Test Catalog

Test Id : SPBX

Epidermal Nerve Fiber Density Consultation, Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Investigation of polyneuropathies

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
SS2PC SpecStain, Grp II, other No, (Bill Only) No
COSPC Consult, Outside Slide No, (Bill Only) No
CUPPC Consult, w/USS Prof No, (Bill Only) No
CRHPC Consult, w/Comp Rvw of His No, (Bill Only) No
MANPC Morph Analysis, Nerve No, (Bill Only) No
LV4RP Level 4 Gross and Microscopic, RB No, (Bill Only) No
CSPPC Consult, w/Slide Prep No, (Bill Only) No
EM Electron Microscopy Yes No
IHPCI IHC Initial No, (Bill Only) No

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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 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 etc.

 

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.

 

See Pathology Consultation Ordering Algorithm in Special Instructions.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Calculation of Epidermal Nerve Fiber Density

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Epidermal Nerve Fiber Density

Aliases
Lists additional common names for a test, as an aid in searching

ENDF

SPBX

Polyneuropathy

Skin punch biopsy

Small fiber neuropathy

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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 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 etc.

 

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.

 

See Pathology Consultation Ordering Algorithm in Special Instructions.

Specimen Type
Describes the specimen type validated for testing

Varies

Necessary Information

Neurology Clinical Notes information is required on Epidermal Nerve Fiber Density Patient Information (T702) in Special Instructions.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

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

Preferred:

Specimen Type: Skin punch biopsy tissue

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) in Special Instructions.

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

 

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

Epidermal Nerve Fiber Density Patient Information (T702) is required, see Special Instructions.

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

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

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Refrigerated (preferred)
Ambient

Useful For
Suggests clinical disorders or settings where the test may be helpful

Investigation of polyneuropathies

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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 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 etc.

 

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.

 

See Pathology Consultation Ordering Algorithm in Special Instructions.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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 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)

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

A consultative report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

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.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Poor fixation, orientation, and improper handling of the tissue may hinder the neuromuscular pathologist's interpretation of the biopsy. See Epidermal Nerve Fiber Density Instructions in Special Instructions.

Supportive Data

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)

Clinical Reference
Recommendations for in-depth reading of a clinical nature

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

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

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.(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; Landowski LM, Dyck PJ, 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)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

12 to 20 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Slides and blocks: Indefinitely

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

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)

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
SPBX Epidermal Nerve Fiber Density In Process
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
601780 Interpretation 59465-5
601791 Participated in the Interpretation No LOINC Needed
601792 Report electronically signed by 19139-5
601793 Addendum 35265-8
601794 Gross Description 22634-0
601795 Material Received 81178-6
601824 Case Number 80398-1
601913 Disclaimer 62364-5

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Create a PDF

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