Procedure and interpretation

1. Interpretation of Nerve Biopsy
by Dr. Sweta Biswas Das
3rd year PGT student
Department of Pathology

2. INTRODUCTION
 Each peripheral nerve
composed of one or more
bundles (fascicles)
 Each nerve fibre
surrounded by loose
vascular supporting tissue
endoneurium
 Each fascicle surrounded
by condensed
collagenous tissue
perineurium
 All fascicles are
surrounded by loose
collagenous tissue
epineurium

3. Peripheral nerve in transverse section

4. INDICATION FOR NERVE BIOPSY
 Vasculitic Neuropathy
 Neuropathy Associated
With Infection
 Inflammatory
Demyelinating
Polyneuropathy
 Sarcoid Neuropathy
 Amyloid Neuropathy
 Diabetic Neuropathy
 Toxic induced
neuropathy

5. SELECTING THE NERVE FOR BIOPSY
 Distal lower limbs –Sural nerve or superficial peroneal
nerve
 Upper limbs-Superficial radial nerve or a branch of ulnar
nerve
 Progressive optic neuropathy-Optic nerve biopsy

6. SURAL NERVE BIOPSY
 Easily identifiable .
 Purely sensory – No motor
deficit occur following biopsy.
 Liable to be affected by
neuropathy
 distal branch of a long nerve.

7. PROCESSING OF NERVE BIOPSY
1.5 2 1.5 5 cm
Neutral-buffered formalin 4 % Glutaraldehyde -180°C liquid Nitrogen
Paraffin section Semithin section
Thin section for EM
Frozen section
H&E
Modified trichrome
Congo red
Toluidine blue
Toluidine blue and
basic fuchsin
H&E
Modified trichrome
Congo red
Cresyl-fast-violet

8. Advantages and Disadvantages of tissue Sections
Frozen section Rapid diagnosis
Immunofluorescent studies
Relative ease for preserving
the longitudinal section for
segmental demyelination
Detail of the cells are not
clear
Paraffin section Details of cell and
anatomical structure
Artifact is unavoidable
Semithin section Detection thinly myelinated
fibers
Detection of onion bulb
Detection clustering of
regenerated fibers
Special training
EM section
The only test for the
unmyelineated fibers
Special training

9. STANING
Different stains Staining for
H&E Morphology, Vasculitis, Inflammation,
Myelin ovoids, axonal degeneration
Masson's Trichrome Fibrosis, Hyalinisation,Vessels
Luxol fast blue Myelin
Toluidine Myelin
Congo red Amyloid
IHC EMA ,S100,MBP,PMP22

10. H&E Stain of peripheral nerve

11. Toluidine blue Stain of peripheral nerve

12. TRICHROME STAIN

13. WHAT TO LOOK FOR
 Status of the epineurium including the blood vessels
 Alterations in the perineurium
 Endoneurium oedema
 Density of the large and small myelinated nerve fibers
 Extent of axonal degeneration and atrophy
 Frequency of bands of Bungner and Myelin
degeneration
 Number of macrophages cluster
 Onion bulb formation
 Inflammatory infiltrates
 Presence/absence of amyloid

14. Wallerian degeneration
 Degeneration of axon
distally following its
interruption
 Distal to injury the axon
disintegrates and the myelin
breaks up into globules
 Macrophages participate in
the removal of axonal and
myelin debris
 Approximation of nerve
ends result in regeneration,
the basement membrane
of the schwann cell survives
and acts as skeleton along
which the axon regrows

15. SEGMENTAL DEMYELINATION
 Scattered destruction
of the myelin sheath
occurs without axonal
damage
 The primary lesion
affects the schwann
cell. Prognosis for
recovery is good
because the muscle is
not denervated

16. PERIPHERAL NERVE DAMAGE

17. ONION BULB FORMATION
 Refers to the concentric laminated layers surrounding
the nerve fibre.
 Best detected in the semithin section
 Pathogenetically , onion bulb formation is indication of
repeated demyelination and remyelination

18. ONION BULB FORMATION

19. INFLAMMATORY DEMYELINATING
POLYNEUROPATHY
 Acute- Guillain Barré Syndrome
 Acute onset immune mediated demyelinating
neuropathy
 Weakness beginning in the distal limbs and rapidly
advances to affect proximal muscle function(ascending
paralysis)
 Prior history of viral infection
 Hallmark of inflammatory neuropathy- presence of
inflammatory cells in the endoneural space of the nerve
 Inflammatory cells are primarily responsible for the
macrophage induced demyelination in these neuropathy

20.  Chronic inflammatory Demyelinating Poly
radiculoneuropathy
 Symmetrical mixed sensorimotor polyneuropathy that
persists for more than 2 months
 Evidence of recurrent demyelination and remyelination
associated with proliferation of Schwann cells
,formation of onion bulbs
INFLAMMATORY DEMYELINATING
POLYNEUROPATHY

21. ONION BULB

22. LEPROSY
 M. leprae is the bacterium that invades peripheral
nerve
 Common nerves are
 Ulnar nerve at the elbow
 Deep peroneal branch at the ankle

23. TUBERCULOID LEPROSY
 Pathological hallmark is an intense inflammatory
granulomatous lesion that severely damages the neural
architecture
 Axon ,schwann cells and myelin lost
 Granulomas in the epineural and perineural spaces &
edoneural space.
 Bacilli are scanty ,
 Localized nerve involvement
 Healing –fibrosis and hyalization in the endoneurium
and thick perineurial and epineurial sheaths

24. TUBERCULOID LEPROSY

25. LEPROMATOUS LEPROSY
 Perineural and endoneural infiltration of enlarged
macrophages and Schwann cells with M leprae bacilli
and inflammatory cells.
 In severe cases the epineurium may be infiltrated by
huge numbers of foamy cells especially around blood
vessels.
 Granulomatous inflammatory response minimal.
 Segmental demyelination and remyelination and loss of
both myelinated and unmyelinated axon
 Symmetric polyneuropathy

26. LEPROMATOUS LEPROSY

27. DIABETIC NEUROPATHY
 Ascending distal symmetric sensorimotor
polyneuropathy
 Patients may be both type 1 and type 2
 Nerve biopsy show reduced numbers of axons,
degenerating myelin sheaths and regenerative axonal
clusters,
 Endoneurial arterioles show thickening ,hyalinization

28. Pathophysiology

29. DIABETIC NEUROPATHY

30. VASCULITIC NEUROPATHY
 Predominantly axonal damage
 Perivascular inflammation with active or chronic vessel
damage
 Patchy /multifocal nerve fibre loss
 hemosiderine deposits

31. Vasculitic neuropathy

32. SARCOID NEUROPATHY
 Noncaseating granuloma in the epineurium
 Axonal degeneration
 Numerous myelin ovoids

33. AMYLOID NEUROPATHY
 Neuropathies are usually distally accentuated and
symmetrical, and multiple mono neuropathies may
occur
 Predominantly of axonal type
 Amyloid may be deposited within endoneurium ,and
epineurial vasculature
 Stain-Congo red and Thioflavin S or T

34. AMYLOID NEUROPATHY

35. TOXIC NEUROPATHIES
 Heavy metals( lead , mercury, arsenic, thallium)
 Drugs
 Interfere Axonal transport ,axonal degeneration,

36. CLASSIFICATION OF TWO MAIN CATEGORIES
AXONAL DEGENERATION
 VASCULITIC
 DIABETIC
 TOXIC
 AMYLOID
 SARCOID
DEMYELINATION
 GBS
 CIDP

37. REFERENCES
 Robbins & Cotran Pathologic basic of disease
 Wheaters funtional histology
 The Washington Manual Of Surgical Pathology

38. THANK YOU