What type of amyloidosis is abdominal fat pad biopsy useful for diagnosing?

Abdominal Fat Pad Biopsy Utility in Amyloidosis

Abdominal fat pad biopsy is most useful for diagnosing AL (light chain) amyloidosis, where it demonstrates 76-95% sensitivity, but has poor sensitivity for ATTR amyloidosis (only 15% for wild-type ATTR and 45% for hereditary ATTR), making it an unreliable screening tool for transthyretin-related disease. 1, 2, 3

Diagnostic Performance by Amyloid Type

AL Amyloidosis (Primary)

• Fat pad aspiration shows the highest sensitivity for AL amyloidosis at 76-95%, making it the preferred initial biopsy site for this subtype 1, 2, 3
• When combined with bone marrow biopsy, the diagnostic yield increases to 90% for systemic AL amyloidosis 2
• Immunohistochemical staining on fat pad specimens can identify the specific light chain type (kappa or lambda) in 67.6% of AL cases 2
• The specificity and positive predictive value are both excellent at 92-100%, meaning a positive result is highly reliable 4, 5

ATTR Amyloidosis (Transthyretin)

• Fat pad biopsy has unacceptably low sensitivity for ATTR cardiac amyloidosis: approximately 15% for wild-type (ATTRwt) and 45% for hereditary (ATTRm) 1
• The high false-negative rate (55-85%) makes fat pad biopsy unreliable for excluding ATTR amyloidosis when clinical suspicion remains high 1, 6
• If fat pad biopsy is negative but ATTR is suspected, endomyocardial biopsy or other clinically affected organ biopsy is mandatory 1

AA Amyloidosis (Secondary)

• Fat pad aspiration demonstrates 66% sensitivity for AA (secondary) amyloidosis, which is intermediate between AL and ATTR 3

Clinical Algorithm for Fat Pad Biopsy Use

When to Perform Fat Pad Biopsy

• Primary indication: When monoclonal protein is detected (suggesting AL amyloidosis), fat pad biopsy should be performed as the first-line tissue diagnosis 1
• Consider as initial biopsy in patients with suspected systemic amyloidosis presenting with renal insufficiency, neuropathy, or plasma cell dyscrasia 4
• Can be combined with bone marrow biopsy to simultaneously assess for plasma cell dyscrasia and increase diagnostic yield 2

When NOT to Rely on Fat Pad Biopsy

• Do not use fat pad biopsy as the sole diagnostic test when ATTR cardiac amyloidosis is suspected (especially with negative monoclonal protein screen) 1, 6
• If bone scintigraphy is positive for ATTR and no monoclonal protein is present, fat pad biopsy adds no diagnostic value 1
• When fat pad biopsy is negative but clinical suspicion remains high, proceed directly to biopsy of the clinically affected organ (heart, kidney, nerve) 1, 7

Critical Pitfalls to Avoid

Technical Limitations

• Inadequate sampling occurs in 9-11% of cases, requiring repeat biopsy or alternative site 4, 5
• Pale-staining amyloid fibrils and collagen birefringence can cause false-negative Congo red interpretation 5
• Even with adequate sampling, sensitivity is only 75% overall, meaning 25% of systemic amyloidosis cases will be missed 4

Clinical Decision-Making Errors

• A negative fat pad biopsy does NOT exclude amyloidosis—31-55% of negative cases require follow-up biopsies that ultimately prove positive 4, 8
• In one autopsy series, a patient with systemic AL involving 8 organs had negative fat pad biopsy both antemortem and postmortem, demonstrating that even multi-organ AL can be missed 8
• Physicians often do not consider fat pad results clinically conclusive, with 55% of positive and 31% of negative cases undergoing additional invasive procedures 4

When Monoclonal Protein is Present

• If any monoclonal protein is detected (even MGUS), endomyocardial biopsy is necessary to definitively distinguish AL from ATTR cardiac amyloidosis, as both can coexist and fat pad biopsy cannot reliably differentiate them 1, 6
• Over 10% of patients with monoclonal gammopathy can have ATTR deposits rather than AL, making amyloid typing by mass spectrometry or immunofluorescence essential 6

Optimal Diagnostic Strategy

For suspected AL amyloidosis: Fat pad biopsy combined with bone marrow examination provides 90% sensitivity and should be the first-line approach 2

For suspected ATTR amyloidosis: Bypass fat pad biopsy entirely and proceed with bone scintigraphy (99mTc-PYP/DPD/HMDP) if no monoclonal protein is present, or endomyocardial biopsy if monoclonal protein is detected 1

For negative fat pad with high clinical suspicion: Proceed immediately to biopsy of the clinically affected organ (endomyocardial, renal, nerve, or rectal biopsy) rather than repeating fat pad aspiration 1, 7, 8