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April 2, 2021

Tubular Aggregates

Tubular aggregates in H&E stain of muscle/nerve biopsy

Considering the clinical vignette from the prior week (elderly male with proximal muscle weakness). Staining the skeletal muscle biopsy with Hematoxylin and Eosin (H&E) in combination with frozen sections evaluated with Modified Gomori Trichrome (MGT) and oxidative stains can provide the neuropathologist with much information, including clues as to the ultrastructural abnormality of this myopathy. Electron microscopy was pursued. Using the images, what is the ultrastructural abnormality shown below in this skeletal muscle biopsy?


Formalin-fixed paraffin-embedding (FFPE) tissue section of skeletal muscle with Tubular Aggregate Myopathy (TAM) demonstrating four nearby muscle fibers with round to ovoid eccentric and subsarcolemmal inclusion-type material with pale somewhat granular eosinophilic (pink-red) staining character (A) with hematoxylin and eosin (H&E) staining. Ultrastructural examination by electron microscopy from the case shows scattered muscle fibers with variably sized sarcoplasmic collections of tubular aggregates (B). (Original magnifications: A. Hematoxylin and eosin (H&E) stain, 400x; B. Electron microscopy, 8000x).

Answer: Tubular aggregates

The neuropathologist has many tools and modalities at their disposal to evaluate skeletal muscle biopsies. After evaluation with routine H&E, as well as special (MGT) and oxidative staining (SDH-COX) preparations on frozen tissue sections, the inclusion-type material, in this case, was determined to be that of tubular aggregates, and not that of mitochondria. In this case, electron microscopy confirmed myopathy with tubular aggregates.


Key Point Take-Away: When indicated, ultrastructural examination with electron microscopy may be helpful. Evaluation with electron microscopy in skeletal muscle biopsies is most commonly used to evaluate cases of suspected metabolic myopathies, and may also be employed to confirm the ultrastructural identified of inclusion-type material, such as this case of myopathy with tubular aggregates.