Please cite this article in press as: V. Krenn, et al., 15 years of the histopathological synovitis score, further development and review: A diagnostic score for rheumatology and orthopaedics, Pathol. – Res. Pract (2017), http://dx.doi.org/10.1016/j.prp.2017.05.005 ARTICLE IN PRESS G Model PRP-51811; No. of Pages 8 Pathology – Research and Practice xxx (2017) xxx–xxx Contents lists available at ScienceDirect Pathology – Research and Practice jou rn al hom epage: www.elsevier.com/locate/prp Review 15 years of the histopathological synovitis score, further development and review: A diagnostic score for rheumatology and orthopaedics V. Krenn a,∗ , G. Perino b , W. Rüther c , V.T. Krenn a , M. Huber d , T. Hügle e , A. Najm f , S. Müller a , F. Boettner b , F. Pessler g,h , W. Waldstein i , J. Kriegsmann a,j , R. Casadonte j , T. Häupl k , S. Wienert l , M.G. Krukemeyer m , S. Sesselmann n , S. Sunitsch o , R. Tikhilov p , L. Morawietz q a MVZ-Zentrum für Histologie, Zytologie und Molekulare Diagnostik, Trier, Germany b Department of Pathology and Laboratory Medicine, Hospital for Special Surgery, New York, USA c Klinik und Poliklinik für Orthopädie, Universitätsklinikum Hamburg-Eppendorf, Germany d Pathologisch-bakteriologisches Institut, Otto Wagner Spital, Vienna, Austria e Hôpital Orthopédique, Lausanne, Switzerland f Rhumatologie, Centre hospital-universitaire de Nantes, France g TWINCORE, Zentrum für Experimentelle und Klinische Infektionsforschung GmbH, Hannover, Germany h Helmholtz-Zentrum für Infektionsforschung, Braunschweig, Germany i Medizinische Universität Wien, AKH-Wien, Universitätsklinik für Orthopädie, Vienna, Austria j Proteopath GmbH, Trier, Germany k Med. Klinik, Rheumatologie und Klinische Immunologie (Charité),Berlin, Germany l VMscope-Berlin, Germany m Paracelsus-Kliniken Deutschland, Osnabrück, Germany n Orthopädische Universitätsklinik Erlangen, Erlangen, Germany o Medizinische Universität Graz – Institut für Pathologie, Austria p Vreden Russian Scientific Research Institute of Traumatology and Orthopedics, Saint Petersburg, Russia q MVZ Fürstenberg-Karree, Berlin, Germany a r t i c l e i n f o Article history: Received 30 March 2017 Accepted 11 May 2017 Keywords: Synovitis score Synovitis Rheumatoid arthritis Arthrosis Semiquantitative evaluation Immunohistochemistry Risk stratification a b s t r a c t The histopathological synovitis score evaluates the immunological and inflammatory changes of synovi- tis in a graduated manner generally customary for diagnostic histopathological scores. The score results from semiquantitative evaluation of the width of the synovial surface cell layer, the cell density of the stroma and the density of the inflammatory infiltration into 4 semiquantitative levels (normal 0, mild 1, moderate 2, severe 3). The addition of these values results in a final score of 0–9 out of 9. On the basis of this summation the condition is divided into low-grade synovitis and high-grade synovitis: A synovitis score of 1 to ≤ 4 is called low-grade synovitis (arthrosis-associated/OA synovitis, posttraumatic synovitis, meniscopathy-associated synovitis and synovitis with haemochromatosis). A synovitis score of ≥ 5 to 9 is called high-grade synovitis (rheumatoid arthritis, psoriatic arthritis, Lyme arthritis, postin- fection/reactive arthritis and peripheral arthritis with Bechterew’s disease). By means of the synovitis score it is therefore possible to distinguish between degenerative/posttraumatic diseases (low-grade synovitis) and inflammatory rheumatic diseases (high-grade synovitis) with a sensitivity of 61.7% and a specificity of 96.1%. The diagnostic accuracy according to ROC analysis (AUC: 0.8–0.9) is good. Since the first publication (2002) and an associated subsequent publication (2006), the synovitis score has nation- ally and internationally been accepted for histopathological assessment of the synovitis. In a PubMed data analysis (status: 14.02.2017), the following citation rates according to Cited by PubMed Central articles resulted for the two synovitis score publications: For DOI: 10.1078/0344-0338-5710261 there were 29 Cited by PubMed Central articles and for the second extended publication DOI:10.1111/j.1365- 2559.2006.02508 there were 44 Cited by PubMed Central articles. Therefore a total of 73 PubMed citations are observed over a period of 15 years, which demonstrates an international acceptance of the score. This synovitis score provides for the first time a diagnostic, standardised and reproducible histopatholog- ical evaluation method enabling a contribution to the differential diagnosis of chronic inflammatory ∗ Corresponding author at: MVZ Zentrum für Histologie, Zytologie und Molekulare Diagnostik, Max-Planck-Straße. E-mail address: krenn@patho-trier.de (V. Krenn). http://dx.doi.org/10.1016/j.prp.2017.05.005 0344-0338/© 2017 Elsevier GmbH. All rights reserved.