Muscle Pathology Surgical Pathology Unknown Conference. November, 2008 Philip Boyer, M.D., Ph.D.
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1 Muscle Pathology Surgical Pathology Unknown Conference November, 2008 Philip Boyer, M.D., Ph.D.
2 Etiologic Approach to Differential Diagnosis Symptoms / Signs / Imaging / Biopsy / CSF Analysis Normal Abnormal Neoplastic Reactive / Hyperplastic Non-Neoplastic Primary Metastatic / Hematogenous Spread / Direct extension Infectious - Inflammatory Toxic - Metabolic Developmental Degenerative Other Vascular - Ischemic (neoplastic divide) Traumatic
3 Case 1
4 History A 75-year-old man presented with a rapid onset and progression of generalized skeletal muscle aches and weakness over a 4-5 day period prior to hospital admission. Difficulty raising his arms above the level of the shoulders Difficulty getting out of chairs and off the commode Laboratory evaluation identified a CPK level of greater than 13,390 U/L (not titrated, normal range, adult male U/L) Past history was significant for: Atherosclerotic coronary and peripheral vascular disease treated with three-vessel coronary vessel bypass grafting Hypercholesterolemia treated with the statin medication Zocor for over a year. He recently had been diagnosed with diabetes and was begun on Glucotrol (glipizide), a sulfonylurea class oral hypoglycemic agent, 2 weeks prior to hospitalization.
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6
7
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9 Acid Phosphatase Histochemistry: Lysosomal Protein
10 Case 2
11 History 56 year-old woman 15 year history of seronegative rheumatoid arthritis Finger stiffness and swelling (PIPs and MCPs) Treatment: Plaquenil Methotrexate Recent 6 12 months: Progressive proximal weakness of arms and legs Dysphagia to pills and water
12 H&E Stain
13 Acid Phosphatase Histochemistry
14 Acid Phosphatase Histochemistry
15
16
17 Case 3
18 History - 6-year old male - History of difficulty walking, particularly in negotiating stairs - Neurologic Examination: - Weakness, proximal greater than distal - Gower sign on arising from floor - Calf muscle hypertrophy - Laboratory Evaluation: - Creatine Kinase = high: >10,000
19
20 H&E
21 H&E
22 Trichrome
23 Spectrin Dystrophin
24 Case 4
25 History - l year old girl (A.O.) - History of congenital weakness - Neurologic Examination: - Weakness, proximal greater than distal - Laboratory Evaluation: - CK elevated (>1,000) - MRI: - White matter abnormality - No evidence of malformation
26
27
28 Dystrophin Laminin Alpha-2 (Merosin)
29 Case 5
30 H&E Low Power H&E
31 Electron Micrograph Electron Microscopy
32 Case 6
33 Histologic Findings H&E
34 Histologic Findings H&E
35 Histologic Findings Trichrome
36 Electron Microscopy
37 Case 7
38 History 21-year-old G2P2 woman with a past medical history significant only for obesity A year prior to the current admission, during the third trimester of her second pregnancy, developed symptoms which continued after delivery of healthy 40-week gestation infant Weight loss pounds Night sweats which continued after term delivery of a healthy infant; total weight loss was Four months prior to admission Arthralgias of the hips and knees Non-pruritic hyperpigmented macular rash involving her arms and torso but sparing her face Working diagnosis: "lupus-like syndrome Course of prednisone which resulted in resolution of the rash and cessation of weight loss Tapering of the prednisone, weight loss continued Two weeks prior to admission Burning sensation involving the soles of both feet with extension to the ankles in a stocking distribution Admitted for evaluation. Thin habitus Liver palpable to 4 cm below the right costal margin Extreme sensitivity to light touch of the feet to the level of the ankles bilaterally Strength and reflexes were normal Labs: CPK 34 U/L (normal adult female U/L), C-reactive protein 6.0 mg/dl (normal < or= 0.8 mg/dl), sedimentation rate 67 (normal female 0-29 mm in 1 hour), and angiotensin converting enzyme 59 U/L (normal U/L ) Chest X-ray: normal
39 Histology - Muscle
40 Histology - Nerve
41 Histology - Liver
42 Histology - Liver
43 Case 8
44 History 28-year-old woman Past Medical History: History of antibody negative myasthenia gravis Medications: None Presentation: Ptosis and swallowing difficulty Neurologic Examination: Ptosis Laboratory Evaluation: CPK 100 Myasthenia panel: negative
45 H&E
46 Trichrome
47 Succinate Dehydrogenase Histochemistry
48 Electron Microscopy
49 Case 9
50 History - 14-year old boy - History of difficulty keeping up with peers during physical activity - Not running, jumping, playing like others due to pain after exercise ( exercise intolerance ) - CPK 8,600 - EMG: myopathic motor units - Biopsy at age 4 identified focal inflammation, diagnosed with inflammatory myopathy - Treated with corticosteroids with some symptomatic improvement - Attempts to reduce corticosteroids resulted in increased CPK levels (500 10,000) but without associated symptoms - Needed wheel-chair by age After strength testing: severe pain and stiffness for several hours but not persistent - Re-evaluated now - Weakness, proximal greater than distal - Laboratory Evaluation: - Creatine Kinase = ~normal - Re-biopsied
51 H&E
52 Trichrome
53 Electron Microscopy
54 2005 Biopsy Myophosphorylase Control Myophosphorylase Patient
55 Case 10
56 History 37-year-old man History since childhood of proximal weakness, lower extremities greater than upper extremities. Family history is significant for "muscular dystrophy" in aunts and uncles Biopsy of one uncle was non-diagnostic with a "whorling pattern" on oxidative preparations The differential diagnosis included a limb-girdle muscular dystrophy and a congenital myopathy.
57 H&E
58 Trichrome
59 Electron Microscopy
60 Case 11
61 History Newborn, 37 weeks gestation, with marked hypotonia Etiology uncertain clinically Muscle biopsy performed
62 H&E
63 Trichrome
64 Case 12
65 History - A - Newborn; delivered at 36 weeks gestation due to a breech position - Respiratory distress was noted at birth - Hypotonia - Congential bilateral hip dislocations - There is no known family history
66 H&E ATPase ph 4.3 Trichrome NADH NADH Electron Microscopy
67 History - B year-old man -- Life-long history of exertional fatigue and muscle tightness -- With multiple episodes of rhabdomyolysis / myoglobinuria -- He has a 5-year-old son - - Easily fatigued - - Proximal weakness
68 Histology H&E ATPase 4.3 Trichrome NADH NADH NADH Thick Section, T. Blue Electron Microscopy
69 Case 13
70 History 35-year-old man Past Medical History: Unremarkable Medications: None Presentation: Diffuse muscle pain / soreness, proximal and distal Neurologic Examination: Pain in multiple muscles; no weakness Laboratory Evaluation: CPK 600 Social History: Hunter in the Upper Peninsula of Michigan
71
72 Case 14
73 History - 56-year-old woman - Past medical history: lupus erythematosus X 5 years - Medications: Immunosuppressives including corticosteroids - Symptoms: Progressive weakness, profound - Proximal-predominant
74 ATPase ph 9.4
75 Histochemical Fiber Typing Type 1 Type 2 Twitch slow fast Turkey Meat Dark drumstick White Breast analogy (weight bearing) (rapid / skilled movement) Metabolism Oxidative Glycolytic Fat More Less Glycogen Less More NADH (oxidative) Dark Light ATPase 4.3 Dark Light 9.4 Light Dark One Slow Fat Red Ox
76 Case 15
77 History 56-year-old man Past Medical History: Unremarkable Medications: None Presentation: Slowly progressive weakness, left leg, then right leg and arms; difficulty swallowing Neurologic Examination: Weakness, distal and proximal Laboratory Evaluation: CPK 150 (normal < 220)
78
79
80 Esterase
81 Neurogenic Changes Fiber type grouping groups of type 1 and type 2 fibers (ATPase ph 9.4 type 2 fibers dark)
82 Case 16
83 History 60 year old woman with a history of chronic obstructive pulmonary disease. Suffered an episode of respiratory failure that required intubation approximately 3 weeks prior to biopsy She has received Neuromuscular blocking agent High dose corticosteroid therapy She has now been extubated and is manifesting significant weakness, legs greater than arms.
84 Electron Microscopy Electron Microscopy, X Magnification: Evaluation of intact (left) and affected (right) myofibers.
85 ANSWERS 1. Myofiber necrosis from statin medication 2. Vacuolar myopathy 3. Duchenne muscular dystrophy 4. Congenital muscular dystrophy, merosin negative 5. Dermatomyositis 6. Inclusion body myositis 7. Sarcoid 8. Mitochondrial disease 9. McArdle's Disease 10. Nemaline myopathy 11. Centronuclear myopathy 12. Central core disease 13. Trichinella spiralis 14. Steroid-induced atrophy 15. ALS 16. Critical Care myopathy
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