Pigmented Villonodular Synovitis Research Articles

Extra-articular tenosynovial giant cell tumor with novel FBN1::CSF1 fusion masquerading as a floor of mouth inflammatory process

Extra-articular tenosynovial giant cell tumor with novel FBN1::CSF1 fusion masquerading as a floor of mouth inflammatory process

Patient Outcomes After Resection of Pigmented Villonodular Synovitis in Patients in King Abdulaziz Medical City.

Introduction Pigmented villonodularsynovitis (PVNS) is a proliferative disorder that affects synovial joints. PVNS, also known as tenosynovial giant cell tumor (TGCT), is a broad term that refers to a variety of diseases, both localized and diffuse. The current study aims to describe the outcomes of PVNS in patients inKing Abdulaziz Medical City (KAMC) Riyadh, Saudi Arabiaespecially after surgical resection, highlighting radiological and pathological evidence of disease recurrence and symptom progression. The study is also concerned with comparison between patients who had adjuvant radiotherapy versus patients who underwent surgery only in addition to comparison between patients who underwent arthroscopic surgery versus those who underwent open surgery. Objective Pigmented villonodular synovitis is a disorder that occurs in the synovial joints with the highest incidence rates in the third and fourth decades. PVNS is categorized into localized and diffuse. The current study aims at defining the recurrence rate and outcomes of PVNS in patients in KAMC between 2008 and 2019. Design A retrospective study that comprises patients with proven PVNS of the knee, hip, and elbow for a minimum follow-up duration of two years. Data was collected from the KAMC database, National Guard Health Affairs, Riyadh, Saudi Arabia. Results Nearly a third of patients reported a prior history of trauma. The knee joint was most frequently involved followed by the ankle followed by the hip. Diffuse PVNS was more common than localized disease with more affection on the right side. The most common presenting symptoms were pain and swelling followed by decreased range of motion (ROM). About one-fifth of patients had undergone prior surgery. 30.8% received adjuvant radiotherapy. Post-operative stiffness or decreased ROM were noted in 23.1% of cases. Half of the patients received follow-up for more than 24 months. Overall recurrence rate was 19.2%. Recurrence rates were significantly higher in patients with left-sided lesions and those with prior surgery but it did not reach statistical significance. Non-statistically significant trends for increased recurrences were also seen with older age, diffuse type PVNS, and knee involvement. Conclusions In summary, this study reports the outcomes of PVNS after surgical resection in patients in King Abdulaziz Medical City. The study showed recurrence rates being significantly higher in patients with left-sided lesions than those with prior surgery. Also, non-statistically significant trends for increased recurrences were also seen with older age, diffuse type PVNS, and knee involvement.

Childhood Tumors around the Knee Revisited: Predilection Sites for Most Entities Confirmed.

Background: The diagnostic work-up of musculoskeletal tumors is a multifactorial process. During the early phase, differential diagnoses are made using basic radiological imaging. In this phase, part of the decision making is based on the patient's age, as well as the incidence and predilection sites of different entities. Unfortunately, this information is based on older and fragmented data. In this study, we retrospectively evaluated all soft-tissue and bone tumors around the knee in children treated at our tertiary center in the last 20 years, with the aim of verifying the data used today. Methods: In this retrospective study, the databank of our tertiary center was used to give an overview of treated tumors around the knee in children. Results: We were able to include 224 children with bone and soft-tissue tumors around the knee. The cohort consisted of 184 bone tumors, of which 144 were benign and 40 malignant. The 40 soft-tissue tumors comprised 30 benign and 10 malignant masses. The most common lesions were osteochondromas (88) in the bone and tenosynovial giant-cell tumors (12) in the soft tissue. Conclusions: With this original work, we were able to verify and supplement earlier studies, as well as deepen our insight into these very rare diseases.

GIANT CELL TUMOUR OF TENDON SHEATH IN THE FOOT: A RARE CASE REPORT

Giant cell tumor of the tendon sheath (GCT-TS) is predominantly encountered in the hand, ranking as the second most common solid tumor after ganglion cysts. Contrary to its prevalence in the upper extremity, GCT-TS manifestation in the foot is exceptionally rare. This report delineates a unique presentation of GCT-TS in the foot of a 25 y old female, who presented with a painful, progressively enlarging mass in the lateral aspect of her foot. This case underscores the diagnostic challenges and therapeutic considerations in managing such an atypical presentation of GCT-TS.

Unveiling the unforeseen: Asymptomatic pigmented villonodular synovitis at popliteal fossa

Pigmented villonodular synovitis (PVNS) are rare, locally aggressive, typically benign neoplasms of joints, bursae, and tendon sheaths. Symptoms include pain, stiffness, swelling, recurrent atraumatic hemarthrosis and limitation in range of motion. Our case study presents an asymptomatic PVNS at the popliteal fossa which was purely an incidental finding in a 32-year-old male with a history of trauma while playing football whose MRI was suggestive of Anterior cruciate ligament (ACL), Medial meniscus tear & a focal nodular hypertrophy at posterior aspect of knee. The patient had no significant past history of trauma, swelling, hemarthrosis or similar pain. ACL Reconstruction, Medial Meniscus balancing and marginal excision and biopsy sent for the same. Biopsy suggestive of PVNS (Localised). This case report emphasizes the importance of considering PNVS in the differential diagnosis of soft tissue swelling without pain, swelling or bleeding, and should be considered as a differential diagnosis of soft tissue swellings in the posterior aspect of the knee.

ISLET-1 expression in soft tissue neoplasms reveals high sensitivity but moderate specificity for desmoplastic small round cell tumors and potential utility as a diagnostic biomarker

ISLET-1 (ISL1) is a LIM-homeodomain transcription factor. Selective ISL1 expression is shown in neuroendocrine, non-neuroendocrine, and some soft tissue tumors including desmoplastic small round cell tumor (DSRCT). We assessed the specificity of ISL1 (clone EP283, 1:500, Cell Marque) in 288 soft tissue tumors, which included 17 DSRCTs and other histologic mimics. Positive staining threshold for ISL1 was set to >10 % of neoplastic cell nuclei at moderate intensity. ISL1 IHC was positive in 15/16 (94 %) DSRCTs with 75 % showing diffuse (>50 %) expression. ISL1 was positive in 1/10 (10 %) Ewing sarcomas (EWS), 7/13 (54 %) alveolar rhabdomyosarcoma (RMS), 14/22 (63 %) embryonal RMS, 7/14 (50 %) synovial sarcomas, 15/16 (93 %) neuroblastoma, 1/5 (20 %) Wilms tumor, 2/4 (50 %) olfactory neuroblastoma, and all 9 Merkel cell carcinomas. Other tumors, including all CIC::DUX4 sarcomas, were negative except 3/27 leiomyosarcomas, and 1 each of angiosarcoma, myxoid liposarcomas, inflammatory myofibroblastic tumor, malignant peripheral nerve sheath tumor, tenosynovial giant cell tumor, dedifferentiated LPS, and 1 ectomesenchymoma. In summary, among the soft tissue tumors tested, ISL1 is a highly sensitive but moderately specific marker for DSRCT and may be useful to distinguish from round cell mimics including EWS and CIC::DUX4 sarcomas. The oncogenic role of ISL1 in these tumors warrants further investigation.

Mapping and Analysis of Protein and Gene Profile Identification of the Important Role of Transforming Growth Factor Beta in Synovial Invasion in Patients With Pigmented Villonodular Synovitis.

Pigmented villonodular synovitis (PVNS) is a rare benign proliferative disease affecting the soft-tissue lining the synovial joints and tendons. Its etiology is poorly understood, largely limiting the availability of current therapeutic options. Here, we mapped the synovial gene and protein profiles of patients with PVNS, revealed a link between synovial inflammation and invasion, and elucidated the potential molecular mechanism involved. The expression of synovial genes from 6 control individuals, 7 patients with osteoarthritis (OA), and 19 patients with PVNS was analyzed via RNA sequencing. Protein profiles from 5 control individuals, 10 patients with OA, and 32 patients with PVNS were analyzed using label-free proteomics. Microarray and reverse transcription-polymerase chain reaction analyses and immunohistochemical staining were used to evaluate inflammatory cytokine and target gene expression levels in synovial tissue, epithelial cells, and synovial fibroblasts (FLSs) derived from tissue of patients with PVNS. Various signaling pathway inhibitors, small interfering RNAs, and Western blots were used for molecular mechanism studies. Transwell migration and invasion assays were subsequently performed. In total, 522 differentially expressed proteins were identified in the tissues of patients with PVNS. By integrating RNA sequencing and microarray analyses, significant changes in the expression of epithelial-mesenchymal transition (EMT)-related genes, including transforming growth factor TGF-b induced, neural cadherin, epithelial cadherin, SNAIL, and TWIST, were confirmed in the tissue of patients with PVNS compared to the control tissue. In vitro, TGFβ induced EMT and increased epithelial cell migration and invasion. Moreover, TGFβ not only promoted interactions between epithelial cells and FLSs but also directly increased the migration and invasion abilities of FLSs by activating the classical Smad2/3 and nonclassical JNK/AKT signaling pathways. This study provides overall protein and gene profiles of PVNS and identifies the crucial role of TGFβ in synovial invasion pathology. Exploring the related molecular mechanism may also reveal a new strategy or target for PVNS therapy.

Pigmented villonodular synovitis of knee with concomitant partial tear of anterior cruciate ligament in skeletally immature patient: A case report

Pigmented villonodular synovitis (PVNS) is benign but locally aggressive proliferative disorder that affects synovial joint, tendon sheaths, and bursae. PVNS is rare in child, while concurrent Anterior Cruciate Ligament (ACL) tear in PVNS is uncommon finding. Previous study reported ACL tear might be a risk factor in adult PVNS but lack of record for pediatric PVNS. We report a case of uncommon concomitant ACL partial tear in an already rare pediatric PVNS. A nine-year old female with pain and swelling on left knee, occurred intermittent every 2 months for 1 year prior to surgery. There was moderate knee movement restriction with history of fall from bicycle 1 year before surgery. No history of knee instability was reported. X-ray only denote joint swelling, while MRI shows intraarticular bodies suspected synovial chondromatosis with hyperintense signal sign of partial ACL tear. The patient underwent arthroscopic evaluation which exhibit intraarticular hyperemic and hypertrophic synovium with loosening anteromedial ACL bundle. Arthroscopic synovectomy was then performed followed by range of motion training and muscle strengthening rehabilitation program. Post-operative histopathological result confirms PVNS assessment. 1 year follow up post-surgery shows no recurrence of pain or swelling with free movement of left knee joint and no disturbance or instability while walking. In this case, partial ACL tear may contribute as risk factor of PVNS in child. Arthroscopic synovectomy with physical rehabilitation program shows good functional result with no recurrence at 1-year follow up.

Vimseltinib improves outcomes in tenosynovial giant cell tumour.

Vimseltinib improves outcomes in tenosynovial giant cell tumour.

Fine-needle aspiration cytology of diffuse type tenosynovial giant cell tumor with malignant trasformation and review of literature.

Tenosynovial giant cell tumors (TGCTs) arise from the synovium of joint, bursa, and tendon sheath. Diffuse type often affects large joints, has higher recurrence rates, metastases, and malignant transformation potential compared to the localized type. The cytopathology of TGCT, a fibrohistiocytic neoplasm distinct from other giant cell-rich soft tissue tumors, is rarely reported. Here we describe cytomorphology of a case of TGCT that was initially diagnosed on fine-needle aspiration cytology (FNAC) consisting of a mixture of singly scattered polygonal or spindle mononuclear cells with hemosiderin laden macrophages, inflammatory cells, and a population of multinucleated osteoclast-like giant cells. Persistent symptoms and repeat excision were consistent with high-grade malignant transformation of the TGCT. Atypical cytologic features in a recurrent, infiltrative, or a metastatic lesion should raise suspicion for malignancy.

ETMR-12. INFANTILE CENTRAL NERVOUS SYSTEM JUVENILE XANTHOGRANULOMA WITH SOMATICCSF1R MUTATION - RESPONSIVE TO IMATINIB MONOTHERAPY

Abstract BACKGROUND Juvenile xanthogranuloma (JXG) of the central nervous system(CNS) is a rare non-Langerhans cell histiocytosis typically affecting children and young adults. CSF1R mutations have been reported for peripheral JXG but have not previously been reported in CNS JXG. Treatment of CNS JXG relies on maximal safe surgical resection followed by cytotoxic chemotherapy, radiotherapy and/or molecular targeted therapy involving MAPK signaling pathway. Imatinib has been effective in treating tenosynovial giant cell tumor with CSF1R mutations. METHODS Case Report RESULTS A 3 month old male presented with fever, lymphadenopathy, and macrocephaly (45.5cm, 99.97%) with bulging fontanelles. Head ultrasound revealed dilated ventricles and brain MRI demonstrated multiple dural-based masses, the largest measuring 6.6 x 5.3 x 5.7 cm was located along the right tentorium and caused obstructive hydrocephalus. Patient underwent right frontal endoscopic third ventriculostomy and choroid plexus cauterization to treat hydrocephalus and right parietal craniotomy to resect the superficial dural-based mass for tissue diagnosis. Pathology was most consistent with a JXG that harbored a somatic CSF1R (NM_001288705.3) mutation. DNA Methylation profiling was unmatched. PET scan was negative for non-CNS lesions. Due to the multiple masses on presentation, the surgical risks of resection of the largest lesion, as well as having a targetable mutation, we opted for medical therapy. As Pexidartinib, a selective CSF1R inhibitor, was not available for infants, patient was started on liquid imatinib 340 mg/m2/day monotherapy. Three months after initiation of imatinib, the smaller parietal lesions resolved and after six months, the largest mass continued to shrink (6.3 x 2.9 x 2.9 cm). Treatment has been well tolerated without adverse events or drug interruptions. CONCLUSION This is the first report of CNS JXG with a CSF1R mutation. Importantly, it demonstrates that imatinib is a potentially safe and effective form of monotherapy for this rare disease.

CO22 Health-Related Quality of Life from a Phase 4 Global Clinical Study to Evaluate Discontinuation and Rechallenge of Pexidartinib in Patients with Tenosynovial Giant Cell Tumor (TGCT) Previously Treated with Pexidartinib

CO22 Health-Related Quality of Life from a Phase 4 Global Clinical Study to Evaluate Discontinuation and Rechallenge of Pexidartinib in Patients with Tenosynovial Giant Cell Tumor (TGCT) Previously Treated with Pexidartinib

RWD170 Real-World Experience of Patients Newly Initiated on Pexidartinib for Tenosynovial Giant Cell Tumor

RWD170 Real-World Experience of Patients Newly Initiated on Pexidartinib for Tenosynovial Giant Cell Tumor

Oncology

The June 2024 Oncology Roundup360 looks at: Chondrosarcoma of the femur: is local recurrence influenced by the presence of an extraosseous component?; Diagnostic challenges in low-grade central osteosarcoma; Single osteotomy technique for frozen autograft (pedicled freezing) in patients with malignant bone tumours; Unplanned resection for small superficial soft-tissue sarcomas: disastrous or simply bad?; Inactivation and replantation of the knee joint: an infeasible surgical method; Active surveillance of diffuse-type tenosynovial giant cell tumours: a retrospective, multicentre cohort study.

Vimseltinib versus placebo for tenosynovial giant cell tumour (MOTION): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

Tenosynovial giant cell tumour (TGCT) is a locally aggressive neoplasm for which few systemic treatment options exist. This study evaluated the efficacy and safety of vimseltinib, an oral, switch-control, CSF1R inhibitor, in patients with symptomatic TGCT not amenable to surgery. MOTION is a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial done in 35 specialised hospitals in 13 countries. Eligible patients were adults (aged ≥18 years) with a histologically confirmed diagnosis of TGCT for which surgical resection could potentially worsen functional limitation or cause severe morbidity. Patients were randomly assigned (2:1) with interactive response technology to vimseltinib (30 mg orally twice weekly) or placebo, administrated in 28-day cycles for 24 weeks. Patients and site personnel were masked to treatment assignment until week 25, unless progressive disease was confirmed earlier. The primary endpoint was objective response rate by independent radiological review using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) at week 25 in the intention-to-treat population. Safety was assessed in all patients who received the study drug. The trial is registered with ClinicalTrials.gov, NCT05059262, and enrolment is complete. Between Jan 21, 2022, and Feb 21, 2023, 123 patients were randomly assigned (83 to vimseltinib and 40 to placebo). 73 (59%) patients were female and 50 (41%) were male. Nine (11%) of 83 patients assigned to vimseltinib and five (13%) of 40 patients assigned to placebo discontinued treatment before week 25; one patient in the placebo group did not receive any study drug. Objective response rate per RECIST was 40% (33 of 83 patients) in the vimseltinib group vs 0% (none of 40) in the placebo group (difference 40% [95% CI 29-51]; p<0·0001). Most treatment-emergent adverse events (TEAEs) were grade 1 or 2; the only grade 3 or 4 TEAE that occurred in more than 5% of patients receiving vimseltinib was increased blood creatine phosphokinase (eight [10%] of 83). One patient in the vimseltinib group had a treatment-related serious TEAE of subcutaneous abscess. No evidence of cholestatic hepatotoxicity or drug-induced liver injury was noted. Vimseltinib produced a significant objective response rate and clinically meaningful functional and symptomatic improvement in patients with TGCT, providing an effective treatment option for these patients. Deciphera Pharmaceuticals.

Efficacy, safety, and patient-reported outcomes of vimseltinib in patients with tenosynovial giant cell tumor: Results from the phase 3 MOTION trial.

11500 Background: Tenosynovial giant cell tumor (TGCT) is a locally aggressive neoplasm caused by dysregulation of the colony-stimulating factor 1 ( CSF1) gene leading to overproduction of CSF1. TGCT requires a therapy with low toxicity as patients (pts) may need long-term treatment; there is an unmet need for an effective, well-tolerated CSF1 receptor (CSF1R)-targeted therapy that improves functional health and quality of life (QoL). Vimseltinib is an investigational, oral, switch-control tyrosine kinase inhibitor specifically designed to selectively and potently inhibit CSF1R. Here we report results from the MOTION trial. Methods: MOTION is a global, phase 3, double-blind study of vimseltinib in pts with symptomatic TGCT not amenable to surgery (NCT05059262). Randomization was 2:1 to vimseltinib 30 mg twice weekly or matching placebo (pbo) for 24 weeks. The primary endpoint was objective response rate (ORR) assessed by blinded independent radiological review (IRR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) at week 25. Key secondary endpoints assessed at week 25 were ORR by IRR per tumor volume score (TVS), change from baseline in active range of motion (ROM) of the affected joint and patient-reported outcomes (PROs; PRO Measurement Information System physical function score [PROMIS-PF], worst stiffness numeric rating scale, and EuroQol Visual Analog Scale [EQ-VAS]), and brief pain inventory worst pain response. Safety was also evaluated. Data cutoff was August 22, 2023. Results: Overall, 123 pts were randomized to vimseltinib (n = 83) or pbo (n = 40). Median age was 44 years, 59% of pts were female, and the most common primary disease location was the knee (67%). ORR at week 25 by IRR per RECIST v1.1 and per TVS were significantly higher for vimseltinib vs pbo (RECIST: 40% vs 0%, P &lt; 0.0001; TVS: 67% vs 0%; P &lt; 0.0001). Significant improvements from baseline to week 25 were observed with vimseltinib vs pbo in active ROM (18.4% vs 3.8%; P = 0.0077), physical function (PROMIS-PF: 3.3-point difference between arms, P = 0.0007), worst stiffness (−1.8-point difference, P &lt; 0.0001), and health status (EQ-VAS: 7.4-point difference, P = 0.0155). There were also significantly more pain responders treated with vimseltinib (48% vs 23%; P = 0.0056). Most non-laboratory treatment-emergent adverse events were grade 1/2, and there was no evidence of cholestatic hepatotoxicity or drug-induced liver injury. Conclusions: Patients treated with vimseltinib experienced statistically significant and clinically meaningful improvements in ORR by RECIST v1.1 and by TVS, active ROM, physical function, stiffness, health status, and pain vs pbo. Vimseltinib is an effective, well-tolerated CSF1R-targeted therapy that demonstrates significant clinical benefit and improves functional health and QoL in pts with symptomatic TGCT not amenable to surgery. Clinical trial information: NCT05059262 .

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