Diffuse Pigmented Villonodular Synovitis Discovered During Revision Total Knee Arthroplasty for Aseptic Loosening: A Case Report

Diffuse Pigmented Villonodular Synovitis Discovered During Revision Total Knee Arthroplasty for Aseptic Loosening: A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Diffuse Pigmented Villonodular Synovitis Discovered During Revision Total Knee Arthroplasty for Aseptic Loosening: A Case Report TAE-HUN LEE, YONG-SIK LEE, GIL-YEONG AHN, JEE-SOO PARK This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8676693/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 13 You are reading this latest preprint version Abstract Background Pigmented villonodular synovitis (PVNS) following total knee arthroplasty (TKA) is an extremely rare disease, typically reported within 9 years of the first surgery. It is often clinically indistinguishable from polyethylene wear-induced synovitis or aseptic loosening. We report a unique case of diffuse PVNS diagnosed 21 years after primary TKA, suggesting that PVNS may be a potential cause of aseptic loosening. Case presentation A 71-year-old male presented with left knee pain persisting for a year. He had undergone primary TKA 21 years prior and maintained excellent function, allowing for full weight-bearing and unrestricted daily activities, for 20 years postoperatively. After asymptomatic period, the patient presented with edema and swelling of the knee joint, and multiple instances of hemarthrosis were identified via joint aspiration. Radiographic and computed tomography (CT) evaluations suggested aseptic loosening of the tibial component with extensive osteolysis. During revision surgery, diffuse synovial hypertrophy characterized by yellowish-brown papillae was discovered. A complete synovectomy and revision TKA were performed. Histopathological examination confirmed the diagnosis of diffuse PVNS. Conclusions In long-term follow-up after TKA, the rapid progression of aseptic loosening following frequent episodes of hemarthrosis suggests a potential causal relationship. We consider this hemarthrosis to be secondary to PVNS. Therefore, it can be inferred that the onset of PVNS triggered frequent hemarthrosis, which subsequently led to the development of aseptic loosening. Knee Joint Total Knee Arthroplasty Hemarthrosis Aseptic loosening Pigmented Villonodular Synovitis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Background Pigmented Villonodular Synovitis (PVNS) is a rare, benign proliferative condition of the synovium. While it can involve any joint, the knee is the most common site of involvement [ 1 ]. The exact etiology remains unclear; however, proposed hypotheses include repetitive trauma, hemarthrosis, localized abnormal cellular activity, or neoplastic processes. PVNS typically presents in either a localized or diffuse form [ 2 , 3 ]. Although rare, PVNS can occur following Total Knee Arthroplasty (TKA), presumed to be a reactive phenomenon to polyethylene wear debris generated from prosthetic components [ 4 , 5 ]. When evaluating the etiology of TKA failure, the prevalence of aseptic loosening may lead clinicians to overlook rare underlying pathologies such as PVNS. Specifically, post-TKA PVNS is clinically and radiologically difficult to distinguish from polyethylene wear-induced synovitis, often resulting in diagnostic delays [ 4 , 6 ]. Previous literature indicates that the diagnosis of PVNS following TKA typically occurs within nine years post-surgery [ 6 , 7 ]. This case report presents a very rare occurrence of PVNS associated with recurrent hemarthrosis, diagnosed 21 years after primary TKA. Case presentation A 71-year-old male patient presented with left knee pain persisting for a year. He had undergone left TKA for osteoarthritis 21 years prior at another institution. There were no medical records indicating potential signs of PVNS in the synovium at the time of the initial surgery, nor was there any postoperative history of PVNS. The function of the affected knee remained excellent for 20 years postoperatively, allowing for full weight-bearing and unrestricted daily activities. 20 years after the initial surgery, the patient experienced frequent joint edema and swelling. Following 3 instances of arthrocentesis revealing hemarthrosis, the patient was subsequently referred for further evaluation. On physical examination upon presentation, tenderness, swelling, and limited range of motion (0–80 degrees) were observed in the knee joint. The patient had no history of trauma, infection, clinically palpable joint effusion or hemarthrosis. Laboratory tests, including C-reactive protein, erythrocyte sedimentation rate, and rheumatoid factor, were within normal limits. Plain radiographs revealed a radiolucent lesion beneath the tibial component, raising suspicion of loosening (Fig. 1 ). Computed tomography (CT) with metal artifact reduction demonstrated distinct osteolytic changes confined to the medial tibial condyle adjacent to the prosthesis (Fig. 2 ). The condition was diagnosed as aseptic loosening of the tibial component, and revision arthroplasty was performed. Intraoperatively, unexpected extensive diffuse synovial hypertrophy characterized by yellowish-brown papillae and nodules was discovered around the prosthesis (Fig. 3 ). The tibial component was loosened from the tibial metaphysis, accompanied by bone defects in the proximal tibia and severe wear of the polyethylene liner. Following complete resection of the affected synovium, revision TKA was performed using the Vanguard SSK Revision Knee System (Zimmer Biomet, Warsaw, IN, USA), consisting of a femoral component, an I-Beam tibial tray, and a 14 mm polyethylene bearing (Fig. 4 ). Gross examination of the resected synovial tissue revealed villonodular fronds on the surface. Histopathological examination using hematoxylin-eosin (H&E) staining confirmed distinct villonodular fronds surrounded by hyperplastic synovial tissue at low magnification (x40) (Fig. 5 A). Characteristic papillary projections and hypercellular, hypertrophic nodular synovium was also observed (Fig. 5 B). At high magnification (x200), the lesion was composed primarily of mononuclear histiocytoid cells with scattered multinucleated giant cells (Fig. 6 A). Additionally, numerous foamy histiocytes and hemosiderin-laden macrophages were prominently present throughout the tissue (Fig. 6 B), confirming the final diagnosis of PVNS. Discussion and conclusions PVNS is a benign proliferative disease involving the synovial membrane of the joint. Although the exact pathogenesis remains not fully elucidated, it is widely considered an inflammatory or neoplastic process. The disease is characterized by excessive proliferation of synovial tissue accompanied by hemosiderin deposition and can manifest in either localized or diffuse forms. PVNS is well recognized for its locally aggressive behavior and high recurrence rate, which are critical considerations for diagnosis and treatment [ 3 , 8 ]. In the present case, a patient who had maintained favorable long-term outcomes for approximately 20 years following TKA began experiencing frequent hemarthrosis over the past year. Upon diagnosis of aseptic loosening, revision TKA was performed, during which diffuse PVNS was incidentally discovered. We encountered a case of diffuse PVNS discovered incidentally during revision TKA performed for aseptic loosening. The patient had undergone primary TKA 21 years prior and maintained excellent function of the affected knee for 20 years. He had no other underlying conditions or history of trauma to the knee, nor had he experienced clinically palpable joint effusion or hemarthrosis. While the pathophysiology of PVNS developing after TKA is unclear, one hypothesis suggests that a chronic foreign body reaction to polyethylene or metal wear debris may induce synovial proliferation [ 4 ]. In this case, the prolonged interval of 21 years is sufficient for simple aseptic loosening caused by polyethylene wear. It is possible that these wear particles triggered the onset of PVNS, leading to frequent hemarthrosis, which is turn suggests a potential cause for aseptic loosening. Furthermore, the fact that the patient remained asymptomatic for 20 years postoperatively suggests that the aseptic loosening progressed rapidly following the recent onset of hemarthrosis. Tan et al. [ 9 ] noted that patients with PVNS undergoing TKA are at risk for postoperative complications, including aseptic loosening. This suggests that the intrinsic aggressive synovial proliferation of PVNS may directly contribute to prosthetic failure. The clinical presentation of post-TKA PVNS is variable. Camp et al. [ 7 ] reported a case presenting with flexion instability. In contrast, the patient remained asymptomatic for 20 years following the primary surgery, after which the condition progressed to aseptic loosening accompanied by frequent episodes of hemarthrosis. This indicates that PVNS can be a cause of long-term failure after TKA and suggests that inferring the diagnosis based solely on clinical signs is challenging. Abbreviations pigmented villonodular synovitis (PVNS) total knee arthroplasty (TKA) computed tomography (CT) Declarations Ethical approval This study is a retrospective case report involving a human subject. Since this study involved the retrospective review of medical records without any additional examinations, procedures, or data collection for research purposes, it was exempted from review by the Institutional Review Board (IRB). Written informed consent was obtained from the patient for the use of their medical records, including clinical information, imaging studies, and histological results. Consent for publication We confirm that written informed consent was obtained from the participant(patient) for the use of clinical information(personal & clinical details along with any identifying images) within the scope that does not compromise their anonymity. Informed consent was obtained from all participants, and the study protocol was approved by the appropriate institutional review board, following the guidelines of the Declaration of Helsinki. Availability of data and materials Materials described in the manuscript, including all relevant raw data, will be freely available to any scientist wishing to use them for non-commercial purposes. Data availability The datasets analyzed during the current study are available from the corresponding author upon request. Competing interests The authors declare no competing interests. Funding This research did not receive any external fundings. Authors' contributions YS Lee, TH Lee and JS Park wrote the main manuscript text. JS Park prepared all figures. YS Lee and GY Ahn conducted the final review. Acknowledgements Not applicable. References Myers BW, Masi AT. Pigmented villonodular synovitis and tenosynovitis: a clinical epidemiologic study of 166 cases and literature review. Med (Baltim). 1980;59:223–38. Aurégan JC, Klouche S, Bohu Y, Lefèvre N, Herman S, Hardy P. Treatment of pigmented villonodular synovitis of the knee. Arthroscopy. 2014;30:1327–41. Flandry F, Hughston JC. Pigmented villonodular synovitis. J Bone Joint Surg Am. 1987;69:942–9. Karl LA, Sundstrom WR. Prosthesis-induced synovitis simulating villonodular synovitis. Wis Med J. 1991;90:165–8. Oni JK, Cavallo RJ. A rare case of diffuse pigmented villonodular synovitis after total knee arthroplasty. J Arthroplasty. 2011;26:e9789–11. Ballard WT, Clark CR, Callaghan JJ. Recurrent spontaneous hemarthrosis nine years after a total knee arthroplasty. A presentation with pigmented villonodular synovitis. J Bone Joint Surg Am. 1993;75:764–s. Camp CL, Yuan BJ, Wood AJ, Lewallen DG. Pigmented villonodular synovitis diagnosed during revision total knee arthroplasty for flexion instability and patellar fracture. Knee. 2016;23:338–41. Tyler WK, Vidal AF, Williams RJ, Healey JH. Pigmented villonodular synovitis. J Am Acad Orthop Surg. 2006;14:376–85. Tan YC, Tan JY, Tsitskaris K. Systematic review: total knee arthroplasty (TKA) in patients with pigmented villonodular synovitis (PVNS). Knee Surg Relat Res. 2021;33:6. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 26 Feb, 2026 Reviews received at journal 24 Feb, 2026 Reviews received at journal 22 Feb, 2026 Reviewers agreed at journal 09 Feb, 2026 Reviews received at journal 05 Feb, 2026 Reviewers agreed at journal 04 Feb, 2026 Reviewers agreed at journal 04 Feb, 2026 Reviewers agreed at journal 30 Jan, 2026 Reviewers invited by journal 30 Jan, 2026 Editor invited by journal 28 Jan, 2026 Editor assigned by journal 24 Jan, 2026 Submission checks completed at journal 24 Jan, 2026 First submitted to journal 23 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8676693","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":583621102,"identity":"09f50d78-bd86-4262-9b5a-6a70c2e5c068","order_by":0,"name":"TAE-HUN LEE","email":"","orcid":"","institution":"Pohang St. Mary's Hospital","correspondingAuthor":false,"prefix":"","firstName":"TAE-HUN","middleName":"","lastName":"LEE","suffix":""},{"id":583621103,"identity":"ca5941cc-288c-4393-9c27-aa9750c9e54a","order_by":1,"name":"YONG-SIK LEE","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA40lEQVRIiWNgGAWjYDACZgY2CIO9B0zx8BGvhecMhAJzD+DXBNUikYPExadFt52B7cGHmsNy5pJvD34uzLGTYWPgPfj4Ax4tZocZ2A1nHDtsbDk7L1l65rZkoMP4kg3w2WJ2mP+bNA9bWuKG2zkG0rzbmIFaeMwk8GthYJP+8y+tfsPNM8a/ebfVg7SY/yCohbHNJsHgBo8Z0JbDYFvweh+kRbK3z8Zww5kcM2vebcd52Jh5jCXO4NNy/gCbxI9vEvIGx88Y3+bdVm3Pz95j+KECjxYsgJk05aNgFIyCUTAKsAAAS8pBVmiEMyAAAAAASUVORK5CYII=","orcid":"","institution":"Pohang St. Mary's Hospital","correspondingAuthor":true,"prefix":"","firstName":"YONG-SIK","middleName":"","lastName":"LEE","suffix":""},{"id":583621104,"identity":"ef187e58-99d3-4c00-a5be-d61fd59586bc","order_by":2,"name":"GIL-YEONG AHN","email":"","orcid":"","institution":"Pohang St. Mary's Hospital","correspondingAuthor":false,"prefix":"","firstName":"GIL-YEONG","middleName":"","lastName":"AHN","suffix":""},{"id":583621105,"identity":"efb46926-840e-4374-bc52-094077d73a5a","order_by":3,"name":"JEE-SOO PARK","email":"","orcid":"","institution":"Pohang St. Mary's Hospital","correspondingAuthor":false,"prefix":"","firstName":"JEE-SOO","middleName":"","lastName":"PARK","suffix":""}],"badges":[],"createdAt":"2026-01-23 08:23:37","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8676693/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8676693/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101789085,"identity":"76301c28-af86-438d-954c-f9c3b7973dfd","added_by":"auto","created_at":"2026-02-03 15:56:07","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1307524,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Anteroposterior (AP) knee radiograph shows an osteolytic lesion on the medial tibial condyle (white arrow), and (B) lateral view demonstrates radiolucent lines at the implant-cement interface (white arrow).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8676693/v1/1a39b13e4c3f523c3db71dc5.png"},{"id":101788999,"identity":"f91301d8-5f44-4cfa-b55f-0bcc4e04035f","added_by":"auto","created_at":"2026-02-03 15:55:52","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":226599,"visible":true,"origin":"","legend":"\u003cp\u003eCoronal computed tomography (CT) reconstruction image shows periprosthetic osteolysis in the medial tibial plateau (white arrow).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8676693/v1/764cbdbcd5afdb227266e6fb.png"},{"id":101789032,"identity":"b6e4d1ff-ac2e-4ee1-89b1-34ce27bd0057","added_by":"auto","created_at":"2026-02-03 15:55:55","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":932622,"visible":true,"origin":"","legend":"\u003cp\u003eGross photograph shows the excised synovium, which appears as a firm, grey-yellowish tissue.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8676693/v1/c15a02e5c2669dcb3d49d760.png"},{"id":101789142,"identity":"54797087-1698-44a3-b39e-9419595a1b89","added_by":"auto","created_at":"2026-02-03 15:56:20","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":826094,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Postoperative anteroposterior (AP) radiograph and (B) lateral radiograph show the knee status after revision total knee arthroplasty.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8676693/v1/2e999efceba02aef6a817303.png"},{"id":101789064,"identity":"cfa48698-6e05-464a-b436-e601b9d1a50d","added_by":"auto","created_at":"2026-02-03 15:56:02","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":737639,"visible":true,"origin":"","legend":"\u003cp\u003ePathologic findings. (A) Hematoxylin and eosin (H\u0026amp;E) stain (×40). It shows exuberant villonodular fronds with overlying synovial tissue. (B) Hematoxylin and eosin (H\u0026amp;E) stain (×40). It reveals nodular hyperplastic synovium with papillary projection and high cellularity.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-8676693/v1/d751f4d38b4a4b84bd570cf1.png"},{"id":101789057,"identity":"7413603a-4755-46e4-bdb9-d5b2840fe2e9","added_by":"auto","created_at":"2026-02-03 15:56:02","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":828488,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Hematoxylin and eosin (H\u0026amp;E) stain (×200). It shows that the tumor tissue is composed of abundant mononuclear histiocytoid cells, admixed with multinucleated giant cells. (B) Hematoxylin and eosin (H\u0026amp;E) stain (×200). It reveals many foamy histiocytes and hemosiderin-containing macrophages.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-8676693/v1/72837c9f352091c7cb608901.png"},{"id":101789226,"identity":"a2d493e3-6b1c-4980-b1b3-a7afc7a0bdc0","added_by":"auto","created_at":"2026-02-03 15:56:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5622727,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8676693/v1/017da304-1712-441a-aa81-14ebd2cfae52.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Diffuse Pigmented Villonodular Synovitis Discovered During Revision Total Knee Arthroplasty for Aseptic Loosening: A Case Report","fulltext":[{"header":"Background","content":"\u003cp\u003ePigmented Villonodular Synovitis (PVNS) is a rare, benign proliferative condition of the synovium. While it can involve any joint, the knee is the most common site of involvement [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The exact etiology remains unclear; however, proposed hypotheses include repetitive trauma, hemarthrosis, localized abnormal cellular activity, or neoplastic processes. PVNS typically presents in either a localized or diffuse form [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough rare, PVNS can occur following Total Knee Arthroplasty (TKA), presumed to be a reactive phenomenon to polyethylene wear debris generated from prosthetic components [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. When evaluating the etiology of TKA failure, the prevalence of aseptic loosening may lead clinicians to overlook rare underlying pathologies such as PVNS. Specifically, post-TKA PVNS is clinically and radiologically difficult to distinguish from polyethylene wear-induced synovitis, often resulting in diagnostic delays [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePrevious literature indicates that the diagnosis of PVNS following TKA typically occurs within nine years post-surgery [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. This case report presents a very rare occurrence of PVNS associated with recurrent hemarthrosis, diagnosed 21 years after primary TKA.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 71-year-old male patient presented with left knee pain persisting for a year. He had undergone left TKA for osteoarthritis 21 years prior at another institution. There were no medical records indicating potential signs of PVNS in the synovium at the time of the initial surgery, nor was there any postoperative history of PVNS. The function of the affected knee remained excellent for 20 years postoperatively, allowing for full weight-bearing and unrestricted daily activities. 20 years after the initial surgery, the patient experienced frequent joint edema and swelling. Following 3 instances of arthrocentesis revealing hemarthrosis, the patient was subsequently referred for further evaluation.\u003c/p\u003e \u003cp\u003eOn physical examination upon presentation, tenderness, swelling, and limited range of motion (0\u0026ndash;80 degrees) were observed in the knee joint. The patient had no history of trauma, infection, clinically palpable joint effusion or hemarthrosis. Laboratory tests, including C-reactive protein, erythrocyte sedimentation rate, and rheumatoid factor, were within normal limits. Plain radiographs revealed a radiolucent lesion beneath the tibial component, raising suspicion of loosening (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eComputed tomography (CT) with metal artifact reduction demonstrated distinct osteolytic changes confined to the medial tibial condyle adjacent to the prosthesis (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The condition was diagnosed as aseptic loosening of the tibial component, and revision arthroplasty was performed.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIntraoperatively, unexpected extensive diffuse synovial hypertrophy characterized by yellowish-brown papillae and nodules was discovered around the prosthesis (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The tibial component was loosened from the tibial metaphysis, accompanied by bone defects in the proximal tibia and severe wear of the polyethylene liner. Following complete resection of the affected synovium, revision TKA was performed using the Vanguard SSK Revision Knee System (Zimmer Biomet, Warsaw, IN, USA), consisting of a femoral component, an I-Beam tibial tray, and a 14 mm polyethylene bearing (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eGross examination of the resected synovial tissue revealed villonodular fronds on the surface. Histopathological examination using hematoxylin-eosin (H\u0026amp;E) staining confirmed distinct villonodular fronds surrounded by hyperplastic synovial tissue at low magnification (x40) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA). Characteristic papillary projections and hypercellular, hypertrophic nodular synovium was also observed (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eB). At high magnification (x200), the lesion was composed primarily of mononuclear histiocytoid cells with scattered multinucleated giant cells (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eA). Additionally, numerous foamy histiocytes and hemosiderin-laden macrophages were prominently present throughout the tissue (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eB), confirming the final diagnosis of PVNS.\u003c/p\u003e "},{"header":"Discussion and conclusions","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003cp\u003ePVNS is a benign proliferative disease involving the synovial membrane of the joint. Although the exact pathogenesis remains not fully elucidated, it is widely considered an inflammatory or neoplastic process. The disease is characterized by excessive proliferation of synovial tissue accompanied by hemosiderin deposition and can manifest in either localized or diffuse forms. PVNS is well recognized for its locally aggressive behavior and high recurrence rate, which are critical considerations for diagnosis and treatment [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the present case, a patient who had maintained favorable long-term outcomes for approximately 20 years following TKA began experiencing frequent hemarthrosis over the past year. Upon diagnosis of aseptic loosening, revision TKA was performed, during which diffuse PVNS was incidentally discovered. We encountered a case of diffuse PVNS discovered incidentally during revision TKA performed for aseptic loosening. The patient had undergone primary TKA 21 years prior and maintained excellent function of the affected knee for 20 years. He had no other underlying conditions or history of trauma to the knee, nor had he experienced clinically palpable joint effusion or hemarthrosis.\u003c/p\u003e \u003cp\u003eWhile the pathophysiology of PVNS developing after TKA is unclear, one hypothesis suggests that a chronic foreign body reaction to polyethylene or metal wear debris may induce synovial proliferation [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this case, the prolonged interval of 21 years is sufficient for simple aseptic loosening caused by polyethylene wear. It is possible that these wear particles triggered the onset of PVNS, leading to frequent hemarthrosis, which is turn suggests a potential cause for aseptic loosening. Furthermore, the fact that the patient remained asymptomatic for 20 years postoperatively suggests that the aseptic loosening progressed rapidly following the recent onset of hemarthrosis.\u003c/p\u003e \u003cp\u003eTan et al. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] noted that patients with PVNS undergoing TKA are at risk for postoperative complications, including aseptic loosening. This suggests that the intrinsic aggressive synovial proliferation of PVNS may directly contribute to prosthetic failure.\u003c/p\u003e \u003cp\u003eThe clinical presentation of post-TKA PVNS is variable. Camp et al. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] reported a case presenting with flexion instability. In contrast, the patient remained asymptomatic for 20 years following the primary surgery, after which the condition progressed to aseptic loosening accompanied by frequent episodes of hemarthrosis. This indicates that PVNS can be a cause of long-term failure after TKA and suggests that inferring the diagnosis based solely on clinical signs is challenging.\u003c/p\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cp\u003epigmented villonodular synovitis (PVNS)\u003c/p\u003e \u003cp\u003etotal knee arthroplasty (TKA)\u003c/p\u003e \u003cp\u003ecomputed tomography (CT)\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003eEthical approval\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study is a retrospective case report involving a human subject. Since this study involved the retrospective review of medical records without any additional examinations, procedures, or data collection for research purposes, it was exempted from review by the Institutional Review Board (IRB). Written informed consent was obtained from the patient for the use of their medical records, including clinical information, imaging studies, and histological results.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe confirm that written informed consent was obtained from the participant(patient) for the use of clinical information(personal \u0026amp; clinical details along with any identifying images) within the scope that does not compromise their anonymity.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eInformed consent\u003c/p\u003e\n\u003cp\u003ewas obtained from all participants, and the study protocol was approved by the appropriate institutional review board, following the guidelines of the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMaterials described in the manuscript, including all relevant raw data, will be freely available to any scientist wishing to use them for non-commercial purposes.\u003c/p\u003e\n\u003cp\u003eData availability\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe datasets analyzed during the current study are available from the corresponding author upon request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCompeting interests\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis research did not receive any external fundings.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; contributions\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eYS Lee, TH Lee and JS Park wrote the main manuscript text. JS Park prepared all figures. YS Lee and\u0026nbsp;GY\u0026nbsp;Ahn conducted the final review.\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMyers BW, Masi AT. Pigmented villonodular synovitis and tenosynovitis: a clinical epidemiologic study of 166 cases and literature review. Med (Baltim). 1980;59:223\u0026ndash;38.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAur\u0026eacute;gan JC, Klouche S, Bohu Y, Lef\u0026egrave;vre N, Herman S, Hardy P. Treatment of pigmented villonodular synovitis of the knee. Arthroscopy. 2014;30:1327\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFlandry F, Hughston JC. Pigmented villonodular synovitis. J Bone Joint Surg Am. 1987;69:942\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKarl LA, Sundstrom WR. Prosthesis-induced synovitis simulating villonodular synovitis. Wis Med J. 1991;90:165\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOni JK, Cavallo RJ. A rare case of diffuse pigmented villonodular synovitis after total knee arthroplasty. J Arthroplasty. 2011;26:e9789\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBallard WT, Clark CR, Callaghan JJ. Recurrent spontaneous hemarthrosis nine years after a total knee arthroplasty. A presentation with pigmented villonodular synovitis. J Bone Joint Surg Am. 1993;75:764\u0026ndash;s.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCamp CL, Yuan BJ, Wood AJ, Lewallen DG. Pigmented villonodular synovitis diagnosed during revision total knee arthroplasty for flexion instability and patellar fracture. Knee. 2016;23:338\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTyler WK, Vidal AF, Williams RJ, Healey JH. Pigmented villonodular synovitis. J Am Acad Orthop Surg. 2006;14:376\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTan YC, Tan JY, Tsitskaris K. Systematic review: total knee arthroplasty (TKA) in patients with pigmented villonodular synovitis (PVNS). Knee Surg Relat Res. 2021;33:6.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Knee Joint, Total Knee Arthroplasty, Hemarthrosis, Aseptic loosening, Pigmented Villonodular Synovitis","lastPublishedDoi":"10.21203/rs.3.rs-8676693/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8676693/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePigmented villonodular synovitis (PVNS) following total knee arthroplasty (TKA) is an extremely rare disease, typically reported within 9 years of the first surgery. It is often clinically indistinguishable from polyethylene wear-induced synovitis or aseptic loosening. We report a unique case of diffuse PVNS diagnosed 21 years after primary TKA, suggesting that PVNS may be a potential cause of aseptic loosening.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 71-year-old male presented with left knee pain persisting for a year. He had undergone primary TKA 21 years prior and maintained excellent function, allowing for full weight-bearing and unrestricted daily activities, for 20 years postoperatively. After asymptomatic period, the patient presented with edema and swelling of the knee joint, and multiple instances of hemarthrosis were identified via joint aspiration. Radiographic and computed tomography (CT) evaluations suggested aseptic loosening of the tibial component with extensive osteolysis. During revision surgery, diffuse synovial hypertrophy characterized by yellowish-brown papillae was discovered. A complete synovectomy and revision TKA were performed. Histopathological examination confirmed the diagnosis of diffuse PVNS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn long-term follow-up after TKA, the rapid progression of aseptic loosening following frequent episodes of hemarthrosis suggests a potential causal relationship. We consider this hemarthrosis to be secondary to PVNS. Therefore, it can be inferred that the onset of PVNS triggered frequent hemarthrosis, which subsequently led to the development of aseptic loosening.\u003c/p\u003e","manuscriptTitle":"Diffuse Pigmented Villonodular Synovitis Discovered During Revision Total Knee Arthroplasty for Aseptic Loosening: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-03 15:53:33","doi":"10.21203/rs.3.rs-8676693/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-26T09:11:17+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-24T07:12:28+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-22T14:50:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"8896256246697928316716407043723626219","date":"2026-02-09T06:38:24+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-06T03:25:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"139423152223735743671773311949499126674","date":"2026-02-04T14:04:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"2752145437355514282002950500907130809","date":"2026-02-04T07:16:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"78411175040350021324508335867138472539","date":"2026-01-30T05:41:17+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-30T05:36:21+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-28T18:00:41+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-24T09:46:24+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-24T09:45:24+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Musculoskeletal Disorders","date":"2026-01-23T07:53:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d1bdff8a-a5b8-41ff-a71d-c2bd84c90264","owner":[],"postedDate":"February 3rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-13T11:56:28+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-03 15:53:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8676693","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8676693","identity":"rs-8676693","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}