Non‐cardiac biopsy sites with high frequency of transthyretin amyloidosis

Abstract

Aims Cardiac scintigraphy, a non-invasive technique for diagnosing ATTR cardiac amyloidosis, lacks specificity in patients with concomitant monoclonal gammopathy (up to 40% of cases). For these patients, amyloid type is often established by endomyocardial biopsy (EMB), which has clinical risk. This study aimed to investigate the frequency of ATTR in amyloid-positive tendon/synovium, urinary bladder, and prostate biopsies, sites for which prior biopsy specimens might exist for patients suspected of having cardiac amyloidosis, and, when available, determine the amyloid type concordance rate with other anatomic sites and provide clinical data regarding subsequent development of cardiac amyloidosis. Methods and results We queried our reference laboratory database of 19,298 amyloid specimens from myriad anatomic sites typed by mass spectrometry-based proteomics (LC-MS/MS) to investigate the frequency of ATTR amyloid in tendon/synovium, urinary bladder, and prostate. The amyloid type was ATTR in 104/138 (75.4%) tendon/synovium, 173/ 453 (38.0%) urinary bladder, and 27/81 (33.3%) prostate samples. Of 62 patients with available clinical data, 12 (19%) had bona fide ATTR cardiac amyloidosis prior to/concomitant with the non-cardiac site biopsy. Of the remaining 14 with followup, 8 developed bona fide and 2 probable cardiac amyloidosis; at last follow-up 4 had no evidence of cardiac amyloidosis. Fourteen of 16 patients (87.5%) for whom we typed both non-cardiac and cardiac sites had concordant amyloid types. There were 2 discordant cases (prostate = ASem1/heart = AL and urinary bladder = AL/heart = ATTR); only the latter is potentially clinically consequential. Conclusions In patients suspected of having cardiac amyloidosis based on cardiac scintigraphy, LC-MS/MS typing of Congophilic deposits in pre-existing biopsy specimens from non-cardiac sites may help establish the cardiac amyloid type, obviating the need for EMB. However, if the amyloid type identified in the non-cardiac site is not in keeping with other clinical features, then EMB for typing the cardiac amyloid might be indicated.

Clinical relevance of amyloid in prostate samples: a report on 40 patients

“…The eventual finding and subsequent typing of previously unnoticed Congophilic deposits may help to establish the cardiac amyloid type, obviating the need for EMB. 50 Our observations are consistent with previous reports in the literature 34,41 suggesting that the prostate is a target tissue for TTR-amyloid deposition, and that amyloid deposits can be detected in the prostate before the onset of more threatening involvement such as cardiac amyloidosis. With the growing number of screening biopsies in younger patients, awareness of this finding among pathologists could increase rates of early detection of the disease which, in time, could affect future treatment and management of these patients by multidisciplinary teams.…”

“…In patients suspected of having cardiac amyloidosis based on cardiac scintigraphy, reviewing pre‐existing biopsy specimens from non‐cardiac sites is mandatory. The eventual finding and subsequent typing of previously unnoticed Congophilic deposits may help to establish the cardiac amyloid type, obviating the need for EMB 50 …”