Transcript Case Study 47

Case Study 47
Julia Kofler, M.D.
Question 1
Clinical history:
The patient is a 67-year-old female with >6 months history
of weakness, mostly in proximal muscles.
EMG studies were consistent with a myopathy with
electrical features of muscle necrosis, inflammation, or
membrane irritability.
Describe the findings seen on needle biopsy of the deltoid
muscle.
Click here to view frozen section H&E slide.
Click here to view paraffin section H&E slide
Click here to view Gomori trichrome slide.
Answer
Hematoxylin and eosin stained frozen sections reveal mildly
increased myofiber size variability without an excess of
internalized nuclei. A few scattered atrophic fibers, but no
degenerating or regenerating fibers or inflammatory infiltrates
are seen. Prominent basophilic stippling is seen in the
majority of myofibers. In addition, several fibers contain one
or more rimmed vacuoles. H&E stained paraffin sections
reveal multiple variably sized vacuoles in most of the fibers.
Gomori trichrome highlights the rimmed vacuoles and
cytoplasmic stippling but does not reveal ragged red fibers.
Question 2
Which stains may be useful to better define the nature of
the vacuoles?
Answer
 Acid phosphatase
 Esterase
Question 3
 What is highlighted in a muscle biopsy by a positive
esterase stain?
 What is highlighted by acid phosphatase?
 Based on the results of these stains, which cellular
organelle is the origin of the vacuoles in our case?
Click here to view esterase slide
Click here to view acid phosphatase slide.
Answer
 Esterase stain highlights neuromuscular junctions,
macrophages, lysosomes and denervated muscle fibers
 Acid phosphatase stain highlights lysosomes and
macrophages
 For both stains, the staining of macrophages is
related
to their high content of lysosomes
 In our case, esterase and acid phosphatase stains
highlight the cytoplasmic stippling and vacuoles in some
but not all fibers.
 The results are consistent with autophagic vacuoles of
lysosomal origin.
Question 4
Which additional clinical information do you need to obtain
to better define the disease process?
Answer
Medication history
Question 5
Which drugs are associated with vacuolar myopathies?
Answer
 Amphiphilic drugs:
- Chloroquine, hydroxychloroquine
- Amiodarone
- Perhexiline maleate
 Inhibitors of microtubule polymerization:
- Colchicine
 Review of the clinical history in our patient revealed
the use of chloroquine
Question 6
Which additional studies can be performed to confirm the
diagnosis?
Answer
Electron microscopy studies
Question 7
What do you see on the following EM pictures?
Answer
Curvilinear bodies, which are characteristic of
chloroquine/hydroxychloroquine related myopathy.
In some cases, curvilinear bodies can be found in the
absence of vacuolar change by light microscopy.
Question 8
What is your final diagnosis?
Answer
Autophagic vacuolar myopathy with curvilinear inclusions,
consistent with hydroxychloroquine/chloroquine myopathy