INCLUSION BODY MYOSITIS

IBM: Inflammation & Focal invasion

H & E stain	Acid phosphatase stain	CD4 stain
Focal invasion of muscle fibers Inflammatory cells invade a focal region of the muscle fiber (arrows). Other regions of the muscle fiber appear intact. Some cells invading the muscle fiber are CD8+ T-cells. Occasional cells are macrophages & stain with acid phosphatase.

Endomysial inflammation

Gomori trichrome

Inflammatory cells in endomysium Linear distribution of cells between muscle fibers (Left) Larger collections of cells around muscle fibers (Right)

Acid phosphatase	Acid phosphatase
Cells around vessel (Left) are mostly T-cells (unstained) Cells near and within muscle fibers (Right) contain more macrophages (Stained red)

IBM: Vacuoles (or Inclusions)

Congo red stained muscle fibers
Vacuoles Muscle fibers with several rimmed vacuoles (arrows) Vacuoles contain blue amorphous material Amyloid in vacuoles visualized with polarized light (bottom left) Small foci of red stained amyloid (arrows) are associated with vacuoles Differential diagnosis: Inclusion body myositis; Distal myopathy; Oculopharyngeal muscular dystrophy

More vacuoles Another muscle fiber with vacuoles (Left; Congo red stain) Vacuoles in 2 muscle fibers (Right; Toluidine blue stain) Vacuoles may be in large or small fibers Vacuoles may contain autophagic debris, or 15 to 18 nm filaments

Vacuoles may contain amyloid-like birefringent (red-green) material (Congo red stain) Muscle fiber with large vacuole (Top) Red-Green birefringent material in vacuole (Middle & Bottom)

IBM: Aggregates

SMI-31 + Congo red stains	Congo Red + Fluorescence with Texas red filter
SMI-31 positive aggregates in IBM IBM (Left): SMI-31 staining in several patterns Aggregates in the cytoplasm of muscle fibers with no vacuoles Occasional small aggregates scattered around the rim of some vacuoles Diffuse increase in cytoplasm of some muscle fibers IBM (Right): No fluorescence of vacuoles or aggregates in muscle fibers for amyloid

αB-crystallin IBM (Left): Clusters of αB-crystallin staining in muscle fibers Normal (Right): No focal staining of muscle fibers

Ubiquitin conjugates: IBM Focal dark staining Staining may be present around rim of vacuoles (arrow) Aggregates are also located in other regions of muscle fibers Increased staining in much of the cytoplasm (right)

Valosin-containing protein (VCP): IBM Focal dark staining Aggregates are mostly small & scattered through muscle fibers Some fibers, especially small, can have increased cytoplasmic staining Occasional vacuoles have some VCP staining

Congo red + β-amyloid stain	Congo red + fluorescence
β-Amyloid: IBM Small focal regions of dark staining (Left) Aggregates are mostly small & scattered through muscle fiber Some fibers, especially small, can have increased cytoplasmic staining Regions of β-Amyloid do not show fluorescence with Congo red stain (Right)

From: R Schmidt

Ultrastructure: Vacuoles contain tubulovesicular material

MHC-1

Normal	IBM
MHC Class-1 up regulation Normal (Left): Staining of capillaries but not muscle fibers IBM (Right): Up-regulation within, and on the surface of, muscle fibers. MHC-1 is also present on inflammatory cells

• MHC-I expression on muscle fibers
• PM with mitochondrial dysfunction