The role of histopathology: Diagnostics of PJI

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1 The role of histopathology: Diagnostics of PJI BSc. Vincent Krenn Sigmund Freud PrivatUniversität Wien ZHZMD Trier

2 2011 In joint replacement operations a histopathological diagnosis is generally advised as pathological processes are responsible for reduced longevity of the arthroplasty and a histopathological clarification is therefore indicated The SLIM-Consensus- Classification is recommended

3 2013

4 SLIM-Consensus classification of Endoprosthetic Pathology Morawietz et al. 2004; Krenn, Morawietz, Perino et al SLIM/neosynovitis Adverse Tissue Reactions -inflammatoric- + Type I Particle type Type II Infectious type Type III Combined type Type IV Indifferent type Necrosis Granulomas Leucocytic Infiltration + Arthrofibrosis particle induced fibrosis fibrosis + Arthrofibrosis not particle induced Bone pathology inflammatory changes (typ I) infectious osteomyelitis (typ II,III) Periprothetische ossification Ossifikation osteopenia osteonecrosis + lymphatic Infiltration Adverse Tissue Reactions -immunologic-

5 Histopathological diagnostics in periprosthetic joint infections, PJI Quantification systems Krenn et al 2014 One-Stage Revision Criteria for SLIM infectious type, type II and type III Two-Stage Revision Criteria for Perispacer- Reaction Bacterial high grade infection Pronounced confluent NG infiltrate Semiquantitative criteria for NG-infiltrate Evaluation in: HE and PAS- staining Abscess formation Confluent microabscesses Necrosis Confluent synovial lining ulcerations Fibrin-Insudationen Macrophages Diagnostic criteria according to : Illgner et al Bacterial low grade infection Minimale diffuse NG-infiltrate Quantitative criteria of NG-infiltrate Evaluation in: Chlorazetatesterase-Reaktion, PAS-Färbung und durch CD15 Expression Microabscesses and diffuse infiltrate NG Focal ulcerations of synovial lining Minimale Fibrin-Insudationen Low to moderate macrophage infiltration Diagnostic criteria according to: Pandey et al Morawietz et. al Fink et. al und 2013 Morawietz et. al Kölbel et al (quantifier software) CD15 Focus Score Krenn VT et al Persistence of infection Variable pronounced NG-Infiltrat and PMMA-depositions Quantitative criteria of NGinfiltrate Evaluation in: Chlorazetatesterase-Reaktion, PAS-staining And by myeloperoxidase expression Microabscesses and diffuse NGinfiltrate Focal synovial lining ulcerations low Fibrin-Insudationen low to moderate Macrophagen PMMA-Particle Diagnostic criteria according to: Gontarewicz et al Partikle characterisation according to the particle algorithme Krenn et al. 2014

6 Microbiology: Staphylococcus epidermidis Coagulase-negative Low-virulence CD15 Focus Score Kölbel et al A stratification into low-virulence and high-virulence microbial pathogens Krenn VT et al Microbiology : Staphylococcus aureus Coagulase-positive High-virulence

7 Stratification into low-virulence and high-virulence microbial pathogens is possible by means of the CD15 focus score: 106/HPF 39/HPF High-virulence microbial pathogens Staphylococcus aureus Streptococcus, type A Escherichia coli Enterococcus faecalis Krenn VT et al Low-virulence microbial pathogens Staphylococcus epidermidis Staphylococcus capitis Staphylococcus caprae Staphylococcus lugdunensis Propionibacterium acnes Corynebacterium Bacillus pumilus

8 CD15 Focus Score Kölbel 2015 et al.; Krenn V.T. et al A count of 39 CD15 NG/focal point was identified as the optimum threshold when diagnosing periprosthetic joint infections (PJI) using the CD15 focus score. If the microbiological findings are used as a gold standard, the diagnostic sensitivity is 0.91, and the specificity is 0.92 (PPV = 0.94; NPV = 0.88; accuracy = 0.92; AUC = 0.95). Due to the high sensitivity, specificity and the stratification in low and high virulence microbial infections the CD15 Focus Score is a valid scoring system for periprosthetic joint infections. It allowed the development of the CD15 quantifier software. (This provides an automated procedure, which shortens the mentally tiring and time-consuming process of microscopic cell counting and thus makes a contribution towards the standardization of tools for diagnosing PJI.)

9 R.K H/2016/5290

10 R.K H/2016/5290 Diagnostic report: SLIM (left hip) with a positive CD15 focus score (59) According to the SLIM consensus classification this type may be classified as SLIM-Type 2 - infectious type Positive microbiologic-immunhistopathologic correlation A CD15 focus score of 59 is indicative for an infection with low pathogenic microbes and is therefore consistent with the microbiologic result: Staphylococcus epidermidis ICD10:A 49.8

11 Conclusion 1-The extended SLIM classification of joint implant related pathology is a practical histopathologic classification based on defined morphological criteria covering the complete spectrum of pathohistology in periprosthetic tissues. Morawietz et al. 2004; Krenn, Morawietz Perino et al 2013, Schaumburger et al Periprosthetic infection: Neutrophil granulocytes can be detected through histochemical methods, more specifically by immune-histopathological techniques and by various quantification systems ( histopathological scores ) leading to the diagnosis of microbial infection which is a defined part of bacterial peri-implant joint infection (PJI) Gontarewicz et al. 2012, Zmistowski et al. 2014, Renz et al CD15 focus score: A count of 39 CD15 NG/focal point was identified as the optimum threshold when diagnosing PJI. If the microbiological findings are used as a gold standard, the diagnostic sensitivity is 0.91, and the specificity is 0.92 (PPV = 0.94; NPV: 0.88; accuracy = 0.92; AUC = 0.95). Krenn VT et al. 2017

12 Krenn VT et al. 2017

13 CD15 focus score infection persistence?

14 CD15 focus score infection persistence Diagnostic report: SLIM (hip) with a positive CD15 focus score (33) According to histopathology: perispacer reaction positive microbiologic-immunhistopathologic correlation A CD15 focus score of 33 indicates that there is no mircobial infection. The histopathological diagnosis consists with the microbiologic result: no indication for a infection persistence ICD-10: T84.9

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17 Thank you for your attention! Prof. Dr. Veit Krenn ZHZMD-Trier BSc.Vincent Krenn Sigmund Freud PrivatUniversität