2. Objectives
Recall the structure and anatomy of peripheral nerves.
Understand the types of connective tissue that bundle
axons together.
Describe the clinical features of myasthenia gravis and
indicate which part of the neuromuscular junction the
antibodies are directed against.
Identify gross, histologic, and clinical features of
schwannomas, neurofibromas and malignant peripheral
nerve sheath tumors.
Diagnose neurofibromatosis type 1 and
neurofibromatosis type 2.
4. Peripheral Nerve
Function PNS is divided into somatic (voluntary) and
autonomic (involuntary) components
Somatic Nervous System
Both sensory and motor
Sensory nerves
Dorsal root ganglia
Motor nerves
Anterior (ventral) horn of spinal cord
7. Peripheral Nerve
Structure Somatic sensory function depends on:
Distal nerve endings
Axon that travels to the dorsal root ganglia
Proximal axon that synapses on neurons in spinal
cord or brainstem
Autonomic nerve fibers outnumber somatic fibers in
the PNS, but signs and symptoms are generally not
prominent features of peripheral neuropathies
8. Peripheral Nerve
Structure
Myelinated axons:
One Schwann cell wraps around the axon multiple
times to create the sheath
Separated from the next by a small space = Node of
Ranvier
10. General Types of Peripheral
Nerve Injury
Axonal Neuropathies
Axons are primary target of
damage
Wallerian degeneration
Axons distal to point of
transection degenerate
Axons begin to fragment
and myelin sheaths unravel
Myelin ovoids
Regeneration begins at site
of transection
1mm per day toward distal
target
Thinner and shorter
11. General Types of Peripheral
Nerve Injury
Demyelinating Neuropathies
Schwann cells with myelin
sheaths are primary targets
Axons are preserved
Myelin sheaths degenerate
in random pattern
Schwann cells initiate repair
and form new myelin
sheaths
Shorter and thinner
Slowed nerve conduction
velocity
Giullain-Barre Syndrome
(Acute Inflammatory
Demyelinating Neuropathy)
12. General Types of
Peripheral Nerve Injury
Neuronopathies
Destruction of neurons
Leads to secondary degeneration of axonal
processes
Caused by infections and toxins
Affects proximal and distal parts of the body
13. Anatomic Patterns of
Peripheral Neuropathies
Mononeuropathies
Affect a single nerve
Trauma, entrapment, infections
Polyneuropathies
Symmetrically affects multiple nerves
Deficits start in feet and ascend
Guillain-Barre – “ascending paralysis”
Mononeuritis Multiplex
Damages several nerves in a haphazard fashion
Polyradiculoneuropathies
Affect nerve roots and peripheral nerves
Diffuse symmetric symptoms
Proximal and distal parts of the body
15. Diseases of the NMJ
Antibody mediated
Myasthenia Gravis
Lambert-Eaton Myasthenic Syndrome
Congenital myasthenic syndromes
Disorders caused by toxins
Botulism
Curare
16. Myasthenia Gravis
Autoimmune
Antibodies against postsynaptic acetycholine receptors
Thymic abnormalities
Fluctuating weakness that worsens with exertion and
over the course of the day
Diplopia and ptosis are common
Repeated electrophysiologic stimulation does not
increase muscle response
Acetylcholinesterase inhibitors have reduced mortality
rates
18. Lambert-Eaton
Myasthenic Syndrome Autoimmune
Antibodies block acetylcholine release by inhibiting
a presynaptic calcium channel
Rapid repeated stimulation does increase muscle
response
Muscle strength is improved after a few seconds of
muscle activity
Present with weakness of extremities
In half of cases, there is an underlying
neuroendocrine carcinoma of the lung
Paraneoplastic syndrome
20. Schwannomas
Benign tumors that exhibit Schwann cell
differentiation and often arise directly from
peripheral nerves
Component of NF2
Loss of expression of merlin
Cells hyperproliferate in response to growth factors
22. Schwannomas
Morphology:
Microscopically, consist of areas referred to Antoni A
and Antoni B areas
Recurrence is common if incompletely resected
Malignant transformation is extremely rare
23. Schwannomas
Symptoms from local compression of involved
nerve, brainstem or spinal cord
Within the cranial vault, most occur at the
cerebellopontine angle, attached to the vestibular
branch of the eighth nerve
Present with tinnitus and hearing loss
Surgical removal is curative
25. Neurofibromas
Benign
More heterogeneous than schwannomas
Three growth patterns:
Superficial cutaneous neurofibromas
Pedunculated, isolated or multiple
Diffuse neurofibromas
Plaquelike skin lesion
Plexiform neurofibromas
Deep or superficial
Only type that can undergo malignant transformation
26. Neurofibromas
Schwann cells show complete loss of NF1 gene
product, neurofibromin
Schwann cells are the neoplastic cells
28. Neurofibromas:
Morphology
Diffuse neurofibroma:
Morphologically similar, but distinct growth pattern
from cutaneous neurofibromas
Diffusely infiltrates dermis and subcutaneous tissue
Entrap fat and appendage structures
Produces a plaquelike appearance
Can grow to large sizes
29. Neurofibromas:
Morphology
Plexiform neurofibromas:
Grow within and expand nerve fascicles
Entrap associated axons
Perineurial layer is preserved
Encapsulated appearance
“Bag of worms” = ropy thickening of multiple
fascicles
“Shredded carrot” = collagen bundles
30. Malignant Peripheral Nerve
Sheath Tumors (MPNST)
85% high grade
Half arise in NF1 patients
Malignant transformation of plexiform neurofibroma
31. MPNST Morphology
Poorly defined
Infiltrate parent nerve
Invade adjacent soft tissues
Fasciculated arrangement of spindle cells
Appears “marbleized” at low power due to variations in
cellularity
Can undergo “divergent differentiation”
Triton tumor
Distinction from undifferentiated sarcoma may be difficult
32. Neurofibromatosis Type
1 Systemic disease
1 in 3000
Non-neoplastic manifestations and a variety of tumors
Neurofibromas (all types)
MPNSTs
Gliomas of optic nerves
Other glial tumors and hamartomatous lesions
Pheochromocytomas
NF1 loss-of-function mutations
Encodes tumor suppressor neurofibromin
34. Neurofibromatosis Type 2
Results in a range of tumors
Bilateral eighth-nerve schwannomas
Multiple meningiomas
Also, gliomas, typically ependymomas of spinal cord
Non-neoplastic lesions
Much less common than NF1
37. Question 3
Myasthenia Gravis characteristically has antibodies
directed against:
A. Presynaptic calcium channels to block
acetylcholine release
B. Presynaptic acetylcholine receptors
C. Postsynaptic acetylcholine receptors
D. Presynaptic neurons to block acetylcholine
release
38. Question 4
What peripheral nerve sheath tumor is described as
a benign well-circumscribed, encapsulated, gray
mass that abuts the nerve without invading it?
39. Question 5
What type of neurofibroma can undergo malignant
transformation?
45. Bibliography
Kumar, Vinay, Abul K. Abbas, Jon C. Aster, and James A. Perkins. Robbins
and Cotran Pathologic Basis of Disease. 9th ed. Philadelphia, PA: Elsevier,
2015. 1227-49. Print.
Motor Unit Image:
https://www.google.com/search?q=motor+unit&espv=2&biw=977&bih=783&so
urce=lnms&tbm=isch&sa=X&ved=0CAYQ_AUoAWoVChMIv5SaoILixgIV0LeA
Ch1XUgg8#imgrc=xLKxBnBz64HvRM%3A
Peripheral Nerve Structure:
http://www.quia.com/files/quia/users/lmcgee/Systems/endocrine-
nervous/neuronstructure2_L.gif
Axon Connective Tissue:
http://www.muskingum.edu/~asantas/Biology%20228/Chapter14_spinalcord_p
art2_files/slide0060_image010.jpg
Myasthenia Gravis: http://www.beverlydoc.com/wp-
content/uploads/2014/01/Myasthenia-Gravis.jpg
