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Muscle 
biopsy 
Dr Neha Mahajan
Normal Muscle
Organization of Skeletal Muscle Including 
Connective Tissue (CT) Compartments 
EPIMYSIUM 
•Loose CT 
•Blood vessels 
PERI...
Normal H&E-stained frozen cross-section of skeletal muscle 
Perimysial 
connective tissue 
Endomysial 
connective tissue 
...
Normal muscle Adult Normal Muscle child
Ultrastructure of a Sarcomere 
Myosin 
I band I band 
H band 
Actin 
Z M Z 
 Extends from Z-band to Z-band. 
A band 
 A ...
Indications of Muscle biopsy 
General reasons: 
Weakness of uncertain cause-generalised, proximal 
,floppy infant syndrome...
Contraindications 
1.Electrolyte disturbance 
2.Most endocrine 
3.Malignant hyperthermia 
4.Periodic paralysis 
5.Poor nut...
Site of biopsy 
• Muscle with moderate disease, NOT severe 
• Muscle belly, not from tendon 
• Proximal myopathies/general...
Bergston Needle 
Technique 
1.Needle Biopsy 
2.Open Biopsy- indicated for 
disorders with patchy pathology
Processing 
Transportation: 
Muscle may be saved in saline moistened guage for several hrs 
Keep the specimen cool 
Do NOT...
Sample size: 0.5 cm diameter 
& 1 1cm length 
Biopsy is processed: 
1.Paraffin embedding 
2.Histochemistry 
3.For electron...
Stains 
1. H&E- gen architecture & morphology 
2.Masson`s trichome-Collagen,fibrosis 
3.Mod Gomori`s Trichome- red ragged ...
Normal ATPase pH 9.4 
 Type I fibers are light 
 Type II fibers are dark
Rapid gomori`s trichome 
stain 
Red ragged fibers,nemaline 
bodies,myelinated fibers 
Nuclei :red purple 
Normal muscle my...
NADH-TR stain 
Sarcoplasmic structural 
details
SDH stain 
For mitochondrial activity
Cytochrome c oxidase 
•Mitochondrial activity 
•Type 1 fibers are darker 
than Type2
OIL RED O 
Accumulation of lipid
Esterase stain 
Lysosomal & phagocytic activity 
 Macrophages are ingesting the remnants of a degenerating fiber. This is...
Observations in routine paraffin sections 
H & E 
Used to evaluate gen architecture of muscle and variation in 
morphology...
Architecture of muscle fascicles -scanner view 
PATCHY Inflammatory myopathies 
FOCAL Neurogenic DIFFUSE Dystrophy
Nuclear changes 
Normal Internalisation of nuclei
Internalisation of nuclei 
• Myotendinous insertion 
• Centronuclear myopathy 
• Myotonic dystrophy 
• Fiber regeneration ...
Ring fibres 
•Limb girdle dystrophy 
•Myotonic dystrophy
Hyaline Fibres 
Duchene muscular 
dystrophy
Whorled fibres 
•Limb girdle muscular dystrophy 
•Chronic neuropathies
Fibre necrosis seen in biopsy specimen 
Pathologic features Disease 
Small groups of necrotic 
DMD 
fibres 
Perifascicular...
Fiber necrosis Perifascicular necrosis
INCLUSIONS 
Nuclear inclusions: 
Oculopharyngeal dystrophy 
Sarcoplasmic Inclusions: 
Myofibrillar myopathy 
Inclusion bod...
Inflammation 
Pathologic feature Disease 
Perivascular, angiocentric DM, connective tissue 
disease ,FSHD 
Endomysial, aro...
Inflammatory myopathy
Atrophy 
Type 1 fiber atophy Type 2 fiber atophy 
•Myotonic dystrophy 
•Nemaline myopathy 
•Centronuclear myopathy 
•Conge...
Normal Atrophy
Hypertrophy 
Type 1 fiber 
hypertrophy 
Type 2 fiber 
hypertrophy 
Type 1&2 fiber 
hypertrophy 
ISMA 
Normal 
Atheletes 
S...
Fiber shape 
Normal muscle-polygonal 
Angular-neurogenic Rounded-myopathic
Fibre splitting 
Limb girdle dystrophy 
IBM
Cores and targets 
Oxidative enzymes are ideal to assess depleted enzyme 
activity 
Cores : Neurogenic atrophy, central co...
Central cores Target fibres
Mottled fibres 
FSHD
Nemaline rods 
Detected by RTC(Rapid gomori trichome) 
Seen in Nemaline myopathy
Mitochondrial Abnormalities 
Ragged red fibres(RTC stain)
Sarcoplasmic vacuoles seen in biopsy specimen 
Pathologic feature Disease 
In centre arranged in size 
gradient 
Freezing ...
Freezing artifact Rimmed Vacuole
Vacuoles in glycogen storage disease
Parasite ( Trichenella Spiralis)
Granulomatous Myositis 
in a Patient with Sarciodosis 
 Granulomas tend not to cause significant 
damage to adjacent myof...
Pyomyositis Gram Positive Cocci
History & examination 
History: 
• Four major pieces of clinical information are critical for the pathologist: 
• Is the c...
LAB Investigations: 
Creatine kinase level: To rule out certain categories of myopathies because 
different myopathies ten...
Myopathies 
INHERITED 
Muscular dystrophies 
DMD,BMD 
FSHD 
LGD 
Distal myopathy 
OPMD 
Myotonic muscular dystrophy 
Con...
Muscular dystrophies 
•Usually not congenital 
•Onset in childhood ,young adults 
•Hereditary diseases ,often with a famil...
Duchenne muscular dystrophy 
• Inheritance- X- linked recessive disorder 
• Defective gene- Dystrophin 
• Onset- usually b...
Others : cardiomyopathy , mental retardation 
Lab. – Serum CK : elevated 20-100x normal 
- EMG : myopathic features 
- Mus...
Becker muscular dystrophy 
• Inheritance – X- linked recessive disorder 
• Defective gene – dystrophin 
• Onset- experienc...
Duchene muscular dystrophy 
Western Blot
DMD 
End stages-extensive 
replacement 
by adipose tissue and 
fibrosis
NORMAL DMD
Myotonic dystrophy 
• Inheritance : AD 
• Defective gene: two types with distinct molecular genetic defects 
-DM1 : expans...
Cont,d 
• - other system manifestations : intellectual impairment, hypersomnia, 
cataract, gonadal atrophy, insulin resist...
Oculopharyngeal dystrophy 
• Inheritance: AD with complete penetrance 
• Defective gene: expansion, poly-A-RNA binding pro...
Fascioscapulohumeral /FSH/ muscular dystrophy 
• Inheritance: AD 
• Onset : childhood or young adulthood 
• Defective gene...
Distal myopathies 
• Notable for their preferential distal distribution of muscle weakness in contrast to 
most muscle con...
Inflammatory and immune 
mediate myopathies 
1.Dermatomyositis 
2.Polymyositis 
3.Inclusion body myositis
Dermatomyositis 
• Inflammatory 
myopathy 
– Prevalence: 1:100,000 in 
general population 
– Female to male prevalence 
of...
Diagnostic Criteria 
• Bohan and Peter Criteria: 
– Symmetric proximal muscle weakness 
• most common symptom 
– typical r...
Grotton’ s Sign: 
An erythematous, scaly eruption over the 
extensor surfaces of the 
metacarpophalangeal joints and digit...
Dermatomyositis 
 Perifascicular atrophy 
 Degeneration 
 Inflammatory cells in the perimysium 
surrounding a blood ves...
Polymyositis 
Symmetrical proximal muscle involvement similar to DM 
Lack of cutaneous involvement,endomyseal inflammatory...
PM DM IBM 
Age at onset >18yrs Adulthood, childhood >50yrs 
sex M=F F>M M>F 
Weakness proximal proximal Proximal, early di...
POLYMYOSITIS, usually endo-myseal
INCLUSION BODY MYOSITIS, “rimmed” vacuoles
Congenital myopathy 
• Rare disorders distinguished from muscular dystrophies by the presence of specific 
histochemical &...
Central core disease 
•AD Ryanodine receptor(RYR1) 
Gene 19q13.1 
•Early onset hypotonia, floppy infant, 
associated skele...
Multicore disease 
•Cong non progressive myopathy(gen 
weakness,hypotonia) 
•Biopsy –type 1 fiber predominance& 
minute co...
Nemaline (Rod)myopathy 
•AR/AD 
•Childhood weakness 
•Ebbing of strength is more in facial & 
proximal limb muscle 
•Facia...
Myotubular/Centronuclear 
myopathy 
•AD/AR/XL 
•MTM 1 gene(Xq27-28) XL 
•Clinical findings-severe congenital hypotonia 
Fl...
Congenital fibre type 
disproportion 
•Atrophy of type 1 fibres, 
hypertrophy of type 2 fibres 
•Detectable at birth, pauc...
Myofibrillar myopathies 
•Heterogenous group of 
disorders(protein surplus 
myopathies) 
•Accumulation of intermediate 
fi...
General questions to keep in mind during 
reporting muscle biopsy 
• Are the muscle fibres abnormal?? 
• Is the pathologic...
Are the muscle fibers abnormal?? 
Size-small or large 
Shape-rounded or angular 
Type-grouping, fiber predominance 
Intern...
• Distribution of atophic fibers 
Grouped-Denervation ,dystrophinopathies 
Scattered-Acute neuropathy or myopathy 
 ACUTE...
• What is the distribution of the pathology?? 
UNIFORM-Dystrophy, fiber type predominance 
REGIONAL 
Patchy fascicular cha...
References 
 Vinay Kumar,Abul.Kabbas,Nelson Fausto. Robbins & Cotran 
Pathological Basis of Disease.8th ed. Chicago,Illin...
Musle biopsy
Musle biopsy
Musle biopsy
Musle biopsy
Musle biopsy
Musle biopsy
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Musle biopsy

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Musle biopsy

  1. 1. Muscle biopsy Dr Neha Mahajan
  2. 2. Normal Muscle
  3. 3. 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
  4. 4. Normal H&E-stained frozen cross-section of skeletal muscle Perimysial connective tissue Endomysial connective tissue Note uniform sizes, polygonal shapes, and eccentric nuclei.
  5. 5. Normal muscle Adult Normal Muscle child
  6. 6. Ultrastructure of a Sarcomere Myosin I band I band H band Actin Z M Z  Extends from Z-band to Z-band. A band  A band includes overlap of actin & myosin.  Note arrangement of thick and thin filaments.
  7. 7. Indications of Muscle biopsy General reasons: Weakness of uncertain cause-generalised, proximal ,floppy infant syndrome Muscle pain ,cramps, stiffness Persistently elevated muscle enzymes(CK) Specific reasons: Hereditary muscle disease in other family members Carrier detection Systemic connective tissue disease & vasculitis Certain metabolic diseases such as storage disease Suspicion of steroid myopathy in treated myositis Exclude drug induced myopathy Conflicting clinical ,EMG or lab findings Confirm/reinforce clinical diagnosis
  8. 8. Contraindications 1.Electrolyte disturbance 2.Most endocrine 3.Malignant hyperthermia 4.Periodic paralysis 5.Poor nutrition 6.Prior Trauma
  9. 9. Site of biopsy • Muscle with moderate disease, NOT severe • Muscle belly, not from tendon • Proximal myopathies/generalised systemic disease- Vastus Lateralis • Other sites-Biceps,gatronemius • Avoid Deltoid,muscle that are site of EMG,injections/trauma • Imaging used to select pathological muscle site in difficult cases.
  10. 10. Bergston Needle Technique 1.Needle Biopsy 2.Open Biopsy- indicated for disorders with patchy pathology
  11. 11. Processing Transportation: Muscle may be saved in saline moistened guage for several hrs Keep the specimen cool Do NOT immerse in saline ,fixative or other liquid Fresh Fixed Glutaraldehyde RESIN section/EM ( 1mm x 0.5 cm) Formalin PARAFFIN (0.5x0.5cm) Snap freeze HISTOCHEMISTRY (0.5x0.5cm)
  12. 12. Sample size: 0.5 cm diameter & 1 1cm length Biopsy is processed: 1.Paraffin embedding 2.Histochemistry 3.For electron microscopy 4.For molecular biology
  13. 13. Stains 1. H&E- gen architecture & morphology 2.Masson`s trichome-Collagen,fibrosis 3.Mod Gomori`s Trichome- red ragged fibres,nemaline bodies,nuclei,myelinated fibres 4.PAS-glycogen 5.Oil red O-neutral lipid 6.Acid phosphatase-lysosomal enzymes,necrotic fibres 7.Crystal voilet, Congo Red-amyloid 8.ATPase PH 9.4 Type 1 fibres pale Type 2 fibres dark 9. ATPase PH 4.6 Type 1 fibres dark Type 2 fibres pale 10. NADH- Sarcoplasmic structural details 11.SDH- oxidative enzyme activity 12.Cytochrome C Oxidase- mitochondrial enzyme activity 13.NSE-lysosomal &macrophage activity
  14. 14. Normal ATPase pH 9.4  Type I fibers are light  Type II fibers are dark
  15. 15. Rapid gomori`s trichome stain Red ragged fibers,nemaline bodies,myelinated fibers Nuclei :red purple Normal muscle myofibrils:Blue Green Intermyofibril muscle membrane: Red Interstitial collagen: Green
  16. 16. NADH-TR stain Sarcoplasmic structural details
  17. 17. SDH stain For mitochondrial activity
  18. 18. Cytochrome c oxidase •Mitochondrial activity •Type 1 fibers are darker than Type2
  19. 19. OIL RED O Accumulation of lipid
  20. 20. Esterase stain Lysosomal & phagocytic activity  Macrophages are ingesting the remnants of a degenerating fiber. This is a non-specific myopathic finding. Neuromuscular junction
  21. 21. Observations in routine paraffin sections H & E Used to evaluate gen architecture of muscle and variation in morphology of individual fibres •Variation in fascicular architecture •Variation in fiber size •Necrosis and degeneration of muscle fibres •Nuclear characteristics •Type & distribution of inflammatory infiltrate •Interstitial changes
  22. 22. Architecture of muscle fascicles -scanner view PATCHY Inflammatory myopathies FOCAL Neurogenic DIFFUSE Dystrophy
  23. 23. Nuclear changes Normal Internalisation of nuclei
  24. 24. Internalisation of nuclei • Myotendinous insertion • Centronuclear myopathy • Myotonic dystrophy • Fiber regeneration • Fiber atrophy • Chronic neuropathies
  25. 25. Ring fibres •Limb girdle dystrophy •Myotonic dystrophy
  26. 26. Hyaline Fibres Duchene muscular dystrophy
  27. 27. Whorled fibres •Limb girdle muscular dystrophy •Chronic neuropathies
  28. 28. Fibre necrosis seen in biopsy specimen Pathologic features Disease Small groups of necrotic DMD fibres Perifascicular necrosis Dermatomyositis Random fibre necrosis PM,IBM Infarcts with large areas of PAN necrosis Extensive,diffuse Rhabdomyolysis
  29. 29. Fiber necrosis Perifascicular necrosis
  30. 30. INCLUSIONS Nuclear inclusions: Oculopharyngeal dystrophy Sarcoplasmic Inclusions: Myofibrillar myopathy Inclusion body myositis
  31. 31. Inflammation Pathologic feature Disease Perivascular, angiocentric DM, connective tissue disease ,FSHD Endomysial, around fibres PM, IBM,viral Nodular Rheumatoid arthritis, granuloma Polymorphs with eosinophils PAN, drug reactions, trichinosis, eosinophilic fascitis
  32. 32. Inflammatory myopathy
  33. 33. Atrophy Type 1 fiber atophy Type 2 fiber atophy •Myotonic dystrophy •Nemaline myopathy •Centronuclear myopathy •Congenital fibre type disproportion Corticosteroid therapy Myasthenia Gravis Disuse Atrophy Acute denervation Paraneoplastic myopathy Pattern of atrophy: Grouped atrophy Chronic neurogenic disorders Panfascicular ISMA(Infantile spinal muscular atrophy) Perifascicular DM(Dermatomyositis)
  34. 34. Normal Atrophy
  35. 35. Hypertrophy Type 1 fiber hypertrophy Type 2 fiber hypertrophy Type 1&2 fiber hypertrophy ISMA Normal Atheletes Sprinters Congenital type disproportion Limb girdle dystrophy,IBM,myotoni a congenita,acromegaly Normal Hypertrophy
  36. 36. Fiber shape Normal muscle-polygonal Angular-neurogenic Rounded-myopathic
  37. 37. Fibre splitting Limb girdle dystrophy IBM
  38. 38. Cores and targets Oxidative enzymes are ideal to assess depleted enzyme activity Cores : Neurogenic atrophy, central core disease Target fibres: Chronic neuropathies CORE TARGET
  39. 39. Central cores Target fibres
  40. 40. Mottled fibres FSHD
  41. 41. Nemaline rods Detected by RTC(Rapid gomori trichome) Seen in Nemaline myopathy
  42. 42. Mitochondrial Abnormalities Ragged red fibres(RTC stain)
  43. 43. Sarcoplasmic vacuoles seen in biopsy specimen Pathologic feature Disease In centre arranged in size gradient Freezing artifact In scattered fibres ,small round osmiophilic ,oil red O positive Lipid storage disorders, Mitochondrial myopathies Often subsarcolemmal PAS + Glycogen storage Rimmed, ubiquitin + IBM ,Distal myopathy, OPMD
  44. 44. Freezing artifact Rimmed Vacuole
  45. 45. Vacuoles in glycogen storage disease
  46. 46. Parasite ( Trichenella Spiralis)
  47. 47. Granulomatous Myositis in a Patient with Sarciodosis  Granulomas tend not to cause significant damage to adjacent myofibers. Giant cell
  48. 48. Pyomyositis Gram Positive Cocci
  49. 49. History & examination History: • Four major pieces of clinical information are critical for the pathologist: • Is the condition a long standing or newly onset condition? • Is the condition progressive or relatively static? • Are there any associated systemic conditions such as heart problem or autoimmune disease? • What is the serum CPK level? • Other helpful clinical information: • History of myoglobinemia. • Family history of neuromuscular disease. • Sex and age. • Results of EMG studies. • Muscle groups being affected. • Presence of contracture. • Muscle groups being involved. • Site of biopsy. • Therapy and medication at the time of biopsy.
  50. 50. LAB Investigations: Creatine kinase level: To rule out certain categories of myopathies because different myopathies tend to generate a different levels of elevation in CPK. •High: (e.g. Dystrophinopathies) 200-300 times of normal. •Intermediate: (e.g. Inflammatory myopathy) 20-30 times of normal. •Low: (e.g. Neurogenic disorder) 2-5 times of normal.
  51. 51. Myopathies INHERITED Muscular dystrophies DMD,BMD FSHD LGD Distal myopathy OPMD Myotonic muscular dystrophy Congenital myopathy Central core disease Multicore disease Centronuclear Cong fibre type disproportion Myofibtillar myopathy Metabolic diseases Glycogen storage diseases Mitochondrial diseases Myoadenylate deficiency Channelopathies ACQUIRED Inflammatory-PM,DM,IBM,granulomatous Infections Trichinosis, cyticercosis,toxoplasma,HIV,Coxackie A&B Toxic Alcohol, Vit E, OPP, snake venoms Drugs Steroids,statins, b blocker, zidovudin, amiodarone,Chloroquine, chlofibrate, vincristine,cyclosporine,opiates Endocrine & metabolic Hypo/Hyperthyroidism Acromegaly Cushing`s syndrome Conn`s disease Osteomalacia Hypercalcemia Hypokalemia NEOPLASTIC Benign-Rhabdomyoma Malignant-RMS
  52. 52. Muscular dystrophies •Usually not congenital •Onset in childhood ,young adults •Hereditary diseases ,often with a family history •Weakness frequently severe ,variable distribution •Proximal in DMD,BMD,LGD •Facial in fascioscapulohumeral dystrophy •Distal in distal myopathy MD •Progressive course •Fiber destruction pathological, damage is random ;not all fibers are affected
  53. 53. Duchenne muscular dystrophy • Inheritance- X- linked recessive disorder • Defective gene- Dystrophin • Onset- usually b/n 3-5yrs age • C/F – progressive weakness of the girdle muscles - difficulty running , jumping, hopping, unable to get up from the floor (Gower’s maneuver) -enlargement of muscles of lower leg a/w weakness- Pseudohypertrophy - contractures( hip, knee, elbow, wrist) with chest deformities →severe pulmonary infections → death at age 16-18yrs
  54. 54. Others : cardiomyopathy , mental retardation Lab. – Serum CK : elevated 20-100x normal - EMG : myopathic features - Muscle biopsy- Fiber necrosis & regeneration Variation in fiber size,internalisation of nuclei proliferation of endomysial connective tissue. Deficiency of dystrophin seen on western blot analysis & immunohistochemical staining. - DNA analysis : mutation of gene that encodes dystrophin
  55. 55. Becker muscular dystrophy • Inheritance – X- linked recessive disorder • Defective gene – dystrophin • Onset- experience difficulty b/n 5- 15yrs of age • C/F – proximal muscles especially of lower extremities are prominently involved. - hypertrophy of muscles , particularly the calves, is an early & prominent finding. - cardiomyopathy may occur , MR is less common • Lab. – CK : elevated - EMG : myopathic - muscle biopsy : similar to DMD : reduced amount or abnormality of dystrophin( Dx) - DNA analysis : deletions or duplications( Dx) • Treatment – supportive • Survival : survive in to the 4th to 5th decade
  56. 56. Duchene muscular dystrophy Western Blot
  57. 57. DMD End stages-extensive replacement by adipose tissue and fibrosis
  58. 58. NORMAL DMD
  59. 59. Myotonic dystrophy • Inheritance : AD • Defective gene: two types with distinct molecular genetic defects -DM1 : expansion CTG repeat - DM2 ( proximal myotonic myopathy – PROMM ): CCTG repeat • C/F – myotonia : usually appears by age 5 yrs - Hatchet- faced appearance: temporalis , masseter , facial muscle atrophy & weakness - frontal baldness in men - foot drop : ankle dorsiflexor weakness - weakness of wrist extensors , finger extensors, & intrinsic hand muscles - early involvement of neck muscle flexors, sternocleidomastoids - dysarthritic speech, nasal voice, swallowing problems due to palatal , pharyngeal, and tongue involvement - respiratory insufficiency : diaphragm & intercostal muscle involvement - cardiac disturbances : conduction block with sudden death : CHF from cor pulmonale 2ry to respiratory failure
  60. 60. Cont,d • - other system manifestations : intellectual impairment, hypersomnia, cataract, gonadal atrophy, insulin resistance, reduced esophageal & colonic motility • Lab. – Dx ; usually based on clinical findings - CK : N or mildly elevated - EMG : evidence of myotonia Biopsy : variation in fiber size, increase in internal nuclei(chains) ring fibers, atrophy which selectively involves type – 1 fibers in 50% Myotonic dystrophy
  61. 61. Oculopharyngeal dystrophy • Inheritance: AD with complete penetrance • Defective gene: expansion, poly-A-RNA binding protein • Onset – usually late onset ( 4th – 5th decade ) • C/F – progressive external ophthalmoplegia ( slowly progressive ptosis, limitation of eye movements with sparing of pupillary rxns. - dysphagia : can be life threatening : may result in repeated episodes of aspiration - mild weakness of the neck and extremities • Lab. – EMG: myopathic features - CK : 2-3x N - BIOPSY : distinct features – presence of tubular filaments in muscle cell nuclei, mild dystrophic changes with nuclear internalisation ,fiber atrophy, interstital fibrosis, rimmed vacuoles in type 1 fibres
  62. 62. Fascioscapulohumeral /FSH/ muscular dystrophy • Inheritance: AD • Onset : childhood or young adulthood • Defective gene: deletion, distal 4q • C/F- facial weakness: initial manifestation - weakness of shoulder girdle muscles : weak arm elevation : scapular winging - weak wrist extension > wrist flexion - foot drop : weakness of anterior compartment muscles of the legs - weakness of the pelvic girdle muscles : 20% - other organ ( rarely) : labile HTN, nerve deafness • Lab. – CK : N or elevated - EMG: myopathic pattern - BIOPSY: Atrophic muscle fibres in clusters/groups in absence of necrosis, Moth eaten fibres and perivascular inflammatory infiltrate
  63. 63. Distal myopathies • Notable for their preferential distal distribution of muscle weakness in contrast to most muscle conditions associated with proximal weakness • Four types : mode of inheritance, age of onset, pattern of weakness 1. Welander DM : AD 2. Tibial MD : AD - late onset, usually after age 40; start in the hands 3. Nonanka DM: AR 4. Miyoshi myopathy : AR - early onset in late teens or twenties; start in the lower limbs • Lab. – CK : only slightly elevated except in Miyoshi myopathy- EMG : myopathic Biopsy : non- specific dystrophic changes selective type1 fiber atrophy in welander DM
  64. 64. Inflammatory and immune mediate myopathies 1.Dermatomyositis 2.Polymyositis 3.Inclusion body myositis
  65. 65. Dermatomyositis • Inflammatory myopathy – Prevalence: 1:100,000 in general population – Female to male prevalence of 2:1 – peak incidence ages 40-50 – Immune complex deposition in the vessels considered to be part of a complement-mediated vasculopathy Hematoxylin and eosin stain (20x) of a muscle biopsy from a patient with dermatomyositis showing perivascular and perimysial inflammation, as well as perifascicular necrosis.
  66. 66. Diagnostic Criteria • Bohan and Peter Criteria: – Symmetric proximal muscle weakness • most common symptom – typical rash – elevated serum muscle enzymes – myopathic changes on EMG – characteristic muscle biopsy abnormalities and absence of histopathologic signs of other myopathies
  67. 67. Grotton’ s Sign: An erythematous, scaly eruption over the extensor surfaces of the metacarpophalangeal joints and digits Heliotrope rash: A reddish-purple eruption on the upper eyelid accompanied by swelling of the eyelid Most specific rash in DM
  68. 68. Dermatomyositis  Perifascicular atrophy  Degeneration  Inflammatory cells in the perimysium surrounding a blood vessel  Inflammatory cells tend to be B-cells.
  69. 69. Polymyositis Symmetrical proximal muscle involvement similar to DM Lack of cutaneous involvement,endomyseal inflammatory involvement Inclusion body myositis Involvement of distal muscles,esp extensors of knee and flexors of wrist,ASYMMETRICAL
  70. 70. PM DM IBM Age at onset >18yrs Adulthood, childhood >50yrs sex M=F F>M M>F Weakness proximal proximal Proximal, early distal involvement Familial association No No Yes, in some cases /familial inflammatory myopathies / Response to treatment good better poor CTDs yes yes Yes, in up to 20% malignacy No yes, in up to 15% of cases No Rash Absent Present Absent Biopsy “primary” inflammation with the CD8/MHC-I complex & vacuoles Perifascicular, perymysial, or privascular infiltrates, perifascicular atrophy Primary inflammation with CD8/MHC-I complex; vacuolated fibers with b-amyloid deposits , cytochrome oxygenase-negative fibers ; signs of chronic myopathy
  71. 71. POLYMYOSITIS, usually endo-myseal
  72. 72. INCLUSION BODY MYOSITIS, “rimmed” vacuoles
  73. 73. Congenital myopathy • Rare disorders distinguished from muscular dystrophies by the presence of specific histochemical & structural abnormalities in muscle fibers. • Onset : infancy or childhood • C/F - progressive muscle weakness ( proximal> distal, legs> arms) & limpness, hypotonia & delayed milestones - skeletal deformities (kyphoscoliosis, club foot, hip dislocation) • Lab. - CK: usually N or slightly elevated - EMG : myopathic/ mostly/; positive sharp waves, myotonic discharges - Biopsy : features specific to each type Congenital myopathies 1.Central core disease 2.Multicore disease 3.Nemaline(Rod) myopathy 4.Centronuclear myopathy 5.Congenital fibre type disproportion 6.Myofibrillar myopathy
  74. 74. Central core disease •AD Ryanodine receptor(RYR1) Gene 19q13.1 •Early onset hypotonia, floppy infant, associated skeletal abnormalities, malignant hyperthermia •Biopsy- cytoplasmic cores in type 1 Fibres(NADH-TR stain)
  75. 75. Multicore disease •Cong non progressive myopathy(gen weakness,hypotonia) •Biopsy –type 1 fiber predominance& minute core like structures in majority of fibres
  76. 76. Nemaline (Rod)myopathy •AR/AD •Childhood weakness •Ebbing of strength is more in facial & proximal limb muscle •Facial dysmorphism •Aggregates of subsarcolemmal spindle shaped particles(nemaline rods) occuring predominantly In type 1 fiber best seen RTC stain
  77. 77. Myotubular/Centronuclear myopathy •AD/AR/XL •MTM 1 gene(Xq27-28) XL •Clinical findings-severe congenital hypotonia Floppy infants, poor prognosis, extraocular palsies & facial asthenia occur simultaneously with involvement of appendicular muscle •BIOPSY- Abundance of centrally located nuclei involving majority of muscle fibres (mostly in type1 fibres)
  78. 78. Congenital fibre type disproportion •Atrophy of type 1 fibres, hypertrophy of type 2 fibres •Detectable at birth, paucity of motor activity & diminished tone •Muscle deterioration tends to continue throughout first decade & then ceases or undergo reversal •Skeletal deformities-hip dislocation ,kyphoscoliosis ,joint contractures
  79. 79. Myofibrillar myopathies •Heterogenous group of disorders(protein surplus myopathies) •Accumulation of intermediate filaments including desmin,actin,myosin,ab crystalline & myomotilin within fibres •Adult onset •Distal weakness,dysphagia & cardiac involvement Desmin myopathy (RTC)
  80. 80. General questions to keep in mind during reporting muscle biopsy • Are the muscle fibres abnormal?? • Is the pathologic process-neurogenic/ myopathic?? • What is the distribution of pathology?? • Are there any diagnostic features??
  81. 81. Are the muscle fibers abnormal?? Size-small or large Shape-rounded or angular Type-grouping, fiber predominance Internal architecture-disordered/lost, vacuoles,Internal nuclei, inclusions Storage/acumulated material-glycogen, lipid, mitochondria Is the pathologic process  NEUROGENIC/MYOGENIC • Shape of muscle fibers ROUND Myopathic ANGULAR Neurogenic
  82. 82. • Distribution of atophic fibers Grouped-Denervation ,dystrophinopathies Scattered-Acute neuropathy or myopathy  ACUTE OR CHRONIC Acute: Myopathy-Muscle fiber regeneration &denevation Neuropathy-Small angular muscle fibers Chronic: Myopathy-increased endomysial connective tissue, muscle fiber hypertrophy Neuropathy-fiber type grouping ,pyknotic nuclear clumps
  83. 83. • What is the distribution of the pathology?? UNIFORM-Dystrophy, fiber type predominance REGIONAL Patchy fascicular changes-inflammatory myopathies,focal denervation Group of muscle fibers Neuropathy -Progressive denervation with reinnervation Myopathy- Myopathic grouping, perifascicular atrophy SCATTERED muscle fibers: Acute myopathy, Acute neuropathy • Are there diagnostic feaures?? INFLAMMATION SITE STORAGE MATERIAL PATHOLOGY other than muscle fibers
  84. 84. References  Vinay Kumar,Abul.Kabbas,Nelson Fausto. Robbins & Cotran Pathological Basis of Disease.8th ed. Chicago,Illinois:Elsevier.2010 .p. 905-969  Stephen S sternburg, Donald A.A,Daryl. Carter,Stacey.E, Oberman H.A. Diagnostic Surgicl Pathology.3rd ed. Newyork: Lippincort Williams &Wilkins;1999.p.1701-1784.  C. Sundaram and Megha S.Uppin,Approach to the interpretation of muscle biopsy ,Nizam institute of medical sciences, Hyderabad.  Ivan Damjanov,Anderson`s Pathology.10th ed.Kansas:Elsevier;2009.Vol2.p2653-2692.  WellerR.O.Systemic Pathology,Nervous system,muscle & eyes.3rd ed/vol4.Chuechill Livingston;1990.p.580-665.

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