From the Guidelines
The diagnostic approach for amyloidosis should begin with clinical suspicion based on presenting symptoms, followed by confirmation through tissue biopsy, with the most recent and highest quality study recommending a systematic evaluation including Congo red staining, immunohistochemistry, mass spectrometry, or genetic testing to determine the specific amyloid type 1. When amyloidosis is suspected due to symptoms like unexplained heart failure, proteinuria, peripheral neuropathy, or hepatomegaly, the first step is to obtain tissue samples for histological examination.
- Common biopsy sites include abdominal fat pad, rectum, kidney, heart, or affected organs.
- The gold standard diagnostic test is Congo red staining of affected tissue, which produces characteristic apple-green birefringence under polarized light when amyloid deposits are present.
- After confirming amyloid deposition, determining the specific amyloid type is crucial through:
- Immunohistochemistry
- Mass spectrometry
- Genetic testing Additional workup includes:
- Serum and urine protein electrophoresis
- Free light chain assay
- Cardiac biomarkers (troponin, BNP)
- Echocardiography
- Organ function tests
- Bone marrow biopsy is often performed in suspected AL amyloidosis to evaluate for plasma cell disorders.
- Nuclear medicine scans like technetium pyrophosphate can help differentiate cardiac ATTR from AL amyloidosis, as recommended by the 2023 ACC expert consensus decision pathway on comprehensive multidisciplinary care for the patient with cardiac amyloidosis 1. This comprehensive approach is necessary because treatment differs significantly based on amyloid type, and early diagnosis improves outcomes by allowing intervention before irreversible organ damage occurs, with recent studies emphasizing the importance of accurate diagnosis and timely treatment to reduce morbidity and mortality 1.
From the Research
Diagnostic Approach for Amyloidosis
The diagnostic approach for amyloidosis involves several steps, including:
- Histological proof of amyloid deposits using Congo red stain 2, 3, 4
- Determination of the type of amyloid protein present, which can be done using immunohistochemistry, immunoelectron microscopy, and mass spectrometry 5, 2, 4
- Detection of the precursor protein responsible for the amyloidosis 4
- Clinical evaluation to assess prognosis and guide therapy 6, 4
Diagnostic Techniques
Various diagnostic techniques are used to diagnose amyloidosis, including:
- Congo red stain, which is currently the gold standard for amyloid detection 2
- Immunohistochemistry, which must be performed and interpreted with caution 2
- Immunoelectron microscopy and mass spectrometry, which are new gold standards for molecular subtyping of amyloid deposits 5
- Technetium scintigraphy, which has made noninvasive diagnosis of transthyretin (ATTR) amyloidosis much easier 6
- Serum amyloid P component (SAP) scintigraphy, which helps to show organ involvement and therapy response 4
Biopsy Sites
Various biopsy sites can be used to obtain tissue for diagnosis, including: