Methotrexate neurotoxicity, H&E

Axonal spheroids are a non-specific marker of axonal damage. Proximal to the point where an axon has been damaged, the cell body and proximal axon are still functioning, and axonal transport mechanisms are still trying to move molecules and organelles toward the distal end of the neuron. However, this stuff cannot get transported past the site of the injury. The accumulated material builds up, the axon swells, and when cut in cross-section, looks like the red blob indicated by the unnecessarily large green arrow in the image above. These swellings are called axonal spheroids.