Belgian recommendations for tissue diagnosis of amyloidosis

BACKGROUND: Amyloidosis is a disorder caused by the extracellular deposition of misfolded protein fibrils, leading to organ dysfunction. Diagnosis remains challenging due to non-specific clinical presentations and the diversity of amyloid subtypes. Accurate identification of the amyloid precursor protein is key for prognostication and treatment strategy. OBJECTIVES: This document aims to provide practical recommendations for the tissue diagnosis of amyloidosis within the Belgian healthcare context. It targets clinicians managing amyloidosis patients and pathologists evaluating biopsies with suspected amyloid deposits. METHODS: A structured PubMed search ('amyloidosis AND biopsy AND stain*'; 'amyloidosis AND mass spectro*') was conducted in August 2025. After exclusion of case reports, preclinical studies, and Alzheimer-related articles, 298 publications were reviewed. Recommendations were formulated based on available evidence and discussed among Belgian clinical and pathology experts. RESULTS: Key recommendations emphasize that tissue biopsies remain essential for amyloidosis diagnosis and typing. Congo red staining with birefringence and fluorescence confirmation is required. Immunohistochemistry and immunofluorescence are first-line subtyping tools, while mass spectrometry serves as a reference method when results remain inconclusive. Centralization of complex analyses in experienced centres is encouraged. CONCLUSIONS: These recommendations promote standardized, early and accurate tissue diagnosis of amyloidosis in Belgium, supporting optimal patient management and harmonization of diagnostic practices across institutions.