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 large cells (Arrow; Histiocyte-like)

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
Necrotic muscle fibers
  Pale
  Loss of NADH staining
Large histiocytic cells
  Neighbor necrotic fibers
  May be NADH positive



 

NADH stain
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 right): 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