Non-cardiac biopsy sites with high frequency of transthyretin amyloidosis

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 follow-up, 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.