Enhancing clinician awareness, promoting multidisciplinary collaboration, and accelerating drug development for pediatric indications are key to improving outcomes. This study provides a crucial evidence base for establishing standardized diagnostic and treatment pathways for pediatric TGCT and calls on the medical community and regulatory agencies to jointly address this overlooked pediatric rare tumor population.

 

Sydney Stern, Patrick F McKenzie, Giacomo G Baldi, Emanuela Palmerini, and Sara Rothschild. Pediatric patients with tenosynovial giant cell tumor: real-world evidence from an observational registry. Orphanet Journal of Rare Diseases.