Limited diagnostic utility of abdominal fat pad biopsy for systemic amyloidosis: A single institution's experience

Abstract Background: As a minimally invasive procedure, abdominal fat pad biopsy is commonly used as an initial diagnostic screening tool in cases of suspected systemic amyloidosis. However, the reported utility of abdominal fat pad biopsies is highly variable in the literature and sample collection methods are not standardized. A clinical suspicion of poor test performance at our 500-bed academic hospital prompted a retrospective review of abdominal fat pad biopsies performed over a period of twenty-seven months. Methods: The laboratory information system was queried for the terms “amyloid”, “fat pad”, and “biopsy” for the period between January 1, 2022 and April 15, 2024. For identified cases, patient charts were reviewed for the indication for biopsy, biopsy results, follow up studies, clinical outcomes, and follow up duration. Tissue volume for each case was calculated based on the maximum tissue volume that could be derived from measurements noted in the gross sample description. For example, the volume of tissue cores was calculated as though the cores were cubic rectangles (using length * diameter * diameter) rather than cylinders (π(diameter/2)2). For quality control, 10 random negative specimens were sent to a reference laboratory for Congo Red staining and pathologic interpretation. Results: Forty-eight biopsies were identified from 47 patients. The average age was 66 ± 11 years and the average follow up duration for confirmed negative biopsies was 24 ± 9 months. Excluding one excisional biopsy, all other biopsies were needle core biopsies that had a median tissue volume of 36 mm3 (average 295 ± 1444 mm3). In terms of indications for biopsy, 18 cases (38%) were for suspected cardiac amyloidosis and 17 (35%) for neuropathy. Patients had a known monoclonal gammopathy in 25 cases (53%). Of the 48 biopsies, 46 (96%) were negative for amyloid by Congo Red and only 2 (4%) were positive. There was 100% agreement for ten random negative cases sent to a reference laboratory for quality control of staining and interpretation. Follow up for the 45 patients with negative fat pad biopsies showed that 10 (22%) had amyloid confirmed in subsequent targeted organ biopsies, of which 6 were AL-type amyloid and 4 were ATTR. Confirmation of the 2 patients with positive fat pad biopsies showed that 1 was positive for AL-type amyloid by mass-spectrometry, while the other was a false positive. Accordingly, the sensitivity of abdominal fat pad biopsy for systemic amyloidosis in our hands was 9%. No relationship between biopsy size, reading pathologist, or the presence monoclonal gammopathy and biopsy results was found. However,patients being evaluated for cardiac amyloidosis were more likely to have false negative fat pad biopsies than those being evaluated for neuropathy. Conclusions: At our institution, abdominal fat pad biopsy showed limited utility in screening patients suspected of having systemic amyloidosis, with only a 9% sensitivity compared to 43% - 91% reported in the literature. Given the wide range of sampled tissue volumes with the vast majority of biopsies yielding tissue volumes less than 100 mm3, far below the recommended 200 mm3 - 700 mm3, we suspect performance can be improved with standardization of the biopsy procedure with minimal tissue submission requirements. We recommend that institutions periodically review the diagnostic performance of abdominal fat pad biopsies to determine if they are meeting expected diagnostic standards.