1. AcquiredDiseases of Muscle:Histologic Features David Lacomis, MD

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

3. Normal H&E-stained frozen cross-section of skeletal muscle Perimysial connective tissue Endomysial connective tissue • 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. Normal Structures: Muscle Spindleand Associated Nerve FibersGomori trichrome Spindle Nerve Twig

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

7. Neuromuscular Junction Electron Microscopy postsynaptic presynaptic

8. Histochemical Staining Intensity Based on Fiber Types NADH= nicotinamide adenine dehydrogenase SDH= succinic dehydrogenase ATPase= adenosine triphosphatase

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

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

11. Normal electron microscopy • 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

12. Classification of Myopathies

13. PolymyositisLongitudinal paraffin-embedded section • Mononuclear inflammatory cell infiltrates and many basophilic regenerating fibers

14. Regenerating fiber (non-specific) Fiber is basophilic due to presence of increased RNA and DNA. Activated plump nuclei and prominent nucleoli PolymyositisLongitudinal paraffin-embedded section (higher power)

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

16. MyophagocytosisEsterase 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. Dermatomyositis ATPase • Perifasicular atrophy and patchy staining ?? # of ATPase ??

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

23. Perifascicular AtrophyNADH-reacted section

24. Dermatomyositis

25. Dermatomyositis 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. Membrane Attack Complex (MAC)Immunohistochemical stain • Increased staining in capillaries in patients with dermatomyositis • Degenerating fibers may also stain.

31. DermatomyositisElectron microscopy • Tubuloreticular inclusion in a capillary endothelial cell

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

33. Lymphocytic inflammation “Rimmed vacuoles”

34. Rimmed vacuoles may be “slit-like”

35. Congo Red • IBM: Vacuoles contain amyloid.

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 Myositisin a Patient with Sarciodosis Giant cell See picture Granuloma 1 • Granulomas tend not to cause significant damage to adjacent myofibers.

43. Parasites: Trichinella spiralis

44. Endocrine Disturbance Type II Fiber AtrophyATPase pH9.4 • Characteristic of most

45. Inherited PolyneuropathyChronic Neurogenic Atrophy • Groups of angulated atrophic fibers • Marked variation in myofiber size

46. Acute DenervationNADH reaction • Manifested by small, darkly staining angulated fibers

47. DenervationEsterase Stain • Denervated fibers also stain darkly with non-specific esterase.

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

49. Chronic Neurogenic AtrophyATPase reaction • Fiber type grouping

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