Histologic and Clinical Evidence About Rare Cases of Concurrent Transthyretin and Light Chain Amyloidosis

Cardiac amyloidosis (CA) is generally accounted for by 2 subtypes: transthyretin amyloidosis (ATTR) and light chain amyloidosis (AL), which comprise >95% of CA cases. Very infrequently, in some patients ATTR and AL occur concurrently.

In patients who test positive for monoclonal protein and who have significant myocardial uptake on Tc-99m-pyrophosphate (Tc-99m-PYP) scintigraphy, it is critical to use endomyocardial biopsy to accurately determine their CA subtype.

In this case study, the researchers used the rare co-occurrence of ATTR and AL to highlight the importance of a comprehensive CA diagnostic workup that includes the use of endomyocardial biopsy to reconcile conflicting data and make an accurate diagnosis. In a retrospective review of cases from a cardiac amyloid database and review of medical records, 2 endomyocardial biopsy–proven cases of concurrent ATTR and AL were identified.

The first case was an 89-year-old woman who presented with renal failure and heart failure. The second case presented at an outpatient clinic; he was an 85-year-old male who exhibited dyspnea on exertion. In each case, the clinical and imaging parameters were highly suggestive of CA. Very significant grade 3 myocardial uptake on Tc-99m-PYP testing was detected, and these 2 patients were initially suspected to have ATTR. They both also had very high serum-free lambda levels and a lambda-M protein on serum and urine immunofixation, prompting endomyocardial biopsy that confirmed CA. Significant amounts of both AL and ATTR amyloid deposits were revealed via immunochemistry, the results of which (co-deposition of ATTR and AL amyloid fibrils) were confirmed by liquid chromatography tandem mass spectrometry.

Although the diagnosis of simultaneous AL and ATTR in one patient is quite rare, it does happen. The clinical and histologic findings from the 2 patients included in this case study revealed that both types contributed significantly to CA. This case highlights that when clinicians suspect a patient may have CA, a thorough diagnostic workup is critical to confirm the proper subtyping, with the understanding that both types can occur simultaneously.

Source: Donnelly J, Gabrovsek A, Sul L, et al. Clinical and histological evidence of concurrent transthyretin (ATTR) and light chain (AL) cardiac amyloidosis in two patients. Presented at: XVII International Symposium on Amyloidosis 2020; September 14-18, 2020. Abstract PT131.

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