Transcript Dermatomyositis

Acquired
Diseases of
Muscle:
Histologic
Features
David Lacomis, MD
Organization of Skeletal Muscle Including
Connective Tissue (CT) Compartments
PERIMYSIUM
•Septa
•Nerve branches
•Muscle spindles
•Fat
•Blood vessels
ENDOMYSIUM
•Muscle fibers
•Capillaries
•Small nerve
fibers
EPIMYSIUM
•Loose CT
•Blood vessels
Normal H&E-stained frozen cross-section of skeletal muscle
Perimysial
connective tissue
Endomysial
connective tissue
Note uniform sizes, polygonal shapes, and eccentric nuclei.
Normal H&E-stained longitudinal paraffin section
 Note the banding pattern.
 Nuclei are eccentrically placed.
Normal Structures: Muscle Spindle
and Associated Nerve Fibers
Gomori trichrome
Spindle
Nerve Twig
Neuromuscular Junctions
 Can be identified by the esterase reaction
due to the presence of acetylcholinesterase.
Neuromuscular Junction
Electron Microscopy
postsynaptic
presynaptic
Histochemical Staining Intensity
Based on Fiber Types
Type I
Slow twitch,
oxidative; stain
dark with Gomori
trichrome, NADH,
SDH, and ATPase
at acidic pH; more
lipid than type II
Type II
Type IIB
Intermediate
Fast twitch,
staining intensity
glycolytic; stain
with ATPase pH4.6
dark with ATPase
at alkaline pH and
with PAS stains, as
well as
phosphorylase
NADH = nicotinamide adenine dehydrogenase
SDH
= succinic dehydrogenase
ATPase = adenosine triphosphatase
Normal ATPase pH 9.4
 Type I fibers are light
 Type II fibers are dark
Ultrastructure of a Sarcomere
Actin
I band
Z
Myosin I band
H band
M
Z
A band
 Extends from Z-band to Z-band.
 A band includes overlap of actin & myosin.
 Note arrangement of thick and thin filaments.
Normal electron microscopy
 Dark Abands
 Light Ibands
 Z-band is
present in
the middle
of the light
band
 Thin
filaments
are
attached
at the Zband
Classification of Myopathies
ACQUIRED
Inflammatory Myopathies
INHERITED
Dystrophies
Polymositis (PM)
Dystrophinopathies
Dermatomyositis (DM)
Limb-Girdle
Inclusion body myositis (IBM)
Myotonic
Granulomatous myositis
Facioscapulohumeral (FSHD)
Infectious myositis
Oculopharyngeal (OPD)
Toxic
Endocrine
Distal
Congenital
Metabolic
Mitochondrial
Glycogen & lipid storage
Polymyositis
Longitudinal paraffin-embedded section
 Mononuclear inflammatory cell infiltrates and
many basophilic regenerating fibers
Polymyositis
Longitudinal paraffin-embedded section (higher power)
 Regenerating fiber (non-specific)
 Fiber is basophilic due to presence of
increased RNA and DNA.
 Activated plump nuclei and prominent nucleoli
Polymyositis
Longitudinal paraffin-embedded section (higher power)
 As regeneration advances, a myotube “bridge” is formed.
Myophagocytosis
Esterase stain
 Macrophages are ingesting the remnants of a degenerating
fiber. This is a non-specific myopathic finding.
Invasion of a Non-necrotic Fiber by
Inflammatory Cells
MHC-1
 Mononuclear cells surround a non-necrotic fiber that
abnormally expresses MHC-1.
 Seen in polymyositis and inclusion body myositis as
well as dystrophies (rarely).
CD8
 Inflammatory infiltrate in polymyositis is endomysial
predominantly of the cytotoxic T-cell type.
Dermatomyositis
 Perifascicular atrophy
 Degeneration
 Inflammatory cells in the perimysium
surrounding a blood vessel
 Inflammatory cells tend to be B-cells.
Dermatomyositis
ATPase
?? # of ATPase ??
 Perifasicular atrophy and patchy staining
 The perifascicular fibers may have an abnormal
purplish appearance with Gomori trichrome.
Perifascicular Atrophy
NADH-reacted section
Dermatomyositis
Dermatomyositis
B-cell
Dermatomyositis
CD4
Dermatomyositis
CD8
Dermatomyositis Inflammatory Infiltrate in Skin
Membrane Attack Complex (MAC)
Immunohistochemical stain
 MAC is the terminal component of the complement pathway.
 It is often deposited in capillaries in dermatomyositis.
Membrane Attack Complex (MAC)
Immunohistochemical stain
 Increased staining in capillaries in patients
with dermatomyositis
 Degenerating fibers may also stain.
Dermatomyositis
Electron microscopy
 Tubuloreticular inclusion in a capillary endothelial cell
Inclusion Body Myositis (IBM)
Invaded fiber
 Features of chronic myopathy with endomysial inflammation
and rimmed vacuoles are characteristic.
Lymphocytic inflammation
“Rimmed vacuoles”
Rimmed vacuoles may be “slit-like”
Congo Red
 IBM: Vacuoles contain amyloid.
IBM: Vacuoles
 Vacuoles are difficult to identify in paraffin sections, but
they may be highlighted by immunohistochemistry against
the heat shock protein Ubiquitin.
IBM Eosinophilic Inclusion (Cytoid Body)
Electron microscopy
IBM Intracytoplasmic (Within Vacuoles) or
Intranuclear Filamentous Inclusions
Pyomyositis Gram Positive Cocci
Granulomatous Myositis
in a Patient with Sarciodosis
Giant cell
See picture Granuloma 1
 Granulomas tend not to cause significant
damage to adjacent myofibers.
Parasites: Trichinella spiralis
Endocrine Disturbance Type II Fiber Atrophy
ATPase pH9.4
 Characteristic of most
Inherited Polyneuropathy
Chronic Neurogenic Atrophy
 Groups of angulated atrophic fibers
 Marked variation in myofiber size
Acute Denervation
NADH reaction
 Manifested by small, darkly staining angulated fibers
Denervation
Esterase Stain
 Denervated fibers also stain darkly
with non-specific esterase.
Chronic Neurogenic Processes
NADH reaction
 Target fibers noted.
 Light center surrounded by a darker rim.
 Generally only seen in type I fibers.
Chronic Neurogenic Atrophy
ATPase reaction
 Fiber type grouping
Werdnig-Hoffman Disease
(Spinal Muscular Atrophy Type I)
Werdnig-Hoffman Disease
(Spinal Muscular Atrophy Type I)
Werdnig-Hoffman Disease
(Spinal Muscular Atrophy Type I)
 Denervated fibers are atrophic but round.
 Interspersed hypertrophic round fibers are usually noted.