Novel eosinophilic neuronal cytoplasmic inclusions in the external cuneate nucleus of humans

We report the occurrence of neuronal cytoplasmic inclusions (NCIs) in the external cuneate nucleus of humans. The NCIs appeared as accumulations of eosinophilic rod-like structures in the neuronal somata in 20 (9.5%) of 211 consecutive autopsy cases. Histochemically, the NCIs were stained bright red with Gomori trichrome, Azan-Mallory and methyl green-pyronin, indicating that they contain protein and RNA. Immunohistochemically, the NCIs were positive for stress granule marker proteins, including Hu-antigen R, eukaryotic translation initiation factor 3 and poly(A)-binding protein 1, but negative for ubiquitin- and autophagy-related proteins. Ultrastructurally, the NCIs were composed of randomly oriented arrays of parallel fibrillar crystalline material with a well-defined substructure consisting of longitudinal striations, and were often associated with ribosome-like granules. These NCIs are morphologically, immunohistochemically and topographically distinct from any other inclusions previously described. Their incidence was found to increase with age. A high incidence was also observed in individuals with noninfectious inflammatory disease. These findings suggest that eosinophilic NCIs in the external cuneate nucleus are novel inclusions and might be formed under stress conditions.