Abstract
Fat pad biopsies (bx) are routinely used in the diagnostic work-up for AL amyloidosis due to their feasibility and low complication rates. However, given their low sensitivity, variations in methodological procedure, and differences across specialty centers, questions have been raised as to whether target organ bx should be pursued directly to facilitate more timely management. We aimed to evaluate real world diagnostic accuracy of fat pad biopsies at our institution and to assess the time lag between date of diagnosis and the initiation of treatment.We collected baseline and treatment data from our institutional database; identifying patients with systemic AL amyloidosis diagnosed between the years 2011-2022. The time of diagnosis was defined as the date of the first positive bx result and baseline data was collected at that point in time. Descriptive statistics were used for data analysis. We used Kruskal-Wallis H-test to compare time-to-treatment between three groups: fat pad and bone marrow (BM) bx positive, negative fat pad bx but a positive target organ bx, and positive target organ bx without a fat pad bx.Among 416 patients with confirmed systemic AL amyloidosis, 100 underwent a fat pad bx, of which 39 were positive by IHC or mass spectrometry, yielding a sensitivity of 39%. 71 patients underwent a kidney bx diagnostic of AL amyloidosis of whom nine also had a negative fat pad bx. 165 patients underwent a cardiac bx diagnostic of AL amyloidosis of which 33 patients also had a fat pad bx; and only 4 were positive and 29 were negative. 364 patients underwent BM bx of which 93 also had a fat pad bx. Among them, 23 were positive for Congo red on both BM and fat pad bx, while 35 were Congo red positive on BM but negative on fat pad bx. In summary, 36 people had a fat pad bx and BM bx but no target organ bx. 35 people had fat pad negative and target organ positive bx vs 4 who had fat pad and target organ positive. 186 people had a target organ bx with no fat pad bx.Among 226 patients with both valid diagnosis and treatment dates, the median time from diagnosis to initiation of treatment ranged from 11 to 26 days across the three groups. Patients were categorized into three groups. The first group included individuals who underwent both fat pad and BM bx (n = 29), with a median time to treatment of 11 days (IQR 7–34) and a mean of 28.5 days (SD 46). The second group consisted of patients who had a negative fat pad bx but a positive target organ bx (n = 31), showing a median of 24 days (IQR 14–78.5) and a mean of 76.8 days (SD 122). The third group included patients who had a positive target organ bx without a fat pad bx (n = 162), with a median time to treatment of 25.5 days (IQR 8.25–59.2) and a mean of 62.7 days (SD 354). There was no statistically significant difference in time to treatment between groups (H = 4.06, p = 0.13).Interestingly, the sensitivity of fat pad bx in our patient population was significantly lower than what has been reported in the literature. This discrepancy may be attributed to differences in technique or other factors that we aim to explore in future analyses; such as age, BMI, type of proceduralist, type of procedure, bx location, kappa/lambda ratio, number of organs involved, and Mayo stage. We also observed a larger proportion of patients undergoing target organ bx without a prior fat pad bx, likely due to high clinical suspicion and the availability of specialized amyloidosis expertise at our center. These factors play an important role in guiding bx selection for diagnosis.When comparing the timing of treatment initiation, patients with a negative fat pad bx but a positive target organ bx had a mean and median time to treatment of 76.8 and 24 days, respectively. In contrast, those with a positive target organ bx alone had corresponding values of 62.7 and 25.5 days. This small difference suggests that a negative fat pad bx does not cause a clinically or statistically significant delay in treatment; rather, the time required to obtain a target organ bx may account for the delay. Notably, in cases where the fat pad bx was positive, this time was nearly halved, indicating that a positive fat pad result can expedite treatment initiation. Therefore, despite its lower sensitivity, fat-pad bx remains a valuable diagnostic tool due to its feasibility and potential to expedite treatment. We plan to further investigate and compare the complication rates of fat pad versus target organ bx.
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