Commonly used special stains and immunostains in liver pathology: diagnostic utility and pitfalls

Despite advances in molecular diagnostics, histochemical and immunohistochemical (IHC) stains remain essential adjuncts in liver pathology, providing critical information for fibrosis assessment, evaluation of metabolic and cholestatic disorders and classification of hepatic neoplasms. This review offers a practical, integrated overview of commonly used special stains and IHC markers in daily practice, emphasising their underlying principles, diagnostic utility and context-dependent limitations. Key histochemical stains—including trichrome, reticulin, Prussian blue, periodic acid–Schiff with diastase, copper stains and orcein—are discussed alongside the IHC markers commonly used to recognise hepatocellular and biliary differentiation, distinguish benign from malignant hepatocellular lesions, classify tumours and subtype hepatocellular adenomas. For each stain, relevant technical considerations and diagnostic applications are presented with a focus on real-world interpretation, common pitfalls, sources of variability and unintended diagnostic insights. Special stains and immunostains are indispensable tools in diagnostic liver pathology, yet each has limitations and none is diagnostic in isolation. They are best deployed in a context-driven manner, with results always interpreted alongside morphology, clinical context and other ancillary studies.