Dysferlin Deficiency

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Dysferlin Deficiency (LGMD 2B)

Amyloid
Chronic
Differential diagnosis
Immune features
MRI
Myopathy
Ultrastructure
Vessels

Dysferlinopathy Pathology: Distinctive Features ¹

Muscle fibers: Necrosis & Regeneration, Scattered
Amyloid: In perimysial vessel walls; Older patients
C_5b-9 staining: Muscle fiber surfaces
MHC1 expression by muscle fibers: Uncommon
Inflammation
- Lymphocytes: Few
- Cells present: Mostly macrophages
Ultrastructure: Sarcolemma irregular

LGMD 2B: Myopathy

H&E stain

Myopathy: General Features
Muscle fibers
Necrosis & Regeneration: Scattered
Sizes: Varied
Replacement of perimysium by fat: Varied Degrees
Connective tissue
Endomysial: Increased
Perimysial: Replaced by fat

H&E stain

Myopathy: Varied Degrees & Patterns of Pathology in same muscle

Myopathy, Mildly active
Varied fiber size
Immature fibers scattered

VvG stain

Severe pathology
Pyknotic nuclear clumps
Replacement of muscle by fat

VvG stain

Active Myopathy

Necrotic Muscle Fibers (Blue Arrow)
Immature Muscle Fibers (Red Arrow)
Myopathic Grouped Small Muscle Fibers (Black Arrow)

VvG stain

Necrotic Muscle fibers: Scattered

H&E stain

H&E stain

Myopathic features
Necrosis (Pale fibers)
Regeneration (Basophilic, smaller fibers)
Fiber size: Varied

Necrotic muscle fibers

Necrotic muscle fiber replaced by phagocytic cells

Congo red stain

Necrotic & Regenerating muscle fibers

Acid phosphatase stain

Immature Muscle Fibers: Type 2C, Intermediate color (Black Arrow)
Capillary Pathology: ATPase staining (Blue Arrow)

ATPase pH 4.3 stain

Immature Muscle Fibers: Irregular internal architecture

NADH stain

Alkaline phosphatase stain

Immature smaller muscle fibers
Alkaline phosphatase positive cytoplasm (Above)
Type 2C fibers (Intermediate staining; Below)

ATPase pH 4.3 stain

ATPase pH 9.4 stain

Type 2 muscle fiber predominance
Most fibers are dark stained with ATPase pH 9.4

Dysferlinopathy: Immune features

C_5b-9 stain

C_5b-9 Complement deposits
Muscle fiber surface membranes: Irregular, Punctate
Muscle fiber cytoplasm: Necrotic fiber

C_5b-9 stain

Inflammation, Lymphocytic: Found in some biopsies

May reflect superimposed immune disorder


Perimysial inflammation Cells in connective tissue between fascicles	Perivascular inflammation Cells around intermediate-sized vessels

Myopathy
Muscle fibers
Sizes: Varied
Internal nuclei
Endomysial connective tissue
Increased between muscle fibers

H&E stain

Chronic & Active Pathology

	H&E stain
Small muscle fibers Rounded Some with basophilic cytoplasm & Large nuclei Often in Myopathic Groups Larger muscle fibers Often hypertrophic Occasionally necrotic

NADH stain

Muscle fiber internal architecture
Coarse staining in scattered muscle fibers
Necrotic fiber shows only pale staining
Pyknotic nuclear clumps: Very small, dark-stained muscle fibers

H&E stain

Varied muscle fiber size
Pyknotic nuclear clumps: Some muscle fibers are very atrophic and composed mainly of nuclei

Late Pathology

H&E stain

Size changes
Small muscle fibers: Rounded; Often in Myopathic Groups
Larger muscle fibers: Often very hypertrophic
Muscle fiber splitting
Endomysial connective tissue: Increased