Histopathology: An investigation so valuable but often neglected in orthopaedic infections

The incidence of osteoarticular infections is steadily increasing, driven by rising road traffic injuries, greater longevity, increasing comorbidities, and the expanding use of orthopaedic implants. Early diagnosis, timely surgical and medical intervention, and optimization of host factors are critical to achieving favorable outcomes. Effective management therefore requires close collaboration among the orthopaedic surgeon, radiologist, histopathologist, microbiologist, and infectious disease specialist. Histopathological evaluation provides direct tissue-level evidence of host response and, occasionally, enables visualization of microorganisms, thereby significantly enhancing diagnostic accuracy. It assists intraoperative decision-making, guides antimicrobial therapy, and helps distinguish infection from its mimics. Despite these advantages, histopathological assessment remains underutilized and inconsistently integrated into routine orthopaedic practice. This narrative review provides a comprehensive overview of the role of histopathology in osteoarticular infections within a multidisciplinary framework. Two principal domains are addressed: quantitative histopathology, in which the number of polymorphonuclear neutrophils per high-power field serves as a surrogate marker of infection, and conventional diagnostic histopathology. The review examines the established role of quantitative histopathology in periprosthetic joint infection and its emerging applications in fracture-related infection. Future directions, including machine learning-assisted automated inflammatory cell detection on whole-slide imaging, are also discussed. In addition, the review explores the importance of conventional histopathology in diagnosing osteomyelitis, elucidating disease etiology, guiding treatment, and identifying conditions that mimic infection. The value of histopathology in culture-negative infections is highlighted, and practical guidance is provided for managing discordant histological and microbiological results. Integration of histopathological findings into established diagnostic frameworks, including the Musculoskeletal Infection Society (MSIS) and International Consensus Meeting (ICM) criteria for periprosthetic joint infection and the Fracture-Related Infection (FRI) consensus definition, is discussed. Finally, the review examines why histopathology remains underutilized despite its diagnostic value and proposes a practical clinical algorithm to optimize its utilization. Histopathology should not be regarded as an optional investigation but as a core component of multidisciplinary diagnosis in osteoarticular infection.