Signet-ring cells are formed by intracytoplasmic accumulations of various substances that push the nucleus to the cellular border. Signet-ring cells in epithelial neoplasms are often regarded as evidence of adenocarcinoma.

The study surveys the rare settings in which signet-ring cells are encountered in dermatopathologic specimens and investigates mechanisms of their formation.

A total of 23 cutaneous tumors with a significant population of signet-ring cells were studied by immunohistochemistry and electron microscopy.

Signet-ring cells were found in a variety of cutaneous neoplasms, including primary cutaneous squamous and basal cell carcinoma and melanoma, as well as in metastatic adenocarcinoma. In all but the metastatic adenocarcinomas the vacuoles were periodic acid Schiff (PAS), PAS-digest, and colloidal iron negative. There was no staining of the vacuoles with antibodies against keratins and vimentin. Electron microscopy showed only empty spaces in all cases.

The signet-ring like appearance of the cells in most of these conditions is probably the result of coalescence of intracytoplasmic vacuoles and not accumulation of secretory products. Signet-ring formation is not specific for cellular lineage but can occur in a variety of cutaneous neoplasms, analogous to other cellular alterations as rhabdoid, granular, clear, spindle, and balloon cells and oncocytes.