Alternative name: B-Cell Inflammatory Myopathy (BCIM)

    Muscle fiber
      Varied size
  Lymphocyte foci (ELS)
    Foci + Vessels
Immune changes
  Cell types
  Endomysial pathology

Ectopic Lymphoid Structures (ELS): Inflammatory cell foci contain vessels (Venules)

Structure: ELS Contain
    Type: High endothelial venules
    Size: Intermediate or Small
    Thick walls
    Endothelial cells: Large; Stain for Acid phosphatase & Esterase
    May be within, at edge of, or outside, regions of inflammation
    B-cells & T-cells
      T/B separation: Occupy somewhat different areas in cell foci
    May be clumped
ELS Locations
  General: Target organs of immune disorders
    Endomysium: Between muscle fibers
    Perimysium: Between fascicles
IIM: Differential Diagnosis of ELS
  Orbital myositis
  Also: Myasthenia gravis, Thymus
ELS: Other Disorders
  Rheumatoid Arthritis/Synovial tissue: Citrullinated protein & Rheumatoid factor antibodies
  Sjögren/Salivary glands: Ro/SSA & La/SSB antibodies
  Hashimoto thyroiditis/Thyroid: Thyroglobulin/Thyroperoxidase antibodies
  Diabetes, Type I/Pancreas
  Lupus erythematosis/Kidneys: dsDNA antibodies
  Multiple sclerosis/Meninges
ELS: Associated Molecules (Lymphoid Neogenesis)
  Lymphoid toxins & chemokines: CXCL12; CXCL13; CCL19; CCL21
  Inflammatory cytokines: IL-17; IL-21; IL-22; IL-23; TNF

ELS Structure

H&E stain
Cell Foci: Contain lymphocytes & vessels

H&E stain

H&E stain
Vessels in cell foci: Large (Above) or Small (Below)

H&E stain

ELS Vessels

H&E stain

H&E stain

CD31 stain
CD31+ endothelial cells are present in
  Small vessels within perivascular inflammatory foci
  Lumen of intermediate-sized vessel
Vessels stain for ATPase (Below)

ATPase pH 4.3 stain

Vessel in region of inflammation
  Endothelial cells: Large; May be Esterase+

Endothelial cells: Large (Arrow)

VvG stain

Esterase stain
Intermediate-sized vessels in inflammatory foci: Endothelial cells
  Stain abnormally for esterase (Arrows) & Acid phosphatase

Esterase stain

H&E stain
Small vessel proliferation within, and at edge of, cell focus

Gomori trichrome stain

Endomysial vessels
  Enlarged in some regions without inflammation

H&E stain

MHC Class I stain
MHC Class I stains
  Endothelium of enlarged endomysial vessels
  Muscle fiber surface membranes

BCIM inflammation: Lymphocyte foci also containing Vessels

Lymphocyte foci: Perimysium

H&E stain
Inflammation: Cell foci
  Cell type: Lymphocytes
  Location: Perimysium, Endomysium or both
Myopathic changes
  Fiber size: Varied
  Endomysial connective tissue: Variably increased

H&E stain
Lymphocyte foci: Perimysium extending into Endomysium

H&E stain

Lymphocyte foci: Endomysium

H&E stain

Gomori trichrome stain
Lymphocyte foci: Endomysium

VvG stain

Congo red stain
Inflammatory cell focus
  Some lymphocytes are clumped
  Inflammatory cell focus contains intermediate-sized & small vessels

H&E stain

VvG stain

Gomori trichrome stain
Lymphocyte inflammation
  Surrounds & contains intermediate-sized & small vessels
  No elastin fibrils in vessel wall.
  Location: Perimysium, Endomysium or both

Congo red stain

BCIM: Cell types in lymphocyte foci

H&E stain
Small dark cells with little cytoplasm surround an intermediate sized, and several small, vessels

CD20 stain
CD20+ B-cells are a prominent component of some perivascular inflammatory foci.

CD4 stain

CD20 stain
CD4 T-lymphocytes in
  endomysial connective tissue

CD20 B-lymphocytes in
  perimysium extending into endomysium

CD4 stain
CD4 T-lymphocytes
  Present in perimysium, extending into endomysium

CD20 stain
CD20 B-lymphocytes
  Present in subset of inflammatory foci
Serial sections: B-cell foci are present in some but not all (arrow) regions of CD4 cellularity

CD3 stain
A minority of the perivascular cells stain for CD3 (T-cells)

CD68 stain
CD68+ macrophages are scattered through the infiltrate and in neighboring connective tissue

Acid phosphatase stain
Acid phosphatase positive histiocytic cells: Scattered through the cell focus
Most cells in focus are Acid phosphatase negative

BCIM: Endomysial pathology

Complement Deposition (C5b-9; MAC) on endomysial connective tissue

C5b-9 stain

C5b-9 stain
BCIM muscle: C5b-9 components of complement
  are deposited in endomysial connective tissue
Control muscle: No C5b-9 components of complement
  are deposited in muscle

C5b-9 deposits
  Endomysial connective tissue
  Necrotic muscle fibers: Cytoplasm

C5b-9 stain

IgM: Deposited on endomysial connective tissue

IgM stain

Brachio-Cervial Inflammatory Myopathy: Myopathic changes

Muscle fiber damge may be
  Necrosis & Regeneration
  Focal invasion by cells
  Small, immature fibers

H&E stain
Muscle fiber necrosis   Muscle fibers in varied stages of necrosis & regeneration

H&E stain
Necrotic muscle fibers: Scattered

H&E stain

Necrotic muscle fibers in varied stages of phagocytosis by histiocytic cells

Acid phosphatase stain

Muscle fiber necrosis: Changes in individual muscle fibers

H&E stain
Early necrosis: Dark muscle fiber with loss of cytoplasmic structure

H&E stain
Later stage of necrosis: Muscle fiber invaded by cells with large nuclei and abundant foamy cytoplasm

H&E stain
Later stage of necrosis: Collapsed muscle fiber largely replaced by cells

CD68 stain
Muscle fiber necrosis: CD68+ histiocytic cells invading fiber

CD68 stain
Segmental muscle fiber necrosis: CD68+ histiocytic cells

CD68 stain
Muscle fiber necrosis: CD68+ histiocytic cells replacing part of a fiber

BCIM: Myopathy, Varied muscle fiber size

Chronic-Severe myopathy
  Varied fiber size
    Bimodal distribution
    Small muscle fibers: Rounded or Polygonal
  Large muscle fibers: Mild hypertrophy
  Internal nuclei: Scattered muscle fibers
  Endomysial connective tissue: Mildly increased

H&E stain

Mild-Moderate myopathy: Varied fiber size
  Fiber sizes: Bimodal distribution
  Type 1 & Type 2 fibers are small and large.

H&E stain

ATPase pH 9.4 stain

BCIM: Muscle fiber Regeneration & Immaturity

Basophilic regenerating muscle fibers: Bluish cytoplasm & Large nuclei

H&E stain

BCIM: Immature muscle fibers, Many, Small size, Type 2C

ATPase pH 4.3 stain
Many muscle fibers are type 2C with intermediate staining.

ATPase pH4.3 stain

ATPase pH 4.3 stain

Immature, small muscle fibers: Cytoplasm stains with alkaline phosphatase

Alkaline phosphatase stain

Immature, small muscle fibers: Cytoplasm stains darkly with NADH

NADH stain

Immature, small muscle fibers: Cytoplasm stains pale with AMPDA

AMPDA stain

BCIM: Focal invasion of muscle fibers by mononuclear cells
  Present in some patients

Acid phosphatase stain

CD4 stain
Focal invasion of muscle fibers

  Upregulation on muscle fibers, especially surface
  Expressed on cells in inflammatory foci

MHC Class I stain

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