When can amyloidosis be conclusively determined to be localized?

Determining Localized Amyloidosis

Amyloidosis can be conclusively determined to be localized only after a comprehensive diagnostic workup has excluded systemic involvement through negative serum and urine immunofixation, absence of clonal plasma cells in bone marrow, and no evidence of multi-organ involvement on imaging and laboratory studies. 1

Diagnostic Criteria for Localized Amyloidosis

• Localized amyloidosis is characterized by amyloid deposition confined to a single organ or tissue, resulting from local synthesis of amyloid protein rather than deposition of proteins produced elsewhere 1, 2
• Positive Congo red staining with apple-green birefringence under polarized microscopy from the affected tissue is required for diagnosis 3
• Negative serum and urine immunofixation electrophoresis (SIFE and UIFE) must be documented to exclude systemic AL amyloidosis 1, 4
• Absence of clonal plasma cell proliferation in bone marrow biopsy is necessary to rule out systemic involvement 5, 1
• No clinical or laboratory evidence of involvement of other organs typically affected in systemic amyloidosis (heart, kidneys, liver, nervous system) 1

Required Diagnostic Workup

• Tissue biopsy with Congo red staining from the affected site showing characteristic apple-green birefringence under polarized light 3
• Typing of amyloid protein using mass spectrometry (preferred method with 88% sensitivity and 96% specificity) or immunohistochemistry to identify the precursor protein 5
• Complete serum studies including:
  • Serum free light chain (sFLC) assay 5, 1
  • Serum immunofixation electrophoresis (SIFE) 5, 1
  • Urine immunofixation electrophoresis (UIFE) 5, 1
• Bone marrow biopsy to exclude plasma cell dyscrasia 5, 1
• Abdominal fat aspiration to screen for systemic amyloid deposits (negative result supports localized disease) 1
• Comprehensive organ assessment to exclude subclinical involvement of other organs:
  • Echocardiography to exclude cardiac involvement 3
  • Renal function tests and proteinuria assessment 5
  • Liver function tests 1
  • Neurological evaluation if clinically indicated 1

Key Distinctions from Systemic Amyloidosis

• Systemic amyloidosis typically affects multiple organs simultaneously, particularly the heart and kidneys 1
• Systemic AL amyloidosis is associated with detectable monoclonal proteins in serum or urine and clonal plasma cells in bone marrow 5, 1
• Systemic amyloidosis requires systemic therapy targeting the underlying protein production, while localized forms often respond to local excision 1, 4
• Long-term follow-up of patients with localized amyloidosis shows they rarely, if ever, progress to systemic disease 2, 4

Common Pitfalls to Avoid

• Failing to perform complete serum and urine studies to exclude systemic AL amyloidosis, even when presentation appears localized 5, 1
• Overlooking subclinical involvement of other organs that may not be clinically apparent at initial presentation 1
• Misdiagnosing amyloid type, which can lead to inappropriate treatment 5
• Assuming AL amyloidosis in patients with monoclonal gammopathy without proper typing, as over 10% of patients with monoclonal gammopathy can have ATTR deposits 5
• Relying solely on serum/urine protein electrophoresis (SPEP/UPEP) without immunofixation, which has lower sensitivity 5

Follow-up Recommendations

• Regular monitoring for potential progression to systemic disease, though this is rare 2, 4
• Periodic reassessment of serum and urine studies to ensure continued absence of monoclonal proteins 1, 4
• Surveillance of the affected organ for local recurrence, as this occurs in approximately 17% of cases 4
• Long-term follow-up is essential, but prognosis is excellent with 10-year survival of 78%, comparable to the general population 4