Comparison Between Positive And False-Negative Sentinel Lymph Nodes In Breast Cancer Patients

Abstract Background: Intra-operative sentinel node biopsy (SNB) is performed for clinically node negative invasive carcinoma (IC). Despite a negative result for metastasis from rapid frozen section (FS) diagnosis of intra-operative SNB, some cases may be diagnosed positive when permanent sections (PS) are analyzed (i.e., false negative). In order to reduce the false-negative rate, it is necessary to determine why macrometastases measuring greater than 2 mm cannot be accurately diagnosed using frozen specimens. The aim of this study was to compare the pathological characteristics of false-negative and positive cases of macrometastasis using FSs. We also reviewed whether there were differences in postoperative prognoses between positive and false-negative cases. Methods: We retrospectively reviewed 1632 intra-operative SNBs collected from 2008 to 2011 at St. Luke’s International Hospital, Tokyo, JAPAN. Of these, 980 patients had undergone surgery for the treatment of IC without neoadjuvant chemotherapy. Lymph nodes were sectioned every 2 mm and examined. For FSs, we performed hematoxylin and eosin (HE) staining, and for PSs, we used HE and cytokeratin (AE1/AE3) staining. Image J (NIH Image, Bethesda, MD, USA) was used for assessment of the metastatic area of lymph nodes. Micro- and macrometastases were defined as metastatic lesions measuring between 0.2 and 2 mm or measuring 2 mm or more, according to TMN classification. Results: Using FSs, we identified 104 patients (10.6%) who were positive for macrometastasis, 16 patients (1.6%) who were positive for micrometastasis, and 860 patients (87.8%) who were negative for metastasis. Of the negative cases, the result was changed to micrometastasis in 37 cases (4.3%) and to macrometastasis (false-negative cases) in 14 cases (1.6%). Ten of the 14 patients did not have additional axillary lymph nodes dissection. The mean age of the patients was 55.1 ± 3.1 years for false-negative cases and 52.3 ± 1.2 years for positive cases. In terms of histological features, there were statistically significant differences between false-negative and positive cases for invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and IDC plus ILC (p < 0.05). There were no statistically significant differences between false-negative and positive cases in terms of the total number of slices for lymph nodes (8.4 ± 1.6 vs. 9.7 ± 0.6, respectively; p = 0.41) but tendency in the number of slices for metastases (2.4 ± 1.2 vs. 4.8 ± 0.5, respectively; p = 0.07). The maximum area ratio of metastasis was significantly lower in false-negative cases than in positive cases (3.0% ± 0.1% vs. 20.0% ± 0.2%, respectively; p < 0.05). There was no significant difference in disease-free survival between false-negative and positive cases (p = 0.43). Conclusions: Although it is necessary to reduce false-negative cases, no difference in prognosis was detected in our study. False-negative cases had lower metastasis area ratios than positive cases diagnosed using rapid diagnosis of intra-operative SNBs, and ILC is known to be high in histological features. Therefore, using AE1/AE3 stain together with rapid diagnosis of intra-operative SNBs may lower the false-negative rate when a diagnosis includes ILC in pre-operation analysis. Citation Format: Eriko Abe, Naoki Hayashi, Toshinao Onoda, Yang Yang, Mieko Uno, Hideko Yamauchi, Sachiko Ohde, Koyu Suzuki. Comparison between positive and false-negative sentinel lymph nodes in breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-32.