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. Abnormal internal architecture: See H & E Gomori trichrome NADH Mitochondria Caveolin-3   Necrotic and regenerating fibers are more common in DM-like disorders in adults (IMPP). Nuclei in small muscle fibers are enlarged and commonly internal.

Batten FE Br J Child Dis 1912;9:247

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 neighbor a long region of avascular perimysium (Center). Normal sized muscle fibers neighbor vascular perimysium (Sides). H&E 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 the 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

ATPase pH 9.4 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 Alkaline phosphatase staining of enlarged capillaries (Arrows) in regions near the smallest muscle fibers.   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

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

Dermatomyositis (DM-VP): Inflammation
Mononuclear cell inflammation: Mostly present in perimysium and associated with 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 Severe muscle fiber atrophy (Top): Few stained capillaries Region neighboring muscle fiber atrophy: Enlarged capillaries Region distant from muscle fiber atrophy: Capillaries have nearly normal size and number Stain: Ulex europaeus agglutinin I

Capillaries: PECAM-1 & Collagen IV stains

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.

H&E stain Endomysial capillaries near regions of perifascicular muscle fiber pathology are commonly enlarged (Arrows).   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 (C_5b-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.

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

• LEFT: C_5b9 complement staining is present on
  • Most punctate Collagen IV endomysial capillary remnants (Yellow)
  • Avascular perimysium without Collagen IV (Green) (Large arrowhead)
• RIGHT: Capillary remnants (Red) have no PECAM1 staining (Yellow-Green) (Arrows and many other similar structures)

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)

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

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

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