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
  Drug-related
    Minocycline
    Anti-TNF-α
Dermatomyositis vs IMPP
IMPP muscle pathology
  Adult-onset IMPP
  HMGCR antibody
  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; TIF1γ
No MDA5
(CADM140)
CK > 1,000 Some Few Most No
MUSCLE
  PATHOLOGY
Inflammation
  Focal
  Location
  Type

Some
Perimysium
Histiocytic

Yes
Perivascular,
Lymphocytic: CD20 cells
No
Perimysium pathology
  Fragmentation
  Cellularity
  Without myopathy
  Alkaline phophatase stain

Common
Histiocytic, Scattered
Some patients
Some patients

Occasional
Lymphocytic, Perivascular
Never
Unusual

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

Often
Never
Common
Regeneration
Rare
Perifascicular
Actin aggregates

Yes
Most patients
Unusual
Vacuoles & Aggregates
Common
No
 

No




Regional
 
Capillaries
 Near myofiber pathology

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


Normal
Absent 
Absent

Normal
Absent 
Absent


Large
Few 
Common

Absent
Common 
Absent


Large
Common
Common

Absent
Absent
Absent
Large Vessel Pathology No Artery + Vein Vein


IMPP Muscle Pathology (Jo-1 antibody positive)

Perimysial Pathology
  Cellularity
    Endomysial
    Perimysial
  Structure: Damage
  Alkaline phosphatase staining
Muscle fiber pathology

Jo-1 myopathy: Perimysial Pathology
Perimysial Fragmentation

H&E stain
Perimysial Damage
  Loculation: Small & Large holes (Above)
  Pallor (Below)
Muscle Fibers
  Small or immature in regions neighboring \perimysial pathology


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


Gomori trichrome stain
Fragmented Perimysium

Gomori trichrome stain

Jo-1 myopathy: C5b-9 deposited on permysium
  C5b-9 may also be deposited on neighboring endomysial connective tissue

C5b-9 stain

Perimysium: Inflammation, Usually histiocytic


H&E stain
Cells in Perimysium
  Size: Large
  Nuclei: Large
  Cytoplasm: Visible around nucleus
  Distribution: Scattered in regions of perimysium

H&E stain

H&E stain

Cells in perimysium: Histiocytic
  Stain for Acid phosphatase, Esterase & CD68

H&E stain

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


CD4 stain
Jo-1 myopathy: CD4 cells in permysium

CD4 stain


Acid phosphatase stain
Endomysial histiocytes
  Scattered in endomysium
  Often with neighboring: Capillary (Arrow) or Small endomysial vessel
  Pattern is common to many active myopathies: Not specific for Jo-1

Acid phosphatase stain


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

Alkaline phosphatase stain

Jo-1 myopathy: Muscle fiber pathology

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

NCAM stain
N-CAM positive atrophic muscle fibers
 

H&E stain


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

NADH stain

Perifascicular Myopathy
  Immature (Smaller, Intermediate-stained) muscle fibers: More common at edge of fascicles

ATPase pH 4.3 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


C5b-9 stain
Jo-1 myopathy: C5b-9 complement deposition
  Necrotic muscle fibers with cytoplasm staining for C5b-9
    Scattered
    More common in near edge of fascicles
  C5b-9 is also present on the surface of muscle fibers

C5b-9 stain


LC3 stain
Jo-1 myopathy: Abnormal muscle fibers
  Scattered, small LC3 aggregates in muscle fiber cytoplasm (Above)
  Abnormal vacuoles in muscle fiber cytoplasm (Below)

MHC-1 stain

Return to Inflammatory myopathies
Return to Jo-1 myositis

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

3/1/2017