DiseasesMuscleAcquired1.ppt

7/30/2019 DiseasesMuscleAcquired1.ppt

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David Lacomis, MD

Acquired

Diseases ofMuscle:

Histologic Features


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Organization of Skeletal Muscle IncludingConnective Tissue (CT) Compartments

EPIMYSIUM

Loose CT

Blood vessels

PERIMYSIUMSepta

Nerve branchesMuscle spindles

Fat

Blood vessels

ENDOMYSIUM

Muscle fibers

Capillaries

Small nervefibers


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Perimysial

connective tissue

Endomysialconnective tissue

Normal H&E-stained frozen cross-section of skeletal muscle

Note uniform sizes, polygonal shapes, and eccentric nuclei.


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Normal H&E-stained longitudinal paraffin section

Note the banding pattern.

Nuclei are eccentrically placed.


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Spindle

Nerve Twig

Normal Structures: Muscle Spindleand Associated Nerve FibersGomori trichrome


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Can be identified by the esterase reaction

due to the presence of acetylcholinesterase.

Neuromuscular Junctions


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Neuromuscular JunctionElectron Microscopy

postsynaptic

presynaptic


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Histochemical Staining IntensityBased on Fiber TypesType I

Slow twitch,

oxidative; stain

dark with Gomoritrichrome, NADH,

SDH, and ATPase

at acidic pH; more

lipid than type II

NADH = nicotinamide adenine dehydrogenase

SDH = succinic dehydrogenase

ATPase = adenosine triphosphatase

Type IIB

Intermediate

staining intensity

with ATPase pH4.6

Type II

Fast twitch,

glycolytic; stain

dark with ATPaseat alkaline pH and

with PAS stains, as

well as

phosphorylase


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Type I fibers are light

Type II fibers are dark

Normal ATPase pH 9.4


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Ultrastructure of a Sarcomere

Extends from Z-band to Z-band.

Note arrangement of thick and thin filaments.

Z ZM

H band

Actin

Myosin I bandI band

A band

A band includes overlap of actin & myosin.


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Dark A-

bands

Light I-

bands

Z-band is

present inthe middle

of the light

band

Thinfilaments

are

attached

at the Z-

band

Normal electron microscopy


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Classification of MyopathiesACQUIRED INHERITED

Inflammatory Myopathies Dystrophies

Polymositis (PM) Dystrophinopathies

Dermatomyositis (DM) Limb-GirdleInclusion body myositis (IBM) Myotonic

Granulomatous myositis Facioscapulohumeral (FSHD)

Infectious myositis Oculopharyngeal (OPD)

Toxic DistalEndocrine Congenital

Metabolic

Mitochondrial

Glycogen & lipid storage


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PolymyositisLongitudinal paraffin-embedded section

Mononuclear inflammatory cell infiltrates and

many basophilic regenerating fibers


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PolymyositisLongitudinal 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


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As regeneration advances, a myotube bridge is formed.

PolymyositisLongitudinal paraffin-embedded section (higher power)


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MyophagocytosisEsterase stain

Macrophages are ingesting the remnants of a degenerating

fiber. This is a non-specific myopathic finding.


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Invasion of a Non-necrotic Fiber byInflammatory Cells


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Mononuclear cells surround a non-necrotic fiber thatabnormally expresses MHC-1.

Seen in polymyositis and inclusion body myositis as

well as dystrophies (rarely).

MHC-1


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CD8

Inflammatory infiltrate in polymyositis is endomysialpredominantly of the cytotoxic T-cell type.


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Dermatomyositis

Perifascicular atrophy

Degeneration

Inflammatory cells in the perimysiumsurrounding a blood vessel

Inflammatory cells tend to be B-cells.


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DermatomyositisATPase

Perifasicular atrophy and patchy staining

?? # of ATPase ??


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The perifascicular fibers may have an abnormal

purplish appearance with Gomori trichrome.


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Perifascicular AtrophyNADH-reacted section


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Dermatomyositis


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Dermatomyositis

B-cell


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DermatomyositisCD4


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DermatomyositisCD8


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Dermatomyositis Inflammatory Infiltrate in Skin


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MAC is the terminal component of the complement pathway.

It is often deposited in capillaries in dermatomyositis.

Membrane Attack Complex (MAC)Immunohistochemical stain


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Membrane Attack Complex (MAC)Immunohistochemical stain

Increased staining in capillaries in patients

with dermatomyositis

Degenerating fibers may also stain.


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DermatomyositisElectron microscopy

Tubuloreticular inclusion in a capillary endothelial cell


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Invaded fiber

Features of chronic myopathy with endomysial inflammationand rimmed vacuoles are characteristic.

Inclusion Body Myositis (IBM)


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Lymphocytic inflammation

Rimmed vacuoles


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Rimmed vacuoles may be slit-like


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IBM: Vacuoles contain amyloid.

Congo Red


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IBM: Vacuoles


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Vacuoles are difficult to identify in paraffin sections, butthey may be highlighted by immunohistochemistry against

the heat shock protein Ubiquitin.


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IBM Eosinophilic Inclusion (Cytoid Body)Electron microscopy


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IBM Intracytoplasmic (Within Vacuoles) orIntranuclear Filamentous Inclusions


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Pyomyositis Gram Positive Cocci


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Granulomatous Myositisin a Patient with Sarciodosis

Granulomas tend not to cause significant

damage to adjacent myofibers.

Giant cell

See picture Granuloma 1


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Parasites: Trichinella spiralis


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Characteristic of most

Endocrine Disturbance Type II Fiber AtrophyATPase pH9.4


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Inherited PolyneuropathyChronic Neurogenic Atrophy

Groups of angulated atrophic fibers

Marked variation in myofiber size


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Acute DenervationNADH reaction

Manifested by small, darkly staining angulated fibers


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Denervated fibers also stain darkly with

non-specific esterase.

DenervationEsterase Stain


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Target fibers noted.

Light center surrounded by a darker rim.

Generally only seen in type I fibers.

Chronic Neurogenic ProcessesNADH reaction


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Fiber type grouping

Chronic Neurogenic AtrophyATPase reaction

Werdnig-Hoffman Disease


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(Spinal Muscular Atrophy Type I)


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Werdnig-Hoffman Disease(Spinal Muscular Atrophy Type I)

Werdnig-Hoffman Disease


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Denervated fibers are atrophic but round.

(Spinal Muscular Atrophy Type I)

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DiseasesMuscleAcquired1.ppt