Muscle Pathology Surgical Pathology Unknown Conference

1. Muscle PathologySurgical Pathology Unknown Conference November, 2008 Philip Boyer, M.D., Ph.D.

2. Etiologic Approach to Differential Diagnosis Symptoms / Signs / Imaging / Biopsy / CSF Analysis Abnormal Normal Neoplastic Non-Neoplastic Reactive / Hyperplastic Developmental Infectious - Inflammatory Primary “Metastatic” / Hematogenous Spread / Direct extension Toxic - Metabolic Degenerative Vascular- Ischemic Other Traumatic (neoplastic divide)

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 40-210 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.

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

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

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

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 - 80-90 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 38-176 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 7.0-46.0 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 12-13 • 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