Clinical Information

Amyloidosis is a group of hereditary and acquired diseases unified by extracellular tissue deposition of misfolded proteins resulting in end organ damage. Amyloidosis can be a systemic or localized disease. Although many cases of amyloidosis are hereditary, most are acquired as the result of an underlying monoclonal B-cell/plasma cell malignancy, as a phenomenon of aging, or as the result of long-standing chronic inflammation. Specific amyloid-related diseases are therefore associated with specific amyloid proteins. These include kappa or lambda immunoglobulin light chains (AL amyloidosis), transthyretin (ATTR amyloidosis), serum amyloid A (AA amyloidosis), and other uncommon subtypes. Because treatment of patients with amyloidosis differs radically for the different amyloid subtypes, it is critically important to accurately identify the proteins that constitute the amyloid deposits.

The basic diagnosis of amyloidosis is typically achieved by Congo red staining of paraffin-embedded tissue biopsy specimens obtained from diverse anatomic sites and demonstrating Congo red-positive, apple-green birefringent, amyloid deposits in the tissues. The next step is to definitively subtype the amyloid deposits. This test fulfills that need. It relies on laser microdissection of Congo red-positive amyloid deposits followed by analysis by liquid chromatography tandem mass spectrometry to accurately determine the identity of the proteins that constitute the amyloid.

Transthyretin amyloidosis is a common form of systemic amyloidosis whose clinicopathologic significance varies significantly depending on the anatomic site of involvement. Although cardiac ATTR deposition is often an indication for disease-modifying therapy, tenosynovial ATTR deposition is considered a potential early marker (risk factor) for subsequent cardiac involvement but does not in itself warrant treatment. Only a minority of patients with tenosynovial ATTR go on to develop cardiac ATTR, and progression, when it occurs, may take many years to decades. Available data suggest that older patients have a higher pretest probability of concurrent cardiac ATTR (median age 77 years, IQR 75-79 years).(1) However, ATTR amyloidosis in other anatomic sites, such as bone marrow, gastrointestinal tract, urinary bladder, prostate, and gallbladder, is a more reliable predictor of concurrent cardiac ATTR amyloidosis.(2-5)