It can be difficult to differentiate the cells of infiltrating gliomas from macrophages associated with demyelinating lesions or cerebral infarcts, especially in tissue with freezing artifact or tissue that is technically suboptimal. We therefore sought to identify a reliable immunohistochemical marker for central nervous system macrophages that could be used on routinely processed tissue. The reactions of commercially available markers [Ham-56, Mac 387, CD68, CR3/43, DRα, lysozyme, CD16, and Ricinus communis agglutinin-1 (RCA-1)] were studied in normal cerebellum, subacute infarcts, viral encephalitis with microglial nodules, radiation necrosis, Alzheimer's disease, medulloblastoma, T-cell lymphoma, oligodendroglioma, gliomatosis cerebri, and microgliomatosis cerebri. We also performed a more extensive investigation of Ham-56 with largely surgical material. We concluded that (a) RCA-1 is a sensitive marker for microglia, either resting or responding to injury, but staining must be interpreted carefully because endothelial cells and reactive astrocytes frequently stain as well. This marker was useful in highlighting focal inflammation in HIV encephalitis, (b) CD68 is a specific marker for resting microglia. A case of microgliomatosis cerebri was intensely stained, (c) Ham-56 is a sensitive, specific (with the exception of endothelial cells), and reliable marker of central nervous system macrophages in routinely processed autopsy and surgical material. It is especially useful in distinguishing the macrophages in demyelinating disease and cerebral infarcts from neoplastic glial cells.
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