Histology & Pathology of Skeletal Ms

Clinically sick muscle 

Neuromuscular disease

Systemic (autoimmune) disorders

Treatment related biopsy:

Repeat biopsy:

- Myopathy (inflammatory, metabolic, congenital, muscular dystrophies)

•   - Peripheral nerve damage (Neuropathy) or
• motor neuron disease  

•   - Distinction of an atypical neurogenic
• disorder from a primary myopathy

- The risk of treatment is high enough that the diagnosis should be confirmed before therapy is started (e.g. high dose steroids,       immunosuppressive agents)

-Hunting pathology!

- Or follow up:

  Evaluate efficacy of the treatment

  Atypical presentation of a rare metabolic disorder not ordinarily suspected before biopsy

A genetic testing is available

• No visible prestation in the biopsy:
• Myasthenia gravis: AB block ACh receptor
• Periodic Paralysis: abnormality in the ion channels of the ms fiber
• Endocrine myopathies: features of thyroid, parathyroid and adrenal disorder.

- Immediately after the biopsy

- Preserves integrity of DNA, RNA and proteins (enzymes)

- Study of skeletal muscle pathology relies heavily on cryostat enzyme histochemistry

- GTA – Electron microscopy

- Formaldehyde: Paraffin processing and routine histology

- Neutraldehyde: another way to fix which travel slowly

Morphology of ms fiber pathology; nuclei

polygonal (not elongate)

Minimal size variation

uniformly pink

multi-nucleated and peripheral nuclei (not much endonucleated) 

Endomysium around the fascicle 

Perimysium around multiple fascicle

Spindle fiber: smaller, receive innervation

tendon insertions site:

Refers to damage of Motor neuron (CNS), axon (PNS) or motor end-plates in the skeletal muscle

no anatomic location indication

Primary damage of the muscle (autoimmune, congenital, metabolic)

Biopsy - Angular atrophy: Neurogenic dysfunction axons (neuropathy), neurons (motor neuron disease)

EM - empty sleeves of basement membrane

Morular formation (nuclear clumps

Sharp-angle and small ms fiber

lower motor neuron --> lower extremity or parts

uper motor neuron --> upper extremity and more global

group angular atrophy 

large neuropathies

Hydrolytic enzyme for NMJ

normal: mosaic presentation 

disease: enlarged and atrophy ms with angular presentation

• pH 9.4 type II
• pH 4.6 type I, IIa, IIb
• pH 4.2 type I, IIc

Mosaic Fiber

• Fiber type differentiation
• - Type I fibers: Slow twitch sustained contraction, mitochondria and lipid rich,
• predominant in postural/continually active muscles (Soleus)

•  - Type II fibers (IIA/IIB): Fast twitch,
• glycogen rich (Biceps, Quadriceps, Deltoid)
•  
• -->ATPase: pH acid: type I
•                  pH alkaline type II

The normal profile of the muscle mosaicism depends on:

  - Type of muscle activity

  - Nervous stimulation (motor neuron dependent)

Congenital type fiber predominance

Neurogenic conditions (introducing “grouping”)

sign of chronic reinnervation

• Fiber
• type grouping represents recovering neurogenic damage

grouping

the ms fiber type that is innervated by the dying neuron is now innervated by the adjacent neuron which could be the innervation of another ms fiber type --> grouping of the same type of ms fiber

• ØHereditary myopathic disease:
•   -Duchenne muscular dystrophy
•   - Centronuclear myopathy

ØInflammatory/autoimmune: dermatomyositis, inclusion body myositis

ØMitochondrial Myopathy

• scar tissue that separate the ms fiber 
• loss of normal variation in size

ØIncreased space in peri- & endomysium (scar tissue): Chronicity of the disease

ØIncreased myofiber size variation

ØRound atrophy

ØInternal nucleation

• ØRegen/degen changes: Small fibers with
• abnormal cytoplasmic reactivity and nuclear features (signifies the intensity
• of turn over in the muscle)

• ØInflammatorycells:
•   - Primary lymphohistiocytic
•   - Secondary histiocytic (clean up and repair signal)

regeneration and degeneration in histologic slide

ØDystrophin deficiency

ØChromosome Xp21; Recessive

ØOnset 3 to 5 yrs

• ØWeakness Proximal > Distal
• •Symmetric 
• •Legs & Arms 
• •Most involved muscles: Adductor magnus
• in legs
• •Relatively spared muscles: Gracilis
• & Sartorius

• ØCourse
• •Reduced motor function by 2 to 3
• years
• •Steady decline in strength: After 6
• to 11 years

ØFailure to walk: 9 - 13 years

lacking dystrophy protein (using western blot)

single internal nuclei

perifascicular atrophy

ØClinical rash/cutaneous necrosis

ØSlowly progressive pelvic and femoral weakness

ØChronic inflammation – (T-CD4)

ØMembrane attack complex

Myoinvasion (Lymphocytes attacking muscle fibers): perimesyum attacking 

Lymphohistiocytic: endomesyum attacking

Stain: HE

• Presentation: 
• -Myopathic changes: 
• ØRandom
• myofiber size variation

• ØRound
• atrophy

• ØRegenerating
• / degenerating fibers

• ØMyositis:
• Inflammation

• -neurogenic process:
• ØAngular fiber atrophy

ØMorular formations

Fiber type groupin

Morphology of Fibrosis, nemaline, rods, ragged red fibers, inclusions

rimmed vacuoles

Ragged Red fibers

stain oxidative enzyme NADH, SDH, COX2

NADH can stain RER core, Tub agg in addition to Mt

SDH and COX2 is specific for Mt

Could provide mean for differential dxn

Alkaline phosphatase: generation, microvascular

Acid phosphatase: lysosomes, macrophages

Regenerating muscle fibers

Microvasculature

Immune disease of connective tissue 

Exclude present of Scar tissue

Indicates site of lysomomal activity:

• -Macrophages engaged in phagocytosis
• of dead fibers (degeneration)

-Lysosomal storage disease

• Acid phosphatase – Lysosomal activity:
• Macrophages, degen fibers