1. David Lacomis, MD Acquired Diseases of Muscle: Histologic Features

2. Organization of Skeletal Muscle Including Connective Tissue (CT) Compartments EPIMYSIUM Loose CT Blood vessels PERIMYSIUM Septa Nerve branches Muscle spindles Fat Blood vessels ENDOMYSIUM Muscle fibers Capillaries Small nerve fibers

3. Perimysial connective tissue Endomysial connective tissue Normal H&E-stained frozen cross-section of skeletal muscle  Note uniform sizes, polygonal shapes, and eccentric nuclei.

4. Normal H&E-stained longitudinal paraffin section  Note the banding pattern.  Nuclei are eccentrically placed.

5. Spindle Nerve Twig Normal Structures: Muscle Spindle and Associated Nerve Fibers Gomori trichrome

6.  Can be identified by the esterase reaction due to the presence of acetylcholinesterase. Neuromuscular Junctions

7. Neuromuscular Junction Electron Microscopy postsynaptic presynaptic

8. 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 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 ATPase at alkaline pH and with PAS stains, as well as phosphorylase

9.  Type I fibers are light  Type II fibers are dark Normal ATPase pH 9.4

10. Ultrastructure of a Sarcomere  Extends from Z-band to Z-band.  Note arrangement of thick and thin filaments. ZZ M H band Actin Myosin I band A band  A band includes overlap of actin & myosin.

11.  Dark A- bands  Light I- bands  Z-band is present in the middle of the light band  Thin filaments are attached at the Z- band Normal electron microscopy

12. Classification of Myopathies ACQUIREDINHERITED Inflammatory Myopathies Dystrophies  Polymositis (PM)  Dystrophinopathies  Dermatomyositis (DM)  Limb-Girdle  Inclusion body myositis (IBM)  Myotonic  Granulomatous myositis  Facioscapulohumeral (FSHD)  Infectious myositis  Oculopharyngeal (OPD) Toxic  Distal EndocrineCongenital Metabolic  Mitochondrial  Glycogen & lipid storage

13. Polymyositis Longitudinal paraffin-embedded section  Mononuclear inflammatory cell infiltrates and many basophilic regenerating fibers

14. 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

15.  As regeneration advances, a myotube “bridge” is formed. Polymyositis Longitudinal paraffin-embedded section (higher power)

16. Myophagocytosis Esterase stain  Macrophages are ingesting the remnants of a degenerating fiber. This is a non-specific myopathic finding.

17. Invasion of a Non-necrotic Fiber by Inflammatory Cells

18.  Mononuclear cells surround a non-necrotic fiber that abnormally expresses MHC-1.  Seen in polymyositis and inclusion body myositis as well as dystrophies (rarely). MHC-1

19. CD8  Inflammatory infiltrate in polymyositis is endomysial predominantly of the cytotoxic T-cell type.

20. Dermatomyositis  Perifascicular atrophy  Degeneration  Inflammatory cells in the perimysium surrounding a blood vessel  Inflammatory cells tend to be B-cells.

21. DermatomyositisATPase  Perifasicular atrophy and patchy staining ?? # of ATPase ??

22.  The perifascicular fibers may have an abnormal purplish appearance with Gomori trichrome.

23. Perifascicular Atrophy NADH-reacted section

24. Dermatomyositis

25. B-cell

26. Dermatomyositis CD4

27. Dermatomyositis CD8

28. Dermatomyositis Inflammatory Infiltrate in Skin

29.  MAC is the terminal component of the complement pathway.  It is often deposited in capillaries in dermatomyositis. Membrane Attack Complex (MAC) Immunohistochemical stain

30.  Increased staining in capillaries in patients with dermatomyositis  Degenerating fibers may also stain.

31. Dermatomyositis Electron microscopy  Tubuloreticular inclusion in a capillary endothelial cell

32. Invaded fiber  Features of chronic myopathy with endomysial inflammation and rimmed vacuoles are characteristic. Inclusion Body Myositis (IBM)

33. Lymphocytic inflammation “Rimmed vacuoles”

34.  Rimmed vacuoles may be “slit-like”

35.  IBM: Vacuoles contain amyloid. Congo Red

36. IBM: Vacuoles

37.  Vacuoles are difficult to identify in paraffin sections, but they may be highlighted by immunohistochemistry against the heat shock protein Ubiquitin.

38. IBM Eosinophilic Inclusion (Cytoid Body) Electron microscopy

40. IBM Intracytoplasmic (Within Vacuoles) or Intranuclear Filamentous Inclusions

41. Pyomyositis Gram Positive Cocci

42. Granulomatous Myositis in a Patient with Sarciodosis  Granulomas tend not to cause significant damage to adjacent myofibers. Giant cell See picture Granuloma 1

43. Parasites: Trichinella spiralis

44.  Characteristic of most Endocrine Disturbance Type II Fiber Atrophy ATPase pH9.4

45. Inherited Polyneuropathy Chronic Neurogenic Atrophy  Groups of angulated atrophic fibers  Marked variation in myofiber size

46. Acute Denervation NADH reaction  Manifested by small, darkly staining angulated fibers

47.  Denervated fibers also stain darkly with non-specific esterase. Denervation Esterase Stain

48.  Target fibers noted.  Light center surrounded by a darker rim.  Generally only seen in type I fibers. Chronic Neurogenic Processes NADH reaction

49.  Fiber type grouping Chronic Neurogenic Atrophy ATPase reaction

50. Werdnig-Hoffman Disease (Spinal Muscular Atrophy Type I)

52.  Denervated fibers are atrophic but round.  Interspersed hypertrophic round fibers are usually noted. Werdnig-Hoffman Disease (Spinal Muscular Atrophy Type I)