Physiology, pathophysiology and diagnostic significance of autophagic changes in skeletal muscle tissue – towards the enigma of rimmed and round vacuoles

Facioscapulohumeral muscular dystrophy presenting with unusual phenotypes and atypical morphological features of vacuolar myopathy

“…Rimmed vacuoles are a characteristic histopathological feature of sporadic inclusion body myositis (s-IBM) and hereditary inclusion body myopathy (hIBM), but are also found frequently in distal myopathies, oculopharyngeal muscular dystrophy (OPMD), rigid spine syndrome, congenital myopathies and some limb girdle muscular dystrophies [16,20,25,33,36]. Morphological and immunohistochemical evidence supports the notion that at least some of these vacuoles are caused by the degeneration of muscle fibre nuclei [9,36]. The morphological triad of rimmed vacuoles, filamentous sarcoplasmic and myonuclear inclusions and inflammatory changes is a hallmark of inclusion body myositis [1].…”

Muscle atrophy, ubiquitin–proteasome, and autophagic pathways in dysferlinopathy

“…When either proteasomal or lysosomal degradation is impaired, or when the amount of material to be degraded exceeds the normal level, ubiquitinated proteins aggregate and can be associated with autophagic vacuoles. Dysfunction in the UPS and/or autophagic pathways has been implicated in some muscle diseases, including inclusion‐body myositis (IBM), Danon disease, and glycogen‐storage disease type II …”

The prevalence of rimmed vacuoles in biopsy‐proven dermatomyositis

“…6 Autophagic vacuole formation may arise in response to genetic or metabolic factors but may also be induced by tissue ischemia. 5 It is noteworthy that the endomysial vasculature is the primary site of pathology in DM, and endothelial cell lysis and capillary necrosis lead to microinfarcts and perifascicular atrophy. It is therefore conceivable that, in DM, tissue hypoperfusion stimulates autophagic vacuole formation.…”

“…5 Given that 17% of our patients with histological DM had rimmed vacuoles, we believe DM should also be added to this list and suggest that an investigation into the role of autophagy in DM would be of interest. …”