. 2021 Feb 25;64(2):125–139. doi: 10.1002/mus.27201

TABLE 2.

Conditions in which nerve biopsies are of moderate importance

Suspected diagnosis	When to biopsy?	When diagnosis can be made without biopsy	Biopsy findings	Other diagnostic tools
Amyloid neuropathy	Other tissues not amenable to biopsy or have negative biopsy.	Amyloidosis pathologically demonstrated in other tissue.	Sensitivity: 80% for TTR amyloid and 30%‐100% for AL amyloid	Extraneural biopsy: Amyloidosis obviates need for nerve biopsy. MR Neurography: Peripheral nerve lesions in asymptomatic TTR mutation carriers. Tc‐labeled cardiac scintigraphy: Diagnose cardiac ATTR amyloidosis Skin biopsy: SFN ESC: Early dysautonomia Periumbilical US: Amyloid deposits
SPN	No evidence of extraneural involvement or negative extraneural biopsy.	Probable SPN: Extraneural NCG in context of typical phenotype and evidence of neuroinflammation on CSF studies or MRI.	Sensitivity: 90.5% in one study.	Muscle biopsy: Can improve yield. Granulomas in muscle rules out tuberculoid leprosy. Nerve US and MR neurography: Higher CSA in specific nerves. MR plexus: Enlargement/enhancement of roots, plexus and nerves
IgG4 related perineural disease/neuropathy	Most patients with neuropathy, especially if: Atypical phenotype No tissue evidence of extraneural IgG4 related disorder Poor steroid response	Typical phenotype with tissue evidence of extraneural IgG4 related disorder, raised serum IgG4 levels and responsive to steroids.	No data	Extraneural biopsy: Evidence of IgG4 disorder MRI in IgG4 related perineural disease: Well circumscribed soft tissue perineural mass that is steroid responsive

Suspected diagnosis

When to biopsy?

When diagnosis can be made without biopsy

Biopsy findings

Other diagnostic tools

Amyloid neuropathy

Other tissues not amenable to biopsy or have negative biopsy.

Amyloidosis pathologically demonstrated in other tissue.

Sensitivity: 80% for TTR amyloid and 30%‐100% for AL amyloid

Extraneural biopsy: Amyloidosis obviates need for nerve biopsy.
MR Neurography: Peripheral nerve lesions in asymptomatic TTR mutation carriers.
Tc‐labeled cardiac scintigraphy: Diagnose cardiac ATTR amyloidosis
Skin biopsy: SFN
ESC: Early dysautonomia
Periumbilical US: Amyloid deposits

SPN

No evidence of extraneural involvement or negative extraneural biopsy.

Probable SPN: Extraneural NCG in context of typical phenotype and evidence of neuroinflammation on CSF studies or MRI.

Sensitivity: 90.5% in one study.

Muscle biopsy: Can improve yield. Granulomas in muscle rules out tuberculoid leprosy.
Nerve US and MR neurography: Higher CSA in specific nerves.
MR plexus: Enlargement/enhancement of roots, plexus and nerves

IgG4 related perineural disease/neuropathy

Most patients with neuropathy, especially if:

Atypical phenotype
No tissue evidence of extraneural IgG4 related disorder

Poor steroid response

Typical phenotype with tissue evidence of extraneural IgG4 related disorder, raised serum IgG4 levels and responsive to steroids.

No data

Extraneural biopsy: Evidence of IgG4 disorder
MRI in IgG4 related perineural disease: Well circumscribed soft tissue perineural mass that is steroid responsive

Abbreviations: AL, light chain amyloid; ATTR, amyloid transthyretin; CSF, cerebrospinal fluid; ESC, electrochemical skin conductance; MRI, magnetic resonance imaging; SPN, sarcoid peripheral neuropathy.