Sural Nerve Biopsy Assessment by Individual Histologic Preparations: An Observational Cohort Study of 100 Consecutive Cases
Pannathat Soontrapa1, Peter Dyck1, P. James B. Dyck1, JaNean Engelstad1, Jenny Davies1, Shahar Shelly4, W. Scott Harmsen1, Jayawant Mandrekar1, Robert Spinner2, Cristiane Ida3, Christopher Klein1
1Department of Neurology, 2Department of Neurosurgery, 3Department of Laboratory Medicine and Pathology, Mayo Clinic, 4Sheba Medical Center
Objective:
To study sural nerve biopsy utility based on different histopathologic techniques.
Background:
Nerve biopsies in select patients assist neuropathy diagnosis. Systematic study of their value to inform and alter treatment recommendations quantifying the value of separate histologic preparations is lacking in evidence-based practice.
Design/Methods:
Consecutive sural nerve biopsies (50 internal and 50 external referrals) were reviewed. Standard histological preparations plus graded teased nerve fibres (GTNF), immunohistochemistry, and epoxy-semithin morphometric analysis were studied. Nerve fibre and interstitial abnormalities were scored for each preparation by three examiners masked to case identification. Multivariate modeling was used to inform on the best combination of tests vs a gold standard of the full biopsy report plus morphometric analysis. Resulting clinicopathological diagnosis and treatment recommendations were reviewed.
Results:
Paraffin-stained sections best recognized interstitial abnormalities: Epineurial inflammation (n=59); vasculitis with vessel wall destruction (n=14); amyloidosis (n=2); and noncaseating granuloma (n=1). Vasculitic neuropathy associated with GTNF axonal degeneration (79%) with OR 3.8, 95%CI [1.001, 14.7], p=0.04, not significantly seen with the other preparations. Teased fibre abnormalities correlated with clinicopathologic diagnosis in demyelinated fibers in chronic inflammatory demyelinating polyradiculoneuropathy, 80% (8/10); amyloidosis, 50% (1/2); adult-onset polyglucosan disease 100% (1/1). GTNF and paraffin stains significantly correlated with fibre density determined by morphometric analysis (GTNF: OR 9.9, p<0.0001, paraffin: OR 3.8, p=0.03), not significant with semithin epoxy: OR 1.1, p=0.90, or immunohistochemistry: OR 2.4, p=0.18). GTNF combined with paraffin sections had the highest accuracy for predicting clinicopathologic diagnosis and fibre density with 0.86 C-stat prediction versus morphometric analysis. Among internal cases sural biopsy aided clinicopathologic diagnosis: immunotherapy initiation (44%); reduced immunotherapy (18%); and escalated immunotherapy (8%).
Conclusions:
Sural nerve biopsy have high diagnostic utility frequently altering treatment recommendations in select patients. Paraffin stains combined with GTNF provide highest diagnostic utility, confidence, inter-rater reliability, and accuracy for diagnosis. Immunostains and epoxy sections have focused utility.