Extraocular muscle ultrastructural pathology in the paraneoplastic phenomenon associated with retinoblastoma

Extraocular muscle biopsies were obtained during enucleation because of advanced intraocular retinoblastoma in four patients admitted to the Service of Ophthalmology at the Caracas University Hospital. Slight limitations of ocular movements and strabismus were present in all cases. The electron microscopical analysis showed muscle fibres with Slight to severe atrophy exhibiting myopathic structures as nemaline, filamentous and zebra bodies. Fibre necrosis was also observed characterized by sarcomeric hypercontraction, autophagia, sarcolemmal disruption, and mitochondrial swelling. Capillary alterations included endothelial proliferation with intraluminal infoldings and, in some cases, capillary degeneration and necrosis. A mononuclear cell infiltration formed by macrophages and scarce mast cells located next to atrophic fibres and altered capillaries was observed. Additionally, neutrophils were found around capillaries and in their wall. Cancer cells invading muscle tissue were not seen. Two different ethiopathogenic mechanisms for muscle damages seem to be present. Because of the similarity between the microvascular changes we observed and those found in the muscle compromise of several autoimmune diseases, an autoimmune component in the ethiopathogenesis of the observed capillary alterations is proposed. On the other hand, abnormalities observed in muscle fibres are very similar to those in neurogenic atrophy. This study represents the first report on an extraocular muscle paraneoplastic phenomenon associated with orbital tumours.