Neuromuscular

Immune Myopathies with Perimysial Pathology (IMPP) 1

Clinical syndromes
  Dermatomyositis: Adult > Child onset
  Graft-vs-Host
  Myopathies with
    Anti-Jo-1 Antibodies
    Other tRNA synthetase antibodies
    High Aldolase & Normal CK
    Minocycline
Dermatomyositis vs IMPP
IMPP muscle pathology
  Adult-onset IMPP
  Jo-1 antibody + pathology
  PL-12 antibody + pathology


IMPP: General

Clinical Features
  Immune myopathies: Similar to Jo-1 & tRNA synthetase antibody related immune myupathies

Pathology
  Perimysial damage: Prominent

Immune Dermatomyopathies: Comparative Features

IM + Perimysial
 Pathology (IMPP)
Dermatomyositis +
  Vascular pathology
Regional Ischemic
  Immune Myopathy
MDA5 antibody
CLINICAL Age range Adult > Child Child or Adult Late Adult Adult
Weakness: Proximal > Distal Common Most All Rare
Skin Raynaud's
Mechanic's hands
Heliotrope rash
Calcification
Rash (70%) Palmar
  Papules & Ulcers
Alopecia
Interstitial lung disease Common Uncommon No Common
Myalgias Common Occasional Common Rare
Neoplasm
  association
No Some: Adults 72% No
SERUM Myositis-associated
 antibody
Jo-1
tRNA synthetase
Mi-2
p140; p155
No MDA5
(CADM140)
CK > 1,000 Some Few Most No
MUSCLE
  PATHOLOGY
Inflammation
  Focal
  Location
  Type
 

Some
Perimysium
Histiocytic

 

Yes
Perivascular,
Lymphocytic
Often with CD20 cells
No
Perimysium pathology
  Fragmentation
  Cellularity
  Without myopathy
  Alkaline phophatase staining

Common
Histiocytic, Scattered
Some patients
Some patients

Occasional
Lymphocytic, Perivascular
Never
Unusual

In necrotic regions
Histiocytic
No
Yes
Muscle fiber pathology
  Perifascicular predominant
    COX staining reduced
    Necrosis & Regeneration
    Internal architecture
    Caveolin-3 aggregates
  Regional necrosis
  Myonuclei

Often
Never
Common
Regeneration
Rare
No
Actin aggregates

Yes
Most patients
Unusual
Vacuoles & Aggregates
Common
No
 

No




Yes
 
Capillaries
 Near myofiber pathology

  Ulex staining
  C5b-9 deposition
  Alkaline phophatase staining
 Amid myofiber pathology
  Ulex staining
  C5b-9 deposition
  Alkaline phophatase staining


Normal
Absent 
Absent

Normal
Absent 
Absent


Large
Few 
Common

Absent
Common 
Absent


Large
Common
Common

Absent
Absent
Absent
Large Vessel
  Pathology
No Perivascular
  inflammation
Veins


IMPP Muscle Pathology (Jo-1 antibody positive)

Jo-1 myopathy: Perimysial Pathology

H&E stain

Perimysial fragmentation
  • The perimysium is loculated with many focal clear areas
  • Cells in the perimysium are most frequently macrophages. Features include
  • Adjacent muscle fibers may show


H&E stain
Perimysium with:
  Damaged structure (Irregular, Pale regions)
  Cellularity: Large cells with cytoplasm & large nuclei
Neighboring myopathology:
  Muscle fibers: Necrotic & Regenerating (Small, Basophilic)

Gomori trichrome stain

VvG stain

Perimysium: Inflammation, Usually histiocytic


H&E stain
Cells in perimysium

Esterase
Esterase positive macrophages

CD68 stain
CD-68 positive cells in perimysium
  and endomysium


Esterase
Perimysium: Esterase positive macrophages


Acid phosphatase

Acid phosphatase
Acid phosphatase positive cells: Predominantly in Perimysium; Scattered in endomysium

Acid phosphatase


Alkaline phosphatase stain
Alkaline phosphatase staining
  Perimysium
  Extends into endomysium
  Muscle fiber cytoplasm (Smaller, immature fibers)

Alkaline phosphatase stain

Jo-1 myopathy: C5b-9 deposited on permysium

C5b-9 stain

Jo-1 myopathy: CD4 cells in permysium

CD4 stain

Jo-1 myopathy: Muscle fiber pathology

H&E stain
Perifascicular myopathy & atrophy
Regeneration & Necrosis of perifascicular fibers

NCAM stain
N-CAM positive atrophic muscle fibers
 


NADH stain
Perifascicular atrophy: Small Muscle fibers are more frequent at the edge of fascicles

NADH stain


MHC-I stain

MHC Class 1 staining
Positive muscle fibers are
  Perifascicular (Above), or
  Diffuse (Right)
  Have Similar patterns in
    DM + Vascular Pathology
Perimysial cells also stain (Below)

MHC-I stain

MHC-I stain

Jo-1 myopathy
  Scattered necrotic muscle fibers with cytoplasm staining for C5b-9
  C5b-9 is also present on the surface of muscle fibers

C5b-9 stain

Jo-1 myopathy
  Scattered, small LC3 aggregates in muscle fiber cytoplasm

LC3 stain

Return to Inflammatory myopathies
Return to Jo-1 myositis

References
1. Curr Opin Rheumatol 2011;23:595-604

3/13/2015