Is mass spectroscopy (MS) of the blood recommended for diagnosing localized amyloidosis?

Mass Spectrometry for Diagnosing Localized Amyloidosis

Mass spectrometry of blood alone is not recommended for diagnosing localized amyloidosis; instead, mass spectrometry of tissue biopsy samples is the gold standard for amyloid typing with 88% sensitivity and 96% specificity. 1, 2

Diagnostic Approach for Amyloidosis

Confirming Amyloid Deposits

• Tissue biopsy with Congo red staining showing characteristic apple-green birefringence under polarized light is required for diagnosis 1, 3
• The affected organ or a surrogate site (abdominal fat, bone marrow, minor salivary glands) should be biopsied 1
• Fine-needle aspiration of abdominal fat is a simple, less-invasive procedure with varying sensitivity depending on amyloid type (84% for AL-CM; 45% for ATTRv-CM; 15% for ATTRwt-CM) 1

Amyloid Typing

• Mass spectrometry-based analysis (LC-MS/MS) of tissue biopsy is the gold standard for amyloid typing 1, 2
• Blood tests alone (including mass spectrometry of blood) are insufficient for diagnosing and typing amyloidosis 1, 3
• Immunohistochemistry or immunogold immunoelectron microscopy can be performed in experienced centers but are less reliable than mass spectrometry 1, 2

Diagnostic Algorithm for Localized Amyloidosis

Step 1: Tissue Biopsy

• Obtain tissue sample from the affected organ 1, 3
• Perform Congo red staining to confirm amyloid deposits 1, 3

Step 2: Amyloid Typing

• Send Congo red positive samples for mass spectrometry (LC-MS/MS) analysis 1, 2
• If LC-MS/MS is not immediately available, samples should be transferred to an experienced reference laboratory 2

Step 3: Exclude Systemic Amyloidosis

• Complete serum studies including serum free light chain assay, serum immunofixation electrophoresis, and urine immunofixation electrophoresis 1, 3
• Bone marrow biopsy to exclude plasma cell dyscrasia 1, 3
• Comprehensive organ assessment to exclude subclinical involvement of other organs 3

Important Considerations

Limitations of Blood Testing

• Blood tests alone cannot diagnose localized amyloidosis 1, 3
• Mass spectrometry of blood is not validated for amyloid typing; tissue biopsy with mass spectrometry is required 1, 2

Common Pitfalls to Avoid

• Misdiagnosing amyloid type, which can lead to inappropriate treatment and harm to the patient 2, 4
• Assuming AL amyloidosis in patients with monoclonal gammopathy without proper typing, as over 10% of patients with monoclonal gammopathy can have ATTR deposits 1, 2
• Relying solely on immunohistochemistry for amyloid typing, which has limitations in specificity and sensitivity compared to mass spectrometry 2, 5
• Failing to perform complete serum and urine studies to exclude systemic AL amyloidosis, even when presentation appears localized 3

Clinical Implications

• Accurate typing is crucial as treatments are type-specific and misdiagnosis can lead to inappropriate, potentially harmful treatment 6, 4
• For suspected AL amyloidosis, collaboration with a hematologist is recommended to guide further evaluation and treatment 1
• For suspected ATTR amyloidosis, DNA mutational analysis is recommended to differentiate between senile (wild-type) and hereditary (variant) forms 2