Primary Signet-ring Cell/Histiocytoid Carcinoma of the Eyelid: A Clinicopathologic Study of 5 Cases and Review of the Literature

Primary cutaneous signet-ring cell carcinomas are rare and aggressive neoplasms. These neoplasms have been mostly described in the eyelids, and more uncommonly, in the axillary skin. Histopathologically, the neoplasm seems to be composed of signet-ring cells or histiocytoid epithelial cells arranged in an Indian file growth pattern between collagen bundles of the dermis. Immunohistochemically, neoplastic cells expressed strong diffuse reactivity for CAM 5.2, CK7, high molecular weight CK, AE1/AE3 and MNF116 cytokeratins, carcinoembryonic antigen, epithelial membrane antigen, gross cystic disease fluid protein-15, p63, mucin-1 (MUC-1), BerEP4, and E-cadherin; moderate positivity for alpha-smooth muscle actin, tissue-specific transcription factor 1, MUC-2, Podoplanin, and N-cadherin; and weak positivity for epidermal growth factor receptor. Estrogen and progesterone receptors show positive results in some cases and negative results in others. The histopathologic and immunohistochemical features of primary signet-ring cell or histiocytoid carcinoma of the eyelid are closely similar to those of histiocytoid lobular carcinoma of the breast, and there are several examples of histiocytoid mammary carcinoma metastatic to the eyelids. Therefore, histopathologic differential diagnosis between primary and metastatic signet-ring cell or histiocytoid eyelid carcinomas is mandatory. In this study, we report our experience with the clinical, histopathologic, and immunohistochemical findings in 5 cases of primary signet-ring cell or histiocytoid carcinoma of the eyelid. We investigated the usefulness of p63, epidermal growth factor receptor, MUC-1, MUC-2, mammaglobin, and E-cadherin as immunohistochemical markers for this histopathologic differential diagnosis. Primary signet-ring cell carcinoma of the eyelid is an aggressive neoplasm that may develop regional or distant metastases, and therefore, it should be excised with wide margins.