Clinical History:
This 40-year-old patient underwent sural nerve biopsy to evaluate for a painful mixed large fiber and small fiber axonal neuropathy. The biopsy showed light microscopic features of a chronic active axonopathic process. Neurofilament immunohistochemical stain performed on a FFPE tissue section showed diffuse significant loss of small diameter unmyelinated axons.
What are the structures indicated by arrows in Image #1? Once you identify these you will notice multiple other such structures in the image.
Image #2 is what normal would look like for comparison.
Answer:
Collagen Pockets
Schwann cells seem to like to wrap things. A single myelinating Schwann cell will wrap a single axon with a myelin sheath. This contrasts with non-myelinating Schwann cells (also know as Remak cells) which form a trough or enclosure to hold (ensheath) multiple small diameter unmyelinated axons (see asterisks in Image #2). When the small unmyelinated axons are lost to damage (axonopathy) the non-myelinating Schwann cells wrap bundles of collagen (i.e. collagen pockets are one morphologic sign of axonal loss).
Note the marked decrease in small diameter unmyelinated axons in Image #1 compared to Image #2.
Reference(s) / Additional Reading:
- Ochoa JL. Recognition of unmyelinated fiber disease: morphologic criteria. Muscle & Nerve 1978;1:375–387; PubMed: 233736.
- Harty BL, Monk KR. Unwrapping the unappreciated: recent progress in Remak Schwann cell biology. Curr Opin Neurobiol. 2017 Dec;47:131-137. doi: 10.1016/j.conb.2017.10.003. Epub 2017 Nov 6. PMID: 29096241; PMCID: PMC5963510.
- Carlsen F, Behse F. Three dimensional analysis of Schwann cells associated with unmyelinated nerve fibres in human sural nerve. J Anat. 1980 May;130(Pt 3):545-57. PMID: 7410198; PMCID: PMC1233173.
- Jessen KR, Mirsky R. The repair Schwann cell and its function in regenerating nerves. J Physiol. 2016 Jul 1;594(13):3521-31. doi: 10.1113/JP270874. Epub 2016 Mar 21. PMID: 26864683; PMCID: PMC4929314.
- Feltri ML, Poitelon Y, Previtali SC. How Schwann Cells Sort Axons: New Concepts. Neuroscientist. 2016 Jun;22(3):252-65. doi: 10.1177/1073858415572361. Epub 2015 Feb 16. PMID: 25686621; PMCID: PMC5181106.
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