title: Adverse reactions to metal debris: histopathological features of periprosthetic soft tissue reactions seen in association with failed metal on metal hip arthroplasties.
abstract: OBJECTIVE
  To describe the histopathology of localised adverse reactions to metal debris (ARMD) seen in association with failed metal on metal (MoM) hip arthroplasties. The nature of aseptic lymphocytic vasculitis associated lesion (ALVAL) is investigated.
  
  
  METHODS
  Periprosthetic soft tissues biopsied at time of revision from failed MoM hip arthroplasties from January 2007 to March 2011 were analysed. The inflammatory cell response was categorised into perivascular lymphocytic cuffing (ALVAL), lymphoid aggregate formation with or without germinal centres, metallosis characterised by sheets of macrophages with intracytoplasmic metallic debris and well-defined granulomas.
  
  
  RESULTS
  123 patient samples were analysed, 36 males (29.2%) and 87 females (70.8%). Three cases showing complete tissue necrosis were excluded. Patients were reviewed between 3.27 to 69.6 months postarthroplasty, with an average of 30.92 months. 103 cases (85.8%) showed ALVAL, 18 cases also showed well-defined granulomas. Of the 103 cases with ALVAL, 60 cases also showed a diffuse chronic lymphocytic synovitis, and 40 cases showed lymphoid aggregates with germinal centres. 17 cases (14.2%) showed pure metallosis. Small vessels showing ALVAL expressed peripheral node addressin.
  
  
  CONCLUSIONS
  ARMD is a spectrum of changes comprising of pure metallosis, ALVAL and granulomatous inflammation. ALVAL, a distinctive inflammatory response seen in ARMD, is a precursor of lymphoid neogenesis. Lymphoid neogenesis documented in a variety of chronic inflammatory conditions most probably contributes to tissue necrosis and prosthetic failure seen in MoM hip arthroplasties. The role of vascular changes in contributing to necrosis is unclear at this stage.
authors.affiliation: Department of Pathology, University hospital of North Tees and Hartlepool NHS Foundation Trust, UK. sonali.natu@nth.nhs.uk
authors.forename: Sonali
authors.initials: S
authors.lastname: Natu
authors.forename: Raghavendra Prasad
authors.initials: RP
authors.lastname: Sidaginamale
authors.forename: Jamshid
authors.initials: J
authors.lastname: Gandhi
authors.forename: David J
authors.initials: DJ
authors.lastname: Langton
authors.forename: Antoni V F
authors.initials: AV
authors.lastname: Nargol
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects* / Q000295:instrumentation; D015815:Cell Adhesion Molecules; D002908:Chronic Disease; D003238:Connective Tissue / Q000187:drug effects / Q000473:pathology*; D005260:Female; D005549:Foreign-Body Reaction / Q000209:etiology / Q000473:pathology*; D006622:Hip Prosthesis / Q000009:adverse effects*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D008670:Metals / Q000009:adverse effects*; D008875:Middle Aged; D009088:Mucoproteins / Q000378:metabolism; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D011474:Prosthesis Design; D011475:Prosthesis Failure / Q000009:adverse effects*; D013585:Synovitis / Q000139:chemically induced / Q000473:pathology; D014657:Vasculitis / Q000139:chemically induced / Q000473:pathology
chemical_list: D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C504265:MADCAM1 protein, human; D008670:Metals; D009088:Mucoproteins