Electron microscopy of Merkel cell carcinoma from formalin-fixed tissue.

Merkel cell carcinomas have characteristic, but not pathognomonic, histomorphologic features. The diagnosis can be confirmed by immunohistochemistry studies and electron microscopy. However, differential diagnostic problems often occur only after all tumor material has been fixed in formalin and embedded in paraffin, which gives poor tissue preservation for electron microscopy. Therefore, in addition to histologic and immunohistochemical studies, parallel ultrastructural investigations were performed on tumor specimens fixed in glutaraldehyde and routinely processed, for electron microscopy, on formalin-fixed tissue and on formalin-fixed paraffin blocks. Formalin fixation led to an almost complete loss of neurosecretory granules and cell membranes; however, the characteristic paranuclear whorls of intermediate filaments were retained in all tumors. Merkel cell carcinomas are immunoreactive for neuron-specific enolase (NSE), but NSE-antisera have only recently become commercially available. Cytokeratin is demonstrable as a paranuclear clump, and this feature was found in four out of six tumors. Thus histologic, immunohistochemical, and electron microscopy studies of formalin-fixed tissue are able to confirm the diagnosis of neuroendocrine Merkel cell carcinoma.