IBM

Inflammatory Myopathies with Vacuoles, Aggregates & Mitochondrial Pathology (IM-VAMP)

H & E stain	Acid phosphatase 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.
CD4 stain	CD3 stain

Gomori trichrome

Inflammatory cells in endomysium

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)

Congo red stained muscle fibers
Vacuoles Muscle fibers with several rimmed vacuoles (arrows) Vacuoles contain blue amorphous material (Top right; Bottom) Nuclei: Some are near vacuoles or enlarged Amyloid in vacuoles visualized with polarized light (Above left, bottom) Small foci of red stained amyloid (arrows) are associated with vacuoles Differential diagnosis: Vacuoles Inclusion body myositis Distal myopathy (HIBM) 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)

Aggregates: General features in IBM-like disorders

SMI-31 + Congo red stains	Congo Red + Fluorescence with Texas red filter
SMI-31 positive aggregates in IBM IBM (Top Left; Bottom): 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 Some aggregates near nuclei Diffuse increase in cytoplasm of some muscle fibers IBM (Right): No fluorescence of vacuoles or aggregates in muscle fibers for amyloid SMI-31 aggregates are not present in PM-Mito biopsies


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)

Congo red + TDP43
TDP-43: IBM Aggregates Small focal regions of dark staining (Left; Above) Aggregates are mostly small & scattered through muscle fiber Large cytoplasmic TDP-43 aggregates (Right; Above) Inflammatory cells (Below): TDP-43 stains inflammatory cells in Endomysium Regions of focal invasion of muscle fibers TDP-43 aggregates are not present in PM-Mito biopsies
Congo red + TDP43
CD4 (Green) + TDP43 (Red) TDP-43: Aggregates & Inflammatory cells in IBM TDP-43 stains Focal aggregates in muscle fibers (Red) Inflammatory cells: Overlap with CD4 (Yellow) CD4 also stains scattered endomysial cells without TDP-43 (Green)
SMI-31 (Green) + TDP43 (Red) TDP-43: Aggregates and cytoplasmic staining with varied relation to SMI-31 staining TDP-43 stains Focal aggregates in muscle fibers: With (Yellow) and without (Red) overlap of SMI-31 SMI-31 also stains Cytoplasm in some fibers without TDP-43 (Green) Rim of internal nucleus (Green; Arrow) associated with neighboring TDP-43 staining (Red)

Congo red + LC3 stain
LC3: IBM Focal regions of dark staining of varied shapes (Top) Aggregates are cytoplasmic, small or large & have varied shapes LC3 aggregates are also present in PM-Mito biopsies (Bottom), unlike SMI-31 or TDP-43
Congo red + LC3 stain

From: R Schmidt

Ultrastructure: Vacuoles contain tubulovesicular material

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

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