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Tenosynovial giant cell tumor (TGCT) is a mesenchymal tumor derived from the synovium of the tendon sheath and joints, most frequently in the large joints. The standard of care for TGCTs is surgical resection. A new targeting approach for treating TGCTs has emerged from studies on the role of the CSF1/CSF1 receptor (CSF1R) in controlling cell survival and proliferation during the pathogenesis of TGCTs. We established four novel cell lines isolated from the primary tumor tissues of patients with TGCTs. The cell lines were designated Si-TGCT-1, Si-TGCT-2, Si-TGCT-3, and Si-TGCT-4, and the TGCT cells were characterized by CSF1R and CD68. These TGCT cells were then checked for cell proliferation using an MTT assay and three-dimensional spheroid. The responses to pexidartinib (PLX3397) and sotuletinib (BLZ945) were evaluated by two-dimensional MTT assays. All cells were positive for α‑smooth muscle actin (α‑SMA), fibroblast activation protein (FAP), CSF1R, and CD68. Except for Si-TGCT-4, all TGCT cells had high CSF1R expressions. The cells exhibited continuous growth as three-dimensional spheroids formed. Treatment with pexidartinib and sotuletinib inhibited TGCT cell growth and induced cell apoptosis correlated with the CSF1R level. Only Si-TGCT-4 cells demonstrated resistance to the drugs. In addition, the BAX/BCL-2 ratio increased in cells treated with pexidartinib and sotuletinib. With the four novel TGCT cell lines, we have an excellent model for further in vitro and in vivo studies.

Purpose: A major component of cells in tenosynovial giant cell tumor (TGCT) consists of bystander macrophages responding to CSF1 that is overproduced by a small number of neoplastic cells with a chromosomal translocation involving the CSF1 gene. An autocrine loop was postulated where the neoplastic cells would be stimulated through CSF1R expressed on their surface. Here, we use single-cell RNA sequencing (scRNA-seq) to investigate cellular interactions in TGCT. Experimental Design: A total of 18,788 single cells from three TGCT and two giant cell tumor of bone (GCTB) samples underwent scRNA-seq. The three TGCTs were additionally analyzed using long-read RNA sequencing. Immunofluorescence and IHC for a range of markers were used to validate and extend the scRNA-seq findings. Results: Two recurrent neoplastic cell populations were identified in TGCT that are highly similar to nonneoplastic synoviocytes. We identified GFPT2 as a marker that highlights the neoplastic cells in TCGT. We show that the neoplastic cells themselves do not express CSF1R. We identified overlapping MAB features between the giant cells in TGCT and GCTB. Conclusions: The neoplastic cells in TGCT are highly similar to nonneoplastic synoviocytes. The lack of CSF1R on the neoplastic cells indicates they may be unaffected by current therapies. High expression of GFPT2 in the neoplastic cells is associated with activation of the YAP1/TAZ pathway. In addition, we identified expression of the platelet-derived growth factor receptor in the neoplastic cells. These findings suggest two additional pathways to target in this tumor.

Diffuse-type tenosynovial giant cell tumor (dt-TGCT) is a benign clonal neoplastic proliferation arising from the synovium. Patients are often symptomatic, require multiple surgical procedures during their lifetime, and have reduced quality of life (QoL). Surgery is the main treatment with relapse rates ranging from 14 to 55%. The treatment strategy for patients with dt-TGCT is evolving. The purpose of this review is to describe current treatment options, and to highlight recent developments in the knowledge of the molecular pathogenesis of dt-TGCT as well as related therapeutic implications.TGCT cells overexpress colony-stimulating factor 1 (CSF1), resulting in recruitment of CSF1 receptor (CSF1R)-bearing macrophages that are polyclonal and make up the bulk of the tumor, has led to clinical trials with CSF1R inhibitors. These inhibitors include small molecules such as pexidatinib, imatinib, nilotinib, DCC-3014 (vimseltinib), and the monoclonal antibody RG7155 (emactuzumab).In conclusion, D-TGCT impairs patients' QoL. The evidence that the pathogenetic loop of D-TGCT can be inhibited has changed the therapeutic armamentarium for this condition. Clinical trials of agents that target CSF1R are currently ongoing. All this new evidence should be taken into consideration within multidisciplinary management.

For drugs with enhanced serious safety risks, Risk Evaluation and Mitigation Strategy (REMS) may be required. Pexidartinib is approved for treatment of adult symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Its approval was conditional on its prescription via a mandatory REMS due to serious and potentially fatal liver injury seen in clinical trials. Turalio® REMS aims to mitigate this risk by ensuring provider education on pexidartinib use and required REMS components, prescriber adherence to baseline and periodic monitoring, and enrolling patients in a registry to further assess safe use and acute, chronic and irreversible hepatotoxicity. Through Turalio REMS, benefits of treating patients with pexidartinib may be preserved.

Giant cell tumor of bone (GCTB) and tenosynovial giant cell tumor (TGCT) share misleadingly similar names, soft texture and brown color macroscopically, osteoclast-like multinucleated giant cells microscopically and localisation in the musculoskeletal system. However, these two tumor types are biologically and clinically two distinct entities with different natural courses of progression and considerably different modes of surgical and medical treatment. In this article, we provide a detailed update on the similarities and the differences between both tumor types. GCTB is a locally aggressive osteolytic bone tumor, commonly seen in patients in their third decade of life. It usually occurs as a solitary lesion in the meta-epiphyseal region of long bones. It can be diagnosed using plain radiographic imaging, CT radiography or MRI to estimate the tumor extent, soft tissue and joint involvement. GCTB is usually treated with intralesional excision by curettage. Systemically, it can be treated with bisphosphonates and denosumab or radiotherapy. TGCT is a rare, slowly progressing tumor of synovial tissue, affecting the joint, tendon sheath or bursa, mostly seen in middle-aged patients. TGCT is usually not visible on radiographs and MRI is mostly used to enable assessment of potential bone involvement and distinguishing between two TGCT types. Localised TGCT is mostly treated with marginal surgical resection, while diffuse TGCT is optimally treated with total synovectomy and is more difficult to remove. Additionally, radiotherapy, intraarticular injection of radioactive isotopes, anti-TNF-α antibodies and targeted medications may be used.

Tenosynovial giant cell tumor (TGCT) is a neoplasm of the joint synovium that can have severe impacts on joint mobility, function, and quality of life. Traditionally, treatment modalities included partial or complete surgical synovectomy, radiotherapy (typically as an adjunct to surgery), and watchful monitoring (no medical or surgical intervention). However, these approaches have been met with varying degrees of success and high recurrence rates, as well as onerous complications and clinical sequelae. Pexidartinib, a colony-stimulating factor 1 receptor (CSF1R) inhibitor, presents a promising molecular approach that targets a neoplastic driver of TGCT. While the introduction of pexidartinib allows clinicians to avoid the significant morbidity associated with traditional treatment options, there are also defined risks associated with pexidartinib treatment. Therefore, patient selection is critical in optimizing treatment modalities in TGCT. The purpose of this literature review is to identify the TGCT patient population that would derive maximal benefit with minimal risk from pexidartinib, and to determine the specific indications and contraindications for selecting pexidartinib over other therapeutic approaches. Specifically, this paper compares the efficacy and safety profile of pexidartinib across clinical and preclinical studies to that of surgery, radiotherapy, and watchful monitoring. Rates of improvement in joint mobility, pain, and recurrence-free survival across studies of pexidartinib have been encouraging. The most common adverse events are mild (hypopigmentation of the hair) or reversible (transient aminotransferase elevation). Severe or permanent adverse events (notably cholestatic hepatotoxicity) are rare. While the optimal treatment strategy remains highly dependent on a patient’s clinical circumstances and treatment goals, pexidartinib has surfaced as a promising therapeutic in cases where the morbidity of surgery or radiotherapy outweighs the benefits.

Tenosynovial giant cell tumor (TGCT) is defined by the World Health Organization (WHO) as a family of lesions most often arising from the synovium of joints, bursae and tendon sheaths. It is composed of synovial- like mononuclear cells, admixed with multinucleate giant cells, foam cells, siderophages and inflammatory cells (1). It can have various clinical manifestations, and is therefore subdivided in a diffuse and a localized/ nodular subtype. Furthermore, the lesions can have an intra- or extra-articular location. The purpose of this paper is to present the case of a 41-year-old male suffering from multifocal extra- and intra-articular TGCT of the right knee, with involvement of the pes anserinus bursa and an anterior cruciate ligament (ACL) autograft respectively. The ACL reconstruction was performed 11 years prior to the diagnosis of the TGCT, using tendons harvested from the pes anserinus. Our case illustrates the risk of transferring TGCT from an extra- to intra-articular location during ACL reconstruction, when using tendons of a pes anserinus prone to develop this condition. To our knowledge, no similar case was published in the literature so far.

OBJECTIVES To develop a novel grading system and appropriate surgical approaches for patients with diffuse type tensosynovial giant cell tumor (D-TGCT) of the temporal bone. STUDY DESIGN Retrospective cohort study. METHODS We retrospectively reviewed 31 patients with temporal bone D-TGCT between June 2012 and July 2021. All patients underwent comprehensive clinical evaluations, including clinical presentations, hearing threshold, imaging studies, surgical approaches, and prognosis. A grading system was developed based on the tumor location and adjacent neurovascular structures involvement according to imaging and intraoperative findings. RESULTS In this study, grade II tumors were the most common (13/31), followed by grades I (7/31), III (7/31), and IV (4/31) tumors. Seven grade I patients received the subtemporal middle cranial fossa approach (SMCF) combined with the canal wall up mastoidectomy and tympanoplasty (CWUT). Nine grade II patients underwent SMCF combined with subtotal petrosectomy (SPTR), and four grade II patients underwent SMCF combined with CWUT. Seven grade III patients received SMCF combined with SPTR and dura mater reconstruction, and four grade IV patients underwent infratemporal fossa approach type B. Gross total resection was achieved in all patients, and the median follow-up time was 30.1 months (range, 4-96 months). Three patients (one grade II, one grade III, and one grade IV) had recurrence during follow-up, and the patient with grade III tumor had two recurrences. CONCLUSIONS Gross total resection is the first-line treatment for patients with D-TGCT of the temporal bone. This novel grading system enables surgeons to select optimal surgical strategy. Long-term follow-up is mandatory postoperatively. LEVEL OF EVIDENCE 4 Laryngoscope, 2021.

Tenosynovial Giant Cell Tumor (TGCT) is a group of typically benign lesions arising from the synovium of joints, bursae and tendon sheaths. Depending on their growth pattern and clinical course, they are divided into localized and diffuse types. It is predominantly caused by a mutation in the stromal cells of the synovial membrane leading to overexpression of the colony stimulating factor 1 that recruits CSF1R-expressing cells of the mononuclear phagocyte lineage into the tumor mass. The lesions contain mainly histiocyte-like and synovial cells accompanied by varying numbers of multinucleated giant cells, mononuclear cells, foam cells, inflammatory cells and hemosiderin deposits. The gold standard for detect- ing and monitoring the disease is MRI, where the characteristic hemosiderin accumulation can be best appreciated, but it is a histological examination that is most conclusive. The main treatment is surgical resection of all pathological tissue, but radio- and chemotherapy are also viable options for certain groups of patients.

Tenosynovial giant cell tumor-diffuse type (diffuse TSGCT) is a benign but locally aggressive proliferative disorder of the synovium. Treatment is usually surgical, although in cases of extensive disease complete synovectomy is not possible and local recurrence rates are high. Pexidartinib (trade name Turalio®), a colony-stimulating factor-1 (CSF-1) inhibitor, was shown in a recent phase III trial to effectively treat diffuse TSGCT and is FDA approved for the treatment of adult patients with symptomatic diffuse TSGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Pexidartinib is available only through a restricted program under a risk evaluation and mitigation strategy (REMS) because of the risk of hepatotoxicity. Magnetic resonance imaging (MRI) is the preferred imaging modality for the diagnosis and surveillance of TSGCT. Here we present three patients with diffuse TSGCT of the knee who underwent multiple MRIs over several years while on pexidartinib. We describe the disease burden and signal characteristics on MRI and correlate with the response reported in the patients' medical records. Given that the use of pexidartinib and other CSF inhibitors is likely to increase, musculoskeletal radiologists should be aware of this novel non-operative treatment and the MRI appearance of diffuse TSGCT during therapy.

We present a case report of a triple location Giant Cell Tumor of tendon sheath appearance on the same flexor tendon sheath of a single digit. There have been scarce descriptions of multiple Giant Cell Tumors of tendon sheath. Multiple tumors may predispose patients to a higher recurrence rate; therefore, recognition and treatment of this rare entity is important.

Background Tenosynovial giant cell tumor (TSGCT) is a benign fibrohistiocytic tumor that affects the synovium of joints, bursa, and tendon sheaths and is categorized into localized TSGCT (LTSGCT) and diffuse TSGCT (DTSGCT). LTSGCT and DTSGCT are characterized by recurrent fusions involving the colony-stimulating factor 1 (CSF1) gene and its translocation partner collagen type VI alpha 3 chain. The fusion gene induces intratumoral overexpression of CSF1 mRNA and CSF1 protein. CSF1 expression is a characteristic finding of TSGCT and detection of CSF1 mRNA and CSF1 protein may be useful for the pathological diagnosis. Although there have been no effective anti-CSF1 antibodies to date, in situ hybridization (ISH) for CSF1 mRNA has been performed to detect CSF1 expression in TSGCT. We performed CSF1 immunohistochemistry (IHC) using anti-CSF1 antibody (clone 2D10) in cases of TSGCT, giant cell-rich tumor (GCRT), and GCRT-like lesion and verified its utility for the pathological diagnosis of TSGCT. Methods We performed CSF1 IHC in 110 cases including 44 LTSGCTs, 20 DTSGCTs, 1 malignant TSGCT (MTSGCT), 10 giant cell tumors of bone, 2 giant cell reparative granulomas, 3 aneurysmal bone cysts, 10 undifferentiated pleomorphic sarcomas, 10 leiomyosarcomas, and 10 myxofibrosarcomas. We performed fluorescence ISH (FISH) for CSF1 rearrangement to confirm CSF1 expression on IHC in TSGCTs. We considered the specimens to have CSF1 rearrangement if a split signal was observed in greater than 2% of the tumor cells. Results Overall, 50 of 65 TSGCT cases, including 35 of the 44 LTSGCTs and 15 of the 20 DTSGCTs, showed distinct scattered expression of CSF1 in the majority of mononuclear tumor cells. MTSGCT showed no CSF1 expression. Non-TSGCT cases were negative for CSF1. FISH revealed CSF1 rearrangement in 6 of 7 CSF1-positive cases on IHC. On the other hand, FISH detected no CSF1 rearrangement in all CSF1-negative cases on IHC. Thus, the results of IHC corresponded to those of FISH. Conclusion We revealed characteristic CSF1 expression on IHC in cases of TSGCT, whereas the cases of non-TSGCT exhibited no CSF1 expression. CSF1 IHC may be useful for differentiating TSGCTs from histologically mimicking GCRTs and GCRT-like lesions.

Introduction Tenosynovial giant cell tumours (TSGCTs) usually arise from the synovial membranes of tendon sheaths, bursa, and joints. They are rarely found in the spine. Lesions of the upper cervical spine (C1/2) are extremely rare, with only 13 previous cases reported in the literature. Of these, all previous anterior upper cervical cases (C1/2) have been deemed unresectable and have been managed with immunotherapy or radiological surveillance. Case presentation We report two cases of TSGCST in the cervical spine: one with a lesion at C1/2 and another at C6/7. Discussion The location of our C1/2 lesion was unique, allowing for a new endoscopic endonasal tissue biopsy method and a new transoral surgical approach for successful gross total resection. Our C6/7 lesion had a more typical location and was removed via a C6/7 laminectomy.

Aims Tenosynovial giant cell tumour (TGCT) is one of the most common soft-tissue tumours of the foot and ankle and can behave in a locally aggressive manner. Tumour control can be difficult, despite the various methods of treatment available. Since treatment guidelines are lacking, the aim of this study was to review the multidisciplinary management by presenting the largest series of TGCT of the foot and ankle to date from two specialized sarcoma centres. Methods The Oxford Tumour Registry and the Leiden University Medical Centre Sarcoma Registry were retrospectively reviewed for patients with histologically proven foot and ankle TGCT diagnosed between January 2002 and August 2019. Results A total of 84 patients were included. There were 39 men and 45 women with a mean age at primary treatment of 38.3 years (9 to 72). The median follow-up was 46.5 months (interquartile range (IQR) 21.3 to 82.3). Localized-type TGCT (n = 15) predominantly affected forefoot, whereas diffuse-type TGCT (Dt-TGCT) (n = 9) tended to panarticular involvement. TGCT was not included in the radiological differential diagnosis in 20% (n = 15/75). Most patients had open rather than arthroscopic surgery (76 vs 17). The highest recurrence rates were seen with Dt-TGCT (61%; n = 23/38), panarticular involvement (83%; n = 5/8), and after arthroscopy (47%; n = 8/17). Three (4%) fusions were carried out for osteochondral destruction by Dt-TGCT. There were 14 (16%) patients with Dt-TGCT who underwent systemic treatment, mostly in refractory cases (79%; n = 11). TGCT initially decreased or stabilized in 12 patients (86%), but progressed in five (36%) during follow-up; all five underwent subsequent surgery. Side effects were reported in 12 patients (86%). Conclusion We recommend open surgical excision as the primary treatment for TGCT of the foot and ankle, particularly in patients with Dt-TGCT with extra-articular involvement. Severe osteochondral destruction may justify salvage procedures, although these are not often undertaken. Systemic treatment is indicated for unresectable or refractory cases. However, side effects are commonly experienced, and relapses may occur once treatment has ceased. Cite this article: Bone Joint J 2021;103-B(4):788–794.

Localized tenosynovial giant cell tumor (GCT) or giant cell tumor of tendon sheath (GCTTS), is a benign nodular lesion that arises from the synovium of the tendon sheath of the hands and foot. GCTTS is characterized by the presence of multinucleated giant cells and proliferation of synovial-like mononuclear cells. A clinical diagnosis of GCTTS is kept as a differential when a firm, nodular mass shows decreased signal intensity on both T1-and T2-weighted MR imaging. Treatment is usually marginal excision of the mass.It is a retrospective study, observed in the past 3 years at a tertiary care hospital. Those cases were included in the study in which histopathological confirmation was available or if clinico-radiological features were confirmatory of the diagnosis of GCTTS when correlated with cytological features.There was a total of 24 cases, out of which 16 were females and 8 males. The tumor was located in the upper limb in 21 cases and in 3 cases the tumor was present in the lower limb. In the upper limb, 18 cases were on the right side and three cases were on the left side. In the lower limb, 1 case was present on the left and 2 on the right side. The cytomorphology consisted of mononuclear stromal cells, multinucleated giant cells, and hemosiderin-laden macrophages in variable numbers.It is important to accurately diagnose and categorize giant cell-containing lesions because their prognosis depends on the exact categorization of the tumor.

This study aimed to characterize giant cell tumor of the tendon sheath (GCTTS) in spine more fully and further validate the therapeutical effect of surgcial resection for treating this neoplasm.Patients diagnosed with spinal GCTTS and received surgical resection in our hospital between January 2009 and September 2021 were identified retrospectively. The clinical data and radiological images were summarized and the clinical outcomes of patients with a follow-up period of more than 12 months were analyzed.Thirty patients with benign GCTTS and one with malignant GCTTS were included. Preoperative radiological images were available in 28 of 30 benign cases. Benign lesions were revealed as soft tissue masses centering on the facet joint with osteolytic bone destruction in 26 patients on CT, and as prevertebral or intramuscular masses without bone erosion in 2. MRI showed the signal of isointensity or hypointensity on T1 weighted images (T1WI) in 25 patients and slightly hyperintense in three. On T2 weighted images (T2WI), 17 lesions displayed homogeneous hypointense signal, and eight lesions possessed heterogeneous signals. The remaining three lesions featured slightly hyperintense signal on T2WI. Follow-up data were available in 23 of 30 benign cases treated with gross-total resection, and two patients experienced recurrence.Spinal GCTTS should be suspected in cases with features such as the mass mainly involving the posterior bone elements, the lack of intralesional calcification, T2-weighted dark signals, and free of any cancer. Gross-total resection is an effective means for treating spinal GCTTS.

Diffuse-type tenosynovial giant cell tumour (D-TGCT) is a non-malignant but locally aggressive tumour driven by overexpression of colony-stimulating factor-1 (CSF1). CSF1R inhibitors are potential therapeutic strategies for patients not amenable to surgery. We report here the long-term outcome of nilotinib in patients with advanced D-TGCT treated within a phase II prospective international study (ClinicalTrials.gov: NCT01261429).Patients were enrolled between December 2010-September 2012 at 11 cancer centres. Eligible patients had histologically confirmed D-TGCT, not amenable to surgery. Patients received nilotinib until evidence of progression, toxicity or a maximum of one year. Long-term data were retrospectively collected after the completion of the phase II trial. Patients with nilotinib treatment ≥12 weeks and follow-up ≥12 months were included for long-term analysis.Forty-eight of 56 enrolled patients were included. Median treatment duration was 11 months; 31 (65%) patients completed the treatment protocol. After 102 months of follow-up (median; range 12-129), 25 patients (52%) had progression. The median progression-free survival (PFS) was 77 months. The five-year PFS rate was 53%. Fifteen patients (n = 15/46; 33%) experienced clinical worsening after 11 months (median). Twenty-seven patients (58%) received additional treatment, after which eleven patients (n = 11/27; 41%) had a second relapse. Nine patients required a subsequent treatment, primarily other CSF1R inhibitors (n = 6/9; 67%). No unfavourable long-term effects were observed.This long-term analysis of nilotinib for advanced D-TGCT showed that about half of the patients had progression and underwent additional treatment after 8.5 years follow-up. Contrarily, several patients had ongoing disease control after limited treatment duration, demonstrating the mixed effect of nilotinib.

Tenosynovial giant cell tumor (TSGCT) represents a family of benign tumors that arise from the synovial tissue of a joint, tendon sheath, or bursa. It usually involves the joints of the extremities and rarely occurs in the head and neck region. Here, we describe a case of a 32-year-old man with a submucosal mass bulging in the posterior pharyngeal wall since one month. The lesion was removed and diagnosed with localized type of TSGCT based on histopathological investigations and clinical presentation. It is very rare that TSGCT occurs in the retropharynx, which reminds clinicians to consider this entity as a possible diagnosis.

Although the pathogenesis of Teno-Synovial Giant Cell Tumor (TSGCT) is not known, inflammation is thought to play a role in the etiology beside some other factors. Many researchers have found a close relationship between hematological parameters such as Mean Platelet Volume (MPV), Platelet/MPV Ratio (Plt/MPV), Monocyte/Neutrophil Ratio (MNR), Neutrophil/Lymphocyte Ratio (NLR), Platelet/Lymphocyte Ratio (PLR) and certain inflammatory, autoimmune and neoplastic diseases. The aim of the present study was to assess the relationship of hematological parameters (NLR, MNR and Plt/MPV) to tumor recurrence and spread after TSGCT surgery. Data from 102 patients who matched the inclusion criteria comprised preoperative hematological parameters, tumor size, anatomic region, side, presence of bone invasion, proximity to joints or neurovascular structures, and postoperative recurrence and complications. The mean follow-up was 54.2 months (±26.5). Recurrence was observed in 12 (11.8%) of the 102 cases. No significant correlation was found between recurrence and hematologic parameter, age, laterality (right-left) or zone (volar-dorsal). There were no significant differences in NLR, Plt/MPV or MNR between patients with and without bone, capsular, nerve or total involvement. The study thus showed that the various inflammatory parameters (NLR, Plt/MPV and MNR) calculated from blood count were not predictive of tumor invasion into anatomical structures or of digital TSGCT recurrence. © 2022 SFCM

We report on a 40-year-old male with a 9-month-long history of snapping of his right hip caused by a previously undescribed etiology of internal extra-articular snapping hip, namely due to a localized tenosynovial giant cell tumor. Both dynamic ultrasound evaluation and MRI proved to be crucial in the diagnosis of this rare entity. Auto-provocation of the snapping showed an anterior hip mass moving posteriorly to the psoas tendon which elucidated the pain and clicking sensation. Subsequent MRI demonstrated a peripheral low-intensity rim due to hemosiderin deposition around the synovial mass which is indicative for pigmented villonodular tenosynovitis. Treatment consisted of arthroscopic shaver burr resection. Immediately postoperatively, the snapping sensation could not be provoked anymore by the patient. The purpose of reporting on this case report is to emphasize several successive learning points. First, dynamic ultrasound aids in diagnosis and differentiation of the types of snapping hip. Second, specific MRI features are suggestive of tenosynovial giant cell tumor, recognizing these traits may prevent delayed diagnosis and subsequent aggravated clinical course. Third, localized pigmented villonodular tenosynovitis around the hip may present as an internal extra-articular snapping hip and is of consideration in the differential diagnosis of recurrent snapping hip.

A 12-year-old boy presented to the pediatric emergency department with a 5-day history of atraumatic, progressively worsening right hip pain and inability to ambulate. He was afebrile and had elevated inflammatory markers (Erythrocyte Sedimentation Rate [ESR]: 42 mm/hr, C-Reactive Protein [CRP]: 6.6 mg/dL) with a normal white blood cell count of 6050 cells/mm3. Given the clinical concern for septic arthritis, joint aspiration of the right hip was done and demonstrated a bloody appearance with a WBC count of 54,999 cells/mm3 and RBC count of 7,000 cells/mm3. MRI of the right hip demonstrated an intra-articular mass suggestive of tenosynovial giant cell tumor/pigmented villonodular synovitis. Subsequent biopsy and excision of the mass confirmed the diagnosis. The acute presentation of tenosynovial giant cell tumor with features mimicking septic arthritis is uncommon. This rare presentation of an already uncommon diagnosis should be considered in a child with an equivocal presentation for severe hip pain because misdiagnosis may lead to unnecessary or inadequately planned surgical treatment of the condition.

Tenosynovial giant cell tumor (TGCT) is a mesenchymal tumor arising from the synovium of tendon sheath and joints, characterized by translocation t(1;2)(p13;q37). Clinical behaviors of TGCT range from favorable to locally aggressive and further research is required to lead the identification of novel therapeutic avenues for TGCT. Patient-derived cell lines are an indispensable tool for interrogating molecular mechanisms underlying the progression of disease. However, only one TGCT cell line is currently available from cell banks, and a paucity of adequate patient-derived cells hinders basic and translational research. This study aimed to establish a novel cell line of TGCT. To this end, a novel cell line, NCC-TGCT1-C1 was established from the primary tumor tissue of a 40-year-old female patient with TGCT. The cells exhibited translocation t(1;2)(p13;q37), generating COL6A3-CSF1 fusion gene. The cells were maintained as a monolayer culture through more than 30 passages over 12 months. The cells exhibited continuous growth and the ability for spheroid formation and invasion. When used in a high-throughput assay to evaluate the anti-proliferative effects of 164 anticancer drugs, the cells responded strongly to a kinase inhibitor such as gefitinib, and mitoxantrone. Our results indicate that the novel TGCT cell line, designated NCC-TGCT1-C1, was successfully established and could be used to study TGCT development and the effects of anticancer agents.

BACKGROUND: Tenosynovial giant cell tumor (TGCT), a rare, locally aggressive neoplasm, overexpresses colony-stimulating factor 1 (CSF1). Surgery is standard with no approved systemic therapy. This phase 3 randomized, double-blind study evaluated pexidartinib, a CSF1 receptor inhibitor, in patients with TGCT. METHODS: In part 1 of this two-part study, 120 patients with symptomatic, advanced TGCT for whom surgery was not recommended were randomized (1:1) to pexidartinib (n=61) or placebo (n=59). Part 2 was open-label pexidartinib for all patients. Primary endpoint was centrally reviewed overall response rate (week 25) by RECIST, version 1.1. Secondary endpoints included range of motion, response rate by tumor volume score (TVS), patient-reported outcomes (PROs), and response duration. Emergence of mixed and cholestatic hepatotoxicity caused the Data Monitoring Committee to stop enrollment six patients short of target. FINDINGS: The overall response rate was higher for pexidartinib versus placebo at week 25 by RECIST (39 vs 0%; p

A tenosynovial giant cell tumor is a benign proliferative disease, mostly arising from the synovial membrane of tendon sheaths, bursae, and joints. Axial skeleton involvement is very rare, but it is often found in the cervical spine. Spinal tenosynovial giant cell tumors often arise at the facet joints; a completely extra-articular spinal tenosynovial giant cell tumor is rare. We report an extremely rare case of tenosynovial giant cell tumor in the upper cervical spine that extended from the posterior atlanto-occipital membrane rather than the facet joint. Herein, the clinical and radiological findings will be reviewed to better our understanding of the characteristics of spinal tenosynovial giant cell tumors, and to help improve their diagnosis despite their non-typical locations of origin.

Background: Benign soft-tissue tumors of the hand are more common than both their benign bone and malignant soft-tissue counterparts. This study evaluates the characteristics and treatment of benign soft tissue tumors in light of 1 institution’s experience. Methods: Histologically confirmed benign soft-tissue tumors of the hand were retrospectively identified using International Classification of Disease codes from 1992 to 2015. A medical chart review was conducted to collect patient demographics, tumor epidemiology, and treatment. Results: A total of 199 soft-tissue tumors were identified. The median patient age at time of treatment was 47.4 ± 14.7 years in age. The majority of tumors were located in the digits (n = 168, 84%) and treated by excision (n = 191, 96%). Localized type tenosynovial giant cell tumors (n = 71, 36%) were the most common and had the highest rates of recurrence (8.5%) in this series. Other frequent histologies included hemangioma, schwannoma, and glomus tumors. Conclusion: Awareness and understanding of tumor characteristics may help physicians with diagnosis and treatment. There is an extensive variety of tumors, but the principles of clinical and imaging diagnosis are common to all of them. Marginal excision for the treatment pain, improvement of function, and cosmetic correction applies to all these tumors independent of the histology.

Tenosynovial giant cell tumor (TGCT) is a benign mesenchymal tumor arising from the synovium of tendon sheats and joints, driven by colony-stimulating factor 1 (CSF1) over-expression. Standard treatment is surgery, but local recurrences are frequent, especially in diffuse TGCT subtype, rarely cured with surgery. When TGCT becomes a chronic condition, which may severely compromise joint function and quality of life, patients may need a systemic therapy. Areas covered: We reviewed the drugs on clinical development in TGCT, focusing on the pharmacodynamics, pharmacokinetics, efficacy, and toxicity profile of pexidartinib, the first drug approved in the US for TGCT, and on the open questions about its optimal use in clinical practice.CSFR1 inhibitors have opened a new avenue for treatment of TGCT patients. Pexidartinib is the first-in-class FDA approved agent for symptomatic locally advanced TGCT, based on a phase III study where pexidartinib showed high anti-tumor activity, improved patient symptoms, and functional outcome. A few cases of potentially life-threatening hepatic toxicity were observed. TGCT patients candidate to pexidartinib need to be carefully selected by the multidisciplinary board of center of expertise, balancing the expected risk-benefit ratio. Close monitoring of liver function and adequate education on the approved indication is warranted.

Background: Tenosynovial giant cell tumor (TSGCT) is the second most common benign tumor of the hand. Even though it is a benign lesion there is still a high incidence of local recurrence (range, 7%–44%) according to data in published papers. In this study, the clinical and epidemiological features of 173 patients who underwent excision of localized TSGCT, the recurrence rates and possible reasons for recurrence were examined in the light of current literature.Methods: Medical records of 173 patients with TSGCT were reviewed. Data on demographic characteristics as well as clinical and intraoperative findings were collected. Patients were asked about the recurrence of the TSGCT and the QuickDASH scoring was applied at the final clinical evaluation after mean follow-up of 81 months.Results: Females were predominantly involved (73%). Patients aged mean 44 years at the time of surgery. There were 93 tumors in flexor zones and 80 tumors in extensor zones of the hand. Of the tumors with flexor zone localization, zone II was most predominantly involved with 46 tumors, and 18 of these were on the index finger. The extensor zones III and IV were mostly involved with 9 tumors each on the middle and ring fingers. A total of 12 recurrences (6.9 %) were determined over the mean follow-up period of 81 months.Conclusions: The characteristics of our patients identified were similar to the previous studies. Surgical excision provides good outcomes in the treatment of TSGCT especially when clear margins are obtained.

Tenosynovial giant cell tumor (TSGCT) of localized type is a common disease occurring mostly in the hands. Diagnosis of this tumor is relatively easy to render with hematoxylin-eosin–stained sections as compared with that of TSGCT of diffuse type. However, very rare cases with chondroid metaplasia that have recently been reported mainly in diffuse type can make pathological differentiation from soft tissue cartilaginous tumors extremely difficult. In this article, the authors present the second reported case of TSGCT of localized type showing extensive chondroid metaplasia. Pathological interpretation was difficult without utilizing immunohistochemistry and fluorescence in situ hybridization. One must be careful not to misdiagnose this lesion as cartilaginous tumors of soft tissue, and we suspect at least some chondroblastoma-like chondroma could be reclassified as TSGCT of localized type with extensive chondroid metaplasia. Morphological, immunohistochemical, and molecular genetic characteristics are presented and discussed.

Pexidartinib (TURALIO™) is an orally administered small molecule tyrosine kinase inhibitor with selective activity against the colony-stimulating factor 1 (CSF1) receptor, KIT proto-oncogene receptor tyrosine kinase (KIT) and FMS-like tyrosine kinase 3 harboring an internal tandem duplication mutation (FLT3-ITD). In August 2019, the US FDA approved pexidartinib capsules for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. This approval was based on positive results from the phase III ENLIVEN trial. Pexidartinib is being investigated in various malignancies as monotherapy or combination therapy. This article summarizes the milestones in the development of pexidartinib leading to its first approval for TGCT.

To propose a simple and practical clinical classification for tenosynovial giant cell tumor (TGCT) of the knee.A retrospective study was conducted to verify the value and significance of this clinical classification. TGCT growth patterns, knee joint capsule, and bone erosion were applied to establish this novel clinical classification. Seventy-eight patients who underwent surgery for TGCT from 2008 to 2016 were identified. This novel clinical classification was retrospectively applied to patients' existing classification, and patients with different TGCT types were statistically compared to verify the significance of the clinical classification.The clinical classification included three types and four subtypes. Type 1: localized TGCT, Subtype 1a: localized intra-articular TGCT, Subtype 1b: localized extra-articular TGCT. Type 2: diffuse TGCT, Subtype 2a: diffuse intra-articular TGCT with bone normal, Subtype 2b: diffuse intra-articular TGCT with bone destruction. Type 3: diffuse TGCT across the knee joint capsule. The mean follow-up time for the 78 patients was 59.6 months. Twenty-one patients were in Subtype 1a, four were Subtype 1b, 38 were Subtype 2a, seven were Subtype 2b, and eight were Type 3. Oncological results and surgical complications differed significantly (P = 0.000, P = 0.000). The mean Musculoskeletal Tumor Society functional scores differed significantly at 27.8 for Type 1 patients, 22.9 for Type 2 patients, and 17.0 for Type 3 patients (P = 0.000).This clinical classification can be easily used to evaluate TGCT of all knees prior to surgery or other treatments and can help determine surgical options.

Tenosynovial giant cell tumors typically arise in the synovium of joints, bursae, or tendon sheaths. They may occur in an intra- or extra-articular location and can be divided into localized and diffuse types. The neoplastic nature of the lesion has been supported by a recurrent

Based on knowledge of kinase switch-control inhibition and using a combination of structure-based drug design and standard medicinal chemistry principles, we identified a novel series of dihydropyrimidone-based CSF1R kinase inhibitors displaying exquisite selectivity for CSF1R versus a large panel of kinases and non-kinase protein targets. Starting with lead compound 3, an SAR optimization campaign led to the discovery of vimseltinib (DCC-3014; compound 20) currently undergoing clinical evaluation for the treatment of Tenosynovial Giant Cell Tumor (TGCT), a locally aggressive benign tumor associated with substantial morbidity. 2021 Elsevier ltd. All rights reserved.

Background The tenosynovial giant cell tumor (TGCT) is a usually benign lesion which arises from the synovium. It affects joints, tendon sheaths and bursae. The clinical course is often unpredictable, and local recurrences frequently occur. The aim of this study was to describe different treatment options, surgical complications, and to develop a follow-up regime based on a systematic literature review and meta-analysis of foot and ankle lesions. Methods and results 1284 studies published between 01/1966 and 06/2021 were identified. 25 met the inclusion criteria, with a total of 382 patients. Of these, 212 patients had a diffuse (dTGCT) and 170 a localized (lTGCT) TGCT. Patients with a dTGCT had a mean age of 36.6±8.2 years, and 55% were female. The overall complication rate was 24% in dTGCT, irrespective of the therapeutic procedure; the mean follow-up was 37.9±27.4 months with a recurrence rate of 21%, and recurrences occurred between 3 and 144 months, the vast majority (86%) within the first 5 years following intervention. Patients with a lTGCT had a mean age of 31.2±5.7 years, and 53% were female. Complications occurred in 12%. The mean follow-up was 51.1±24.6 months, the recurrence rate was 7%, and recurrence occurred between 1 and 244 months after intervention. Conclusion Diffuse TGCTs of the foot and ankle region have a remarkable recurrence rate irrespective of therapeutic procedures, and most lesions reoccurred within 5, with more than half of these in the first 2 years. The lTGCTs are well treatable lesions, with a low recurrence and a moderate complication rate. Based on these findings, we propose a follow-up regime for the dTGCT including a clinical survey and MR imaging 3 months after surgical intervention (baseline), followed by twice-yearly intervals for the first 2 years, yearly intervals up to the fifth year, and further individual follow-up due to the fact that recurrences can even occur for years later. For the lTGCT a clinical survey and MRT is proposed after 3–6 months after intervention (baseline), followed by annual clinical examination for 3 years, and in case of symptoms MR-imaging. Larger prospective multi-center studies are necessary to confirm these results and recommendations.

Background: Whether arthroscopic or open surgical management for diffuse-type tenosynovial giant cell tumor (D-TGCT) of the knee is associated with a lower rate of recurrence is unknown. Methods: PubMed, Scopus, Web of Science, Cochrane, and EMBASE were searched on December 3, 2020. Retrospective studies that reported on recurrence rates for arthroscopic versus open management of D-TGCT were included. A total of 16 studies evaluating 1143 patients with D-TGCT of the knee were included (nopen = 551, narthroscopic = 350 patients, and narthroscopic/open = 23 patients). Random-effects meta-analyses were used to summarize and compare the reported recurrence rates, stratified by approach and overall recurrence. The meta-analysis was registered with PROSPERO. Results: The recurrence rate per year (incidence) for arthroscopic procedures was 0.11 (95% CI 0.08 to 0.16, P < 0.0001) and for open procedures was 0.07 (95% CI 0.04 to 0.13, P < 0.0001). There was a 1.56 times (95% CI 1.04 to 2.34, P = 0.0332) increased risk of recurrence when treating D-TGCT of the knee with an arthroscopic approach. When evaluating only the subset of studies that had data for both arthroscopic and open approaches, the incidence rate per year for arthroscopic procedures was 0.17 (95% CI 0.11 to 0.27, P < 0.0001) and for open procedures was 0.11 (95% CI 0.06 to 0.19, P < 0.0001). The rate of overall complications was 0.04 (95% CI 0.01 to 0.08, P < 0.0001). Conclusion: Arthroscopic surgical management of D-TGCT of the knee in our study resulted in a 1.56 times risk of recurrence as compared with the open approach. The percent of overall complications was minimal.

Objectives To review the clinical and imaging data of spinal giant cell tumour of the tendon sheath (GCTTS) to improve our understanding of the disease. Methods The imaging findings, clinicopathological features and clinical outcomes of 14 patients with pathologically confirmed spinal GCTTS were analysed retrospectively. Results All 14 patients had a single spinal lesion, including ten cervical vertebra lesions and four thoracic vertebra lesions. CT scan findings: The lesions showed osteolytic bone destruction and were centred on the facet joint, eroding the surrounding bone with a paravertebral soft tissue mass. MRI scan findings: all the lesions manifested predominantly as isointense or hypointense on T1-weighted imaging (T1WI). On T2-weighted imaging (T2WI), eight lesions were hypointense, and four were isointense. The remaining two lesions showed slight hyperintensity. The enhanced scans of eight lesions showed moderate to marked homogeneous or heterogeneous enhancement. PET/CT findings: Among the five patients who underwent PET/CT, three presented lesions with well-defined, sclerotic borders, and the uptake of 18F-FDG was markedly increased. One lesion showed an ill-defined border and an uneven increase in 18F-FDG uptake with an SUVmax value of 8.9. A recurrent lesion was only found on PET/CT 45 months after surgery and the SUVmax was 5.1. Conclusions Spinal GCTTS is extremely rare. Osteolytic bone destruction in the area of the facet joint with a soft tissue mass and hypointensity on T2WI images are indicative of the spinal GCTTS. GCTTS shows high uptake of 18F-FDG, and PET/CT is helpful in detecting recurrent lesions.

Tenosynovial giant cell tumor, also known as giant cell tumor of the tendon sheath (GCT-TS), is a solitary, nodular, firm, benign, soft-tissue tumor that arises from the synovial lining of a tendon. The etiology is unknown. It is a rare soft-tissue tumor, with an overall incidence of one in 50,000 individuals, and usually affects people aged between 30 and 50 years. Magnetic resonance imaging tends to be the imaging modality of choice, used for surgical preparation. Widely accepted treatment involves local excision with or without radiotherapy. The author presents a case study involving a patient with an abnormally large, longstanding GCT-TS, diagnosed with clinical examination and imaging modalities, surgically excised, and further confirmed by pathology reports. Topic of discussion includes a review of GCT-TS.

Tenosynovial giant cell tumor is the common term used to describe a group of soft-tissue tumors that share a common etiologic link. These tumors are relatively infrequent in the foot and ankle, and occasionally they may be the cause of destruction of the adjacent bone structures. We report the imaging appearance and pathologic findings of two patients with localized tenosynovial giant cell tumor of the forefoot. Both of these patients underwent surgical gross total resection. However, one of the patients experienced a recurrence. Their clinical, radiologic, and pathologic features, with their treatment protocol, are summarized retrospectively, and related literature is reviewed in an attempt to enhance the understanding of these tumor lesions. Clinicians should perform a careful preoperative and postoperative examination and complete tumor surgical resection with the aim of reducing local recurrence.

Purpose: To assess the response to pexidartinib treatment in six cohorts of adult patients with advanced, incurable solid tumors associated with colony-stimulating factor 1 receptor (CSF1R) and/or KIT proto-oncogene receptor tyrosine kinase activity. Patients and Methods: From this two-part phase I, multicenter study, pexidartinib, a small-molecule tyrosine kinase inhibitor that targets CSF1R, KIT, and FMS-like tyrosine kinase 3 (FLT3), was evaluated in six adult patient cohorts (part 2, extension) with advanced solid tumors associated with dysregulated CSF1R. Adverse events, pharmacokinetics, and tumor responses were assessed for all patients; patients with tenosynovial giant cell tumor (TGCT) were also evaluated for tumor volume score (TVS) and patient-reported outcomes (PRO). CSF1 transcripts and gene expression were explored in TGCT biopsies. Results: Ninety-one patients were treated: TGCT patients (n = 39) had a median treatment duration of 511 days, while other solid tumor patients (n = 52) had a median treatment duration of 56 days. TGCT patients had response rates of 62% (RECIST 1.1) and 56% (TVS) for the full analysis set. PRO assessments for pain showed improvement in patient symptoms, and 76% (19/25) of TGCT tissue biopsy specimens showed evidence of abnormal CSF1 transcripts. Pexidartinib treatment of TGCT resulted in tumor regression and symptomatic benefit in most patients. Pexidartinib toxicity was manageable over the entire study. Conclusions: These results offer insight into outcome patterns in cancers whose biology suggests use of a CSF1R inhibitor. Pexidartinib results in tumor regression in TGCT patients, providing prolonged control with an acceptable safety profile.

Purpose: Osteochondral destruction and high recurrence rate after surgery are major concerns during the treatment course of tenosynovial giant cell tumor. The aims of this study were to elucidate rates of local recurrence and osteochondral destruction, and demographic factors correlated with osteochondral destruction and recurrence rate after surgery. Methods: Eighty surgically treated patients (knee: 49, ankle and foot: 12, hip: 10, others: 9) were included in this study. Factors including age, disease type (diffuse/localized), location, existence of osteochondral destruction were analyzed to be correlated with local recurrence or development/progression of osteochondral destruction. Results: The 5-year local recurrence free survival rate was 71.4 %. Diffuse type (n=59, localized: n=21) (P=0.023) and knee location (P=0.002) were independent risk factors for local recurrence. Diffuse type (P=0. 009) was a significant risk factor, and knee location (P=0. 001) was a negative factor for osteochondral destruction at the initial examination. Progression of osteochondral destruction was observed more often in cases with local recurrence (P=0.040) and findings of osteochondral destruction at the initial examination (P=0.029).Conclusions: Diffuse type is a factor that should be noted for both local recurrence and osteochondral destruction, and local recurrence occurs but osteochondral destruction is less observed for knee location.

Tenosynovial giant cell tumor rarely affects the facet joints of the spine. We describe FDG PET/CT findings in a case of tenosynovial giant cell tumor arising from the left L2 to L3 facet joint. The tumor caused osteolytic bone destruction of the facet joint and showed intense FDG uptake with SUVmax of 10.4. This case indicates tenosynovial giant cell tumor should be included in the differential diagnosis of abnormal facet joint FDG accumulation.

Macrophages can be co-opted to contribute to neoplastic, neurologic, and inflammatory diseases. Colony-stimulating factor 1 receptor (CSF1R)-dependent macrophages and other inflammatory cells can suppress the adaptive immune system in cancer and contribute to angiogenesis, tumor growth, and metastasis. CSF1R-expressing osteoclasts mediate bone degradation in osteolytic cancers and cancers that metastasize to bone. In the rare disease tenosynovial giant cell tumor (TGCT), aberrant CSF1 expression and production driven by a gene translocation leads to the recruitment and growth of tumors formed by CSF1R-dependent inflammatory cells. Small molecules and antibodies targeting the CSF1/CSF1R axis have shown promise in the treatment of TGCT and cancer, with pexidartinib recently receiving FDA approval for treatment of TGCT. Many small-molecule kinase inhibitors of CSF1R also inhibit the closely related kinases KIT, PDGFRA, PDGFRB, and FLT3, thus CSF1R suppression may be limited by off-target activity and associated adverse events. Vimseltinib (DCC-3014) is an oral, switch control tyrosine kinase inhibitor specifically designed to selectively and potently inhibit CSF1R by exploiting unique features of the switch control region that regulates kinase conformational activation. In preclinical studies, vimseltinib durably suppressed CSF1R activity in vitro and in vivo, depleted macrophages and other CSF1R-dependent cells, and resulted in inhibition of tumor growth and bone degradation in mouse cancer models. Translationally, in a phase I clinical study, vimseltinib treatment led to modulation of biomarkers of CSF1R inhibition and reduction in tumor burden in TGCT patients.

Case A 17-year-old boy presented to the clinic complaining of right hip pain after soccer participation. Clinical findings and imaging studies led to the diagnoses of femoroacetabular impingement and diffuse tenosynovial giant cell tumor (TGCT). Comprehensive arthroscopic management and biopsy revealed a diagnosis of osteosarcoma. The patient subsequently underwent chemotherapy, surgical resection, and reconstruction. Conclusion Osteosarcoma of the proximal femur may mimic TGCT on imaging studies because osteosarcoma may show changes suggestive of inflammation. We recommend heightened clinical awareness and a comprehensive differential workup in the management of presumed TGCT about the hip in the pediatric patient population.

Tenosynovial giant-cell tumor (TGCT) is an intraarticular giant-cell tumor of the synovial tissue and tendon sheaths which often mimics multiple conditions on presentation. This case report describes a previously asymptomatic 67-year-old man with preliminary clinical and laboratory evaluation suggestive of septic arthritis; however, arthroscopy revealed diffuse synovitis, and biopsy confirmed TGCT. To our knowledge, this is the first report of TGCT presenting as septic arthritis in an adult patient. This diagnosis should be considered in evaluation of acute, atraumatic knee pain with associated inflammatory marker elevation.

In this report, the authors describe a child presenting at 6 months old with a rapidly expanding extracranial left temporal mass concerning for malignancy. The mass was successfully treated at 16 months with radical surgical excision. The patient was found to have a tenosynovial giant cell tumor, diffuse type, completely encased by the temporalis muscle. To our knowledge, this is the first report of a case of diffuse type tenosynovial giant cell tumor in the temporalis muscle, without articular involvement, presenting in an infant.

Identification of risk factors for recurrence of tenosynovial giant cell tumors of the hand is crucial to provide adequate preoperative counseling and tailor surgical treatment. However, the risk factors are still controversial, which are the subject of this research.Recently, we conducted a retrospective cohort study of 135 consecutive patients with giant cell tumors of the tendon sheath of the hand from January 2010 to July 2016. All patients underwent surgical excision, received necessary imaging examinations, and had routine follow-up and thus were identified as those who had recurrence by confirmation of reoperation, and the duration ranged from 24 to 103 months (mean, 53.5 ± 21.4 months). There were 14 local recurrences (10.4%) within 6 to 24 months, respectively, after surgery. Data pertaining to sex, age, tumor sites, tumor size, tumor number, course of disease, bone erosion, tumor growth patterns, anesthesia mode, and the surgeon's experience were all extracted, and Cox regression models were used to estimate recurrence rate with adjustment for potential confounders.According to the Cox regression analysis, the recurrence rate after surgery was significantly higher in patients with a diffused form than in those with a localized one (P = 0.001); in addition, patients with 2 or more tumors had a much higher postoperative recurrence rate than did those with only 1 tumor (P = 0.023).This study suggested that the recurrence rate of tenosynovial giant cell tumors of the hand was closely related to the tumor number and tumor growth patterns.

Tenosynovial giant cell tumors (TGCTs) are characterized by rearrangements of CSF1, thought to drive overexpression of macrophage colony-stimulating factor (CSF1), thereby promoting tumor growth and recruitment of non-neoplastic mononuclear and multinucleated inflammatory cells. While fusions to collagen promoters have been described, the mechanism of CSF1 overexpression has been unclear in a majority of cases. Two cohorts of TGCT were investigated for CSF1 rearrangements using fluorescence in situ hybridization (FISH) and either RNA-seq or DNA-seq with Sanger validation. The study comprised 39 patients, including 13 localized TGCT, 21 diffuse TGCT, and five of unspecified type. CSF1 rearrangements were identified by FISH in 30 cases: 13 translocations, 17 3' deletions. Sequencing confirmed CSF1 breakpoints in 28 cases; in all 28 the breakpoint was found to be downstream of exon 5, replacing or deleting a long 3' UTR containing known miRNA and AU-rich element negative regulatory sequences. We also confirmed the presence of CBL exon 8-9 mutations in six of 21 cases. In conclusion, TGCT in our large cohort were characterized by variable alterations, all of which led to truncation of the 3' end of CSF1, instead of the COL6A3-CSF1 fusions previously reported in some TGCTs. The diversity of fusion partners but consistent integrity of CSF1 functional domains encoded by exons 1-5 support a hypothesis that CSF1 overexpression results from transcription of a truncated form of CSF1 lacking 3' negative regulatory sequences. The presence of CBL mutations affecting the linker and RING finger domain suggests an alternative mechanism for increased CSF1/CSF1R signaling in some cases.

Tenosynovial giant cell tumor (TSGCT) is a rare neoplasm. Although surgical resection is the widely accepted primary treatment for TSGCT, recurrences are frequent, and patients' joint function may be severely compromised. Previous studies reported that CSF1-COL6A3 fusion genes were identified in approximately 30% of TSGCTs. The aim of our study was to comprehensively clarify the genomic abnormalities in TSGCTs. We performed whole exome sequencing in combination with target sequence validation on 34 TSGCT samples. RNA sequencing was also performed on 18 samples. RNA sequencing revealed fusion transcripts involving CSF1, including novel CSF1-VCAM1, CSF1-FN1 and CSF1-CDH1 fusions, in 13/18 (72%) cases. These fusion genes were validated by chromogenic in situ hybridization. All CSF1 fusions resulted in the deletion of CSF1 exon 9, which was previously shown to be an important negative regulator of CSF1 expression. We also found that 12 (35%) of the 34 TSGCT samples harbored CBL missense mutations. All mutations were detected in exons 8 or 9, which encode the linker and RING finger domain. Among these mutations, C404Y, L380P and R420Q were recurrent. CBL-mutated cases showed higher JAK2 expression than wild-type CBL cases (p = 0.013). CSF1 fusion genes and CBL mutations were not mutually exclusive, and both alterations were detected in six of the 18 (33%) tumors. The frequent deletion of CSF1 exon 9 in the fusion transcripts suggested the importance of this event in the etiology of TSGCT. Our results may contribute to the development of new targeted therapies using JAK2 inhibitors for CBL-mutated TSGCT.

The clinical and imaging characteristics of fibromas of the tendon sheath (FTS) closely resemble those of giant cell tumors of the tendon sheath (GCTTS). We aimed to study MRI features of FTS and GCTTS to distinguish the two entities and improve their differential diagnosis. We retrospectively analyzed data from 18 patients (9 men, 9 women; age, 17–62 years) and 24 patients (13 men, 11 women; age, 15–67 years) treated between May 2011 and May 2016, with histologically confirmed FTS and GCTTS, respectively. Specific MRI features of the two groups were compared using the independent sample t tests and chi-square tests. FTS exhibited round or oval shapes. Proton-weighted images (PDWI) showed heterogeneous hypointensity that appeared striped or disordered and was located in the lesion center. Enhanced scans demonstrated asymmetrical signal in the foci. GCTTS mostly exhibited a lobulated or casting mold pattern, with a hypointense ring on PDWI. The hypointense components appeared granular/flaky or separated, sometimes behaving as a uniform signal on PDWI. Significant differences in the following features were observed between the two groups: lesion morphology (p