Neuromuscular

Brachio-Cervical Inflammatory Myopathy (BCIM)

Alternative names
  Specific: B-Cell Inflammatory Myopathy (BCIM)
  General: Polymyositis

Myopathy
  Immaturity
  Necrosis
  Regeneration
  Focal invasion
  Varied size
Immune features
  Lymphocyte foci (ELS)
    Endomysium
    Perimysium
    Foci + Vessels
    Cell types
  Complement
  Endomysial pathology
  MHC-I
Vessels

Clinical

H&E stain

Inflammatory Cell Foci: Ectopic Lymphoid Structures (ELS) 1

Lymphocyte foci contain: B-cells & Atypical vessels (Venules)

Nosology Structure: ELS Contain
Ectopic Lymphoid Structures (ELS): Locations
IIM: Neuromuscular Differential Diagnosis of ELS
Ectopic Lymphoid Structures (ELS): Other Disorders
Ectopic Lymphoid Structures (ELS): Associated Molecules (Lymphoid Neogenesis)

ELS: Location


H&E stain
ELS in Perimysium
  Lymphocyte foci: Multiple
  Location: In abnormally widened perimysium

Gomori trichrome stain

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

H&E stain

H&E stain

H&E stain

ELS Vessels

Large
Small


H&E stain
ELS Vessel: Large
  Endothelium: Prominent; Large cells
  Wall: Thick
  Location: Often in center of ELS

Gomori trichrome stain

NADH stain
ELS Vessel: Large
  Endothelium: Cells stain for NADH & Esterase

Esterase stain

ELS Vessel: Large
  Smooth muscle: Thin layer outside endothelium

ATPase pH 9.4 stain

ELS Vessel: Large
  Few histiocytic cells in wall

Acid phosphatase stain

ELS Vessels: Small
  Distributed through cells focus

H&E stain

H&E stain

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

ATPase pH 4.3 stain

Vessels in an ELS cell focus
  May be large & small
  Large vessel in center of cell focus

ATPase pH 4.3 + TB stain

Vessel in region of inflammation (Arrow)
  Endothelial cells
    Large
    Often Esterase+
  Vessel wall: No fibrils

VvG

Endothelial cells in vessel: Large (Arrow)

VvG stain


VvG stain
Intermediate-sized Vessel in region of inflammation
  Endothelial cells: Large; Often Esterase+
  Vessel wall: No fibrils

Gomori trichrome stain
Vessels in ELS: May have cellular walls

Gomori trichrome stain

Congo red stain

Endothelial cells in vessels in EGC (ELS)

Esterase stain

Esterase stain
Endothelial cells in vessels in EGC (ELS): Esterase +

Esterase stain

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

Esterase stain


H&E stain
Vessel proliferation within, and at edge of, cell focus
  Vessels
    May be Large (Right, Below) or small (Left & Above)
    Larger & Contain more endothelial cells than capillaries

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

BCIM: Necrotic muscle fiber
  Invaded by large histiocytic cells
  Pale cytoplasm

H&E phosphatase 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 histiocytic cells & lymphocytes
  Present in some patients

H&E stain
Focal invasion of muscle fibers

Acid phosphatase stain

CD4 stain

BCIM: MHC Class I
  Upregulation on muscle fibers, especially surface
  Expressed on cells in inflammatory foci

MHC Class I stain

References
1. Curr Opin Immunol 2019 Feb 21;57:46-52

Return to Neuromuscular Home Page
Return to Inflammation
Return to Inflammatory myopathies
Return to BCIM

4/15/2019