Signet ring-like cells: no longer a "signature" of glandular differentiation

The term "signet ring" is used to describe a cell with an eccentric nucleus that is compressed to the periphery of the cell by a large cytoplasmic vacuole or by a substance accumulated within the cytoplasm. In pathology, these cells have been traditionally associated with adenocarcinomas. We describe two cases of cutaneous tumors that contained signet ring-like cells. Because of the morphology of the cells and the fact that one patient had a past history of lung cancer, the possibility of metastatic adenocarcinoma was considered. Upon further investigation, the tumors proved to be a primary cutaneous squamous cell carcinoma and a basal cell carcinoma; surgical management was curative. Because signet ring changes may pose a diagnostic challenge, we review the various benign and malignant cutaneous lesions that have been reported to contain signet ring cells and we explore the possible causative mechanisms of this phenomenon.