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Aim: Real-world treatment patterns in tenosynovial giant cell tumor (TGCT) patients remain unknown. Pexidartinib is the only US FDA-approved treatment for TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Objective: To characterize drug utilization and treatment patterns in TGCT patients. Methods: In a retrospective observational study using IQVIA's linked prescription and medical claims databases (2018–2021), TGCT patients were stratified by their earliest systemic therapy claim (pexidartinib [N = 82] or non-FDA-approved systemic therapy [N = 263]). Results: TGCT patients treated with pexidartinib versus non-FDA-approved systemic therapies were predominantly female (61 vs 50.6%) and their median age was 47 and 54 years, respectively. Pexidartinib-treated patients had the highest 12-month probability of remaining on treatment (54%); 34.1% of pexidartinib users had dose reduction after their first claim. Conclusion: This study provides new insights into the unmet need, utilization and treatment patterns of systemic therapies for the treatment of TGCT patients. Plain language summary Treatment patterns in patients with tenosynovial giant cell tumors in the USA This database study is the first investigation of how drugs are used to treat patients with tenosynovial giant cell tumor (TGCT) in the real world. We researched adult TGCT patients from IQVIA's prescription and medical claims databases who started treatment with pexidartinib (N = 82) or other non-US FDA-approved systemic therapies (N = 263). The patients included in this analysis were mostly women (61.0 and 50.6%) and their median age was 47 and 54 years for pexidartinib and other non-FDA-approved systemic therapies, respectively. The patients treated with pexidartinib were most likely to remain on treatment (54.0%) at the end of the first year. Most patients (79.3%) started pexidartinib treatment at a total daily dose of 800 mg/day, as per the product label. Only 34.1% of patients had reduced medication dose during follow-up. Of note, this study found that TGCT patients were treated with other systemic therapies which remain unproven to be safe and effective in medical studies of TGCT. Given the unmet need, and with pexidartinib being the only approved systemic treatment in USA, there is an opportunity for the larger population of adult TGCT patients to benefit from its use. Further research is needed to identify barriers for access to pexidartinib and treatment of TGCT patients. Summary points Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive neoplasm affecting the synovial membrane lining joints, bursae and tendon sheaths. Pexidartinib is currently the only systemic treatment approved by the US FDA for the treatment of adult patients with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Other systemic therapies have been investigated in clinical studies of TGCT patients, none of them have been approved by the FDA for the treatment of TGCT specifically. Using a real-world claims database, this study characterized TGCT patients newly treated with pexidartinib or other unapproved systemic treatments and described their treatment patterns, including treatment duration and dosing. In this study, we found that although the median duration of pexidartinib treatment was not reached, patients on pexidartinib had the highest 12-month probability of remaining on treatment. Dose reductions after the first medication claim were commonly observed in the pexidartinib cohort (34.1%) and some patients (9.8%) had evidence of dose increase. Dose levels of the non-FDA-approved systemic therapies were consistent with the recommended dosages for other indications, as per their label, none of which were TGCT. As expected, 63.6–82.9% of TGCT patients treated with non-FDA-approved systemic therapies discontinued treatment at 12 months. This study provided novel insights into how systemic therapies for TGCT are used in real-world clinical practice, where surgery has been the standard of care. Given the large unmet need for the treatment of TGCT patients, and as pexidartinib is the only regulatory-approved systemic treatment, there is opportunity for its wider use in this patient population. [ABSTRACT FROM AUTHOR]

Abstract Background Pigmented villonodular synovitis is a rare yet locally invasive disorder impacting synovial tissues. This case report delineates the atypical manifestation of pigmented villonodular synovitis in the talonavicular joint, detailing its diagnostic complexity and successful management. Case presentation A 56-year-old Iranian patient with a 4-year history of chronic ankle pain, initially diagnosed with degenerative joint disease post-trauma based on imaging, underwent talonavicular fusion surgery. An unexpected pigmented villonodular synovitis mass was encountered during the procedure. Subsequent interventions encompassed tumor resection, talonavicular joint fusion, and allograft bone grafting. Despite the initial intervention, persistent pain and nonunion necessitated a secondary procedure, involving joint surface curettage and autograft bone grafting. At the 12-month follow-up, the patient remained pain-free without tumor recurrence. Conclusion This case report highlights the significance of considering pigmented villonodular synovitis as a crucial differential diagnosis in chronic ankle pain, even when there is evidence of degenerative joint disease and a history of trauma. Magnetic resonance imaging serves a crucial role in accurate diagnosis. Treatment necessitates precise tumor removal, appropriate bone grafting techniques and secure fixation. Level of evidence: IV.

Background: Pigmented villonodular synovitis is a rare yet locally invasive disorder impacting synovial tissues. This case report delineates the atypical manifestation of pigmented villonodular synovitis in the talonavicular joint, detailing its diagnostic complexity and successful management. Case presentation: A 56-year-old Iranian patient with a 4-year history of chronic ankle pain, initially diagnosed with degenerative joint disease post-trauma based on imaging, underwent talonavicular fusion surgery. An unexpected pigmented villonodular synovitis mass was encountered during the procedure. Subsequent interventions encompassed tumor resection, talonavicular joint fusion, and allograft bone grafting. Despite the initial intervention, persistent pain and nonunion necessitated a secondary procedure, involving joint surface curettage and autograft bone grafting. At the 12-month follow-up, the patient remained pain-free without tumor recurrence. Conclusion: This case report highlights the significance of considering pigmented villonodular synovitis as a crucial differential diagnosis in chronic ankle pain, even when there is evidence of degenerative joint disease and a history of trauma. Magnetic resonance imaging serves a crucial role in accurate diagnosis. Treatment necessitates precise tumor removal, appropriate bone grafting techniques and secure fixation. Level of evidence: IV. [ABSTRACT FROM AUTHOR]

Aims: Tenosynovial giant cell tumour (TGCT) is a rare benign tumour of the musculoskeletal system. Surgical management is fraught with challenges due to high recurrence rates. The aim of this study was to describe surgical treatment and evaluate surgical outcomes of TGCT at an Australian tertiary referral centre for musculoskeletal tumours and to identify factors affecting recurrence rates. Methods: A prospective database of all patients with TGCT surgically managed by two orthopaedic oncology surgeons was reviewed. All cases irrespective of previous treatment were included and patients without follow-up were excluded. Pertinent tumour characteristics and surgical outcomes were collected for analysis. Results: There were 111 total cases included in the study; 71 (64%) were female, the mean age was 36 years (SD 13.6), and the knee (n = 64; 57.7%) was the most commonly affected joint. In all, 60 patients (54.1%) had diffuse-type (D-TGCT) disease, and 94 patients (84.7%) presented therapy-naïve as "primary cases" (PC). The overall recurrence rate was 46.8% for TGCT. There was a statistically significant difference in recurrence rates between D-TGCT and localized disease (75.0% vs 13.7%, relative risk (RR) 3.40, 95% confidence interval (CI) 2.17 to 5.34; p < 0.001), and for those who were referred in the ”revision cases” (RC) group compared to the PC group (82.4% vs 48.9%, RR 1.68, 95% CI 1.24 to 2.28; p = 0.011). Age, sex, tumour volume, and mean duration of symptoms were not associated with recurrence (p > 0.05). Conclusion: Recurrence rates remain high even at a tertiary referral hospital. Highest rates are seen in D-TGCT and “revision cases”. Due to the risks of recurrence, the complexity of surgery, and the need for adjuvant therapy, this paper further supports the management of TGCT in a tertiary referral multi-disciplinary orthopaedic oncology service. Cite this article: Bone Jt Open 2023;4(11):846–852.

This article discusses a case of sudden knee joint swelling in a 61-year-old male with a nodular lesion of Hoffa's fat pad. The patient presented with pain, swelling, and reduced range of motion in the left knee joint. An MRI revealed a nodular lesion in the fat pad of Hoffa, fluid in the suprapatellar bursa and knee joint, and edema in the biceps femoris muscle. The lesion was surgically resected and diagnosed as local pigmented villonodular synovitis (PVNS) of the knee. PVNS is a rare neoplastic synovial disease characterized by joint effusions, bone erosion, and synovial hyperplasia. It primarily affects young adults and is most commonly found in the knee and hip joints. The diagnosis of PVNS can be suggested on MRI, and excision and tissue sampling are required for a definitive diagnosis. PVNS should be differentiated from other synovial lesions with hemosiderin deposition. [Extracted from the article]

Various uses of posterior knee arthroscopy have been shown, including all-inside repair of posterior meniscal lesions, posterior cruciate ligament (PCL) reconstruction or PCL avulsion fixation, extensile posterior knee synovectomy for pigmented villonodular synovitis or synovial chondromatosis, posterior capsular release in the setting of knee flexion contractures, and loose bodies removal. Posterior arthroscopy provides direct access to the posterior meniscal borders for adequate abrasion and fibrous tissue removal. This direct view of the knee posterior structures enables the surgeon to create a stronger biomechanical repair using vertical mattress sutures. During PCL reconstruction, posterior arthroscopy gives the surgeon proper double access to the tibial insertion site, which can result in less acute curve angles and the creation of a more anatomic tibial tunnel. Moreover, it gives the best opportunity to preserve the PCL remnant. Arthroscopic PCL avulsion fixation is more time-consuming with a larger cost burden compared to open approaches, but in the case of other concomitant intra-articular injuries, it may lead to a better chance of a return to pre-injury activities. The high learning curve and overcaution of neuromuscular injury have discouraged surgeons from practicing posterior knee arthroscopy using posterior portals. Evidence for using posterior portals by experienced surgeons suggests fewer complications. The evidence suggests toward learning posterior knee arthroscopy, and this technique must be part of the education about arthroscopy. In today's professional sports world, where the quick and complete return of athletes to their professional activities is irreplaceable, the use of posterior knee arthroscopy is necessary.

Background: Tenosynovial giant cell tumor (TGCT) is a benign proliferative disease affecting synovial membranes. There are 2 forms, localized (L-TGCT) and diffuse (D-TGCT), which although histologically similar behave differently. It is locally invasive and is treated in most cases by operative excision. The aim of this study was to assess current practice, how the patients' presentation affected their outcome, as well as review the recurrence rates and complications. Methods: A retrospective analysis of 123 cases was performed in patients treated between 2003 and 2019 with TGCT of the foot and/or ankle. Data were collected on age at presentation, radiologic pattern of disease, location of disease, treatment provided, and recurrence rates. The minimum follow-up was 2 years with a mean of 7.7 years. Results: There were 61.7% female patients with a mean age of 39 (range, 11-76) years. L-TGCT accounted for 85 (69.1%) cases and D-TGCT for 38 (30.9%). The most prevalent preoperative symptoms were a palpable mass (78/123) and pain (65/123). Radiologically confirmed recurrence in the operative group was noted in 14.5% (16/110) cases. This comprised 4% (3/75) of operatively treated L-TGCT and 37% (13/35) of operatively treated D-TGCT. Patients with pain on presentation and those with erosive changes on presenting magnetic resonance imaging (MRI) were more likely to have persistent postoperative pain (P <.001 for both). Where patients had both preoperative pain and erosive changes, 57.1% had postoperative pain. Thirteen cases were managed nonoperatively where symptoms were minimal, with 1 case requiring surgery at a later date. Conclusion: Outcomes of TGCT management are dependent on the disease type, extent of preoperative erosive changes, and presence of preoperative pain. These data are useful for counseling patients regarding the outcomes of surgical intervention and help guide the timing of intervention. Level of Evidence: Level III, retrospective cohort study. [ABSTRACT FROM AUTHOR]

Key Clinical Message: In this case report, total knee arthroplasty was performed in a patient with pigmented villonodular synovitis. During surgery, severe black discoloration of the articular cartilage and menisci was observed in the patient. According to literatures, this is the first case report of severe articular cartilage pigmentation in a patient with pigmented villonodular synovitis. [ABSTRACT FROM AUTHOR]

This is the first report on a localized pigmented villo-nodular synovitis (PVNS or TSGCT) occurring in the trochanteric bursa. Bursal involvement in PVNS is extremely rare. Most often PVNS occurs either as a localized or diffuse lesion in a major synovial joint, such as the knee, ankle joint or hip joint. In principle, all synovial structures can be involved. The case reported here is remarkable regarding the long period between the occurrence of the first symptoms and the final diagnosis as well as the age of the female patient (75 yrs).Therapeutically a complete resection was performed in order to avoid recurrence. More then three years later the patient did well and there has been no evidence of recurrence yet.

Key Clinical Message In this case report, total knee arthroplasty was performed in a patient with pigmented villonodular synovitis. During surgery, severe black discoloration of the articular cartilage and menisci was observed in the patient. According to literatures, this is the first case report of severe articular cartilage pigmentation in a patient with pigmented villonodular synovitis.

BackgroundTenosynovial giant cell tumors (TGCTs) or giant cell tumors of tendon sheath are neoplasms that arise in the synovium. They can be categorized as nodular (localized) or diffuse type (D-TGCT). Historically, surgery has been the mainstay of therapy, but diffuse type disease recurs at a high rate and treatment often requires increasingly morbid procedures. Elucidation of the importance of the colony-stimulating factor (CSF1)/CSF1 receptor (CSF1R) pathway in the pathogenesis of this disease has created significant interest in targeting this pathway as a novel TGCT treatment approach. Pexidartinib, a selective tyrosine kinase inhibitor against CSF1R, showed an 83% disease control rate (52% with partial response and 31% with stable disease) in a recent phase 1 study of patients with TGCT.Case presentationWe present an illustrative example of a TGCT patient who would have required a morbid operation who derived considerable clinical benefit from pexidartinib treatment. Her tumor volume decreased by 48% after 4 months of treatment, and 55 months after starting treatment the patient exhibits continued disease stability with minimal clinical symptoms, and significant improvement in functional status.ConclusionsThis case illustrates the effectiveness of systemic therapy in controlling a disease associated with high surgical morbidity. This approach may be especially useful in the treatment of extra-articular disease which often invades neurovascular bundles; as the effectiveness in metastatic disease is still unknown. In the future, systemic treatment for TGCT may be appropriate for the neoadjuvant setting to decrease disease burden prior to surgery with the aim of decreasing recurrence rates. However, properly designed prospective studies will need to be carried out to answer these questions.

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. [ABSTRACT FROM AUTHOR]

Abstract Background Diffuse pigmented villonodular synovitis (DPVNS) is a challenging tumor-like disorder that mainly occurs in the anterior aspect of the knee joint. The growth may sometimes extend to the posterior knee joint. Surgical excision is the mainstream treatment for DPVNS, and the posterior approach of tumor excision is adopted when the dominant tumor shows posterior extension. However, the optimal surgical approach over the posterior knee remains unknown. Methods Patients with DPVNS of the knee joint who received the posterior approach of synovectomy from 1995 to 2019 were retrospectively reviewed to describe the modified separate posterior (SP) approaches, and evaluate the treatment outcomes in a case series of DPVNS knees. The results of the SP approach was also compared with those of traditional direct posterior (DP) approach. Postoperative functional outcomes were evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) standardized questionnaire and clinician-completed Musculoskeletal Tumor Society (MSTS) functional rating system at outpatient department. Results A total of 20 DPVNS knees were included. Thirteen patients who received SP approaches were included in the SP group, while seven patients who received the DP approach were included in the DP group. The median follow-up times were 5.7 years (IQR, 2-8.8) in the SP group and 3 years (IQR, 2-5.3) in the DP group. Both groups showed satisfactory safety. The SP group presented higher postoperative mean WOMAC (91.23 ± 7.20) and mean MSTS (24.23 ± 2.68) than the DP group (mean WOMAC: 76.00 ± 16.57; mean MSTS: 22.43 ± 4.69). The Wilcoxon signed-rank test was use to compare preoperative and postoperative range of motion (ROM) for each group. The significant difference in SP group (p = 0.004) was found while p = 0.131 in DP group. Conclusions The SP approach provides an effective approach with satisfactory outcomes for the surgical treatment of DPVNS knees.

Introduction: Early synovectomy is considered as the main treatment of pigmented villonodular synovitis (PVNS) of the hip in young patients with preserved cartilage. The purpose of the study is to evaluate outcomes of arthroscopic management for PVNS of the hip. Methods: Patients who underwent primary hip arthroscopy for the treatment of histology-confirmed PVNS by the senior author between January 2012 and December 2016 were retrospectively reviewed. We excluded patients who had less than 1-year follow-up or had undergone primary surgeries with other surgeons and then received revision hip arthroscopic procedures by the senior author. The recurrence of PVNS and postoperative condition of affected hip were assessed by follow-up magnetic resonance imaging (MRI). Patient-reported outcomes of modified Harris hip score (mHHS) and 12-item International Hip Outcome Tool (iHOT-12) were collected at latest follow-up. Results: Nine patients (2 males, 7 females) with a mean age of 24.3 ± 11.2 years (range 14–44 years) were included in this study. Localized PVNS was observed in four patients, and diffuse PVNS was observed in five patients. No patient presented with advanced osteochondral destruction. Five patients received single adjuvant radiosynoviorthesis. No patient had evidence of recurrence based on follow-up MRI. Patient-reported outcomes were obtained in eight patients at mean 55.8 ± 26.1 months (range 24–84 months) after the index surgery. The mean mHHS was 94.6 ± 4.9 (range 84.7–100) and the mean iHOT-12 was 93.3 ± 20.2 (range 50–120). No patient needed secondary surgery during the follow-up period. Conclusion: Arthroscopic subtotal synovectomy can offer favorable short to mid-term outcomes in the treatment of hip PVNS in case of no advanced osteochondral damage at presentation. [ABSTRACT FROM AUTHOR]

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. • TGCT is mainly driven by CSF1 overexpression. • Nilotinib was the CSF1R inhibitor investigated in a phase II clinical trial in TGCT. • This is the first study describing the long-term efficacy of nilotinib on D-TGCT. • Nilotinib showed mixed long-term efficacy regarding progression-free survival. • The current role of nilotinib in TGCT is questionable. [ABSTRACT FROM AUTHOR]

Background: Diffuse pigmented villonodular synovitis (DPVNS) is a challenging tumor-like disorder that mainly occurs in the anterior aspect of the knee joint. The growth may sometimes extend to the posterior knee joint. Surgical excision is the mainstream treatment for DPVNS, and the posterior approach of tumor excision is adopted when the dominant tumor shows posterior extension. However, the optimal surgical approach over the posterior knee remains unknown. Methods: Patients with DPVNS of the knee joint who received the posterior approach of synovectomy from 1995 to 2019 were retrospectively reviewed to describe the modified separate posterior (SP) approaches, and evaluate the treatment outcomes in a case series of DPVNS knees. The results of the SP approach was also compared with those of traditional direct posterior (DP) approach. Postoperative functional outcomes were evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) standardized questionnaire and clinician-completed Musculoskeletal Tumor Society (MSTS) functional rating system at outpatient department. Results: A total of 20 DPVNS knees were included. Thirteen patients who received SP approaches were included in the SP group, while seven patients who received the DP approach were included in the DP group. The median follow-up times were 5.7 years (IQR, 2-8.8) in the SP group and 3 years (IQR, 2-5.3) in the DP group. Both groups showed satisfactory safety. The SP group presented higher postoperative mean WOMAC (91.23 ± 7.20) and mean MSTS (24.23 ± 2.68) than the DP group (mean WOMAC: 76.00 ± 16.57; mean MSTS: 22.43 ± 4.69). The Wilcoxon signed-rank test was use to compare preoperative and postoperative range of motion (ROM) for each group. The significant difference in SP group (p = 0.004) was found while p = 0.131 in DP group. Conclusions: The SP approach provides an effective approach with satisfactory outcomes for the surgical treatment of DPVNS knees. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 detecting 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cases: We used the modified Stoppa approach in a 17-year-old man with a retained bullet in his acetabular fossa. The acetabular hole was used to irrigate the hip joint. We also used this approach in a 29-year-old woman with right hip pain and limping to remove an isolated tenosynovial giant cell tumor ("localized pigmented villonodular synovitis") in the acetabular fossa expanding through the acetabulum. Discussion: We believe that this approach should become more familiar because it offers a simple alternative for treating acetabular pathologies mainly involving the acetabular fossa, sparing patients the hazards of capsulotomy, trochanteric osteotomy, dislocation, and traction and fluid pressure in hip arthroscopy. [ABSTRACT FROM AUTHOR]

Abstract Background Diffuse pigmented villonodular synovitis (PVNS) of the knee is a rare proliferative joint disease associated with high recurrence rates following surgical treatment. Intra-articular joint instability in conjunction with PVNS implies complex reconstructive strategies due to the destructive nature of the disease. Case presentation Here, we present the case of a young patient with refractory PVNS and a chronic ipsilateral anterior cruciate ligament (ACL) rupture. Clinically, the patient presented with a grade 3 pivot shift phenomenon, indicating anterolateral rotational instability. Usually, PVNS implies a contraindication for ACL reconstruction due to the degenerative and pro-inflammatory joint microenvironment that is induced and maintained by PVNS. Therefore, we have performed a modified Lemaire extra-articular stabilization resulting in significant clinical improvement and subjective joint stability. In the latest follow-up examination at 12 months, the patient reported subjective joint stability and no swelling. In the clinical examination, the patient showed dynamic joint stability during walking. Additionally, the patient presented with grade 0 in pivot-shifting compared to the contralateral knee. The Lachman test exhibited no increased side-to-side difference and a firm endpoint. Conclusions Extra-articular anterolateral stabilisation of the knee in patients having anterolateral knee instability combined with PVNS is a safe and efficient surgical treatment option yielding significant clinical improvement as well as subjective joint stability.

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Introduction: Pigmented villonodular synovitis (PVNS), also known as giant-cell tumour of the tendon sheath (GCTT), is a rare, benign proliferative tumour affecting the inner lining of synovial joints and tendon sheets. Information on treatment needs of PVNS patients to inform drug development is currently scarce. We conducted an exploratory qualitative study with PVNS patients to generate insights into the objective and emotional aspects related to their medical journey and experiences of living with this disease.Methods: A 4-day study using an online bulletin board (OBB), an asynchronous, online qualitative research platform, was conducted with patients recruited via physician referral who underwent screening questions to ensure eligibility for the study and willingness to participate. The discussion was moderated, was structured and allowed open answers in response to other participants' posts.Results: Eleven patients (4 from the USA, 4 from the UK and 3 from Canada; 45% female), aged 28-57 years, suffering from PVNS for 2-27 years participated in the study. Key patient insights from the study were: (1) pain was the topmost, spontaneous thought that the participants associated with PVNS, constituting a significant emotional and psychological burden; (2) surgery (arthroscopy) did not completely ameliorate symptoms associated with PVNS, as the relapse rate was high in these patients; (3) PVNS has a substantial negative financial impact on patients, their families and the healthcare system; (4) orthopaedic specialists/surgeons predominantly managed PVNS, as surgery is currently the only therapeutic option.Conclusion: PVNS patients expressed an urgent need for a medical drug treatment, which can reduce pain, avoid relapses and provide an alternative to surgery, the current standard of care. [ABSTRACT FROM AUTHOR]

Introduction: Tenosynovial giant cell tumor (TGCT) is a benign clonal neoplastic proliferation arising from the synovium often causing pain, swelling, joint stiffness, and reduced quality of life. The optimal treatment strategy in patients with diffuse-type TGCT (dt-TGCT) is evolving. Surgery is the main treatment, with a high recurrence rate and surgery-related morbidity. Radiotherapy is associated with important side effects. TGCT cells overexpress colony-stimulating factor 1 (CSF1). Pexidartinib (Turalio™) is a selective CSF1 R inhibitor, which was recently approved by the FDA for the treatment of TGCT.Areas Covered: This article reviews the pharmacological properties, clinical efficacy, and safety of pexidartinib.Expert Opinion: Pexidartinib was effective with an acceptable safety profile for advanced TGCT in phase I-III studies. The phase III trial (ENLIVEN) in unresectable TGCT met its primary endpoints of overall response rate. These results led to FDA approval for this TGCT population. Mixed or cholestatic hepatotoxicity was observed in rare cases. For this reason, pexidartinib is currently available only through a Risk Evaluation and Mitigation Strategy (REMS) Program in the USA. TGCT significantly impairs patients' quality of life. The approval of pexidartinib has changed the therapeutic armamentarium for this condition. However, strict monitoring of liver function is warranted. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract The tumor-permissive and immunosuppressive characteristics of tumor-associated macrophages (TAM) have fueled interest in therapeutically targeting these cells. In this context, the colony-stimulating factor 1 (CSF1)/colony-stimulating factor 1 receptor (CSF1R) axis has gained the most attention, and various approaches targeting either the ligands or the receptor are currently in clinical development. Emerging data on the tolerability of CSF1/CSF1R-targeting agents suggest a favorable safety profile, making them attractive combination partners for both standard treatment modalities and immunotherapeutic agents. The specificity of these agents and their potent blocking activity has been substantiated by impressive response rates in diffuse-type tenosynovial giant cell tumors, a benign connective tissue disorder driven by CSF1 in an autocrine fashion. In the malignant disease setting, data on the clinical activity of immunotherapy combinations with CSF1/CSF1R-targeting agents are pending. As our knowledge of macrophage biology expands, it becomes apparent that the complex phenotypic and functional properties of macrophages are heavily influenced by a continuum of survival, differentiation, recruitment, and polarization signals within their specific tissue environment. Thus, the role of macrophages in regulating tumorigenesis and the impact of depleting and/or reprogramming TAM as therapeutic approaches for cancer patients may vary greatly depending on organ-specific characteristics of these cells. We review the currently available clinical safety and efficacy data with CSF1/CSF1R-targeting agents and provide a comprehensive overview of ongoing clinical studies. Furthermore, we discuss the local tissue macrophage and tumor-type specificities and their potential impact on CSF1/CSF1R-targeting treatment strategies for the future.

The CT arthrogram is an underrated diagnostic study of the joint. Although MRI is considered superior to CT in joint imaging due to its higher resolution, CT arthrograms provide unique insights into the knee joint, with simultaneous dynamic assessment and an option for management in some conditions. In this pictorial essay, I will discuss the standard techniques and various pathologies affecting the knee joint and their CT arthrography appearance., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Institute of Radiology.)

Tenosynovial giant cell tumor (TSGCT) is a rare proliferative disorder of the synovium. Because of its aggressive nature and recurrence potential, treatment of TSGCT involves surgical resection with or without synovectomy. There is currently a paucity of literature describing the surgical management of TSGCT at the elbow. The aim of this study was to evaluate clinical outcomes and recurrence rates following open and arthroscopic excision of TSGCT in the elbow. Electronic databases were searched for relevant articles relating to surgical management of TSGCT of the elbow. We included all patients who received surgical treatment for TSGCT, with no age limitations. We excluded any nonsurgical treatment studies. Seventy-seven articles were identified for screening, and a total of 27 patients from 24 studies were included for the review. The patients' mean (standard deviation [SD]) age was 40.3 (21.7) years, and the most common presenting symptoms included pain (18/27, 66.7%), swelling (19/27, 70.4%), and decreased range of motion of the elbow (9/27, 33.3%). The majority of patients underwent open excision with or without synovectomy (23/27, 85.1%). Of those undergoing open procedures, 16 (16/23,69.6%) had diffuse TSGCT and 14 (14/23, 60.9%) remained symptom free for a mean (SD) follow-up of 38.9 (25.4) months. Four patients (4/27, 14.8%) were treated arthroscopically, all of whom had diffuse disease. Our review found that open synovectomy appears to be an effective treatment for both localized and diffuse TSGCT in the elbow, and arthroscopic synovectomy is emerging as a method of surgical management for diffuse TSGCT. However, because of the limited number of patients undergoing surgery for TSGCT, further studies are needed to make a definite conclusion. [ABSTRACT FROM AUTHOR]

Pigmented villonodular synovitis (PVNS) is a benign lesion that usually occurs in tendon sheaths, in burses or in the large joints synovia of the extremities. The pathogenesis of PVNS is still not clear, recently defined as a benign clonal neoplastic proliferation. PVNS is often asymptomatic and it is incidentally diagnosed in the majority of cases; given its local aggressiveness and the high rate of local recurrences it requires wide excision to be successfully treated. In rare cases PVNS can have malignant features sometimes with metastatic diffusion. The malignant form is often associated to the presence of colony-stimulating factor 1 (CSF1) gene mutation. In this report we present a brief literature review and the first case of recurrent hip PVNS with vertebral metastases, associated to an unusual genetic mutation. [ABSTRACT FROM AUTHOR]

Pigmented villonodular synovitis (PVNS) is a benign disease that rarely undergoes malignant transformation. Th ere are two types of disease: localized (nodular tenosynovitis) and diff used (pigmented villonodular synovitis/tenosynovitis) with intra- or extra-articular locations. The second one is limited to synovium of the burse (PVNB) or tendon sheath (PVNTS). The intraarticular lesions are usually located in the knee, hip, ankle and elbow joints. Histologically, PVNS is a tenosynovial giant cell tumor, characterized by proliferation of two types of mononuclear cells -- predominantly small, histiocyte-like cells and larger cells with dense cytoplasm, reniform or lobulated nucleus, with accompanying multinucleated giant cells and macrophages overloaded with hemosiderin that give typical image on MRI -- currently selected as a gold standard for its diagnosis. The classic X-ray and CT are non-specific but similar to ultrasound should be used to evaluate disease progression and treatment response if radiotherapeutic and pharmacological methods were selected for treatment. An open arthroscopic surgery could also be applied in selected cases. [ABSTRACT FROM AUTHOR]

The tumor-permissive and immunosuppressive characteristics of tumor-associated macrophages (TAM) have fueled interest in therapeutically targeting these cells. In this context, the colony-stimulating factor 1 (CSF1)/ colony-stimulating factor 1 receptor (CSF1R) axis has gained the most attention, and various approaches targeting either the ligands or the receptor are currently in clinical development. Emerging data on the tolerability of CSF1/ CSF1R-targeting agents suggest a favorable safety profile, making them attractive combination partners for both standard treatment modalities and immunotherapeutic agents. The specificity of these agents and their potent blocking activity has been substantiated by impressive response rates in diffuse-type tenosynovial giant cell tumors, a benign connective tissue disorder driven by CSF1 in an autocrine fashion. In the malignant disease setting, data on the clinical activity of immunotherapy combinations with CSF1/CSF1R-targeting agents are pending. As our knowledge of macrophage biology expands, it becomes apparent that the complex phenotypic and functional properties of macrophages are heavily influenced by a continuum of survival, differentiation, recruitment, and polarization signals within their specific tissue environment. Thus, the role of macrophages in regulating tumorigenesis and the impact of depleting and/or reprogramming TAM as therapeutic approaches for cancer patients may vary greatly depending on organ-specific characteristics of these cells. We review the currently available clinical safety and efficacy data with CSF1/CSF1R-targeting agents and provide a comprehensive overview of ongoing clinical studies. Furthermore, we discuss the local tissue macrophage and tumor-type specificities and their potential impact on CSF1/CSF1R-targeting treatment strategies for the future. [ABSTRACT FROM AUTHOR]

A 17-yr-old, female, captive-born reticulated giraffe ( Giraffa camelopardalis) presented with acute-onset lameness of the right metacarpophalangeal (fetlock) joint. Despite multiple courses of treatment, the lameness and swelling progressively worsened over a 3.5-yr period, and the giraffe was euthanized. At necropsy, gross and microscopic changes in the right, front fetlock and associated flexor tendon sheath included villous synovial hyperplasia and the formation of discrete pigmented nodules within synovial membranes. Histologically, the nodules were composed of abundant, fibrous connective tissue with heavy macrophage infiltration, hemosiderin deposition, and distinctive, multinucleated cells that resembled osteoclasts. These findings were consistent with pigmented villonodular synovitis (PVNS), a rare condition affecting both humans and animals. Although the pathophysiology of PVNS is poorly understood, lesions exhibit features of both neoplastic and reactive inflammatory processes. This case report represents, to the authors' knowledge, the first description of PVNS in a nondomestic ungulate. [ABSTRACT FROM AUTHOR]

Various uses of posterior knee arthroscopy have been shown, including all-inside repair of posterior meniscal lesions, posterior cruciate ligament (PCL) reconstruction or PCL avulsion fixation, extensile posterior knee synovectomy for pigmented villonodular synovitis or synovial chondromatosis, posterior capsular release in the setting of knee flexion contractures, and loose bodies removal. Posterior arthroscopy provides direct access to the posterior meniscal borders for adequate abrasion and fibrous tissue removal. This direct view of the knee posterior structures enables the surgeon to create a stronger biomechanical repair using vertical mattress sutures. During PCL reconstruction, posterior arthroscopy gives the surgeon proper double access to the tibial insertion site, which can result in less acute curve angles and the creation of a more anatomic tibial tunnel. Moreover, it gives the best opportunity to preserve the PCL remnant. Arthroscopic PCL avulsion fixation is more time-consuming with a larger cost burden compared to open approaches, but in the case of other concomitant intra-articular injuries, it may lead to a better chance of a return to pre-injury activities. The high learning curve and overcaution of neuromuscular injury have discouraged surgeons from practicing posterior knee arthroscopy using posterior portals. Evidence for using posterior portals by experienced surgeons suggests fewer complications. The evidence suggests toward learning posterior knee arthroscopy, and this technique must be part of the education about arthroscopy. In today's professional sports world, where the quick and complete return of athletes to their professional activities is irreplaceable, the use of posterior knee arthroscopy is necessary.

Tenosynovial giant cell tumour (TSGCT; synonym, pigmented villonodular synovitis (PVNS)) is a rare low-grade mesenchymal neoplasm of either intra-articular or extra-articular origin. The etiopathogenesis of TSGCT is still uncertain, but recent studies showed a translocation involving colony-stimulating factor 1 (CSF-1) gene in a subset of cases. Histological features mimicking TSGCT can sometimes be encountered in periprosthetic interface membranes. To investigate the frequency and morphologic spectrum of this phenomenon, we conducted a systematic analysis of 477 periprosthetic interface membranes and performed immunohistochemical analysis on a subset of lesions compared to genuine TSGCT. In 26 of 477 periprosthetic membrane samples (5 %), at least some TSGCT-like features were found and 18 cases (4 %) strongly resembled it. Wear particles were detected in 100 % of the TSGCT-like lesions but only in 63.3 % of the whole cohort of periprosthetic membranes (p value <0.001). Immunohistochemistry comparing true TSGCT and TSGCT-like membranes showed similar inflammatory infiltrates with slightly elevated CD3+/CD8+ T lymphocytes and a slightly higher proliferation index in TSGCT samples. In conclusion, TSGCT-like changes in periprosthetic membranes likely represent exuberant fibrohistiocytic inflammatory response induced by wear particles and should be distinguished from genuine (neoplastic) TSGCT. Although TSGCT and TSGCT-like periprosthetic membranes represent different entities, their comparable morphology might reflect analogous morphogenesis. [ABSTRACT FROM AUTHOR]