Pigmented Villonodular Synovitis Research Articles

Vimseltinib for tenosynovial giant cell tumour

Vimseltinib for tenosynovial giant cell tumour

Cytoplasmic PPARγ Significantly Correlates With P53 Immunohistochemical Expression and Tumor Size in Localized Tenosynovial Giant Cell Tumor.

Tenosynovial giant cell tumor (TGCT)is a monoarticular fibrohistiocytic benign or locally aggressive soft tissue tumor that originates from the synovium of joints, bursae, and tendon sheaths.It has an inflammatory neoplastic nature, with a clinical presentationranging from pain, swelling, stiffness, and limited range of movement to joint instability and blockage. Its uncommon incidence leads to a poorly understood pathogenesis. Localized formsof TGCT (LTGCT) can cause significant morbidity, interfere with daily patient activities, and decrease the patient's quality of life in challenging cases. This study aimed to investigate the immunohistochemical expression of PPARγ (peroxisome proliferator-activated receptor gamma) and P53 in LTGCT to understand the disease better and offer potential therapeutic targets. The study is cross-sectional, in which 27 LTGCT cases were collectedfrom the Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.Solitary and multiple LTGCT cases retrieved between January 2018 and December 2022 were included, and immunohistochemically stained with anti-PPARγ and P53 antibodies. The TGCT samples were excluded if they were insufficient for sectioning, processing, and interpretation, over-fixed, had process artifacts, or were of the diffuse TGCT type. Scoring of stain expression was performed by ImageJ (National Institutes of Health, Bethesda, MD) analysis using the threshold method and was expressed in percent area/high power field. Clinicopathological correlations were analyzed. All the 27 collected LTGCT cases were located in the small joints of patients' hands. Cases with solitary LGTCTs constituted 55.6%(n = 15), while 44.4% (n = 12) had multipleLTGCTs related to one affected site/case (e.g., multiple tumors in one finger). PPARγ was expressed in the cytoplasm of mononuclear and multinucleated tumor cells and foamy histiocytes, while P53 expression was mainly in mononuclear cells' nuclei. PPARγ significantly correlated with P53 expression (r = 0.9 and P = 0.000). PPARγ (r = 0.4 and P = 0.02) and P53 (r = 0.5 and P = 0.01) were positively correlated with tumor size. Only P53 expression was positively correlated with tumor multiplicity (r = 0.4 and P = 0.03). Using the receiver operating characteristic curve test, the P53 cutoff score detecting the multiplicity of TGCTs was ≥20.5%, with a 75% sensitivity and 80% specificity. PPARγ and P53 have a significant role in LTGCT growth, while P53 plays a role in tumor multiplicity. They can be possible targets in LTGCTs unfit for excision.

Twelve-year Experience for Tenosynovial Giant Cell Tumors of Tendon Sheath: A Review of 95 Cases from A Single Institution

Twelve-year Experience for Tenosynovial Giant Cell Tumors of Tendon Sheath: A Review of 95 Cases from A Single Institution

A Large Pigmented Villonodular Synovitis of the Proximal Tibiofibular Joint Mimicking Soft Tissue Sarcoma: A Case Report and Review of Literature

A Large Pigmented Villonodular Synovitis of the Proximal Tibiofibular Joint Mimicking Soft Tissue Sarcoma: A Case Report and Review of Literature

MRgFUS ablation of a recurrent tenosynovial giant cell tumor in the foot using ExAblate 2100 system in combination with patient immobilization device

IntroductionMagnetic Resonance–guided Focused Ultrasound (MRgFUS) treatment for certain anatomy locations can be extremely challenging due to patient positioning and potential motion. This present study describes the treatment of a recurrent tenosynovial giant cell tumor of the plantar forefoot using the ExAblate 2100 system in combination with patient immobilization device. MethodsPrior to the treatment, several patient immobilization devices were investigated. Vacuum cushions were selected and tested for safety and compatibility with the treatment task and the MR environment. ResultsDuring the treatment, one vacuum cushion immobilized the patient's right leg in knee flexion and allowed the bottom of the foot to be securely positioned on the treatment window. Another vacuum cushion supported the patient upper body extended outside the scanner bore. 19 sonications were successfully executed. The treatment was judged to be successful. No immediate complications were observed. ConclusionsMRgFUS treatment of a recurrent tenosynovial giant cell tumor of the right plantar forefoot was successful with the use of patient immobilization vacuum cushions. Implications for practiceThe immobilization system could be utilized to aid future MRgFUS treatment of lesions in challenging anatomic locations. Various sizes of the vacuum cushions are available to potentially better accommodate other body parts and treatment configurations.

A Successful Arthroscopic Management of a Benign but Locally Aggressive Tenosynovial Giant Cell Tumour in the Shoulder.

Introduction Pigmented villonodular synovitis (PVNS) is a relatively rare disorder affecting the synovial membrane and tendon sheath of a joint. It rarely affects the shoulder joint. This prospective study aims to document the challenges encountered in achieving total synovectomy and assesses the clinical outcomes of arthroscopic synovectomy for PVNS in shoulder patients. Methods This is a prospective study conducted from April 2017 to September 2023. This monoarticular disease was observed among six patients (four females and two males). All patients underwent arthroscopic extensile synovectomy with biopsy and culture. The outcomes were measured using Constant score,American Shoulder and Elbow Surgeons (ASES), and University of California Los Angeles (UCLA) scores. All patients were followed up for a minimum of 36 months after arthroscopic synovectomy. Results All intraoperative findings were consistent with PVNS and confirmed with histopathological examination. All patients achieved a satisfactory, painless range of movements following surgery. The individual Constant score improved from a mean value of 64.83 to 94.50, the ASES score improved from a mean value of 81.15 to 99.73, and the UCLA score improved from a mean value of 23.16 to 34.83 post-arthroscopic intervention, proving its effectiveness. No recurrences were reported after 36 months of follow-up. Conclusion PVNS can be easily missed, and one must have a high index of suspicion to diagnose early.Delayed presentation of the disease had led to severe destruction of the joint. Early diagnosis and arthroscopic intervention prior to joint destruction are crucial for achieving a good functional outcome. Incomplete excision may lead to recurrence of the disease. Therefore, we propose extensile arthroscopic synovectomy of the shoulder, wherein by expecting and addressing the intraoperative challenges, complete excision can be achieved, thus preventing recurrence.

A RARE CASE OF TENOSYNOVIAL GIANT CELL TUMOR IN PALMAR ASPECT OF RING FINGER OF LEFT HAND

Introduction: Giant cell tumor of the tendon sheath (GCTTS) is an uncommon benign soft tissue tumor of unknown etiology. It is seen more commonly in hand than ankle and foot. It presents as a painless and palpable swelling. Its diagnosis is mostly established by histopathology after surgical resection, although pre-operative imaging and fine-needle aspiration cytology (FNAC) support its suspicion. Herein, a case of GCT of flexor tendon sheath of the right ring finger is reported due to its rarity. Case Report: A 30-year-old female presented with complaints of swelling over the front of the right ring finger for 6months.. The swelling was spontaneous, painless, and very slowly progressive. Examination revealed a 2 cm * 1.5 cm firm swelling situated on the palmar aspect of the right ring finger over proximal inter phalangeal joint. Swelling was well defined, having smooth surface, uniformly firm consistency and could be moved sideways easily. X-ray of the hand showed localized soft tissue shadow in the involved area without any bony involvement. Ultrasonography of the finger showed soft tissue mass.MRI revealed Moderate to intense heterogeneous enhancement suggesting giant cell tumor.. Excisional biopsy was done. Histopathology showed typical features of GCTTS. Conclusion: GCTTS should be kept as a differential diagnosis in soft tissue tumors of hand in adults. FNAC followed by excisional biopsy is diagnostic and curative, but the patient should be followed up for detecting and managing recurrences.

Intra-Articular Nodular Fasciitis of the Knee, A Rare Clinical Presentation and Histological Diagnosis: A Case Report.

Nodular fasciitis is a rare, benign soft tissue lesion that can prove to be difficult to diagnose, especially when intra-articular. A 17-year-old female softball player presents with several year history of right knee pain and swelling initially attributed to patellar maltracking refractory to non-operative and operative management. Initial pathology suggested tenosynovial giant cell tumor; however, further tissue diagnosis revealed nodular fasciitis, which was eventually resected. Intra-articular nodular fasciitis of the knee is rare and may easily be misdiagnosed due to its nonspecific clinical presentation. Careful histological examination can aid in diagnosis. Nodular fasciitis should be considered in the differential diagnoses for intra-articular lesions of the knee joint.

Exploration of the molecular biological mechanisms and review of postoperative radiotherapy cases in tenosynovial giant cell tumors.

Tendon Sheath Giant Cell Tumor (TGCT) is a benign tumor that primarily grows within joints and bursae. However, it has a high postoperative recurrence rate, ranging from 15% to 45%. Although radiotherapy may reduce this recurrence rate, its applicability as a standard treatment is still controversial. Furthermore, the pathogenic mechanisms of TGCT are not clear, which limits the development of effective treatment methods. The unpredictable growth and high recurrence rate of TGCT adds to the challenges of disease management. Currently, our understanding of TGCT mainly depends on pathological slice analysis due to a lack of stable cell models. In this study, we first reviewed the medical records of two female TGCT patients who had undergone radiotherapy. Then, by combining bioinformatics and machine learning, we interpreted the pathogenesis of TGCT and its associations with other diseases from multiple perspectives. Based on a deep analysis of the case data, we provided empirical support for postoperative radiotherapy in TGCT patients. Additionally, our further analysis revealed the signaling pathways of differentially expressed genes in TGCT, as well as its potential associations with osteoarthritis and synovial sarcomas.

Invasion Patterns and Long-Term Clinical Outcomes of Diffuse Tenosynovial Giant Cell Tumor of the Ankle Joint.

The invasion patterns and long-term outcomes ofdiffuse tenosynovial giant cell tumor (D-TSGCT) of the ankle joint remain unclear. Seven patients who visited our department between 2011 and 2023 and were diagnosed withD-TSGCT of the ankle joint by contrast-enhanced MRI and a pathological diagnosis were included. The invasion patterns of ankle D-TSGCT on MRI were investigated. The recurrence rate and clinical symptoms were examined in five patients followed up for more than seven years after total resection. In seven patients (1 male/6 females, mean age 37.0±16.6 years, range 15-57 years) with D-TSGCT of the ankle joint, contrast-enhanced MRI at the initial presentation showed invasion within the ankle joint, extending along the tendon sheath, within the talocalcaneal joint, and in the tarsal sinus in 100% of cases, around the deltoid ligament in 86%, within the plantar surface in 43%, invasion of the interosseous membrane in 57%, around the Achilles tendon in 29%, and scalloping on the talocrural joint in 43%. The mean time from mass awareness to the first visit was 51.9±80.0 months (range 1-240 months). Gross total resection, defined as the removal of all tumors as gauged by MRI, was initially performed on 6/7 patients. One patient underwent partial resection of only the anterior part of the tumor. Of the six cases in which gross total resection was performed, 5 had long-term follow-up of more than seven years post-operatively, and one case is still only one year post-operatively. The long-term results offive patients followed for more than seven years after total resection were as follows: a mean follow-up period of 125 months (range 89-171 months), a 100% recurrence rate, a mean time to recurrence of 27.5±19.2 months (range 7-60 months), and a 16% reoperation rate. In the last follow-up, osteoarthritic changes were observed radiographically in 2/5 patients (40%), both of whom had scalloping of the talocrural joint on MRI at the time of the initial diagnosis. Four of the five patients (80%) had no clinical symptoms in the last follow-up. Ankle D-TSGCT presents with a strong local infiltrative pattern inside and outside the ankle joint along the tendon sheath, radical resection may be difficult, and the recurrence rate may be higher than previously reported. On the other hand, there are many cases that remain free of clinical symptoms in the long term after recurrence, and surgical indications for ankle D-TSGCT need to consider function preservation as well as recurrence rates.

A Rare Case Report of Fungal Synovitis Presenting as Pigmented Villonodular Synovitis

Synovitis is a disorder that develops when the synovial tissue or joint lining becomes inflamed. The term pigmented villonodular synovitis (PVNS) refers to a form of tenosynovial giant cell neoplasm affecting the tendon and joint soft-tissue lining. We describe the rare case of a 37-year-old male presenting with complaints of swelling in the left knee following trauma. Patients have a limited range of motion. There is a previous history of an accident 1 year back for which he was operated. Recent magnetic resonance imaging (MRI) revealed anterior cruciate ligament and posterior cruciate ligament avulsion fracture. The clinical diagnosis and radiologic findings were in favor of PVNS. Histopathological examination revealed the presence of fungus. It was further confirmed by fungal culture, for which the patient was given antifungals and was further followed up in the orthopedics outpatient clinic. Thus, we diagnosed fungal synovitis in a patient who came with clinical presentation and MRI findings suggestive of PVNS.

Uncommon synovial pathologies

The synovium is a specialized tissue lining the synovial joints, bursae, and tendon sheaths of the body. It is affected by various localized and systemic disorders. Synovial diseases can be broadly classified as inflammatory, infectious, degenerative, proliferative, hemorrhagic, and neoplastic. Injuries to other structures within the joint, such as cartilage, may also be caused by pathological processes that affect the synovium. Early detection of synovial diseases is critical to avoid irreversible joint damage. Understanding the typical imaging features of synovial diseases can help in accurate diagnosis and prompt treatment. Therefore, imaging plays a crucial role in detecting synovial diseases at an early stage. This pictorial review highlights the unusual synovial pathologies, such as synovial chondromatosis, pigmented villonodular synovitis (PVNS), giant cell tumor of tendon sheath (GCTT), hemophilic arthropathy, lipoma arborescens, and synovial sarcoma.

Physiologically Based Pharmacokinetic Absorption Model for Pexidartinib to Evaluate the Impact of Meal Contents and Intake Timing on Drug Exposure.

Pexidartinib is a systemic treatment for patients with tenosynovial giant cell tumor not amenable to surgery. Oral absorption of pexidartinib is affected by food; administration with a high-fat meal (HFM) or low-fat meal (LFM) increases absorption by approximately 100% and approximately 60%, respectively, compared with the fasted state. Pexidartinib is currently dosed 250mg orally twice daily with an LFM (approximately 11-14 g of total fat). We developed a physiologically based pharmacokinetic model to determine the impact on drug exposure of dose timing with respect to meals, meal type, and caloric content. A 15%-16% increase in plasma exposure was predicted when consuming an HFM 1hour after dosing with an LFM, but almost no effect on pharmacokinetics was predicted when an HFM was consumed 3 hours or more before or after pexidartinib dosing with an LFM. Exposure was not significantly affected when pexidartinib was taken with a 500-kcal LFM over the range of fat (approximately 11-14 g of total fat; 20%-25% calories from fat) for an LFM. These findings on timing of pexidartinib dose with respect to meals should be considered by patients and physicians to reduce the potential for side effects.

Giant Cell Tumor of the Tendon Sheath of the Hand: Analysis of Factors Impacting Recurrence.

Background Giant cell tumors of the tendon sheath (GCTTS) of the hand are considered the second most common benign tumors of the hand after ganglion cysts. Excision biopsy is considered the standard treatment at present. They are notorious for having a very high rate of recurrence as given in many studies. Many factors are said to be associated with recurrence of the tumors. The goal of this study is to evaluate the long-term results of a series of 48 patients operated on at a single institute and to find out if there is any correlation between the proposed risk factors with recurrence. Methods A retrospective analysis was done in cases of GCTTS operated on between 2015 and 2021. The patients were invited for follow-up for a minimum of 2 years, and the patient files were reviewed. Further data were collected at follow-up including recurrence, range of movement, sensation, skin necrosis, scarring, and digital neuropathy. A data analysis was done. The correlation between the proposed risk factors and recurrence was calculated with the Pearson correlation coefficient. A p -value of less than 0.05 was considered statistically significant. Results During the 6 years, 48 patients were operated on. Recurrence was observed in eight patients (16%) at an average of 38.7 months from the time of surgery. Of the risk factors, tumors with satellite nodules and tumor adjacency to joint correlated significantly with recurrence. No complications were observed during follow-up. Conclusion GCTTS of the hand has a high propensity to recur. The presence of satellite nodules and proximity to interphalangeal joints are two important risk factors for recurrence. Magnification during surgery ensures complete excision of the tumor and reduces the chance of recurrence.

Real-world drug utilization and treatment patterns in patients with tenosynovial giant cell tumors in the USA.

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 54years, 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.

Unusual presentation of talonavicular joint pigmented villonodular synovitis: a case report

BackgroundPigmented 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 presentationA 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.ConclusionThis 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.

CORR Insights®: What Are the Recurrence Rates, Complications, and Functional Outcomes After Multiportal Arthroscopic Synovectomy for Patients With Knee Diffuse-type Tenosynovial Giant-cell Tumors?

CORR Insights®: What Are the Recurrence Rates, Complications, and Functional Outcomes After Multiportal Arthroscopic Synovectomy for Patients With Knee Diffuse-type Tenosynovial Giant-cell Tumors?

Recurrence-Free Survival after Synovectomy and Subsequent Radiosynoviorthesis in Patients with Synovitis of the Knee-A Retrospective Data Analysis.

Persistent knee synovitis leads to joint discomfort, incapacitating inflammation, and functional limitations. The conventional approach has involved surgical procedures to eliminate the actively inflamed synovial membrane. This study aims to investigate the recurrence-free survival and functional outcome after synovectomy and subsequent radiosynoviorthesis (RSO) in patients with knee synovitis. Thirty-seven knees diagnosed with pigmented villonodular synovitis (PVNS), rheumatoid arthritis (RA), and peripheral spondyloarthritis underwent synovectomy and subsequent RSO between May 2005 and October 2016. The mean age was 34.9 ± 15.1 years, and the mean follow-up period was 84 ± 36.4 months. Clinical outcomes were assessed using the Oxford Knee Score and the presence of swelling and pain at the last follow-up. Recurrence-free survival denotes the duration from synovectomy to surgical re-synovectomy. In general, twelve knees underwent re-synovectomy after a mean follow-up of 34.8 ± 24.9 months. The recurrence-free survival was 83.8% at two years, 71.3% at five years, and 61.7% at ten years. The subgroup analysis revealed recurrence-free survival at two years in 63.6% of patients with PVNS, 86.7% of those with RA, and 100% of individuals with peripheral spondyloarthritis. This study demonstrates that combined therapy for synovitis is an effective approach, significantly improving clinical outcomes.

Diffuse-Type Tenosynovial Giant Cell Tumor: What Are the Important Findings on the Initial and Follow-Up MRI?

Tenosynovial giant cell tumor (TSGCT) is a rare soft tissue tumor that involves the synovial lining of joints, bursae, and tendon sheaths, primarily affecting young patients (usually in the fourth decade of life). The tumor comprises two subtypes: the localized type (L-TSGCT) and the diffuse type (D-TSGCT). Although these subtypes share histological and genetic similarities, they present a different prognosis. D-TSGCT tends to exhibit local aggressiveness and a higher recurrence rate compared to L-TSGCT. Magnetic resonance imaging (MRI) is the preferred diagnostic tool for both the initial diagnosis and for treatment planning. When interpreting the initial MRI of a suspected TSGCT, it is essential to consider: (i) the characteristic findings of TSGCT-evident as low to intermediate signal intensity on both T1- and T2-weighted images, with a blooming artifact on gradient-echo sequences due to hemosiderin deposition; (ii) the possibility of D-TSGCT-extensive involvement of the synovial membrane with infiltrative margin; and (iii) the resectability and extent-if resectable, synovectomy is performed; if not, a novel systemic therapy involving colony-stimulating factor 1 receptor inhibitors is administered. In the interpretation of follow-up MRIs of D-TSGCTs after treatment, it is crucial to consider both tumor recurrence and potential complications such as osteoarthritis after surgery as well as the treatment response after systemic treatment. Given its prevalence in young adult patents and significant impact on patients' quality of life, clinical trials exploring new agents targeting D-TSGCT are currently underway. Consequently, understanding the characteristic MRI findings of D-TSGCT before and after treatment is imperative.

Insights into the Distribution Patterns of Foot and Ankle Tumours: Update on the Perspective of a University Tumour Institute.

The rarity of foot and ankle tumours, together with the numerous histological entities, presents a challenge in accumulating sufficient patients to draw reliable conclusions. Therefore, we decided to present an update of a retrospective analysis of their distribution patterns, comprising 536 cases of foot and ankle tumours presented to our tumour board between June 1997 and June 2023. Our aim was to provide a comprehensive overview of the prevalence and distribution patterns of benign and malignant bone and soft tissue tumours of the foot and ankle. A total of 277 tumours involved bone (51.7%). Of these, 242 (87.4%) were benign and 35 (12.6%) were malignant. In addition, 259 soft tissue tumours (48.3%) were found, of which 191 (73.7%) were benign and 68 (26.3%) were malignant. The most common benign bone tumours were simple bone cysts, enchondromas, osteochondromas, aneurysmal bone cysts, and lipomas of bone. Common benign soft tissue tumours included a tenosynovial giant cell tumour, haemangioma, plantar fibromatosis, schwannoma, and lipoma. The most common malignant soft tissue tumours were synovial sarcoma, malignant melanoma, and myxofibrosarcoma. In terms of anatomical location, the hindfoot was the most common site (28.7%), followed by the midfoot (25.9%), ankle (25.4%), and forefoot (20.0%). The distribution of benign entities often follows typical patterns, which may facilitate an early diagnosis even without biopsy (e.g., simple bone cyst, plantar fibromatosis). On the other hand, the distribution patterns of many rare or malignant entities are inconsistent. Individual soft tissue malignancies occur very sporadically, even over long periods of time and in specialized tumour centres. It is therefore important to recognise that any suspicious mass in the foot and ankle must be considered a possible malignancy until proven otherwise.