Muscle Histology

Muscle types

Type I and II.  Based on histochemical reaction for myosin adenosine triphosphatase (ATPase)

Type 1 muscle fibers:  These are slow twitch, fatigue resistant, have slow oxidative metabolism (high number of mitochondria), and low glycolytic activity, stain lightly at alkaline pH (9.4) and darkly at acidic pH (4.6)

Type IIa muscle fibers:  These are fast twitch, intermediate fatigue-resistant, fast oxidative and glycolytic metabolism, stain darkly at alkaline pH (9.4) and lightly at acidic pH (4.6)

Type IIb muscle fibers: 

Type IIc muscle fibers are undifferentiated and embryonic type.  Comprise only 1-2% in adults.

Type 2 muscle atrophy: disuse, cachexia, steroid-induced, myotonia congenita

Type 1 muscle may be preferentially atrophied in myotonic dystrophy type 1.

Muscle staining

Stains

Muscle Histology

Under light microscopy, appears polygonal with visible, but not excessive amount of connective tissue.  There should be no or few inflammatory cells or necrotic muscle fibers.  The distribution of the muscle fiber types is assessed with myofibrillary ATPase at 3 pH: 4.3, 4.6, and 9.4.  Muscle tissue exposed to these different pHs result in muscle fiber displaying distinct staining qualities based upon their biochemical substrate mechanisms.  The checkerboard appearance of different muscle fiber types becomes apparent at 30 weeks.  In normal muscle there is <12% difference in the largest mean fiber diameters between all 3 muscle fiber types.  

Muscle fibers are polygonal in shape. Mean fiber diameter is 16 um @ 1 year and increases by 2 um until age of 5 years, and then 3 um until age 9 years. By 10 years mean diameter ranges 39 - 42 um. Normal adult size  is reached by 15 years with mean diameter range 50 - 73 um depending on the specific muscle seen.

True target: neurogenic disorders

Internalized nuclei vs central nuclei (dystrophic pattern)

In DM, MAC stain is deposited around small blood vessels. In dystrophies like FSHD and dysferlinopathies MAC are reported around the sarcolemma.

In muscular dystrophies muscle fibers are more rounded than polygonal, more contracted and darker. Fibers with big nuclei.

Loss of myosin heavy chains on EM seen in CIM.

Paradigm of chemical energy conversion into mechanical energy within muscle fibers:  Components

Myopathies are logically categorized base on what part of the system is involved.

Muscles to biopsy 

Muscle to biopsy for proximal myopathies:  Biceps brachii, deltoid, triceps brachii, quadriceps.

Muscles to biopsy for distal myopathies:  Forearm extensor muscles, tibialis anterior , gastrocnemius

Pathological analysis of tibialis anterior and gastrocnemius may be confounded by neurogenic changes secondary to asymptomatic lumbosacral radiculopathies or concomitant peripheral neuropathy.

Cervical paraspinal muscles:  Isolated drop head.

Peroneus brevis and superficial fibular nerve biopsy: suspected vasculitis.

Handling muscle biopsy tissue wrapped lightly in saline moistened gauze to prevent overwetting or overdrying and should be immediately sent to pathology lab for processing. Do not put biopsy specimen on saline or fixative. 

Type 1 muscle predominance on biopsy:  Inherited myopathies (centronuclear, reducing bodies, RYR1 mutation, central core, CACNA1S congenital myopathy, CACNA1S congenital myopathy which is allelic to HypoKPP1, malignant hyperthermia, TTPP1), demyelinating neuropathies, CIDP, ACTA1, SBMA, ACTN2, LGMD1A, MYBPC3, PTPLA/HACD1, SECISBP2, SCN4A, SEPN1, STAC3, ZAK.