Pigmented villonodular synovitis

The aim of this study was to provide the outcomes and to analyze the recurrence of Pigmented Villonodular Synovitis (PVNS) of the ankle joint treated by surgical synovectomy. Thirty-one PVNS cases of the ankle, including 5 localized PVNS cases and 26 diffuse PVNS cases, were treated in our institute between 2004 and 2015. The median age was 35 (range 18-63) years. The 5 localized PVNS cases were treated with partial synovectomy (group I); 10 diffuse PVNS cases limited to intra-articular synovium received arthroscopic comprehensive synovectomy (group II); and 16 cases with diffuse PVNS spreading to extra-articular tendon sheaths underwent combined arthroscopic and open synovectomy (group III). Adjuvant radiotherapy was provided in groups II and III. The American Orthopaedic Foot and Ankle Society (AOFAS) score and subjective grading of procedure were used to evaluate the results. Twenty-seven patients were followed with a median of 54 (range 15-108) months. In the three groups, the average AOFAS score improved from 75 (in all three groups) points preoperatively to 100 (group I), 97 (group II), and 90 points (group III) postoperatively. The rate of good-to-excellent result was 100% in group I and II and 73.3% in group III. Only in group III, recurrence occurred in five cases. Diffuse PVNS of the ankle can be successfully managed with surgical synovectomy and adjuvant radiotherapy. Radiotherapy is not needed for localized PVNS. The recurrence rate in PVNS patients with extra-articular extension is higher. IV.

Introduction: Tenosynovial giant cell tumor (TSGCT) (synonym - pigmented villonodular synovitis) - is a rare benign proliferative lesion of the synovial sheath, localized in the joint capsule, bursa or tendon sheath and characterized by locally destructive growth. Depending on the prevalence within the joint elements, the presence of a capsule around the tumor, histophotographic features of cell structure and clinical behavior TSGCT can be divided to localized or diffuse type. The aim of the study was researching of histopathological properties of diffuse-type TSGCT, determine the parameters its morphological indicators and to find out the correlation between these morphological and clinical parameters. Materials and methods: The research material was used biopsy (resect) of pathological lesions from 50 patients who were diagnosed and histologically verified diffuse-type TSGCT. Microscopic examinations of the stained sections and their photo archiving were carried out with use of a Olympus-CX 41 light optical microscope. Group measurable parameters (mean values and Pearson tetrachoric index (association coefficient) were calculated in groups of comparison for morphological and clinical indices of TSGCT. The mean values were compared by Student's test, P value of ≤0.1 was considered statistically significant. Results: Correlation analysis of indicators that accounted for the pairs of cases «clinic - morphology» revealed the relationships, that had the highest parameters of the association coefficient between such indicators: «presence of villous growths» - «severity of hemosiderosis» (if hypertrophied synovial villi available, with vascular injection and pronounced proliferation of synovial cells, there is also a significant accumulation of hemosiderin pigment); «presence of villous growths» - «type of predominant cellular proliferates» (if cells of TSGCT diffuse type consists of monotonous sheets of stromal cells, with uniform, oval to reniform nuclei, the proliferation of villi in synovial layer is non-distinctive); «presence of nodes» - «kind of stroma» (if nodes predominate, their histological structure is mainly represented by polymorphic clusters of synovitis cells in the form of cells, strands, chains, solid formations, among immature connective tissue with low hyalinosis); «cell size (area, cm²)» - «severity of haemosiderosis» and «cell size (area, cm²)» - «the number of multinucleated giant cells» (there is a pronounced deposition of pigment and accumulation of osteoclast-like multinucleated giant cells type, although usually their number is relatively small compared to the localized type of TSGCT). Conclusions: Morphological parameters, that we have identified, characterize pathological changes in the tissues of TSGCT; careful analysis of the frequency of their occurrence in the different comparison groups made it possible to establish intergroup differences and correlations between individual indicators, which were previously unknown or not obvious. Our study was determine to analyze of incidence rates and correlation relationships, revealed some previously unknown differences and dependencies that are important for understanding the pathogenesis, improvement of diagnosis and prognosis of diffuse-type TSGCT.

Bilateral pigmented villonodular synovitis of the knee

Tenosynovial giant cell tumors arise from synovium of joints, bursae, or tendon sheaths, and are classified into localized and diffuse types based on the growth pattern and clinical behavior. The mononuclear component of these tumors includes small histiocytoid cells and large mononuclear cells, which are positive for desmin in about 50% of cases. This study seeks to further characterize the immunophenotype of these tumors, and investigates the utility of clusterin as a diagnostic marker. Immunostaining for clusterin was performed on 40 cases of tenosynovial giant cell tumor (11 localized and 29 diffuse). Most cases were also stained for desmin, CD163, CD21, and CD35. Four cases were stained for podoplanin/D2-40 and CXCL13. Clusterin staining was diffuse and strong in the large mononuclear cells in all cases. Desmin positivity in the large cells was identified in 24 out of 34 cases (71%), but was seen in only a subset of cells (<5% to 80%), with 19 out of 24 cases (79%) showing positivity in 10% or less. The large cells were positive for podoplanin in 4 out of 4 cases, but negative for CD163, CD21, CD35, and CXCL13. The smaller histiocytoid cells were positive for CD163 and negative for all other markers. When present, non-neoplastic synoviocytes were positive for clusterin and podoplanin, and focally positive for desmin. Clusterin is a highly sensitive marker for tenosynovial giant cell tumors, which has diagnostic utility in challenging cases. The observed staining patterns provide evidence linking the large mononuclear cells with normal synoviocytes and support that tenosynovial giant cell tumors are neoplasms showing synovial differentiation.

Pigmented villonodular synovitis (PVNS) is a synovial tumour-like lesion that frequently causes osteolysis. PVNS contains numerous macrophages and osteoclast-like giant cells. In this study, we have analysed the cytochemical and functional characteristics of mononuclear and multinucleated cells in PVNS and determined the cellular and humoral mechanisms underlying giant cell formation and resorption in PVNS. Giant cells and CD14(+) and CD14(-) mononuclear cell populations were isolated from PVNS synovial tissue and cultured alone or in the presence and absence of the osteoclastogenic factors, RANKL and M-CSF. Osteoclast formation and activity was assessed by expression of TRAP and evidence of lacunar resorption. Giant cells in PVNS expressed an osteoclast-phenotype (CD51(+) , TRAP(+) , CD14(-) , HLA-DR(-) ) and were formed only in cultures of mononuclear cells that expressed the macrophage marker CD14. Osteoclast formation required RANKL and occurred in both the presence and absence of exogenous M-CSF. CD14(-) cells in PVNS expressed RANKL. Lacunar resorption by PVNS-derived giant cells was abolished by the addition of the bisphosphonate, zoledronate. Our findings indicate that osteoclasts form by a RANKL-dependent mechanism from CD14(+) mononuclear phagocytes in PVNS. Osteoclast formation occurred even in the absence of exogenous M-CSF, a finding which is in keeping with over-expression of M-CSF playing a pathogenic role in this condition. Anti-osteoclast resorptive treatment may be useful to control osteolysis in PVNS.

A case of pigmented villonodular synovitis, with few clinical symptoms, arising from the temporomandibular joint

&lt;div&gt;AbstractPurpose:&lt;p&gt;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 &lt;i&gt;CSF1&lt;/i&gt; 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.&lt;/p&gt;Experimental Design:&lt;p&gt;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.&lt;/p&gt;Results:&lt;p&gt;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.&lt;/p&gt;Conclusions:&lt;p&gt;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.&lt;/p&gt;&lt;/div&gt;

The authors successfully treated a rare case of pigmented villonodular synovitis (PVNS) that originated from the lumbar facet joint (L4-5). A 43-year-old man presented with a complaint of left severe sciatica causing difficulty in walking. Magnetic resonance imaging (MRI) demonstrated an extradural mass on the left side at L4 and the mass compressed the dural tube and was continuous with the left L4-5 facet joint. A computed tomography myelogram revealed an extradural defect of contrast medium at the L4 level and an erosion of the L4 lamina. A total synovectomy with unilateral osteoplastic laminectomy was performed. The histological findings were a diagnosis of PVNS. The patient's symptoms resolved completely and the MRI at postoperative 3 years demonstrated no recurrence of PVNS. It is important to totally remove the synovium, which is the origin of PVNS in order to prevent the recurrence. We think that our procedure is reasonable and adequate for lumbar PVNS.

Twenty-nine cases of pigmented villonodular synovitis (PVS) of the knee in 27 patients were reviewed to determine characteristic roentgenographic findings. All cases met strict histologic criteria for diagnosis. Four cases were localized PVS (LPVS), and 25 cases were diffuse PVS (DPVS). Roentgenographic findings were largely in the soft tissues. Cystic invasion of bone or degenerative changes were rare, although present in some cases. When present in DPVS, these changes were most pronounced in the patellofemoral articular surface. In the cases of DPVS, large posterior tumefactions did not correlate with extraarticular extension. Clinical behavior of PVS was governed more by anatomic site and form of disease than by the severity of histologic or roentgenographic findings.

Objectives:A tenosynoival giant cell tumor known as pigmented villonodular synovitis (PVNS) is a rare, benign, yet locally aggressive neoplasm arising from the synovium. Although most frequently encountered in the knee joint, PVNS is secondly most commonly seen in the hip joint. Occurrence of PVNS in the hip may destroy intra-articular soft tissue and bone, and at times invade extra-articular tissues. There are two categorizations of PVNS: localized and diffuse. The localized manifestation, often referred to as nodular, involves a focal or limited area of the synovium, while the diffuse manifestation involves more widespread areas throughout the synovium. Surgical management by resection of the PVNS within the hip joint has been described with open procedures and arthroscopic procedures. Although surgical management has been shown to be promising, PVNS has a high recurrence rate, of 15-50%. To date, we present the largest cohort of hip joint PVNS managed by arthroscopic synovectomy with mid-term follow-up.Methods:A cohort of 19 patients were diagnosed with hip PVNS and underwent arthroscopic synovectomy between 2008 and 2016. Patients were identified preoperatively based on suspected MRI findings of PVNS or intraoperatively after unexpected PVNS was identified during arthroscopy for another pathology. We assessed patients’ functional ability at a minimum of 2-years follow-up using five patient reported outcome measures (PROMs): mHHS (modified Harris Hip Score), HOS (Hip Outcome Score), iHOT-33 (international Hip Outcome Tool), NAHS (Non-Arthritic Hip Score), and LEFS (Lower Extremity Functional Score).Results:Nineteen patients with hip PVNS were treated with an arthroscopic hip synovectomy. Sixteen of the patients completed patient reported outcome measures. This cohort consisted of 7 (44%) females and 9 (56%) males. The mean patient age was 37 years (range, 25-54). Mean follow-up was 83 months (6.9 years), ranging from 24 months (2 years) to 123 months (10.3 years). Eight (50%) patients had diffuse PVNS and 8 (50%) of patients had nodular PVNS. Laterality of the arthroscopic procedure was 8 (50%) right hip and 8 (50%) left hip. Five (31%) of the patients had a smoking history, while 11 (69%) were non-smokers. Four (25%) had a cam lesion, 4 (25%) had a pincer lesion, 8 (50%) had neither cam nor pincer lesion, and 0 (0%) had combined cam and pincer lesion. Fourteen (88%) patients had histologically confirmed PVNS. Eleven (69%) patients had MRI suspected PVNS prior to arthroscopy, while 5 (31%) patients had unexpected PVNS discovered intraoperatively. Concomitant pathology addressed at the time of arthroscopy, includes 11 (79%) labral tear repair. For the sixteen patients that completed patient reported outcome measures, the mean mHHS was 78.2 (SD, 10.6). Mean HOS-ADL was 10 (SD, 10). Mean HOS-SSS was 21 (SD, 20). Mean iHOT-33 was 69.4 (SD, 16.3). Mean NAHS was 86.5 (SD, 10.2). Mean LEFS was 70.8 (SD, 7.7). A mean percentage of maximal function was 88.6% (SD, 9.8%). To date, 0 (0%) patients have shown evidence of recurrence upon physical exam, follow-up MRI, or repeat arthroscopy.Conclusion:Based on the largest arthroscopically managed cohort of PVNS in the hip to date, we conclude that arthroscopic synovectomy is a reliable and effective treatment of hip PVNS. Patients reported good functional outcomes without evidence of recurrence in a 19 patient cohort with an average follow-up of almost 7 years.

Pigmented villonodular synovitis (PVNS) is a proliferative lesion originating from synovial tissue with a locally aggressive behaviour. We analysed the pathogenetic role of apoptosis resistance for sustained cell proliferation in PVNS. The expression of bcl-2, p53 and Ki-67 was examined in 80 cases of PVNS using immunohistochemistry. In 43 of these cases, DNA content and distribution of cell-cycle phases were investigated by flow cytometry. Additionally, 10 cases of PVNS were analysed by multi-parametric flow cytometry for expression of p53, caspase3, and bcl-2 and by TUNEL to detect DNA fragmentation. No apoptotic cell fractions were detected in any investigated cases. Expression of bcl-2 was found in 84% of cases (up to 6.5% of cells) and was significantly associated with DNA-fragmentation observed by TUNEL (p=0.037). Orthologous p53 expression was observed in 37% of cases. The level of p53 expression correlated with the proliferative activity and the expression of both caspase3 (p=0.017) and bcl-2 (p=0.0013). (No statistically significant correlations between expression of bcl-2, p53, caspase3, DNA fragmentation or proliferative index and age, sex of patients, disease recurrence, growth pattern or size of lesion were found). Apoptosis resistance is a critical event in the progression of PVNS and may contribute to the survival of the proliferating synovial cells in PVNS and to the permanent slow progression of these lesions.

Pigmented villonodular synovitis (PVNS) is a relatively rare benign proliferative disorder of the synovium, and it commonly occurs in the knee joint. A unique case of huge PVNS originating around the elbow joint that required upper arm amputation is reported. A 74-year-old woman had a 5-month history of right elbow pain and noticed a mass measuring 8 × 5 cm on the olecranon side. She had a past history of undergoing tumor resection and flap surgery 9 years earlier, diagnosed as a giant cell tumor involving the right elbow region. She had chronic renal failure, with a shunt on the right forearm. On magnetic resonance imaging, the tumor around the elbow joint showed low signal intensity on T1-weighted images and low to high intensity on T2-weighted images. It was thought that it was difficult to preserve the limb because of the size of the tumor and the shunt blood vessel. Therefore, upper arm amputation was performed. The histological diagnosis was PVNS. There was no recurrence of PVNS postoperatively. In the treatment of PVNS, initial surgery with complete resection of the synovial membrane and careful postoperative follow-up are considered important. J Med Cases. 2020;11(7):201-203 doi: https://doi.org/10.14740/jmc3503

Effectiveness of arthroscopic excision based on the distribution of the tenosynovial giant cell tumor around knee joint

Pigmented villonodular synovitis with chondroid metaplasia, resembling chondroblastoma of the bone: a report of three cases

Pigmented Villonodular Synovitis of the Temporomandibular Joint Presenting as a Middle Cranial Fossa Tumor