Transcript Muscle Pathology Histopathology Unknown Cases

Muscle Pathology
Surgical Pathology Unknown Conference
November, 2008
Philip Boyer, M.D., Ph.D.
Etiologic Approach to Differential Diagnosis
Symptoms / Signs / Imaging / Biopsy / CSF Analysis
Normal
Abnormal
Neoplastic
Primary
Non-Neoplastic
Reactive /
Hyperplastic
“Metastatic” /
Hematogenous
Spread /
Direct extension
Toxic Metabolic
Other
(neoplastic divide)
Developmental
Infectious Inflammatory
Degenerative
Vascular
- Ischemic
Traumatic
Case 1
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.
Acid Phosphatase Histochemistry: Lysosomal Protein
Case 2
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
H&E Stain
Acid Phosphatase
Histochemistry
Acid Phosphatase
Histochemistry
Case 3
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
H&E
H&E
Trichrome
Spectrin
Dystrophin
Case 4
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
Dystrophin
Laminin Alpha-2 (Merosin)
Case 5
H&E – Low Power
H&E
Electron Micrograph
Electron Microscopy
Case 6
Histologic Findings
H&E
Histologic Findings
H&E
Histologic Findings
Trichrome
Electron Microscopy
Case 7
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
Histology - Muscle
Histology - Nerve
Histology - Liver
Histology - Liver
Case 8
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
H&E
Trichrome
Succinate Dehydrogenase Histochemistry
Electron Microscopy
Case 9
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
H&E
Trichrome
Electron Microscopy
2005
Biopsy
Myophosphorylase – Control
Myophosphorylase – Patient
Case 10
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.
H&E
Trichrome
Electron Microscopy
Case 11
History
 Newborn, 37 weeks gestation, with marked hypotonia
 Etiology uncertain clinically
 Muscle biopsy performed
H&E
Trichrome
Case 12
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
H&E
ATPase pH 4.3
Trichrome
NADH
NADH
Electron Microscopy
History - B
-----
54-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
Histology
H&E
NADH
ATPase 4.3
NADH
Trichrome
NADH
Thick Section, T. Blue
Electron Microscopy
Case 13
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





Case 14
History
- 56-year-old woman
- Past medical history: lupus erythematosus X 5 years
- Medications: Immunosuppressives including
corticosteroids
- Symptoms: Progressive weakness, profound
- Proximal-predominant
ATPase pH 9.4
Histochemical Fiber Typing







Twitch
Turkey Meat
analogy
Metabolism
Fat
Glycogen
NADH (oxidative)
ATPase


4.3
9.4
Type 1
Type 2
sLow
Dark – drumstick
(weight bearing)
Oxidative
More
Less
Dark
fast
White – Breast
(rapid / skilled movement)
Glycolytic
Less
More
Light
Dark
Light
Light
Dark
“One Slow Fat Red Ox”
Case 15
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)




Esterase
Neurogenic Changes
Fiber type grouping – groups of type 1 and type 2 fibers (ATPase pH 9.4 – type 2 fibers dark)
Case 16
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.
Electron Microscopy
Electron Microscopy, 30000 X Magnification: Evaluation of intact (left) and
affected (right) myofibers.
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