Neuromuscular

DERMATOMYOSITIS: Childhood type 2
  Dermatomyositis with Vascular Pathology (DM-VP)

Capillary pathology
  H&E stain
  Alkaline phosphatase
  Endothelial stains
    Ulex
    Immunohistochemistry
  Ultrastructure
Complement deposition
Inflammation
MHC Class I
Perifascicular atrophy
  GT stain
  H&E stain
  NADH stain
  Mitochondrial stains
  Alkaline phosphatase
Muscle fiber pathology

DM: Adult pattern

Br J Child Dis 1912;9:247


Dermatomyositis with Vascular Pathology (DM-VP)
  Muscle fiber atrophy: Perifascicular distribution

  • Smallest (atrophic) muscle fibers are located near regions of "avascular" perimysium
    • Muscle fibers near perimysial vesels are larger.
  • Atrophic muscle fibers near the "avascular" perimysium have abnormal internal architecture, but are not necrotic.
  • Nuclei in small muscle fibers are enlarged and commonly internal.

Original Pathologic Description of Dermatomysitis with Vascular Pathology

Batten FE Br J Child Dis 1912;9:247
MUSCLE FIBER ATROPHY ALONG AVASCULAR PERIMYSIUM
Atrophic perifascicular muscle fibers neighbor a long region of avascular perimysium (Center).
Normal sized muscle fibers neighbor vascular perimysium (Sides).


H&E stain
Atrophic perifascicular muscle fibers neighbor long regions of avascular perimysium.


Gomori trichrome stain

Atrophic perifascicular muscle fibers neighbor a long region of avascular perimysium.


H&E stain
Atrophic perifascicular muscle fibers have basophilic cytoplasm and large nuclei.
Some perifascicular muscle fibers have basophilic or eosinophilic aggregates

H&E stain
Perifascicular muscle fiber pathology: Cytoplasmic aggregates (dark staining) & Internal nuclei.

VvG stain

Perifascicular pathology: Other stains

NADH

NADH stain
Muscle fibers near avascular perimysium are small & stain darkly
MITOCHONDRIAL

The extent of the perifascicular muscle fiber pathology in active DM is often more prominent on cytochrome oxidase stain.
SDH stain is not reduced.
Reduced cytochrome oxidase staining is not typically present in IMPP syndromes which have a different pattern of perifascicular muscle fiber pathology.

Cytochrome Oxidase

COX stain
Muscle fibers near avascular perimysium are small & have pale COX staining
Succinate Dehydrogenase

SDH stain
Muscle fibers near the avascular perimysium are small & have normal or dark SDH staining
Mildy reduced COX stain in perifascicular muscle fibers with normal size. (Arrow; Right)

COX stain

Perifascicular atrophy: ATPase pH 9.4 stain

ATPase pH 9.4 stain
Perifascicular atrophy is often more obvious on ATPase stains.
Small fibers are both types I & II.

ATPase pH 4.3

ATPase pH 4.3 stain

Type IIC muscle fibers (interrmediate staining) are present in regions of atrophy and larger muscle fibers.
Few, or no, type 1 muscle fibers in regions of most severe atrophy at edge of fascicles (Below; Arrow).


ATPase pH 4.3 stain

PAS

PAS stain
Increased glycogen staining in small perifascicular muscle fibers (Bottom).1

Alkaline Phosphatase
Enlarged capillaries (Arrows) in regions neighboring the smallest muscle fibers: Also see
  Fewer capillaries stain among larger fibers or amid the smallest fibers at the edge of fascicles.



Alkaline phosphatase stain

Alkaline phosphatase may stain several different structures in patients with dermatomyositis.

Alkaline phosphatase stain

Alkaline phosphatase stain

Alkaline phosphatase stain
Perimysium
Vascular staining.
More common in children
Endomysium
Capillary staining, especially
in perifascicular regions.
Perimysium
Diffuse staining.
More common in adults
Rare in children


Perifascicular atrophy: Muscle fiber pathology

Muscle fibers in regions of perifascicular pathology show several abnormalities in addition to being small.
Some muscle fibers have vacuolar or reticulated cytoplasm (Below).
Muscle fiber nuclei are enlarged.
Muscle fiber necrosis is rare.
 
H&E stain

Muscle fibers may also have
  Coarse internal architecture with basophilia (Left, Arrow), or
  Internal nuclei (Right).
The abnormal internal architecture may be better visualized on Gomori trichrome
 
H&E stain

Abnormal internal architecture in dermatomyositis muscle fibers is more apparent on Gomori trichrome stains.
The abnormalities may be present in both small and large muscle fibers.
Rod-like structures (cytoplasmic bodies) may occur (Bottom).


 

 

GT stain

Aggregates: Caveolin-3
Aggregates and increased cytoplasmic staining are common in perifascicular muscle fibers
with abnormal internal architecture in DM-VP.
 
Caveolin-3 stain

LC-3 aggregates: More prominent in muscle fibers toward edge of fascicle

LC-3 aggregates: Irregular shaped in muscle fiber cytoplasm

Dermatomyositis (DM-VP): Inflammation

Mononuclear cell inflammation:
  Mostly present in perimysium
  Located near or around intermediate-sized vessels.


 
H&E stain

H&E stain

Mononuclear cell inflammation:
Stains for CD4 and, in some regions, CD20 (B-cells)
Commonly perivascular.

CD4 stain

CD20 stain

Congo red stain


Childhood dermatomyositis (DM-VP): Capillary pathology


Capillaries: Ulex staining or endothelium


Stain: Ulex europaeus agglutinin I

Dermatomyositis: Capillaries
  Capillary pathology is patchy and most prominent in perifascicular regions.
  Capillary staining with Ulex lectin is often absent in regions with small perifascicular muscle fibers (Above left).
  Capillaries in regions near perifascicular atrophy are often enlarged (Above right).


Stain: Ulex europaeus agglutinin I

Control: Capillaries are abundant and small

CAPILLARY PATHOLOGY: Regional
Muscle fiber atrophy (Top): Few stained capillaries
Region neighboring muscle fiber atrophy (Purlieu; Middle & Below):   Enlarged capillaries
  Increased staining for alkaline phosphatase; Also see
Region distant from muscle fiber atrophy: Capillaries have nearly normal size and number

Stain: Ulex europaeus agglutinin I (UEAI)

Endomysial capillaries in region neighboring muscle fiber atrophy (Purlieu):
  Abnormal staining for alkaline phosphatase: Also see

Alkaline phosphatase stain

Capillaries: PECAM-1 & Collagen IV stains

Normal capillaries
Dermatomyositis
  Enlarged capillaries
  Capillary remnants


NORMAL ENDOMYSIAL CAPILLARIES

Endothelium + Collagen IV
Collagen IV (Red & Yellow) stains capillary walls and basal lamina around muscle fibers.
PECAM1 stains capillary endothelium in lumens (Green) and overlaps Collagen IV (Yellow) in walls.


Dermatomyositis (DM-VP): ENLARGED ENDOMYSIAL CAPILLARIES near regions of Perifascicular Atrophy

Endothelium + Collagen IV
Collagen IV (Red & Yellow) stains capillary walls and basal lamina around muscle fibers.
PECAM1 stains capillary endothelium in lumens (Green) and some overlaping Collagen IV (Yellow) in walls.


Enlarged endomysial capillaries (Arrows)
Location: Neighbor regions of perifascicular muscle fiber pathology .
 
H&E stain

Dermatomyositis (DM-VP): SMALL ENDOMYSIAL CAPILLARY REMNANTS in areas of Perifascicular Atrophy


Endothelium + Collagen IV
Collagen IV (Red) stains small capillary wall remnants (Arrow) without lumens.
PECAM1 stains little, or no, capillary endothelium.




Pericytes & Cells + Collagen IV
Collagen IV (Red & Yellow) stains round capillary remnants and basal lamina around muscle fibers.
PDGFRβ stains capillary pericytes (Yellow) overlapping Collagen IV and elongated endomysial cells (Green).



Dermatomyositis (DM-VP) Capillaries: Ultrastructure
Small endomysial capillary residua (Arrow) with thick basal lamina but no endothelium in area of perifascicular atrophy
  (Distinguished from thin basal laminae of nearby muscle fibers (Arrowhead))
    Neighboring pericyte cytoplasm provides evidence of the structure's microvascular origin)



Well preserved capillary amidst normal muscle fibers has normal size and morphology.
The capillary is composed of endothelial cells (E) surrounded by thick basal laminae and pericyte processes (P).



Childhood dermatomyositis (DM-VP): Complement (C5b-9) deposition in endomysial capillaries



Stain: C5b-9 components of complement (Membrane attack complex)
Dermatomyositis: C5b-9 deposition in endomysial capillaries
Changes are patchy and most prominent in perifascicular regions amid small muscle fibers.
C5b-9 is deposited on damaged capillaries that have lost their endothelium.

Stain: C5b-9 components of complement (Membrane attack complex)
Normal control
No C5b-9 deposition in endomysial capillaries in control muscle


C5b9 complement compared to PECAM1 staining of Punctate Capillary Remnants
C5b9 complement (Green) with Collagen IV (Red)
PECAM1 (Green) with Collagen IV (Red)

Childhood dermatomyositis (DM-VP): Perimysial Vascular Pathology

Dermatomyositis (DM-VP): Vascular Perimysium
  Contains abnormal vascular fragments (Yellow)
  Has increased PECAM1 staining
  Located away from perifascicular muscle fiber atrophy
  PECAM1 (Green) + Collagen IV (Red): Overlap = Yellow

Normal: Vascular Perimysium
  Contains normal intermediate-sized vessels with lumens
  Has minimal PECAM1 staining
  PECAM1 (Green) + Collagen IV (Red): Overlap = Yellow

Childhood dermatomyositis (DM-VP): MHC Class I upregulation


Stain: MHC Class I

DM-VP: MHC I up on muscle fibers, mild,
  especially near perimysium
A similar pattern may occur in IMPP syndromes

Stain: MHC Class I

DM-VP: MHC I up on muscle fibers, severe
  Diffusely on the surface and within muscle fibers

Stain: MHC Class I

Normal: MHC I not present in muscle fibers.
Staining is only on capillaries
 
MHC Class I upregulation
  Mild
  More in perifascicular region
  May occur in regions without severe myofiber damage
MHC Class I upregulation
  Dffuse
  Slightly more prominent in perifascicular region
  May occur in regions without severe myofiber damage


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References
1. Neuromuscul Disord 2006;16:391-393
2. Muscle Nerve 2010; Online April


8/6/2014