Erika Buratti, Giulia Ricchezze, Luca Tomassini, Francesco De Micco, Roberto Scendoni
Determining the cause of death in decomposed bodies is a major challenge in forensic pathology, as autolysis and putrefaction severely compromise tissue morphology and limit the value of conventional macroscopic and histological examinations. In this context, histopathological special stains and immunohistochemical (IHC) techniques have been explored as complementary tools capable of detecting residual markers of ante-mortem pathophysiological processes. This review evaluates current evidence on the applicability, diagnostic contribution, and limitations of histopathological and IHC markers in decomposed human remains. A systematic search of PubMed, Scopus, and Web of Science identified studies assessing these techniques for cause-of-death determination. Twelve studies, comprising 145 cases, met inclusion criteria. Putrefaction grading was inconsistently reported. Routine hematoxylin and eosin staining was frequently non-informative in advanced decomposition, whereas selected special stains and targeted IHC markers retained diagnostic value in specific contexts, including hypoxia, hemorrhage, traumatic brain injury, anaphylaxis, and muscle injury. However, methodological heterogeneity and variable marker selection limited comparability across studies. Overall, histopathological and IHC analyses may provide useful adjunctive information in decomposed bodies, but their diagnostic utility remains selective and context-dependent, requiring cautious integration with macroscopic and ancillary findings.