Two types of amyloidosis presenting in a single patient: a case series

Abstract

The amyloidoses are a group of disorders with overlapping clinical presentations, characterized by aggregation and tissue deposition of misfolded proteins. The nature and source of the amyloidogenic protein determines therapy, therefore correct subtyping is critical to patient management. We report the clinicopathologic features of nine patients diagnosed with two amyloid types confirmed by liquid chromatography-coupled tandem mass spectrometry. The most common types were transthyrethin ( n = 9) and immunoglobulin-derived ( n = 7). Two patients did not have immunoglobulin-derived amyloidosis despite the presence of a monoclonal gammopathy. Eight patients were diagnosed with two types concurrently, and one patient had an 11-year interval between diagnoses. Histopathological distribution of amyloid was variable with vascular, interstitial, and periosteal deposits seen. Identification of a second type was incidental in seven patients, but led to genetic counselling in one patient and therapy directed at both amyloid subtypes in another. With longer survival of myeloma and AL amyloidosis patients and increasing prevalence of patients with wild-type transthyretin amyloidosis due to an aging population, the phenomenon of two amyloid types in a single patient will be encountered more frequently. In light of revolutionary new therapies for transthyretin amyloidosis (patisiran, tafamidis, and inotersen), recognition of dual amyloid types is highly clinically relevant.

Should the Reporting of Bone Marrow Positivity for Amyloid Be Revised?: A Critical Assessment Based on 66 Biopsies From a Single Institution

“…In our study, in the 2 patients with AA amyloidosis, deposits were limited to the vessel wall; similar findings have been reported in earlier publications. 20,23,24 Of our 2 cases of bone marrow biopsy tissue involvement in ATTR, in one case deposits were limited to the vessel wall, whereas in the other case, deposits were limited to periosseous soft tissue; similar observations were also reported by Sidiqi et al 21 and Wolf et al 23 Our limited experience with 3 cases of ATTR autopsy bone marrow samples (M.M.P., unpublished data, 2019) also showed no evidence of stromal deposits. Unfortunately, in the largest series of bone marrow biopsies in patients with ATTR reported to date, the location of amyloid deposits was not specified.…”

“…The majority of bone marrow pathology reports simply describe the presence or absence of amyloid deposits in the biopsy specimen and do not specify their spatial location. 10,14,[17][18][19][20][21] In rare studies, 10,14,[18][19][20][21] where the presence of amyloid deposits in the bone marrow, vessels, or stroma was described, vascular amyloid deposits were most frequently encountered.…”

Proteomic Analysis for the Diagnosis of Fibrinogen Aα-chain Amyloidosis

“…In conclusion, the diagnosis of AFib amyloidosis may be diagnosed confidently on the basis of the proteomics algorithm reported here, which takes into account the probability-based identity score of FibA compared with that of other potential amyloid proteins, the score relationship between the fibrinogens Aα, Bβ, and γ chains, coverage of the p.449-621 region, and the presence of an amyloidogenic FibA variant. A general amyloidosis diagnostic algorithm has been reported recently 37 . Although algorithms offer an objective approach to amyloid identification, we are of the firm opinion that proteomics results always should be examined in conjunction with clinical details together with the results of immunohistochemistry, genetic results, and clinical biochemistry.…”

Diagnostic amyloid proteomics: experience of the UK National Amyloidosis Centre

“…It is generally accepted that amyloid deposits are associated with a single amyloidogenic protein, although it is common to identify multiple amyloid precursor proteins by proteomics in a single sample. In some cases the amyloid can arise from two precursor proteins [43][44][45][46][47]. For example, in cardiac amyloid samples from elderly patients it is common to identify light chains derived from a monoclonal gammopathy together with TTR arising through age-related deposition of wild-type protein.…”