title: Utility of intraoperative frozen section histopathology in the diagnosis of periprosthetic joint infection: a systematic review and meta-analysis.
abstract: BACKGROUND
  The accuracy of intraoperative periprosthetic frozen section histologic evaluation in predicting a diagnosis of periprosthetic joint infection prior to microbiologic culture results is unknown.
  
  
  METHODS
  We performed a systematic review and meta-analysis of all longitudinal studies that compared frozen section histologic results with simultaneously obtained microbiologic culture at the time of revision total hip or total knee arthroplasty. The data sources were Ovid MEDLINE, Ovid EMBASE, the Cochrane Library, ISI Web of Science, and SCOPUS, from the inception of each database to January 2010.
  
  
  RESULTS
  Twenty-six studies involving 3269 patients undergoing revision hip or knee arthroplasty met the inclusion criteria. A culture-positive periprosthetic joint infection was confirmed in 796 (24.3%) of the patients. Frozen section results, using any of the diagnostic criteria chosen by the investigating pathologist, had a pooled diagnostic odds ratio of 54.7 (95% confidence interval [CI], 31.2 to 95.7), a likelihood ratio of a positive test of 12.0 (95% CI, 8.4 to 17.2), and a likelihood ratio of a negative test of 0.23 (95% CI, 0.15 to 0.35) for the diagnosis of periprosthetic joint infection. Fifteen studies utilizing a threshold of five polymorphonuclear leukocytes (PMNs) per high-power field to define a positive frozen section had a diagnostic odds ratio of 52.6 (95% CI, 23.7 to 116.2), and six studies utilizing a diagnostic threshold of ten PMNs per high-power field had a diagnostic odds ratio of 69.8 (95% CI, 33.6 to 145.0). There was no significant difference between the diagnostic odds ratio or likelihood ratios associated with these thresholds. The moderate to high heterogeneity among the included studies was unexplained by variability in the study design, diagnostic criteria for acute inflammation, reference standard for periprosthetic joint infection, or prevalence of infection. This heterogeneity could be due to differences in the inclusion and exclusion criteria, tissue sampling error, experience or technique of the pathologists, number of microscopic fields visualized, and field diameter examined.
  
  
  CONCLUSIONS
  Intraoperative frozen sections of periprosthetic tissues performed well in predicting a diagnosis of culture-positive periprosthetic joint infection but had moderate accuracy in ruling out this diagnosis. Frozen section histopathology should therefore be considered a valuable part of the diagnostic work-up for patients undergoing revision arthroplasty, especially when the potential for infection remains after a thorough preoperative evaluation. The optimum diagnostic threshold (number of PMNs per high-power field) required to distinguish periprosthetic joint infection from aseptic failure could not be discerned from the included studies. There was no significant difference between the diagnostic accuracy of frozen section histopathology utilizing the most common thresholds of five or ten PMNs per high-power field.
authors.affiliation: Department of Medicine, University of Illinois College of Medicine at Rockford, 1601 Parkview Avenue, Rockford, IL 61107, USA. gtsaras@uic.edu
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Tsaras
authors.forename: Awele
authors.initials: A
authors.lastname: Maduka-Ezeh
authors.forename: Carrie Y
authors.initials: CY
authors.lastname: Inwards
authors.forename: Tad
authors.initials: T
authors.lastname: Mabry
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Erwin
authors.forename: M Hassan
authors.initials: MH
authors.lastname: Murad
authors.forename: Victor M
authors.initials: VM
authors.lastname: Montori
authors.forename: Colin P
authors.initials: CP
authors.lastname: West
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Osmon
authors.forename: Elie F
authors.initials: EF
authors.lastname: Berbari
mesh_terms: D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects* / Q000379:methods; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects* / Q000379:methods; D016001:Confidence Intervals; D005260:Female; D005500:Follow-Up Studies; D005629:Frozen Sections / Q000706:statistics & numerical data*; D006801:Humans; D007430:Intraoperative Care / Q000379:methods; D016013:Likelihood Functions; D008137:Longitudinal Studies; D008297:Male; D016017:Odds Ratio; D011183:Postoperative Complications / Q000473:pathology / Q000601:surgery; D016459:Prosthesis-Related Infections / Q000175:diagnosis / Q000473:pathology* / Q000601:surgery*; D012086:Reoperation / Q000379:methods; D018570:Risk Assessment; D016896:Treatment Outcome