The contribution of the histopathological examination to the diagnosis of adverse local tissue reactions in arthroplasty

Giorgio Perino, Ivan De Martino, Lingxin Zhang, Zhidao Xia, Jiri Gallo, Shonali Natu, David Langton, Monika Huber, Anastasia Rakow, Janosch Schoon, Enrique Gomez-Barrena, Veit Krenn

Research output: Contribution to journalArticlepeer-review


The histopathological examination of the periprosthetic soft tissue and bone has contributed to the identification and description of the morphological features of adverse local tissue reactions (ALTR)/adverse reactions to metallic debris (ARMD). The need of a uniform vocabulary for all disciplines involved in the diagnosis and management of ALTR/ARMD and of clarification of the parameters used in the semi-quantitative scoring systems for their classification has been considered a pre-requisite for a meaningful interdisciplinary evaluation. This review of key terms used for ALTR/ARMD has resulted in the following outcomes: (a) pseudotumor is a descriptive term for ALTR/ARMD, classifiable in two main types according to its cellular composition defining its clinical course; (b) the substitution of the term metallosis with presence of metallic wear debris, since it cannot be used as a category of implant failure or histological diagnosis; (c) the term aseptic lymphocytic-dominated vasculitis-associated lesion (ALVAL) should be replaced due to the absence of a vasculitis with ALLTR/ALRMD for lymphocytic-predominant and AMLTR/AMRMD for macrophage-predominant reaction. This review of the histopathological classifications of ALTR/ARMD has resulted in the following outcomes: (a) distinction between cell death and tissue necrosis; (b) the association of corrosion metallic debris with adverse local lymphocytic reaction and tissue necrosis; (c) the importance of cell and particle debris for the viscosity and density of the lubricating synovial fluid; (d) a consensus classification of lymphocytic infiltrate in soft tissue and bone marrow; (e) evaluation of the macrophage infiltrate in soft tissues and bone marrow; (f) classification of macrophage induced osteolysis/ aseptic loosening as a delayed type of ALTR/ARMD; (g) macrophage motility and migration as possible driving factor for osteolysis; (h) usefulness of the histopathological examination for the natural history of the adverse reactions, radiological correlation, post-marketing surveillance, and implant registries. The review of key terms used for the description and histopathological classification of ALTR/ARMD has resulted in a comprehensive, new standard for all disciplines involved in their diagnosis, clinical management, and long-term clinical follow-up.

Original languageEnglish (US)
Pages (from-to)399-419
Number of pages21
JournalEFORT Open Reviews
Issue number6
StatePublished - 2021
Externally publishedYes


  • adverse local tissue reaction
  • adverse lymphocytic-dominated vasculitis-associated lesion
  • adverse reaction to metallic debris
  • macrophage death
  • metal-on-metal hip implants
  • metallosis
  • osteolysis
  • pseudotumor

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine


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