Sensitivity of Nerve and Skin Biopsy and Fat Aspirate for Amyloid in Symptomatic Hereditary ATTR Amyloidosis With Peripheral Neuropathy.

Abstract

The aim of this study was to compare the sensitivity of nerve biopsy, fat aspirate, and skin biopsy in detecting amyloid in symptomatic hereditary transthyretin amyloidosis with peripheral neuropathy (ATTRv-PN). We identified patients with ATTRv-PN (2012-2023) seen at one of the Mayo Clinic 3 sites in Minnesota, Florida, and Arizona. Patients with symptomatic PN confirmed by a neurologist or EMG, who underwent an abdominal fat aspiration, skin biopsy, or nerve biopsy, were included. All patients had a pathogenic <i>TTR</i> variant and either a positive tissue biopsy or a positive pyrophosphate cardiac scintigraphy scan. Demographic, clinical, laboratory, and pathologic data were reviewed. Of the 195 patients with symptomatic ATTRv-PN seen, 111 were included. The median age was 64.2 years (interquartile range 56.9-70.1), and 74.8% were male. Fat aspirate was positive for amyloid in 50 of 103 patients (sensitivity 48.5%, 95% CI 0.39-0.59), skin biopsy in 17 of 32 (sensitivity 53.1%, 95% CI 0.35-0.71), and nerve biopsy in 20 of 21 (sensitivity 95%, 95% CI 0.76-1.0). Skin biopsy yielded a higher sensitivity (60% vs 24%; <i>p</i> = 0.02, n = 25) in patients who underwent skin biopsy and fat aspirate. Nerve biopsies are more sensitive than fat aspirate or skin biopsy for tissue diagnosis in this retrospective cohort of patients with symptomatic ATTRv-PN. Skin biopsy was slightly more sensitive than fat aspirate. This study provides Class IV evidence that a nerve biopsy, fat aspirate, and skin biopsy can accurately diagnose hereditary transthyretin amyloidosis in patients presenting with polyneuropathy. Nerve biopsies are more accurate than fat aspirates or skin biopsies in identifying patients with hereditary transthyretin amyloidosis.