ORIGINAL ARTICLE – BREAST ONCOLOGY A Comparison of Clinical and Pathologic Assessments for the Prediction of Occult Nipple Involvement in Nipple-Sparing Mastectomies Alan Stolier, MD 1 , Jonathan C. Stone, MD 2 , Krzysztof Moroz, MD 2 , Cynthia W. Hanemann, MD 3 , Leslee McNabb, MD 3 , Steven D. Jones, MD 1 , and Michelle Lacey, PhD 4 1 Department of Surgery, Tulane University Medical Center, New Orleans, LA; 2 Department of Pathology, Tulane University Medical Center, New Orleans, LA; 3 Department of Radiology, Tulane University Medical Center, New Orleans, LA; 4 Department of Mathematics, Tulane University, New Orleans, LA ABSTRACT Background. Nipple-sparing mastectomy (NSM) for both risk reduction and cancer is increasing. In the cancer set- ting, most studies suggest the use of both clinical and intraoperative biopsy criteria in patient selection. This study examines the use of both biopsy and clinical criteria in women undergoing total nipple-removing mastectomy. Methods. The study consisted of 58 patients undergoing total mastectomy without nipple sparing. Biopsies of the subareola tissue (SA), proximal nipple (NC) contents and radial sections of the residual nipple (NR) were examined microscopically. Tumor size and distance from the nipple were also noted. Results. Using clinical criteria alone, the false negative rate was 53.8 % and a false positive rate of 44.4 %. When adding subareola and nipple core biopsies to clinical cri- teria the false negative rate fell to 7.7 % but the false positive rate remained at 44.4 %. When using only SA and NC biopsies to predict occult nipple involvement, the false negative rate was 11.8 %. In 4 cases the NC was positive while the SA was negative for cancer and in 6 cases the SA was positive and NC negative. In 2 cases both the NC and SA biopsies were negative while the NR was positive. Conclusions. This study supports a more limited role in the use of clinical criteria for evaluating patients for NSM. This maximizes the number of patients who are candidates for NSM with minimal risk of nipple involvement. It was also noted that intraoperative biopsies are not totally reli- able in predicting occult nipple involvement. A presumed advantage of nipple-sparing mastectomy (NSM) compared with standard mastectomy or skin-spar- ing mastectomy (SSM) is its typically superior cosmetic result. In fact, patient satisfaction surveys consistently demonstrate satisfaction with retention of the nipple-areola complex (NAC). 1–4 However, NSM in the cancer setting has a risk of occult cancer remaining in the nipple, which may serve as a site of local recurrence. Despite this risk, NSM continues to gain in popularity for both risk reduction and cancer treatment. 5–7 Although a current lack of uni- versally agreed upon criteria for offering NSM in the cancer setting exists, a standard approach is in develop- ment. This evolving approach includes clinical criteria, such as distance from the nipple and tumor size and intraoperative biopsies of both the tissue beneath the NAC and biopsy of tissue within the nipple papilla (nipple coring). 8–11 Many clinical criteria have been identified that seem to increase the risk of occult nipple involvement. 12–19 The criteria include factors, such as proximity of the cancer to the nipple, tumor size, axillary node involvement, multi- centricity, and lymphovascular invasion. The identification of nodal involvement, multicentricity, and lymphovascular invasion as predictive factors in identifying occult nipple involvement have been inconsistent. The most consistently identified criteria, however, have been the breast tumor size and the distance of the tumor from the nipple. 20 Conse- quently, in this study tumor size and tumor to nipple distance were used to hypothetically categorize NSM as not clinically appropriate. Ó Society of Surgical Oncology 2012 First Received: 22 January 2012 A. Stolier, MD e-mail: alanstolier1@gmail.com Ann Surg Oncol DOI 10.1245/s10434-012-2511-3