Which pathologic findings are characteristic of centronuclear myopathies (CNMs)?

Updated: Mar 11, 2019
  • Author: Matthew Harmelink, MD; Chief Editor: Amy Kao, MD  more...
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Answer

The pathologic hallmark of all myotubular myopathies (X-linked and autosomal) is the predominance of type-1 fibers with large, centrally placed nuclei, as shown below. Centronuclear/myotubular myopathy can be due to several different mutations, but all affected proteins have a role in membrane trafficking or in the maintenance of skeletal muscle fiber orignization, especially in the postitioning of nuclei. [51]

However, it is not known how any of the above mutations cause the pathologic abnormality. In DNM2 -related centronuclear myopathy the additional finding of radiating sarcoplasmic strands from the central nuclei is often present, often best seen on NADH staining. [52]

Most fibers are small and round and resemble fetal myotubes, which normally have central nuclei. The central part of the fiber contains an abundance of mitochondrial enzymes and glycogen, but lacks myosin ATPase activity.

Type-1 muscle fiber hypotrophy is usually present. A variable degree of endomysial fibrosis and fatty replacement is present, often depending on time course and severity with more severe abnormalities increasing with age.

Internal nuclei (not necessarily centrally placed) are more common in patients with RYR1 mutations. [52]

Necklace fibers—fibers with internalized nuclei in a basophilic ring just below the sarcolemma—have been described in patients with MTM1 and DNM2 mutations. [53, 54]

Immunohistochemical studies have shown persistence of fetal vimentin and desmin and of neonatal myosin, giving further credence to the maturational arrest of muscle fibers.

Muscle fibers with central nuclei can also be seen in denervation, muscle fiber regeneration, and any chronic myopathy.


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