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.
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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.
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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.
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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.
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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.
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