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Breast cancer surgical options now include nipple-sparing mastectomy (NSM), but there has been much controversy regarding the oncologic safety of the preserved nipple. This study evaluates frequency and patterns of occult nipple involvement in a large contemporary cohort of patients, aiming to improve patient selection for NSM. A total of 2323 consecutive mastectomy specimens with grossly unremarkable nipples were evaluated by sagittal sections through the entire nipple and subareolar tissue. Sixteen different clinical and tumor parameters were examined to predict cancerous nipple involvement. Nipple involvement was noted in 331 of 2323 (14.2%) mastectomy specimens. Occult nipple involvement rate was 10.7% (248 cases). Occult nipple involvement usually occurs as ductal carcinoma in situ. In univariate analysis, patient age, tumor size, tumor-to-nipple distance, tumor central location, tumor type, lymph node status, lymphatic vascular invasion, histologic grade, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER-2) amplification, and multicentric or multifocal tumor were associated with positive nipple involvement. By multivariate logistic regression analysis with the entire selection process, tumor size, tumor-to-nipple distance, central location, lymph node status, lymphatic vascular invasion, HER-2 amplification, and multicentric or multifocal tumor were shown to be associated with nipple involvement by carcinoma. Nearly 90% women undergoing mastectomy did not have occult nipple involvement. NSM may be a viable option in appropriate patient selection and setting. NAC preservation would be appropriate in HER-2 negative, axillary lymph node, and lymphatic vascular negative patients with small, solitary tumors located on the periphery of the breast.

To investigate the possible roles of E-selectin and its ligand, Sialyl Lewis X, in lymph node metastasis of invasive micropapillary carcinoma of the breast, 100 cases of invasive micropapillary carcinoma and 97 cases of invasive ductal carcinoma were analyzed immunohistochemically for the expression of E-selectin and Sialyl Lewis X, along with CD34, to measure the microvessel density of invasive micropapillary carcinoma. We found that the number of E-selectin—positive vessels was greater in invasive micropapillary carcinoma than in invasive ductal carcinoma, and it was significantly correlated with the histological grade, the number of positive lymph nodes, and the microvessel density of invasive micropapillary carcinoma. The Sialyl Lewis X expression of invasive micropapillary carcinoma was higher than that of invasive ductal carcinoma, which was also associated with lymph node metastasis. In invasive micropapillary carcinoma, the Sialyl Lewis X expression was predominantly in the stroma-facing surface of the cell clusters and the adjacent stroma, while in invasive ductal carcinoma it was largely intracytoplasmic or intercellular. These findings suggested that E-selectin and Sialyl Lewis X might play an important role in lymph node metastasis in invasive micropapillary carcinoma. The expression pattern of Sialyl Lewis X in invasive micropapillary carcinoma suggested that the reversal of cell polarity of invasive micropapillary carcinoma might be as an important factor for the morphogenesis and possibly the pathogenesis, especially their higher rates of lymph node metastasis.