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. Cite this article: EFORT Open Rev 2021;6:399-419. DOI: 10.1302/2058-5241.6.210013.

Centre for Nanohealth Swansea University Medical School Singleton Park Swansea UK

Department of Orthopaedics Faculty of Medicine and Dentistry University Hospital Palacky University Olomouc Czech Republic

Department of Orthopedics and Orthopedic Surgery University Medicine Greifswald Greifswald Germany

Department of Pathology and Laboratory Medicine Sinai Health System Toronto Canada

Department of Pathology University Hospital of North Tees and Hartlepool NHS Foundation Trust Stockton on Tees UK

Division of Orthopaedics and Traumatology Fondazione Policlinico Universitario Agostino Gemelli IRCCS Rome Italy

MVZ Zentrum für Histologie Zytologie und Molekulare Diagnostik GmbH Trier Germany

Orthopaedic Department Freeman Hospital Newcastle upon Tyne UK

Pathologisch bakteriologisches Institut Otto Wagner Spital Wien Austria

Servicio de Cirugía Ortopédica y Traumatología Hospital Universitario La Paz IdiPAZ Universidad Autónoma de Madrid Madrid Spain

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