Neuromuscular

Large Histiocyte Immune Myopathy (LHIM) 1

Necrosis
  Peripheral
Histiocytic cells
Nosology: Macrophage Activation Syndromes (Hemophagocytic Lymphohistiocytosis)

Gomori trichrome stain
Necrotic muscle fibers
  Scattered
  Dark-stained or Pale
  Some are associated with cells

H&E stain
Necrotic muscle fibers

H&E stain

Necrosis Pattern: Scattered Muscle Fibers


C5b-9 stain

Myophagocytosis
Progressive phagocytosis of muscle fibers (from their outside) by large multinucleated cells.
Muscle fibers are necrotic with a hyaline appearance.

H&E stain
Congo red stain

Myophagocytosis: Muscle fiber Pathology


Gomori trichrome stain
Histiocytic cells
  Multinucleated & large
  Neighbor necrotic muscle fibers

H&E stain
Congo red stain

H&E stain

H&E stain
Necrotic muscle fibers are pale or dark.
Multinucleated large cells, neighbor necrotic fibers

H&E stain

VvG stain
Necrotic muscle fibers are pale or dark.
Multinucleated large cells, neighbor necrotic fibers

VvG stain

VvG stain

NADH stain
NADH stain
Necrotic muscle fibers: Pale; Loss of NADH staining.
Multinucleated large histiocytic cells: Neighbor necrotic fibers; May be NADH positive.

NADH stain
 

NADH stain
Muscle Fiber Necrosis: Patterns & Relation to Histiocytes
  LHIM: Necrotic muscle fiber cytoplasm is mainly at periphery of muscle fibers
  Typical Necrosis in other disorders: Necrotic muscle fiber cytoplasm diffusely in muscle fibers (Bottom Right)

C5b-9 green; HAM56 red
Histiocytes (HAM56 stain; Red): Present around, and within, damaged, C5b-9 stained (Green) cytoplasm
C5b-9 stained (Green) cytoplasm: In periphery of muscle fibers
Necrosis pattern typical of other disorders (Bottom rightt): C5b-9 diffusely stains cytoplasm of necrotic muscle fiber
Muscle Fiber Necrosis

Bar = 10 µM
Muscle fiber: Focal, subsarcolemmal dissolution of myofibrils (Arrow)
Histiocytic cells: Present in neighboring endomysial connective tissue.

Bar = 10 µM
Histiocytic cells
  Surrounding (White arrow), apposed to, & invading (Black arrow), a necrotic muscle fiber (*)
Necrotic muscle fiber
  Pale cytoplasm
  Almost complete dissolution of myofibrils and sarcoplasmic organelles
Non-necrotic muscle fibers: Located at left side in image

Bar = 2 µM
Necrotic muscle fiber
  Surrounded by intact basal lamina
  Misoriented sarcomeres with Z-bands (Arrow) & glycogen are scattered, and organelles lost
  Amorphous granular material has replaced muscle fiber cytoplasm

Alkaline phosphatase stain
Alkaline phosphatase: Hemophagocytic cells stain black.

Histiocytic (Myophagocytic) cells


Acid phosphatase stain
Myophagocytic cells (red) progressively phagocytose & replace muscle fibers..

CD68 green; Collagen IV red
CD163 green; Collagen IV red
Histiocytes (Green)
  Outside (Above left) & Progressing through muscle fiber basal lamina (red; Arrow)

CD163 green; Collagen IV red

Bar = 2 µM
Activated histiocytes or macrophages
  Large cells near myofibers
  Surface membranes
    Wavy
    Pseudopodia
      Thin, Irregular
      Project between muscle fiber basement membrane & surface sarcolemmal membrane
  Cytoplasm
    Cntains abundant, variably-sized, irregularly-shaped membrane-bound phagocytic vacuoles
    Vacuoles contain: Debris; Abundant smooth endoplasmic reticulum; Mitochondria
  Nuclei
    Irregular membranes
    Markedly larger size than endomysial macrophages
    Prominent nucleoli.
    Some large histiocytic cells contain several nuclei
Muscle fiber: Small region of myofibrillar dissolution neighbors histiocytic cell (Arrow)

Bar = 2 µM
Histiocyte processes (Arrow)
  Between basal lamina & Necrotic muscle fiber cytoplasm
  Rich in organelles
    Smooth endoplasmic reticulum
    Mitochondria
    Vacuoles: Clear or contain granular debris
Histiocyte processes (Arrow)
    Between basal lamina & Necrotic muscle fiber cytoplasm
Muscle fiber surface sarcolemma under histiocyte process
    Disrupted or irregular
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References
1. Neurology 2019;92:e1763-e1772

3/23/2021