Pigmented Villonodular Synovitis Research Articles

Randomized placebo-controlled double-blind phase II study of zaltoprofen for patients with diffuse-type and unresectable localized tenosynovial giant cell tumors: The REALIZE study.

BackgroundA tenosynovial giant cell tumor (TGCT) is a locally aggressive benign neoplasm arising from intra- or extra-articular tissue, categorized as localized (L-TGCT, solitary lesion) and diffuse (D-TGCT, multiple lesions) TGCT. Surgical excision is the mainstay of the treatment, and a high local recurrence rate of approximately 50% has been reported. We focused on zaltoprofen, a nonsteroidal anti-inflammatory drug that can activate peroxisome proliferator-activated receptor gamma (PPARγ) and inhibit the proliferation of TGCT stromal cells. Therefore, we conducted a randomized trial to evaluate the safety and effectiveness of zaltoprofen in patients with D-TGCTs or unresectable L-TGCTs.MethodsThis randomized, placebo-controlled, double-blind, multicenter trial evaluated the safety and efficacy of zaltoprofen. In the treatment group, zaltoprofen (480 mg/day) was administered for 48 weeks; the placebo group received similar dosages without zaltoprofen. The primary outcome was progression-free rate (PFR) 48 weeks after treatment administration. Disease progression was defined as the following conditions requiring surgical intervention: 1) repetitive joint swelling due to hemorrhage, 2) joint range of motion limitation, 3) invasion of the adjacent cartilage or bone, 4) severe joint space narrowing, and 5) increased tumor size (target lesion).ResultsForty-one patients were allocated to the zaltoprofen (n=21) or placebo (n=20) groups. The PFR was not significant between the zaltoprofen group and the placebo group at 48 weeks (84.0% and 90.0%, respectively; p=0.619). The mean Japanese Orthopedic Association knee score significantly improved from baseline to week 48 in the zaltoprofen group (85.38 versus 93.75, p=0.027). There was a significant difference between the values at 48 weeks of placebo and zaltoprofen group (p=0.014). One severe adverse event (grade 3 hypertension) was observed in the zaltoprofen group.DiscussionThis is the first study to evaluate the efficacy and safety of zaltoprofen in patients with TGCT. No significant differences in PFR were observed between the groups at 48 weeks. Physical function significantly improved after zaltoprofen treatment. The safety profile of zaltoprofen was acceptable. This less invasive and safer treatment with zaltoprofen, compared to surgical removal, could be justified as a novel approach to treating TGCT. Further analysis of long-term administration of zaltoprofen should be considered in future studies.Clinical Trial RegistrationUniversity Hospital Medical Information Network Clinical Trials Registry, identifier (UMIN000025901).

PD-L1 Status in Tenosynovial Giant Cell Tumors.

Background and Objectives: Tenosynovial giant cell tumors (TSGCTs) are benign soft tissue tumors that are divided into localized- and diffuse-type tumors, according to the World Health Organization classification of soft tissue tumours. The diffuse-type TSGCT sometimes behave aggressively and poses treatment challenges especially in patients with neurovascular involvement. Symptomatic patients who are not good candidates for surgery due to high morbidity risk may benefit from medical therapy. Objectives: Drugs that target programmed death ligand 1 (PD-L1) are among a new generation of medical therapy options, which, recently, have been explored and have displayed promising results in various cancer types; therefore, we aimed to investigate the PD-L1 status of TSGCTs as a possible therapeutic target. Materials and Methods: We assessed the PD-L1 status of 20 patients (15 men and 5 women, median age = 39 years) that had been diagnosed with TSGCTs in a single institution, between 2018 and 2020. The patients had localized- (n = 7) and diffuse-type (n = 13) TSGCTs. Formalin-fixed paraffin-embedded (FFPE) blocks were retrospectively retrieved from the pathology department. An immunohistochemical analysis was performed in sections of 3 micron thickness from these blocks. Results: Seventy-five percent of our patients with TSGCTs were immunopositive to PD-L1 staining. Conclusions: Taking into consideration the high positivity rate of PD-L1 staining in TSGCTs, PD-L1 blockage may be used as a valuable medical treatment for TSGCTs; however, further studies are needed.

Tenosynovial giant cell tumors of digits: MRI differentiation between localized types and diffuse types with pathology correlation.

To compare the MRI findings between the localized- and diffuse-type tenosynovial giant cell tumors (TSGCTs) of digits with pathology correlation. Twenty-eight patients with newly diagnosed TSGCTs of digits (22 localized and 6 diffuse types) who underwent preoperative MRI and surgical excision were included from Jan. 2015 to September 2021. MRI findings regarding nodularity, margins, morphology of hypointensity with pathology correlation, and disease extent (bone erosion, articular involvement, muscle involvement, tendon destruction, and neurovascular encasement) were assessed. Diffuse type was significantly larger (P = 0.006), more multinodular on both MRI and pathology (P = 0.038, both) with significant agreement, and infiltrative on both MRI and pathology (P < 0.001, both) with substantial agreement, and showed central granular on MRI and strong hemosiderin deposition on pathology (P = 0.022 and P = 0.021) with moderate agreement than localized type. Localized type showed significantly more frequent peripheral capsules on both MRI and pathology (P < 0.001, both) with moderate agreement than diffuse type. However, the septum on both MRI and pathology showed no statistically significant difference between the two groups (P = 0.529 and P = 0.372) without significant agreement. The disease extent was more severe in the diffuse type than the localized type regarding articular involvement (P < 0.001), muscle involvement (P < 0.001), and tendon destruction (P = 0.010). No statistically significant differences were found between the two groups regarding bone erosion (P = 0.196) or neurovascular bundle encasement (P = 0.165). Diffuse-type TSGCTs of digits presented as locally aggressive lesions with larger, multinodular, infiltrative masses exhibiting stronger hemosiderin deposition and more severe disease extents of articular, muscle, and tendon involvement than the localized type.

475P Safety and efficacy of vimseltinib in tenosynovial giant cell tumour (TGCT): Long-term phase I update

TGCT is a rare, locally aggressive neoplasm caused by upregulation of the colony-stimulating factor 1 (CSF1) gene, resulting in aberrant CSF1 expression and the recruitment of CSF1 receptor (CSF1R)-dependent inflammatory macrophages. Vimseltinib is an oral switch-control tyrosine kinase inhibitor specifically designed to selectively and potently inhibit CSF1R. We report long-term safety and efficacy for patients (pts) with TGCT from the phase I arm (dose escalation) of the phase I/II study.

Atraumatic Ankle Pain Misdiagnosed As Anxiety In Nonathlete College Student

HISTORY: 19 y/o woman with nine months of burning right ankle pain. Saw PCP after four months of pain with bland exam, pain felt to be a component of her anxiety and increased activity recommended. At five-month mark she sprained her left ankle; home physical therapy plan from student health sports clinic improved left ankle pain and worsened right ankle pain. When right ankle pain began to limit walking she returned to student health, where x-rays were normal and an ultrasound showed a 2.5 cm x 0.5 cm complex hypoechogenic mass with thickened lining consistent with a ganglion cyst. She was referred to our clinic for a sports medicine evaluation and MRI. She initially saw a non-sports physician who ordered the MRI but also felt that her anxiety was the main driver of her symptoms. On seeing the sports medicine team, her pain had evolved to burning in the right ankle limiting ambulation, standing, and sleep at night. She indicated the path of the peroneal tendons around the malleolus as the site of pain. PHYSICAL EXAM: Tearful and concerned that we would also think her anxiety was the cause of her pain. Bilateral pes planus. Skin was warm and well perfused without lesions, redness, or ecchymoses. There was fullness and tenderness to palpation to her right sinus tarsi, and pain there with passive eversion of the ankle. There was no pain over peroneal tendons with ambulation, palpation, or resisted ROM. 5/5 strength without pain to dorsiflexion, plantarflexion, eversion, and inversion. DIFFERENTIAL DIAGNOSIS: 1) Sinus Tarsi Syndrome 2) Peroneal tendinopathy3) Ganglion Cyst 4) Pigmented Villonodular Synovitis (PVNS)TESTS & RESULTS: MRI R Ankle/hindfoot w/wo contrast: Intra-articular, well-defined enhancing mass lateral to the talus measuring 3.7 x 2.9 x 2.9 cm, extends into and obliterates the sinus tarsi without surrounding soft tissue or bone marrow edema. No erosions.No other abnormality. Leading differential consideration includes PVNS, FINAL/WORKING DIAGNOSIS: Pigmented Villonodular Synovitis TREATMENT & OUTCOMES:1)Biopsy confirmed tenosynovial giant cell tumor, diffuse type (PVNS). 2)Tumor resected by ortho-oncology, final pathology: 4.3 cm diffuse-type tenosynovial giant cell tumor (PVNS). 3)At five months post-op pain and activity tolerance much improved.

1509P Efficacy and safety of vimseltinib in tenosynovial giant cell tumour (TGCT): Phase II expansion

TGCT is a rare, locally aggressive neoplasm caused by upregulation of the colony-stimulating factor 1 (CSF1) gene, resulting in aberrant CSF1 expression and recruitment of CSF1 receptor (CSF1R)-dependent inflammatory macrophages. Vimseltinib is an oral switch control tyrosine kinase inhibitor specifically designed to selectively and potently inhibit CSF1R. We report safety, efficacy, and preliminary patient-reported outcome data for patients (pts) with TGCT treated with the recommended phase 2 dose (RP2D; 30 mg twice weekly).

1486MO The synovial and systemic pharmacokinetics and pharmacodynamics of intra-articular administration of the CSF1 receptor antibody AMB-05X in a phase II proof-of-concept trial in tenosynovial giant cell tumor

It is well established that CSF1 action at the CSF1R mediates the formation and expansion of TGCT – a benign but locally aggressive neoplasm. Indeed, oral or intravenous administration of CSF1R inhibitors may yield tumor regression over weeks to months of repeat dosing. With these systemic exposures, on-target side effects such as liver enzyme elevation and facial edema often present and may complicate the treatment paradigm. We hypothesized that administration of a potent, inhibitory anti-CSF1R antibody, AMB-05X, into the affected synovium could yield sustained, high local concentrations with low systemic exposures and thus enable tumor regression with minimal pharmacologic side effects. 8 TGCT patients with confirmed TGCT of the knee were enrolled in a Phase 2 study wherein AMB-05X was administered intra-articular (IA) at a dose of 150 mg every 2 weeks over a 12-week treatment period. The synovial and serum pharmacokinetics of AMB-05X were monitored. CSF1 levels in the joint and serum were also quantitated as a pharmacodynamic marker since inhibitor action at the CSF1R interferes with native and tumor-derived CSF1 elimination. The clearance of antibodies administered intra-articular is not well characterized and, in fact, has often been regarded as short-lived. The unique formulation of AMB-05X administered at the dose and regimen employed in this proof-of-concept study yielded high local concentrations that were sustained beyond expectations such that accumulation over the dosing period was extensive (>5-fold). Importantly, systemic exposures were consistently approximately 1/5 that of the synovial concentrations. Moreover, pharmacodynamic elevation of CSF1 levels was approximately 20-fold greater in synovial fluid vs serum. CSF1 levels in both compartments achieved a plateau, indicative of full receptor engagement, early in the treatment period. The AMB-05X PK and PD results support expansion of the clinical development of AMB-05X in TGCT with IA treatment at a comfortable interval of once-monthly or less.

Interactions in CSF1-Driven Tenosynovial Giant Cell Tumors.

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. 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. 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. 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.

Acquired hip joint pathologies in childhood

Anumber of different acquired pathologies can affect the pediatric hip joint. The classical and relatively common reactive, inflammatory or traumatic entities have to be differentiated from each other. Rarer and very rare pathologies, such as neoplastic entities or tenosynovial giant cell tumor, must also be considered in the differential diagnostics. The correct diagnosis, treatment planning and follow-up monitoring require close coordination between the departments of pediatric radiology and pediatric orthopedics. Sonography often represents the initial diagnostic step, followed by conventional radiography. Further evaluation of hip joint pathologies requires magnetic resonance imaging. In selected cases computed tomography can also be indicated.

Discovery of vimseltinib (DCC-3014), a highly selective CSF1R switch-control kinase inhibitor, in clinical development for the treatment of Tenosynovial Giant Cell Tumor (TGCT)

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.

FNAC study of giant cell tumor of tendon sheath (localized tenosynovial giant cell tumor): Clinico-radiological correlation and cytopathological features.

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.

Long-term follow-up of nilotinib in patients with advanced tenosynovial giant cell tumours: Long-term follow-up of nilotinib in TGCT

BackgroundDiffuse-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). MethodsPatients 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. ResultsForty-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. ConclusionThis 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 tumours of the upper and lower cervical spine: two case reports

IntroductionTenosynovial 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 presentationWe report two cases of TSGCST in the cervical spine: one with a lesion at C1/2 and another at C6/7.DiscussionThe 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.

Outcome of Arthroscopic Synovectomy for Diffuse Pigmented Villonodular Synovitis of the Knee in Sudanese Patients

Background: Diffuse pigmented villonodular synovitis (DPVNS) of the knee is a difficult tumor to eradicate, the gold standard treatment has traditionally been surgical excision with total synovectomy of the affected joint, either with an open or arthroscopic approach. In this study, we are focusing on arthroscopic surgical synovectomy.&#x0D; Objectives: Aimed to study the outcome of arthroscopic synovectomy for diffuse pigmented villonodular synovitis of the knee in Haj Alsafi Teaching Hospital.&#x0D; Methodology: Observational retrospective hospital-based study, performed in the Orthopedic Department, 12 patients (8 males and 4 females) with the diffuse form of PVNS of the knee were enrolled in the study after qualification. The clinical diagnosis was confirmed by magnetic resonance imaging and post-surgical histo-pathological examination. All patients underwent complete synovectomy through standard anterior, medial and lateral, then medial, lateral suprapatellar and posteromedial portals. Each patient was evaluated before and after treatment and followed up for a minimum of 18 months (range: 18 – 54 months) using the Lysholm score and International Knee Documentation Committee (IKDC) score.&#x0D; Results: The average age group of patients was (9–63years) with male predominance (66.7 %). Left knee more frequently affected(58.3%). None of the study participants had previous surgical history 100%. Both Lysholm and IKDC scores were significantly improved in all study participants. Regarding paired sample statistics, the mean for the score preoperatively and postoperatively was improved from 54.9 to77.9.Recurrence reported in one participant (8.3%). There was a statistical association between pre and post-operative LYSHOLM and IKDC scores and recurrence, hence p-value =0.000.&#x0D; Conclusion: Arthroscopic synovectomy is an appropriate treatment for knee DPVNS with agood clinical and functional outcome and with a low recurrence rate.

Chondroid Tenosynovial Giant Cell Tumor of the Temporomandibular Joint Presenting as a Deep-Lobe Parotid Tumor

Tenosynovial giant cell tumor (TGCT) is a rare benign craniofacial soft-tissue tumor characterized by overgrowth of the synovial tissue, tendon sheath, bursa, and joint structure. It is classified into two types, diffuse and localized TGCT, and has rarely been reported in the temporomandibular joint. The etiology of TGCT is unknown, and the management of TGCT varies depending on the tumor location and treatment-related morbidity. Here, we describe the case of a 47-year-old man who presented with a complaint of a right parotid mass that had slowly increased over 2 months and was associated with ear fullness. Initially, the lesion was painless, but pain during chewing without any limitation of the jaw movement developed subsequently. The patient was diagnosed with diffuse TGCT with chondroid metaplasia.

Treatment updates on tenosynovial giant cell 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.

Surgical management of 144 diffuse-type TGCT patients in a single institution: A 20-year cohort study.

Surgery is the mainstay of treatment for tenosynovial giant cell tumors (TGCTs). However, achieving a cure through surgery alone remains challenging, especially for the diffuse-type (D-TGCT). Our goal was to describe the surgical management of patients with D-TGCT related to large joints, treated between 2000 and 2020. We analyzed the effect of (in)complete resections and the presence of postoperative tumor (POT) on magnetic resonance imaging(MRI) on radiological and clinical outcomes. A total of 144 patients underwent open surgery for D-TGCT, of which 58 (40%) had treatment before. The median follow-up was 65 months. One hundred twenty-five patients underwent isolated open surgeries, in which 25 (20%) patients' D-TGCT was intentionally removed incompletely. POT presence on the first postoperative MRI was observed in 64%. Both incomplete resections and POT presence were associated with higher rates of radiological progression (73% vs. 44%; Kaplan-Meier[KM]analysis p = 0.021) and 59% versus 7%; KManalysis p < 0.001), respectively. Furthermore, patients with POT presence clinically worsened more often than patients without having POT (49% vs. 24%; KManalysis p = 0.003). D-TGCT is often resected incompletely and tumor presence is commonly observed on the first postoperative MRI, resulting in worse radiological and clinical outcomes. Therefore, surgeons should try to remove D-TGCT in toto and consider other multimodal therapeutic strategies.

Pigmented villonodular synovitis: literature review and case report

Pigmented villonodular synovitis (PVNS) is a rare disease, its diagnosis has certain difficulties. This is due to the absence of characteristic etiological factors and clinical manifestations of PVNS, as well as the insufficient level of knowledge among doctors. The article presents a review of the literature on the diagnosis and treatment of PVNS, as well as a clinical case, which peculiarity is the late diagnosis of this disease, despite the presence of its certain clinical and morphological manifestations.

A Case of Pigmented Villonodular Synovitis

Tenosynovial giant cell tumors (TGCT) are a rare group of generally non-malignant tumors that involves the synovium and tendon sheath. A young female patient presented to the outpatient department with a complaint of unilateral knee swelling and pain. She was evaluated as such and based on a provisional diagnosis of benign synovial proliferation, she was treated with an arthroscopic resection. We discuss our case and discuss the possible medical therapies to prevent recurrence.

Contribution of the Ultrasound Techniques in the Evaluation of Knee Joint Damage in the Case of Pigmented Villonodular Synovitis and Rheumatoid Arthritis.

This is a prospective study to evaluate the clinical value of high-frequency ultrasound (HFUS), superb microvascular imaging (SMI), and contrast-enhanced ultrasound (CEUS) in differentiation of pigmented villonodular synovitis (PVNS) and highly active rheumatoid arthritis (RA). Twenty PVNS patients and 24 active RA patients were selected to undergo HFUS, SMI, and CEUS examinations. The characteristics of HFUS, SMI, and CEUS in PVNS and RA were compared, and the differential diagnosis performances of HFUS, SMI, and CEUS in PVNS and RA were evaluated by receiver operating characteristic (ROC) analysis. There were statistically significant in joint effusion, synovial thickness, synovial morphology, synovial echo, synovial vessel shape, synovial enhanced direction, and enhanced pattern between PVNS and RA (P < .05). However, no statistically significant were found in bone erosion, synovial boundary, blood signal grading of synovium, synovial enhanced strength, and CEUS quantitative parameters (including PI, TTP, S, MTT, and AUC) (P > .05). The AUC of HFUS, SMI, and CEUS for differential diagnosis PVNS and RA were 0.832, 0.675, and 0.817, respectively. The AUC of HFUS + SMI, HFUS + CEUS, SMI + CEUS, HFUS + SMI + CEUS were 0.923, 0.940, 0.817, and 0.940, respectively. The AUC of HFUS + SMI and HFUS + CEUS was higher than that of each alone (P < .05). HFUS, SMI, and CEUS can be used as supplementary methods for diagnosis and differential diagnosis in PVNS and active RA. What is more, the combination of HFUS + SMI and HFUS + CEUS was suggested.