26542 Epidermal Nerve Fiber Density Consultation, Varies (SPBX)

​ENDF

SPBX

Polyneuropathy

Skin punch biopsy

Small fiber neuropathy

​Investigating polyneuropathies

Specimen Type: Skin punch biopsy tissue

Supplies: A Skin Punch Biopsy Kit containing fixatives, buffer, and cryoprotectant is required (no substitutions accepted). For ordering information, call 507-284-8065.

Preferred source: Distal leg, mid-thigh, dorsal foot, and lower abdomen

Collection Instructions:​

1. The standard biopsy for evaluating distal small fiber sensory neuropathy includes two 3-mm skin punch biopsies from the same side of the body.

2. Prepare and transport specimen per instructions on the Epidermal Nerve Fiber Density Instructions, available on the Mayo Clinic Laboratories website page (T703).

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Specimen Type: Slides

Additional Information:

1. Slides reacted with PGP 9.5, using a PGP 9.5 protocol for visualizing epidermal nerve fibers, are required.

2. Hematoxylin and eosin-stained slides and Congo red-stained slides are optional.

Specimen Type: Tissue block and PGP9.5-reacted slides

Additional Information:

1. Slides reacted with PGP 9.5, using a PGP 9.5 protocol for visualizing epidermal nerve fibers, are required.​.

2. Tissue block may be used to create hematoxylin and eosin-stained slides and Congo red-stained slides.

Note: Visualization of epidermal nerve fibers cannot be done on paraffin blocks.

SHIPPING INSTRUCTIONS:

Transport specimen per instructions on the Epidermal Nerve Fiber Density Instructions, available on the Mayo Clinic Laboratories website page (T703).

NECESSARY INFORMATION​.

The following information is required:

1. Epidermal Nerve Fiber Density Patient Information (T702) is required, containing the following information:

-Patient name and date of birth

-Name and phone number of the referring pathologist or ordering physician​.

-Anatomic site and collection date

2. Additional clinical information:

-Clinical notes

-Nerve Conduction Studies/Electromyography results, if performed

All requisition and supporting information must be submitted in English.

Special stains and studies performed on the case should be sent with the case for review. In order to determine an accurate diagnosis, some of these stains or studies may be deemed to warrant repeat testing, at an additional charge, at the discretion of the reviewing Mayo Clinic neuromuscular pathologist. In addition, testing requested by the referring physician (immunostains, molecular studies, etc) may not be performed if deemed unnecessary by the reviewing Mayo Clinic neuromuscular pathologist. For all consultations, ancillary testing necessary to determine a diagnosis is ordered at the discretion of the Mayo Clinic neuromuscular pathologist. An interpretation, which includes an evaluation of the specimen and determination of a diagnosis, will be provided within a formal pathology report.​

​All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

​Poor fixation, orientation, and improper handling of the tissue may hinder the neuromuscular pathologist's interpretation of the biopsy. For more information see Epidermal Nerve Fiber Density Instructions.

Small fiber peripheral neuropathy is a common neurological complaint and a frequent source of morbidity in many patient populations. Direct investigation of small fiber involvement has been limited as most classical techniques (eg, electromyography, nerve conduction studies, and nerve biopsy) focus on large diameter nerve fibers and may be normal in patients with small fiber neuropathies.

The advent of epidermal skin biopsies and PGP 9.5 (protein gene product 9.5) immunohistochemistry allows the direct visualization and morphologic assessment of small sensory fibers innervating the skin.(1) Assessment of intraepidermal nerve fiber density has been used to reliably demonstrate pathologic abnormalities in small fiber neuropathy of various etiologies including diabetes, HIV, systemic lupus erythematosus, and neurosarcoidosis. Further, the technique has been validated, shown to have acceptable sensitivity and specificity, and is minimally invasive. The publication of normative data for commonly tested sites such as the distal and proximal legs and arms permits direct comparison of patients to age- and sex-matched controls facilitating localization and diagnosis.(2-4)

Based on class 1 evidence and American Medical Association CPT code review process acceptance, intraepidermal nerve fiber density (IENFD) measurements are now an accepted investigational method in the workup of polyneuropathy, including the characterization and diagnosis of varieties of length-dependent small fiber polyneuropathies. IEFND measurements have been incorporated in recent practice guidelines published by the American Academy of Neurology and the European Federation of Neurological Science.(5,6)

​The number of intraepidermally originating nerve fibers that cross the basement membrane between the dermis and epidermis are counted in several sections.(2,5) The total linear length of the epidermis is measured using standard morphometric techniques and a density of epidermal nerve fibers (number of fibers/mm) is reported. This value is compared to previously published normative data.