BCIM

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
Within lymphocyte foci

Clinical

H&E stain

Inflammatory Cell Foci: Ectopic Lymphoid Structures (ELS) ¹

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

Nosology

Extralymphatic Germinal Centers (EGC)
Tertiary Lymphoid Structures (TLS)

Structure: ELS Contain

Vessels
- Type: High endothelial venules
- Size: Intermediate or Small
- Walls
  - Size: Thick
  - No fibrils: Unlike normal veins
- Endothelial cells
  - Size: Large
  - Stain for
    - Features of normal endothelial cells: UEA I, CD31, MHC 1
    - Feature specific for ELS vessels: Esterase
- May be within, at edge of, or outside, regions of inflammation
Lymphocytes
- B-cells & T-cells
  - T/B separation: Occupy somewhat different areas in cell foci
- May be clumped
No Capsule or Afferent lymphatic vessels

Ectopic Lymphoid Structures (ELS): Locations

General: Target organs of immune disorders
Muscle

Endomysium: Between muscle fibers
Perimysium: Between fascicles
- BCIM
- Other systemic immune disorders

IIM: Neuromuscular Differential Diagnosis of ELS

Ectopic Lymphoid Structures (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
Graft rejection, chronic
Solid tumors

Ectopic Lymphoid Structures (ELS): Associated Molecules (Lymphoid Neogenesis)

Lymphoid toxins & chemokines: CXCL12; CXCL13; CCL19; CCL21
Inflammatory cytokines: IL-17; IL-21; IL-22; IL-23; TNF
Enzyme activation-induced cytidine deaminase (AID; AICDA)

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 cell 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 (C_5b-9; MAC) on endomysial connective tissue

C5b-9 stain	C5b-9 stain
BCIM muscle: C_5b-9 components of complement are deposited in endomysial connective tissue	Control muscle: No C_5b-9 components of complement are deposited in muscle

C_5b-9 deposits
Endomysial connective tissue
Necrotic muscle fibers: Cytoplasm

C_5b-9 stain

IgM: Deposited on endomysial connective tissue

IgM stain

Brachio-Cervical 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