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Expanded teased nerve fibre pathological conditions in disease association
  1. Min Xu1,2,
  2. Marcus Pinto1,
  3. Chenjing Sun1,3,
  4. Janean K Engelstad1,
  5. P James Dyck1,
  6. Peter J Dyck1,
  7. Christopher J Klein1,4
  1. 1 Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA
  2. 2 Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China
  3. 3 Navy Teaching Hospital, Beijing, China
  4. 4 Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
  1. Correspondence to Christopher J Klein, Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA; klein.christopher{at}


Objective To describe an expanded teased nerve fibre classification in disease association.

Methods We reviewed four newly proposed teased nerve fibre types (Types J–M): Type J, rope-like fibres; K, fibril-like clumps of osmium positivity; L, cellular debris along and within nerve fibres; M, circular axonal inclusions surrounded by thin myelin. Different clinical pathological entities were studied for these fibre types including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP: N=20); amyloid polyneuropathy (N=20); intraneural B-cell lymphoma (N=20) or adult-onset polyglucosan body disease (APBD: N=6) in comparison with 112 disease controls. Student’s t-test was used to test significance of association between the identified fibre types and the specific clinical diagnosis.

Results Each fibre type significantly associated (p<0.001) with particular disease categories: Type J, 60% of CIDP cases; Type K, 75% of amyloid cases; Type L, 75% of intraneural lymphoma cases; Type M, 100% of APBD cases. Rarely were these fibres found in the other disease control cases ≤3% of cases. In three cases, the teased fibre findings were so striking additional paraffin nerve preparations were made to make the pathological diagnosis when initial paraffin sections were non-diagnostic.

Conclusions Teased nerve fibre Types J–M associate with commonly seen pathological diagnosis and are helpful in the consideration of specific neuropathy diagnoses.

  • teased fibre
  • biopsy
  • peripheral neuropathy

Statistics from

Teased nerve fibre preparations are labour intensive but noted to have advantage over routine paraffin and epoxy-embedded thin section in sensitivity to see nodal and internodal segments of individual nerve fibres at high resolution.1 2 Early demyelinating features not visible on semithin epoxy preparations are quantifiable by teased fibres.3 Histological classifications of teased nerve fibres help characterise the pathological process, extent and type of nerve injury.1 Earlier classifications described nine types of teased fibres,4 5 Types A–I: (A) normal; (B) excessive myelin wrinkling; (C) demyelination (single or multiple nodal focal segments without myelin of varied length); (D) demyelination (as in C fibres) with remyelination (thin myelin with myelin but being less than 50% of normal thickness); (E) axonal degeneration (ovoids or balls of myelin degeneration); (F) remyelinating fibres (thin myelin less than 50% of surrounding myelin thickness without other features); (G) tomaculae (myelin reduplication with thick myelin between nodal structures); (H) axonal degeneration (myelin ovoids and balls) with remyelination; (I) proximal demyelination with distal axonal degeneration (figure 1).

Figure 1

(Left) Prior classification and examples of teased fibre classifications, Types A-I modified and reproduced with permission.5 (Right) Fibre Types J-M; with the routine histopathological preparations and the specific diagnosis shown. Fibre Type J: The whole length of fibres is uniformly covered by thick layers of collagen and Schwann cells forming a tight “rope-like” structure. The normal myelin and Ranvier’s nodes are not visible. Semi-thin toluidine blue sections show the characteristic onion bulbs appearance from fibroblast proliferation and nerve enlargement with loss of normal Schwann cell architecture in a case of CIDP. Fibre Type K: Patchy amorphous materials stick to fibres with small associated collections of cells. Shown is amyloid deposition in a transthyretin-related hereditary amyloidosis case confirmed by hematoxylin & eosin and Congo red stain confirms amyloid deposition, which appears apple green under polarizing light. Fibre Type L: Teased fibres of right brachial plexus from a large-B cell lymphoma case. Lots of cellular structures adhere tightly to the fibres in a uniform pattern. The nodes of Ranvier are not visible. Immunohistochemical studies show a large mononuclear cell infiltrate in the endoneurium, most of which are positive for a B-cell marker-CD20 (left) and largely negative for the T-cell marker CD8 (right). Fibre Type M: Nerve fibres are enlarged by the round polyglucosan bodies within the axons. Semithin transection sections showing a polyglucosan body containing, focally enlarged axons and the polyglucosan body positive on periodic acidSchiff staining.

When a nerve is sampled systematically through its full thickness, the patterns of teased fibre abnormalities can help quantify the extent and type of nerve injury, and also provide insight into the pathological cause. For example, in sural nerve biopsies with multiple groupings of E-fibres both at early and late stages, vasculitic neuropathy is typical.3 6 G-fibres frequently occur in hereditary neuropathy with pressure palsies from PMP22 deletions, but can also be seen in chronic acquired demyelinating forms.7 The extent of reproducibility of grading teased fibre abnormalities has been commented to be potentially helpful in multicentre clinical trials of neuropathy.8 Teased fibres have greater sensitivity in identifying early demyelinating features versus epoxy semithin sections.

We present four new teased fibre types, expanding the original classification of teased fibres to Types A–M. The four new Fibre Types (J–M) frequently associate with unique clinical entities, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), amyloid neuropathy, intraneural lymphoma and adult onset polyglucosan disease (APBD) and were previously classified as unclassifiable. We investigate the use of expanding the classification to include these fibre types in assistance of making a pathological neuropathy diagnosis.


With institutional review board approval, using our electronic medical record database prior established diagnostic criteria, we identified patients with a clinical electrophysiological diagnosis of CIDP9 (N=20), AL primary (eight cases) or TTR amyloid neuropathy (12 cases) (total N=20),10 peripheral nerve intraneural B-cell lymphoma (N=20)11 or APBD (N=6) enzymatically and/or genetically confirmed to have defect in brancher enzyme.12 All patients had peripheral nerve biopsies including with teased fibre preparations performed within our peripheral service line clinical laboratory.

To assess the specificity of the proposed fibre types (J–M), we also evaluated for the same fibre types in 112 randomly chosen controls that had other or no specific diagnosis. The search was conducted starting at present time going backwards over time until the set accrual numbers were met for disease entities and controls. As part of our routine practice, we sample 100 teased fibres.2 Examiners were blinded to the specific diagnosis in each case, and newly classified (previously listed as unclassified fibres) fibre Types J–M were counted: Type J, thick ‘rope like’ thick widened fibres without nodal structures exhibiting little or no osmium staining; Type K, acellular osmium tetroxide stained positive clumps along the length of the nerve; Type L, multiple cellular structures around and within teased fibres; Type M, large circular axonal inclusions surrounded by thin myelin (figure 1). Student’s t-test was used to test significance of association between the identified fibre types and the specific clinical diagnosis. For the cases where one of these fibre types was found, the available paraffin and epoxy sections were reviewed to ascertain the extent of pathological findings.


The results are summarised in table 1. Significant associations were found between each of the newly classified fibre types and the specific clinical diagnosis studied (p<0.001). These fibre Types J–M were commonly found in cases with the studied specific clinical diagnoses, ranging from 60% in CIDP for Type J to 100% in APBD for Type L. The K fibre types were seen in both AL amyloidosis (seven cases, 88%) and hereditary transthyretin amyloidosis (seven cases, 58%). These fibre types were not or rarely seen in other clinical diagnoses and controls. Fibre Type L appears to be the least specific found in 10% of cases with amyloid and CIDP, but much more commonly in lymphoma cases (75%), and from the control subset we identified one leprosy case with this fibre type. We then searched our database to identify four additional leprosy cases having undergone nerve biopsy and two also had L fibres, that is, 60% of leprosy cases had Type L fibres, with a median of five fibres per case; range, 0–12 (online supplementary figure 1). Fibre Types J–M although frequently associated with a specific clinical diagnosis often had small total numbers from 100 sampled fibres (table 1).

Supplementary data

Table 1

Teased fibre Types J–M in diseases and controls

The routine pathological investigations with paraffin sections and epoxy-embedded samples were then specifically reviewed that had fibre Types J–M, examples in figure. The patients with CIDP with Type J fibres had onion bulbs with collagent replacement of Schwann cell architecture seen on epoxy sections. Patients with Type K fibres and amyloid had amyloid deposits seen on Congo red paraffin staining. Lymphoma cases having Type L fibres had sheet-like collections of CD20-positive B cells, within atypical lymphoid cells diagnostic of B-cell lymphoma. Lastly, frequent polyglucosans (>10 per low-power field) were seen on luxol-fast-blue staining in all cases with Type M fibres characteristic of APBD. The rare control patients where these fibre types were found also underwent re-review of paraffin and epoxy sections, and apart from the leprosy cases mentioned, no other clinical diagnosis was found to link with the specific diagnosis considered here.

Three patients, two with amyloid and one with APBD, had teased fibre changes that suggested the diagnosis when the initial paraffin sections were non-diagnostic. Specifically, suspicion from the teased fibre findings (K-type in the amyloid and M fibre types in the APBD cases) led to additional sections being cut facilitating the interstitial pathological diagnosis.


In this study, we define four new types of teased fibres, demonstrating their strong association with specific pathological diagnoses: Type J with CIDP, Type K with amyloid, Type L with lymphoma and leprosy, and Type M with APBD. In Type K and L fibres, the underlying interstitial pathological causes, namely amyloid deposition and lymphomatous cells, are seen within and juxtaposed the fibres. The association of lymphomatous cells in teased fibres had previously been described and shown in one case.13 Additionally, patients have been described with amyloid fibril deposition approximated closely alongside teased fibres, similar to those described here.14 15Our study shows that these teased fibre findings are in fact relatively common in the diagnosis of nerve lymphomatosis and amyloid, occurring in up to 75% of patients when 100 fibres are reviewed in each case. Also, we note with Type M fibres in APBD we saw these in 3% of controls, all of whom were over age 70 years, and reviewed not to have clinical features of APBD, that is, no urinary incontinence, lumbosacral polyradiculopathy or dementia. Importantly, although common in patients, these fibres often represent only a small number of the total fibres studied, and therefore studying an adequate number of fibres is needed not to miss what can associate with a specific diagnosis.

Because our study’s starting point was to identify patients with a specific clinical–pathological diagnosis, we cannot conclude the sensitivity of these teased fibres in the considered diagnoses. However, in three of the studied cases, the teased fibre findings were suggestive enough to lead to request for additional paraffin sections facilitating a specific pathological diagnosis in amyloid and APBD. Therefore, when teased fibre types J-M are found, additional paraffin section sampling should be considered when the clinical history is suspicious for these specific diagnoses and original interstitial sampling is inconclusive. Finding these fibre types should increase the likelihood of the pathological diagnosis and will be helpful to include in the current teased fibre classification.


The authors wish to thank the Society for Support of Neurologic Education and Research for their support of this work.


View Abstract


  • MX and MP contributed equally.

  • Contributors MX, MP, CS, JKE, PJamD, PetJD and CJK were involved in acquisition and interpretation of data. MX and CJK drafted the manuscript and MP, CS, JKE, PJamD and PetJD provided revisions and edits. JKE prepared the images and edited the captions.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval Mayo Clinic Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data statement We submit an additional image of leprosy case with specific fibre types.

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