RARE DISEASE
Tenosynovial giant cell tumor
Tenosynovial giant cell tumor
Tenosynovial giant cell tumor
Synonyms: Diffuse-type GCT, Diffuse-type giant cell tumor, Pigmented villonodular synovitis, TGCT, TSGCT
Synonyms: Diffuse-type GCT, Diffuse-type giant cell tumor, Pigmented villonodular synovitis, TGCT, TSGCT
Synonyms: Diffuse-type GCT, Diffuse-type giant cell tumor, Pigmented villonodular synovitis, TGCT, TSGCT
Drug discovery
10
drugs
With orphan designations
Overview
Tenosynovial Giant Cell Tumor (TGCT) is a benign, locally aggressive neoplasm arising from synovial tissue in joints, bursae, or tendon sheaths. It comprises two subtypes: localized (GCTTS), often affecting small joints like hands, and diffuse (PVNS/D-TGCT), typically involving large joints (knee/hip). Driven by CSF1 overexpression, it causes pain, swelling, and joint dysfunction. While nonmalignant, recurrence rates are high (14–55% for diffuse type), and malignant transformation is rare (<50 cases reported) [1][3][6][12].
Burden
Healthcare costs: Post-diagnosis costs increase by 66% (localized) and 34% (diffuse), driven by ambulatory care and surgeries [4][13].
Work loss: Patients experience 3× more disability days and 2× higher indirect costs vs. controls [9][13].
Morbidity: Chronic pain, joint degeneration, and reduced quality of life, particularly with diffuse TGCT [4][10][14].
Key molecular drivers (CSF1/CSF1R) and emerging targeted therapies are reshaping management paradigms [3][8].
Therapies
Surgery: First-line for localized TGCT (recurrence: 8–20%) and select diffuse cases (recurrence: 33–50%) [5][10][12]. Arthroscopic or open synovectomy preferred.
CSF1R inhibitors: Pexidartinib (FDA-approved) and vimseltinib reduce tumor bulk and symptoms [3][5][8].
Adjunctive therapies: Radiation (for inoperable cases) and physical therapy for functional recovery [12][14].
Categories: rare systemic and rheumatological diseases
Research Papers
595 drug discovery papers about Tenosynovial giant cell tumor, with 1 first-in-class and 7 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
595 drug discovery papers about Tenosynovial giant cell tumor, with 1 first-in-class and 7 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-17 | Two cases of giant cell tumours of the orbit: one case of giant cell tumor associated with Paget's disease of bone and one case of tenosynovial giant cell tumor.
Giant cell tumors (GCT) are a rare group of fibrohistiocytic neoplasms that may originate from bone or soft tissue. They are typically found in the extremities or trunk and are rarely reported in the head and neck. While they are benign, they may grow rapidly and be locally destructive. To our knowledge, only three case reports of giant cell tumors of soft tissue involving the orbit have been reported in the literature. We report two cases: one case of giant cell tumor associated with Paget's disease of the bone and one of tenosynovial giant cell tumor.
2026-08-02 | Endobronchial pulmonary metastasis in malignant tenosynovial giant cell tumor: A rare cause of central airway obstruction.
Tenosynovial giant cell tumor (TGCT) is a rare mesenchymal neoplasm arising from the synovium, tendon sheath, or bursa. Although the localized and diffuse forms of TGCT are typically considered benign, malignant TGCT characterized by marked histologic atypia and increased mitotic activity may exhibit aggressive clinical behavior. Pulmonary metastasis from malignant TGCT is rare and, in previously reported cases, pulmonary involvement has predominantly been described as parenchymal nodules or pleural lesions. In this article, we describe a rare case of endobronchial pulmonary metastasis occurring approximately 72 months after the initial diagnosis of malignant TGCT originating from the tendon sheath of the knee.
2026-07-01 | Inflammation-driven neoplastic-like progression in tenosynovial giant cell tumor: The cellular crosstalk between synovial macrophages and fibroblast-like synoviocytes
Tenosynovial giant cell tumor (TGCT), as a mesenchymal disorder, continues to pose diagnostic challenges due to its dual inflammatory and neoplastic pathological features. Current therapeutic strategies, including synovectomy, radiotherapy, and adjuvant CSF1R inhibitors, demonstrate limited efficacy in preventing and treating disease recurrence, highlighting the urgent need to elucidate its underlying pathogenic drivers. In this study, we employed single-cell RNA sequencing on human diffuse TGCT synovial tissues, integrated with in vitro fibroblast-like synoviocytes (FLS)-macrophages coculture models and functional assays, to comprehensively analyze cellular crosstalk and malignant-like behaviors, validated through molecular profiling and pharmacological interventions. Integrated molecular profiling unveiled a pathogenic reciprocal crosstalk between synovial macrophages and FLS in TGCT. M2-polarized macrophages promoted FLS invasiveness through SEMA4A/PLXNB2 signaling, mediated by the PLXNB2/RAP2A/YAP1 axis. Single-cell transcriptomics further identified a macrophage-induced MMP1 + MMP3 + FLS subpopulation with potent pro-invasive activity. Conversely, FLS induced M2 polarization via GAS6–MERTK activation, highlighting a self-sustaining signaling circuit contributing to TGCT progression. These results provide new insights into TGCT pathogenesis and identify potential candidate targets for interrupting its self-sustaining pathogenic loop, which deserve further in vivo validation.
2026-06-13 | Efficacy and recurrence of arthroscopic synovectomy plus postoperative low-dose radiotherapy (30-36 Gy) for knee diffuse-type tenosynovial giant cell tumor
Context Diffuse-type tenosynovial giant cell tumor (D-TGCT) of the knee is a rare, benign but locally aggressive synovial neoplasm for which complete surgical synovectomy is the mainstay of treatment, though postoperative recurrence rates remain high. This study aimed to evaluate the efficacy and recurrence rate of arthroscopic synovectomy combined with postoperative low-dose radiotherapy (LD-RT) for knee D-TGCT. Method A retrospective analysis was conducted on 98 patients who underwent arthroscopic synovectomy for knee D-TGCT between January 2020 and August 2023. Based on treatment regimen, patients were divided into a surgery-only group (n = 53) and a combined radiotherapy group (n = 45; receiving postoperative LD-RT of 30-36 Gy). Pain visual analogue scale (VAS) scores, Lysholm knee scale scores, International Knee Documentation Committee (IKDC) scores, and knee range of motion (ROM) were assessed preoperatively and at 3, 6, and 12 months postoperatively. Patients were followed for at least 2 years, with MRI every 6 months to detect recurrence. Result Among the 98 patients, 53 underwent surgery alone and 45 received additional LD-RT. Both groups showed significant improvement in VAS, Lysholm, IKDC, and ROM over time, with no significant intergroup differences at any follow-up (all P > 0.05). The recurrence rate was significantly lower in the combined radiotherapy group (2/45, 4.44%) than in the surgery-only group (10/53, 18.87%) ( P = 0.030). Local skin pigmentation occurred only in the radiotherapy group (6/45, 13.33%) ( P = 0.020). Summary For knee D-TGCT, arthroscopic synovectomy combined with postoperative LD-RT significantly reduces recurrence compared to surgery alone, though it is associated with an increased risk of localized skin pigmentation.
2026-05-28 | Vimseltinib vs. pexidartinib: An indirect comparison of response rate in the treatment of tenosynovial giant cell tumor.
e23567 Background: Tenosynovial giant cell tumor (TGCT) is a locally aggressive but rare neoplasm of the synovium, tendon sheaths, and bursae frequently affecting major joints with a mean age of diagnosis at 35 to 50 years. Surgical resection is the mainstay of treatment. While generally not life-threatening, inadequate treatment is associated with a significant decrease in quality of life. TGCT also overexpresses colony-stimulating factor I (CSF 1) which has been successfully targeted with an inhibitor, Pexidartinib, which has been the only systemic therapy available for TGCT not amenable to surgical resection. Vimseltinib is an overall switch control-tyrosine kinase inhibitor which does not have the associated hepatotoxicity of pexidartinib. No head-to-head clinical trial between these agents has been performed; this indirect treatment comparison seeks to establish their relative efficacy, by comparing rates of radiological response by RECIST criteria in their major trials. Methods: Data pertaining to the ENLIVEN (pexidartinib vs. placebo) and MOTION (vimseltinib vs. placebo) clinical trials was analyzed; overall response rates were extracted along with 95% confidence intervals. ENLIVEN was a phase 3 multinational randomized double-blind placebo controlled clinical trial with 1:1 randomization and MOTION was a phase 3 randomized double-blind placebo controlled clinical trial with 2:1 randomization. The placebo arm was used as the common comparator. Baseline patient population characteristics were compared along with treatment emergent adverse events. The relative overall response was compared using the Bucher method for indirect treatment comparison. Upper and lower limits of the 95% confidence intervals were also calculated. Results: A hazard ratio of 1.03 was obtained using indirect treatment comparison, indicating that these agents have similar overall response rates. The upper and lower limits of the confidence intervals were 0.66 and 1.59 which makes the comparison statistically insignificant. Inclusion of baseline patient characteristics were also modeled and did not significantly alter the outcome. Simulation studies of patient compliance and disease progression due to discontinuation/suspension secondary to adverse drug related reactions tends to favor vimseltinib. Conclusions: Vimseltinib appears to be as effective as pexidartinib in producing similar response rates as documented by radiological response by RECIST criteria. However, given that vimseltinib appears to have a better toxicity profile than pexidartinib, it may offer a better treatment option to patients with TGCT as both agents have been shown to have similar response rates.
antibodies
2026-02-03 | Identification of a potential relationship between pigmented villonodular synovitis and atherosclerosis using comprehensive bioinformatics analyses.
This study investigates the pathogenesis of Pigmented Villonodular Synovitis (PVNS) using bioinformatics approaches shared with atherosclerosis (AS). Common genes from GSE3698 and GSE28829 were identified. A PPI network was constructed using the STRING database and analyzed with Cytoscape, MCODE, and cytoHubba to determine hub genes. These underwent GO and KEGG enrichment analysis. Candidate genes were identified by integrating cytoHubba and machine learning, and validated via immunohistochemistry and the GSE100927 dataset. Immune infiltration in PVNS and its association with candidate genes were examined, followed by scRNA-seq analysis using GSE155527. Analysis of 43 shared genes implicated immune responses in both diseases. CSF2RB was identified as a key candidate gene through PPI, machine learning, and immunohistochemistry. Immune infiltration confirmed immune dysregulation and linked CSF2RB to multiple immune cells. scRNA-seq revealed increased macrophages, T cells, and endothelial cells in PVNS, with CSF2RB highly expressed in macrophages and mast cells. CSF2RB may serve as a diagnostic and therapeutic target for PVNS. scRNA-seq indicates disrupted immune cell composition in PVNS, characterized by significant increases in macrophages and T cells.
2025-08-28 | Diagnosis and Treatment Options in Pigmented Villonodular Synovitis of the Knee: A Narrative Review.
Background: Pigmented villonodular synovitis (PVNS), also known as tenosynovial giant cell tumor, is a rare proliferative disorder of the synovial membrane that primarily affects the knee joint. Despite advances in imaging and surgical techniques, diagnosis is often delayed, and optimal treatment remains debated. Methods: A Narrative review was conducted according to PRISMA guidelines using PubMed, MEDLINE, and Scopus databases from January 2000 to December 2024. Studies reporting on epidemiology, clinical features, imaging, treatment, and outcomes of PVNS were included. Results: Sixty-six studies encompassing 120 patients were included. The majority of cases were diffuse PVNS. MRI was the most effective imaging tool. Arthroscopic synovectomy was the most common treatment, though recurrence rates remained high, particularly in diffuse forms. Adjuvant treatments, including radiosynoviorthesis and biologic therapies such as infliximab or pexidartinib, were employed in recurrent or unresectable cases. Conclusions: Early diagnosis and complete surgical excision remain the mainstay of treatment. Combined open and arthroscopic approaches are recommended in diffuse PVNS. Further prospective studies are needed to define optimal long-term management.
2025-06-17 | Chondroid Diffuse Tenosynovial Giant Cell Tumor of the Temporomandibular Joint: A Case of a Rare Maxillofacial Tumor With Unique Pathophysiology and Therapeutic Considerations.
Diffuse tenosynovial giant cell tumors (D-TGCT) represent a rare group of benign proliferative lesions originating from the synovium of joints, bursae, and tendon sheaths, with infrequent involvement of the temporomandibular joint (TMJ). Among these, chondroid D-TGCT, previously known as pigmented villonodular synovitis with chondroid metaplasia, constitutes an even rarer subtype displaying a specific affinity for the TMJ. Despite its distinctive nature, only a limited number of cases (n = 30) of chondroid D-TGCT have been extensively documented in existing literature. This case report highlights an unusual instance of chondroid variant of D-TGCT within the TMJ and introduces novel adjuvant therapeutic techniques to prevent recurrence. Given the absence of definitive treatment protocols, our objective is to review existing literature on predictive markers for D-TGCT, aiming to facilitate timely diagnosis via core biopsy technique, and explore potential adjunctive therapeutic modalities that could complement surgical resection, especially in managing these locally aggressive tumor variants.
2025-05-27 | Satisfactory functional outcomes and low recurrence rates at a mean 10-year follow-up after combined staged synovectomy and external radiotherapy for diffuse pigmented villonodular synovitis of the knee.
Diffuse pigmented villonodular synovitis (PVNS) of the knee is a locally destructive lesion that tends to recur following surgical synovectomy. This study aims to evaluate the long-term functional outcomes and recurrence rates of combined staged synovectomy and external radiotherapy in managing diffuse PVNS of the knee. The data of twenty-three patients who had a diffuse PVNS of the knee between June 2011 and September 2017 were retrospectively collected. The patients underwent combined staged anterior arthroscopic and open posterior synovectomy followed by low-dose external radiotherapy (average 3000 cGy). Functional outcomes were assessed preoperatively and at the final follow-up using the International Knee Documentation Committee (IKDC) score, Musculoskeletal Tumor Society (MSTS) score, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score, and SF-36 score, along with the knee motion measurements. Statistical analysis evaluated the changes in functional scores and recurrence rates, with a p-value < 0.05 as the cut-off level of significance. The mean follow-up time was 121.1 ± 20.2 months, with a minimum of 85 months. At the final follow-up, the mean range of motion (ROM) improved from 84.1 ± 16.2° to 110.4 ± 9.7°. The WOMAC score increased significantly from 44.5 ± 5.1 to 81.5 ± 6.3 (p < 0.00001). The IKDC score improved from 43.7 ± 8.1 to 79.1 ± 7.4 (p < 0.00001), MSTS scores from 6.7 ± 2.1 to 20.3 ± 5.7 (p < 0.00001), and SF-36 scores from 28.6 ± 7.4 to 77.4 ± 11.5 (p < 0.00001). Two recurrent cases were documented at the last follow-up visit (8.6%), with a minor complication rate of 21.7%. Combined staged synovectomy and external radiotherapy is an effective treatment for diffuse PVNS of the knee. It has demonstrated significant functional improvement and low recurrence rates over extended follow-up periods, supporting its role as a durable and reliable treatment strategy. Level IV, retrospective cohort.
2024-12-25 | Treatment of Tenosynovial Giant Cell Tumor of the Cervical Spine with Postoperative Anti-RANKL Antibody (Denosumab) Administration.
Tenosynovial giant cell tumor (TGCT) is a fibrous histiocytic tumor originating in the synovial membrane. While cervical TGCT may not be considered a common diagnosis preoperatively because it is relatively rare, it has a high recurrence rate and should be considered. Total resection is preferable, but it can be challenging due to the risk of damaging the vertebral artery. Denosumab has shown effectiveness as a postoperative treatment for osteolytic bone lesion. Denosumab administration coupled with close follow-up might offer an effective postoperative treatment option for unresectable TGCT with bone invasion.
gene therapies
2023-08-18 | Recurrent diffuse tenosynovial giant cell tumor of the knee treated with adjuvant radiotherapy: A case report.
TGCT (tenosynovial giant cell tumor) is a mono-articular proliferative condition that begins in the synovial membranes. Diffuse TGCT (DTGCT) has more prominent symptoms with high risks of recurrency. In this case, we presented a 32-year-old male with recurrent case of DTGCT. The patient has been treated with arthroscopic synovectomy with the recurrence of disease. The patient was finally treated by open synovectomy combined with arthroscopy followed by adjuvant radiotherapy. The aim of this case is to report the success of open synovectomy combined with arthroscopy followed by 31 cycle of adjuvant radiotherapy in the recurrent case of DTGCT. Open synovectomy combined with arthroscopic synovectomy followed by adjuvant RT is a promising treatment modality in patient with DTGCT.
2023-01-06 | Exploration of comorbidity mechanisms and potential therapeutic targets of rheumatoid arthritis and pigmented villonodular synovitis using machine learning and bioinformatics analysis
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease. Pigmented villonodular synovitis (PVNS) is a tenosynovial giant cell tumor that can involve joints. The mechanisms of co-morbidity between the two diseases have not been thoroughly explored. Therefore, this study focused on investigating the functions, immunological differences, and potential therapeutic targets of common genes between RA and PVNS. Methods: Through the dataset GSE3698 obtained from the Gene Expression Omnibus (GEO) database, the differentially expressed genes (DEGs) were screened by R software, and weighted gene coexpression network analysis (WGCNA) was performed to discover the modules most relevant to the clinical features. The common genes between the two diseases were identified. The molecular functions and biological processes of the common genes were analyzed. The protein-protein interaction (PPI) network was constructed using the STRING database, and the results were visualized in Cytoscape software. Two machine learning algorithms, least absolute shrinkage and selection operator (LASSO) logistic regression and random forest (RF) were utilized to identify hub genes and predict the diagnostic efficiency of hub genes as well as the correlation between immune infiltrating cells. Results: We obtained a total of 107 DEGs, a module (containing 250 genes) with the highest correlation with clinical characteristics, and 36 common genes after taking the intersection. Moreover, using two machine learning algorithms, we identified three hub genes (PLIN, PPAP2A, and TYROBP) between RA and PVNS and demonstrated good diagnostic performance using ROC curve and nomogram plots. Single sample Gene Set Enrichment Analysis (ssGSEA) was used to analyze the biological functions in which three genes were mostly engaged. Finally, three hub genes showed a substantial association with 28 immune infiltrating cells. Conclusion: PLIN, PPAP2A, and TYROBP may influence RA and PVNS by modulating immunity and contribute to the diagnosis and therapy of the two diseases.
small molecules
2026-08-17 | Two cases of giant cell tumours of the orbit: one case of giant cell tumor associated with Paget's disease of bone and one case of tenosynovial giant cell tumor.
Giant cell tumors (GCT) are a rare group of fibrohistiocytic neoplasms that may originate from bone or soft tissue. They are typically found in the extremities or trunk and are rarely reported in the head and neck. While they are benign, they may grow rapidly and be locally destructive. To our knowledge, only three case reports of giant cell tumors of soft tissue involving the orbit have been reported in the literature. We report two cases: one case of giant cell tumor associated with Paget's disease of the bone and one of tenosynovial giant cell tumor.
2026-08-02 | Endobronchial pulmonary metastasis in malignant tenosynovial giant cell tumor: A rare cause of central airway obstruction.
Tenosynovial giant cell tumor (TGCT) is a rare mesenchymal neoplasm arising from the synovium, tendon sheath, or bursa. Although the localized and diffuse forms of TGCT are typically considered benign, malignant TGCT characterized by marked histologic atypia and increased mitotic activity may exhibit aggressive clinical behavior. Pulmonary metastasis from malignant TGCT is rare and, in previously reported cases, pulmonary involvement has predominantly been described as parenchymal nodules or pleural lesions. In this article, we describe a rare case of endobronchial pulmonary metastasis occurring approximately 72 months after the initial diagnosis of malignant TGCT originating from the tendon sheath of the knee.
2026-07-01 | Inflammation-driven neoplastic-like progression in tenosynovial giant cell tumor: The cellular crosstalk between synovial macrophages and fibroblast-like synoviocytes
Tenosynovial giant cell tumor (TGCT), as a mesenchymal disorder, continues to pose diagnostic challenges due to its dual inflammatory and neoplastic pathological features. Current therapeutic strategies, including synovectomy, radiotherapy, and adjuvant CSF1R inhibitors, demonstrate limited efficacy in preventing and treating disease recurrence, highlighting the urgent need to elucidate its underlying pathogenic drivers. In this study, we employed single-cell RNA sequencing on human diffuse TGCT synovial tissues, integrated with in vitro fibroblast-like synoviocytes (FLS)-macrophages coculture models and functional assays, to comprehensively analyze cellular crosstalk and malignant-like behaviors, validated through molecular profiling and pharmacological interventions. Integrated molecular profiling unveiled a pathogenic reciprocal crosstalk between synovial macrophages and FLS in TGCT. M2-polarized macrophages promoted FLS invasiveness through SEMA4A/PLXNB2 signaling, mediated by the PLXNB2/RAP2A/YAP1 axis. Single-cell transcriptomics further identified a macrophage-induced MMP1 + MMP3 + FLS subpopulation with potent pro-invasive activity. Conversely, FLS induced M2 polarization via GAS6–MERTK activation, highlighting a self-sustaining signaling circuit contributing to TGCT progression. These results provide new insights into TGCT pathogenesis and identify potential candidate targets for interrupting its self-sustaining pathogenic loop, which deserve further in vivo validation.
2026-06-13 | Efficacy and recurrence of arthroscopic synovectomy plus postoperative low-dose radiotherapy (30-36 Gy) for knee diffuse-type tenosynovial giant cell tumor
Context Diffuse-type tenosynovial giant cell tumor (D-TGCT) of the knee is a rare, benign but locally aggressive synovial neoplasm for which complete surgical synovectomy is the mainstay of treatment, though postoperative recurrence rates remain high. This study aimed to evaluate the efficacy and recurrence rate of arthroscopic synovectomy combined with postoperative low-dose radiotherapy (LD-RT) for knee D-TGCT. Method A retrospective analysis was conducted on 98 patients who underwent arthroscopic synovectomy for knee D-TGCT between January 2020 and August 2023. Based on treatment regimen, patients were divided into a surgery-only group (n = 53) and a combined radiotherapy group (n = 45; receiving postoperative LD-RT of 30-36 Gy). Pain visual analogue scale (VAS) scores, Lysholm knee scale scores, International Knee Documentation Committee (IKDC) scores, and knee range of motion (ROM) were assessed preoperatively and at 3, 6, and 12 months postoperatively. Patients were followed for at least 2 years, with MRI every 6 months to detect recurrence. Result Among the 98 patients, 53 underwent surgery alone and 45 received additional LD-RT. Both groups showed significant improvement in VAS, Lysholm, IKDC, and ROM over time, with no significant intergroup differences at any follow-up (all P > 0.05). The recurrence rate was significantly lower in the combined radiotherapy group (2/45, 4.44%) than in the surgery-only group (10/53, 18.87%) ( P = 0.030). Local skin pigmentation occurred only in the radiotherapy group (6/45, 13.33%) ( P = 0.020). Summary For knee D-TGCT, arthroscopic synovectomy combined with postoperative LD-RT significantly reduces recurrence compared to surgery alone, though it is associated with an increased risk of localized skin pigmentation.
2026-05-28 | Vimseltinib vs. pexidartinib: An indirect comparison of response rate in the treatment of tenosynovial giant cell tumor.
e23567 Background: Tenosynovial giant cell tumor (TGCT) is a locally aggressive but rare neoplasm of the synovium, tendon sheaths, and bursae frequently affecting major joints with a mean age of diagnosis at 35 to 50 years. Surgical resection is the mainstay of treatment. While generally not life-threatening, inadequate treatment is associated with a significant decrease in quality of life. TGCT also overexpresses colony-stimulating factor I (CSF 1) which has been successfully targeted with an inhibitor, Pexidartinib, which has been the only systemic therapy available for TGCT not amenable to surgical resection. Vimseltinib is an overall switch control-tyrosine kinase inhibitor which does not have the associated hepatotoxicity of pexidartinib. No head-to-head clinical trial between these agents has been performed; this indirect treatment comparison seeks to establish their relative efficacy, by comparing rates of radiological response by RECIST criteria in their major trials. Methods: Data pertaining to the ENLIVEN (pexidartinib vs. placebo) and MOTION (vimseltinib vs. placebo) clinical trials was analyzed; overall response rates were extracted along with 95% confidence intervals. ENLIVEN was a phase 3 multinational randomized double-blind placebo controlled clinical trial with 1:1 randomization and MOTION was a phase 3 randomized double-blind placebo controlled clinical trial with 2:1 randomization. The placebo arm was used as the common comparator. Baseline patient population characteristics were compared along with treatment emergent adverse events. The relative overall response was compared using the Bucher method for indirect treatment comparison. Upper and lower limits of the 95% confidence intervals were also calculated. Results: A hazard ratio of 1.03 was obtained using indirect treatment comparison, indicating that these agents have similar overall response rates. The upper and lower limits of the confidence intervals were 0.66 and 1.59 which makes the comparison statistically insignificant. Inclusion of baseline patient characteristics were also modeled and did not significantly alter the outcome. Simulation studies of patient compliance and disease progression due to discontinuation/suspension secondary to adverse drug related reactions tends to favor vimseltinib. Conclusions: Vimseltinib appears to be as effective as pexidartinib in producing similar response rates as documented by radiological response by RECIST criteria. However, given that vimseltinib appears to have a better toxicity profile than pexidartinib, it may offer a better treatment option to patients with TGCT as both agents have been shown to have similar response rates.
antibodies
2026-02-03 | Identification of a potential relationship between pigmented villonodular synovitis and atherosclerosis using comprehensive bioinformatics analyses.
This study investigates the pathogenesis of Pigmented Villonodular Synovitis (PVNS) using bioinformatics approaches shared with atherosclerosis (AS). Common genes from GSE3698 and GSE28829 were identified. A PPI network was constructed using the STRING database and analyzed with Cytoscape, MCODE, and cytoHubba to determine hub genes. These underwent GO and KEGG enrichment analysis. Candidate genes were identified by integrating cytoHubba and machine learning, and validated via immunohistochemistry and the GSE100927 dataset. Immune infiltration in PVNS and its association with candidate genes were examined, followed by scRNA-seq analysis using GSE155527. Analysis of 43 shared genes implicated immune responses in both diseases. CSF2RB was identified as a key candidate gene through PPI, machine learning, and immunohistochemistry. Immune infiltration confirmed immune dysregulation and linked CSF2RB to multiple immune cells. scRNA-seq revealed increased macrophages, T cells, and endothelial cells in PVNS, with CSF2RB highly expressed in macrophages and mast cells. CSF2RB may serve as a diagnostic and therapeutic target for PVNS. scRNA-seq indicates disrupted immune cell composition in PVNS, characterized by significant increases in macrophages and T cells.
2025-08-28 | Diagnosis and Treatment Options in Pigmented Villonodular Synovitis of the Knee: A Narrative Review.
Background: Pigmented villonodular synovitis (PVNS), also known as tenosynovial giant cell tumor, is a rare proliferative disorder of the synovial membrane that primarily affects the knee joint. Despite advances in imaging and surgical techniques, diagnosis is often delayed, and optimal treatment remains debated. Methods: A Narrative review was conducted according to PRISMA guidelines using PubMed, MEDLINE, and Scopus databases from January 2000 to December 2024. Studies reporting on epidemiology, clinical features, imaging, treatment, and outcomes of PVNS were included. Results: Sixty-six studies encompassing 120 patients were included. The majority of cases were diffuse PVNS. MRI was the most effective imaging tool. Arthroscopic synovectomy was the most common treatment, though recurrence rates remained high, particularly in diffuse forms. Adjuvant treatments, including radiosynoviorthesis and biologic therapies such as infliximab or pexidartinib, were employed in recurrent or unresectable cases. Conclusions: Early diagnosis and complete surgical excision remain the mainstay of treatment. Combined open and arthroscopic approaches are recommended in diffuse PVNS. Further prospective studies are needed to define optimal long-term management.
2025-06-17 | Chondroid Diffuse Tenosynovial Giant Cell Tumor of the Temporomandibular Joint: A Case of a Rare Maxillofacial Tumor With Unique Pathophysiology and Therapeutic Considerations.
Diffuse tenosynovial giant cell tumors (D-TGCT) represent a rare group of benign proliferative lesions originating from the synovium of joints, bursae, and tendon sheaths, with infrequent involvement of the temporomandibular joint (TMJ). Among these, chondroid D-TGCT, previously known as pigmented villonodular synovitis with chondroid metaplasia, constitutes an even rarer subtype displaying a specific affinity for the TMJ. Despite its distinctive nature, only a limited number of cases (n = 30) of chondroid D-TGCT have been extensively documented in existing literature. This case report highlights an unusual instance of chondroid variant of D-TGCT within the TMJ and introduces novel adjuvant therapeutic techniques to prevent recurrence. Given the absence of definitive treatment protocols, our objective is to review existing literature on predictive markers for D-TGCT, aiming to facilitate timely diagnosis via core biopsy technique, and explore potential adjunctive therapeutic modalities that could complement surgical resection, especially in managing these locally aggressive tumor variants.
2025-05-27 | Satisfactory functional outcomes and low recurrence rates at a mean 10-year follow-up after combined staged synovectomy and external radiotherapy for diffuse pigmented villonodular synovitis of the knee.
Diffuse pigmented villonodular synovitis (PVNS) of the knee is a locally destructive lesion that tends to recur following surgical synovectomy. This study aims to evaluate the long-term functional outcomes and recurrence rates of combined staged synovectomy and external radiotherapy in managing diffuse PVNS of the knee. The data of twenty-three patients who had a diffuse PVNS of the knee between June 2011 and September 2017 were retrospectively collected. The patients underwent combined staged anterior arthroscopic and open posterior synovectomy followed by low-dose external radiotherapy (average 3000 cGy). Functional outcomes were assessed preoperatively and at the final follow-up using the International Knee Documentation Committee (IKDC) score, Musculoskeletal Tumor Society (MSTS) score, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score, and SF-36 score, along with the knee motion measurements. Statistical analysis evaluated the changes in functional scores and recurrence rates, with a p-value < 0.05 as the cut-off level of significance. The mean follow-up time was 121.1 ± 20.2 months, with a minimum of 85 months. At the final follow-up, the mean range of motion (ROM) improved from 84.1 ± 16.2° to 110.4 ± 9.7°. The WOMAC score increased significantly from 44.5 ± 5.1 to 81.5 ± 6.3 (p < 0.00001). The IKDC score improved from 43.7 ± 8.1 to 79.1 ± 7.4 (p < 0.00001), MSTS scores from 6.7 ± 2.1 to 20.3 ± 5.7 (p < 0.00001), and SF-36 scores from 28.6 ± 7.4 to 77.4 ± 11.5 (p < 0.00001). Two recurrent cases were documented at the last follow-up visit (8.6%), with a minor complication rate of 21.7%. Combined staged synovectomy and external radiotherapy is an effective treatment for diffuse PVNS of the knee. It has demonstrated significant functional improvement and low recurrence rates over extended follow-up periods, supporting its role as a durable and reliable treatment strategy. Level IV, retrospective cohort.
2024-12-25 | Treatment of Tenosynovial Giant Cell Tumor of the Cervical Spine with Postoperative Anti-RANKL Antibody (Denosumab) Administration.
Tenosynovial giant cell tumor (TGCT) is a fibrous histiocytic tumor originating in the synovial membrane. While cervical TGCT may not be considered a common diagnosis preoperatively because it is relatively rare, it has a high recurrence rate and should be considered. Total resection is preferable, but it can be challenging due to the risk of damaging the vertebral artery. Denosumab has shown effectiveness as a postoperative treatment for osteolytic bone lesion. Denosumab administration coupled with close follow-up might offer an effective postoperative treatment option for unresectable TGCT with bone invasion.
gene therapies
2023-08-18 | Recurrent diffuse tenosynovial giant cell tumor of the knee treated with adjuvant radiotherapy: A case report.
TGCT (tenosynovial giant cell tumor) is a mono-articular proliferative condition that begins in the synovial membranes. Diffuse TGCT (DTGCT) has more prominent symptoms with high risks of recurrency. In this case, we presented a 32-year-old male with recurrent case of DTGCT. The patient has been treated with arthroscopic synovectomy with the recurrence of disease. The patient was finally treated by open synovectomy combined with arthroscopy followed by adjuvant radiotherapy. The aim of this case is to report the success of open synovectomy combined with arthroscopy followed by 31 cycle of adjuvant radiotherapy in the recurrent case of DTGCT. Open synovectomy combined with arthroscopic synovectomy followed by adjuvant RT is a promising treatment modality in patient with DTGCT.
2023-01-06 | Exploration of comorbidity mechanisms and potential therapeutic targets of rheumatoid arthritis and pigmented villonodular synovitis using machine learning and bioinformatics analysis
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease. Pigmented villonodular synovitis (PVNS) is a tenosynovial giant cell tumor that can involve joints. The mechanisms of co-morbidity between the two diseases have not been thoroughly explored. Therefore, this study focused on investigating the functions, immunological differences, and potential therapeutic targets of common genes between RA and PVNS. Methods: Through the dataset GSE3698 obtained from the Gene Expression Omnibus (GEO) database, the differentially expressed genes (DEGs) were screened by R software, and weighted gene coexpression network analysis (WGCNA) was performed to discover the modules most relevant to the clinical features. The common genes between the two diseases were identified. The molecular functions and biological processes of the common genes were analyzed. The protein-protein interaction (PPI) network was constructed using the STRING database, and the results were visualized in Cytoscape software. Two machine learning algorithms, least absolute shrinkage and selection operator (LASSO) logistic regression and random forest (RF) were utilized to identify hub genes and predict the diagnostic efficiency of hub genes as well as the correlation between immune infiltrating cells. Results: We obtained a total of 107 DEGs, a module (containing 250 genes) with the highest correlation with clinical characteristics, and 36 common genes after taking the intersection. Moreover, using two machine learning algorithms, we identified three hub genes (PLIN, PPAP2A, and TYROBP) between RA and PVNS and demonstrated good diagnostic performance using ROC curve and nomogram plots. Single sample Gene Set Enrichment Analysis (ssGSEA) was used to analyze the biological functions in which three genes were mostly engaged. Finally, three hub genes showed a substantial association with 28 immune infiltrating cells. Conclusion: PLIN, PPAP2A, and TYROBP may influence RA and PVNS by modulating immunity and contribute to the diagnosis and therapy of the two diseases.
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Drug Discovery Landscape
10 orphan drug designations for Tenosynovial giant cell tumor, including 2 approved therapies.
10 orphan drug designations for Tenosynovial giant cell tumor, including 2 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
3,3-Dimethyl-N-(6-methyl-5-{[2-(1-methyl-1H-pyrazol-4-yl)pyridine-4-yl]oxy}pyridine-2-yl)-2-oxopyrrolidine-1-carboxamide hydrochloride hydrate | small molecules | EMA | 2023-12-13 | — | Merck Europe B.V. |
Emactuzumab | antibodies | EMA | 2022-03-16 | — | Synox Therapeutics Limited |
2-(isopropylamino)-3-methyl-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-4(3H)-one [ROMVIMZA] | small molecules | EMA | 2019-12-16 | 2025-09-24 | Deciphera Pharmaceuticals (Netherlands) B.V. |
Cabiralizumab | antibodies | EMA | 2016-12-12 | — | [INACTIVE] TMC Pharma (EU) Limited |
Cabiralizumab | antibodies | FDA | 2016-01-11 | — | Five Prime Therapeutics, Inc. |
Pexidartinib hydrochloride [Turalio] | small molecules | EMA | 2015-03-19 | — | Daiichi Sankyo Europe GmbH |
Lacnotuzumab | antibodies | EMA | 2014-10-15 | — | Novartis Europharm Limited |
Lacnotuzumab | antibodies | FDA | 2014-08-19 | — | Novartis Pharmaceuticals Corp |
recombinant humanized monoclonal antibody of the immunoglobulin G1 subclass directed against colony stimulating factor-1 receptor expressed on macrophages | antibodies | FDA | 2014-05-14 | — | Genentech, Inc. |
pexidartinib [TURALIO] | small molecules | FDA | 2014-02-14 | 2019-08-02 | Daiichi Sankyo, Inc. |
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