Diagnosis and typing of systemic amyloidosis: The role of abdominal fat pad fine needle aspiration biopsy

Abstract

Introduction:Systemic amyloidosis (SA) has a broad nonspecific clinical presentation. Its diagnosis depends on identifying amyloid in tissues. Abdominal fat pad fine needle aspiration (FPFNA) has been suggested as a sensitive and specific test for diagnosing SA.Materials and Methods:Thirty-nine FPFNA from 38 patients (16 women and 20 men, age range 40–88 years) during a 15-year period were reviewed. Smears and cell blocks were stained with Congo red (CR). A panel of antibodies (serum amyloid protein, serum amyloid A, albumin, transthyretin, kappa light chain and lambda light chain) was used on six cell blocks from five patients. The FNA findings were correlated with clinical and histological follow-up.Results:FPFNAs were positive, confirmed by CR in 5/39 (13%), suspicious in 1/39 (3%), negative in 28/39 (72%), and insufficient for diagnosis in 5/39 (13%) of cases. In all the positive cases, SA was confirmed within 2–16 weeks. Among the 28 negative cases, SA was diagnosed in 21, the rest were lost to follow-up. Among the insufficient cases, SA was diagnosed in four and one was lost to follow-up. Specificity was 100%, whereas sensitivity was 19%. SA typing using cell block sections was successful in three, un-interpretable in one, and negative in two cases.Conclusion:FPFNA for SA is not as good as previously reported. This may be due to different practice setting, level of experience, diagnostic technique, or absence of abdominal soft tissue involvement. A negative result of FPFNA does not exclude SA. Immune phenotyping of amyloid is possible on cell block.

Genotype and Phenotype of Transthyretin Cardiac Amyloidosis

“…Amyloidosis, at present, remains a pathologic diagnosis and, as demonstrated by these data, various tissues are often obtained to confirm the diagnosis. Unfortunately, the most accessible tissue (fat pad) has an unacceptably low sensitivity for establishing this potentially fatal diagnosis (23,24) and EMB, the gold standard for diagnosis, is not widely available and requires specialized expertise and techniques for adequate interpretation. With the emergence of potentially disease-modifying therapies, including TTR stabilizers (25,26) and TTR silencers (27,28), the need for early diagnosis is clear given that these therapies are designed to reduce further deposition but not address the effect of already deposited amyloid.…”

Diagnosis of secondary amyloidosis in alkaptonuria

“…Quantification of SAA concentration in tissue on regular occasions will similarly reflect the accumulation, stabilization or even regression of deposited amyloid. Abdominal subcutaneous fat tissue seems to be very suitable for this purpose [ 17 , 22 ], because it is easy to obtain by aspiration, but, at least in some cases, it has limited sensitivity and turned out inadequate [ 23 - 25 ]. In fact, subcutaneous abdominal fat CR staining is positive in approximately 80% of patients with AL amyloidosis and less than 65% of patients with AA amyloidosis [ 24 ].…”

Confirming the Diagnosis of Amyloidosis

“…As such, use of a large-bore needle is recommended (e.g., 16 G) and aspiration should be performed at multiple sites on the abdominal wall if required [18]. The high diagnostic sensitivity for ASFA has often been reported by specialised amyloidosis centres [20, 21] and may be difficult to achieve in non-specialist settings [22]. As such, collaboration between the clinician and the pathology service is required before this technique is put into practice.…”