The Big Eye in the 21st century: the role of electron microscopy in modern diagnostic neuropathology.

Electron microscopy (EM) remains a powerful and even essential tool in modern diagnostic neuropathology. tumors are still encountered that defy histological or immunohistochemical classification, and EM can often provide answers in these cases. Tumors of the CNS for which EM is useful include unusual or atypical variants of meningioma, ependymoma, and schwannoma; oligodendroglioma-like tumors composed of small "clear" cells; and small "blue cell" tumors of childhood. EM is of great value in identifying site of origin for metastatic adenocarcinomas of unknown origin-an under-recognized and under-utilized potential for this technique. EM is useful in the diagnosis of peripheral nerve sheath tumors and gastrointestinal autonomic nerve tumors. EM is also important in the evaluation of certain congenital, inherited and metabolic diseases-including ceroid lipofuscinoses, CADASIL syndrome, certain myopathies, and mitochondrial encephalomyopathies--and of certain toxic and drug-induced peripheral neuropathies. An important application of EM is its utility in initiating a workup of an atypical tumor or metabolic condition, for which clinical and histological clues point in no obvious direction. In these situations, EM may provide either an answer outright (including answers to questions not asked) or important clues that guide further workup and narrow the range of diagnostic possibilities.