Test Id : SPBX

A battery of enzyme histochemical stains or immunostains are performed; other tests can be performed, as indicated, at an additional charge.

Wet tissue for consultation: When adequately prepared tissue is provided, routine testing will include PGP 9.5 (protein gene product 9.5) immunostain, morphometric analysis, Congo red stain, and hematoxylin and eosin stain. PGP 9.5 reactions cannot be done on previously embedded tissue, eg, paraffin blocks, epoxy blocks.

Slides and blocks sent for consultation must include PGP 9.5-reacted sections:

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.

For more information see Pathology Consultation Ordering Algorithm.

Transport specimen per instructions on the Epidermal Nerve Fiber Density Instructions (T703).

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.

Preferred:

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 (T703)

Specimen Stability: Refrigerated (preferred)/Ambient

Acceptable:

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 Stability: Ambient (preferred)/Refrigerated

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.

Specimen Stability: Ambient (preferred)/Refrigerated

• Epidermal Nerve Fiber Density Patient Information
• Epidermal Nerve Fiber Density Instructions
• Pathology Consultation Ordering Algorithm

Epidermal Nerve Fiber Density Patient Information (T702) is required.

Investigating polyneuropathies

A battery of enzyme histochemical stains or immunostains are performed; other tests can be performed, as indicated, at an additional charge.

Wet tissue for consultation: When adequately prepared tissue is provided, routine testing will include PGP 9.5 (protein gene product 9.5) immunostain, morphometric analysis, Congo red stain, and hematoxylin and eosin stain. PGP 9.5 reactions cannot be done on previously embedded tissue, eg, paraffin blocks, epoxy blocks.

Slides and blocks sent for consultation must include PGP 9.5-reacted sections:

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.

For more information see Pathology Consultation Ordering Algorithm.

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)

An interpretive report will be provided.

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.

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.

Investigators at Mayo Clinic (Bolton, Winkelmann, Dyck) did previous work on cutaneous receptors preceding the recent work on intraepidermal nerve fiber densities. With recent findings, PJ Dyck and colleagues have developed the technique to national standards.(7)

1. Lauria G, Lombardi R, Camozzi F, Devigili G: Skin biopsy for the diagnosis of peripheral neuropathy. Histopathology. 2009 Feb;54(3):273-285

2. McArthur JC, Stocks EA, Hauer P, Cornblath DR, Griffin JW: Epidermal nerve fiber density: normative reference range and diagnostic efficiency. Arch Neurol. 1998 Dec;55(12):1513-1520

3. Goransson LG, Mellgren SI, Lindal S, Omdal R: The effect of age and gender on epidermal nerve fiber density. Neurology. 2004 Mar 9;62(5):774-777

4. Umapathi T, Tan WL, Tan NCK, Chan YH: Determinants of epidermal nerve fiber density in normal individuals. Muscle Nerve. 2006 Jun;33(6):742-746

5. Lauria G, Cornblath DR, Johansson O, et al: EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy. Eur J Neurol. 2005 Oct;12(10):747-758

6. England JD, Gronseth GS, Franklin G, et al: Practice parameter: evaluation of distal symmetric polyneuropathy: role of autonomic testing, nerve biopsy, and skin biopsy (an evidence-based review). Report of the American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Academy of Physical Medicine and Rehabilitation. Neurology. 2009 Jan 13;72(2):177-184

7. Engelstad JK, Taylor SW, Witt LV, et al: Epidermal nerve fibers: confidence intervals and continuous measures with nerve conduction. Neurology. 2012 Nov 27;79(22):2187-2193

8. England JD, Gronseth GS, Franklin G, et al: Evaluation of distal symmetric polyneuropathy: the role of autonomic testing, nerve biopsy, and skin biopsy (an evidence-based review). Muscle Nerve. 2009 Jan;39(1):106-115

9. Landowski LM, Dyck PJB, Engelstad J, Taylor BV: Axonopathy in peripheral neuropathies: Mechanisms and therapeutic approaches for regeneration. J Chem Neuroanat. 2016 Oct;76(Pt A):19-27. doi: 10.1016/j.jchemneu.2016.04.006)

• Epidermal Nerve Fiber Density Patient Information
• Epidermal Nerve Fiber Density Instructions
• Pathology Consultation Ordering Algorithm

Immunohistochemical preparations are prepared using standard immunohistochemical techniques for PGP 9.5.(5) Using light microscopy, epidermal nerve fiber density is counted from PGP 9.5-reactive sections. Hematoxylin- and-eosin and Congo red stains are also reviewed.(Unpublished Mayo method)

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This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

88305 (if appropriate)

88313 (if appropriate)

88321 (if appropriate)

88323 (if appropriate)

88323-26 (if appropriate)

88325 (if appropriate)

88348 (if appropriate)

88356 (if appropriate)

88342 (if appropriate)

Sample Reports

Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports

International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports