r Biomar ula ke c rs Iacuzzo et al., J Mol Biomark Diagn 2017, 8:6 le o & M D f i DOI: 10.4172/2155-9929.1000359 a o g l Journal of Molecular Biomarkers n a o n r s i u s o J ISSN: 2155-9929 & Diagnosis Research Article Open Access Evaluation of Sentinel Lymph Node Intraoperative Touch Imprint Cytology in Breast Cancer Surgery Cristiana Iacuzzo1, Marina Troian1, Laura Bonadio1, Deborah Bonazza3, Chiara Dobrinja1*, Gabriele Bellio1, Serena Scomersi1,2, Fabiola Giudici2, Fabrizio Zanconati2,3 and Marina Bortul1,2 1Department of General Surgery, University Hospital of Trieste, Azienda Sanitaria Universitaria Integrata di Trieste, Trieste, Italy 2Breast Unit, Azienda Sanitaria Universitaria Integrata di Trieste, Azienda Sanitaria Universitaria Integrata di Trieste, Italy 3Department of Histopathology, University Hospital of Trieste, Azienda Sanitaria Universitaria Integrata di Trieste, Trieste, Italy Abstract Background: One of the strongest prognostic factor for breast cancer is the regional lymph node status, which can be evaluated intraoperatively by sentinel lymph node biopsy. Many methods (e.g. frozen section, touch imprint cytology (TIC) and one-step nucleic-acid amplification) are available to detect metastatic cells in axillary lymph nodes. The aim of this study is to evaluate the feasibility of using TIC to detect metastatic cells in sentinel lymph nodes. Methods: This is a retrospective single center cohort analysis conducted on prospectively recorded data. The study included all patients admitted to the Department of General Surgery of Trieste University Hospital for invasive clinically node-negative breast cancer who underwent sentinel lymph node assessment by means of TIC. Results: Between January 2015 and December 2016, 343 patients (338 females and 5 males) underwent breast surgery and sentinel lymph node TIC. Patient’s median age was 66 (33-92) years. The sensitivity of TIC was 54% (95% C.I. 39% to 69%), whereas its specificity and accuracy were 99% (95% C.I. 98% to 100%) and 90%, respectively. The median time required to obtain the result was 20 (15-45) min. The overall cost per each TIC analysis was about 20.50€. Conclusion: Touch imprint cytology appears to be a fast, cost-effective and reliable technique to intraoperatively detect breast cancer lymph node metastasis. Keywords: Breast cancer; Touch imprint cytology; Lymph node; negative breast cancer who underwent SLN assessment by means Metastases; Axillary dissection of TIC at the Department of General Surgery, University Hospital of Trieste, between January 2015 and December 2016. Introduction During the time-frame considered, 507 surgical procedures for Breast cancer is the most common malignancy in female and the breast cancer or ductal carcinoma in situ were performed, 119 of which second cause of death in women [1]. One of the strongest predictors presented synchronous nodal metastasis and required concurrent of long-term prognosis in primary breast cancer is the regional lymph axillary dissection. Among the 388 tumors without lymph node node status [2]. Sentinel lymph-node (SLN) biopsy is currently preferred metastases, 27 patients were not eligible for the study because they over axillary dissection as the standard of care for axillary staging in presented with ductal carcinoma in situ. In 10 cases, nodal sampling early, clinically node-negative breast cancer [3]. The actual treatment was performed because of failure to identify SLN and the patients were reckons on axillary dissection in case of nodal macrometastases (i.e., thus not included in this study. 0.2-2.0 mm), whereas no further surgical treatment is required if no metastases are found [2-4]. The significance of occult micrometastases Preoperative evaluation is still controversial, but recent studies reported that surgical treatment Breast Imaging-Reporting and Data System (BI-RADS®) of the for occult micrometastases could be avoided since it does not appear to American College of Radiology was used to refer to breast composition improve survival [5-7]. categories and to assess categories for mammogram, ultrasound (US) Several methods are available to intraoperatively detect metastatic and magnetic resonance imaging (MRI) [10]. cells in axillary lymph nodes. The most common ones include frozen All patients with suspected breast lesions at mammogram and section (FS), touch imprint cytology (TIC) [8] and one-step nucleic- breast ultrasound (US) underwent either US-guided fine-needle acid amplification (OSNA) [9]. The aim of this study is to evaluate the feasibility of using TIC to detect metastatic cells in sentinel lymph nodes. *Corresponding author: Chiara Dobrinja, Department of General Surgery, University Hospital of Trieste, Azienda Sanitaria Universitaria Integrata di Trieste, Materials and Methods Trieste, Italy, Tel: +39 0403994152; E-mail: [email protected] This is a retrospective single center cohort analysis conducted on Received May 24, 2017; Accepted July 16, 2017; Published July 18, 2017 prospectively recorded data extracted from the database of the Breast Unit Citation: Iacuzzo C, Troian M, Bonadio L, Bonazza D, Dobrinja C, et al. (2017) of Trieste University Hospital, Italy. The database collected all patients Evaluation of Sentinel Lymph Node Intraoperative Touch Imprint Cytology in Breast affected by both benign and malignant breast pathologies since 2004. Cancer Surgery. J Mol Biomark Diagn 8: 359. doi: 10.4172/2155-9929.1000359 Copyright: © 2017 Iacuzzo C, et al. This is an open-access article distributed under Eligibility the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and This study included all patients with invasive clinically node- source are credited. J Mol Biomark Diagn, an open access journal Volume 8 • Issue 6 • 1000359 ISSN:2155-9929 Citation: Iacuzzo C, Troian M, Bonadio L, Bonazza D, Dobrinja C, et al. (2017) Evaluation of Sentinel Lymph Node Intraoperative Touch Imprint Cytology in Breast Cancer Surgery. J Mol Biomark Diagn 8: 359. doi: 10.4172/2155-9929.1000359 Page 2 of 5 aspiration cytology (FNAC) or a stereotactic biopsy to obtain a definitive diagnosis. Axillary US was always performed preoperatively to evaluate the nodal status. If abnormal lymph nodes were detected on imaging, a FNAC was carried out to confirm a possible nodal involvement. All patients with certain diagnosis of invasive breast cancer were visited by a skilled breast surgeon. Surgical treatment All cases were preoperatively analyzed on a multidisciplinary meeting by the members of the Breast Unit of Trieste University Hospital, officially recognized by the European Society of Mastology (EUSOMA) in 2016. Surgical treatment was decided according to: breast volume – Figure 1: Touch imprint citology, x40 hematoxylin-eosin stain, of axillary lymph- tumor dimension ratio, molecular subtypes (when available), and node: single and clustered carcinomatous elements with glandular morphology patient preference. All patients underwent either breast conservative on a background of lymphocytic elements. surgery (i.e., quadrantectomy) or mastectomy. determined using fluorescence in situ hybridization. Ki-67 values were Patients without nodal involvement underwent SLN biopsy. measured as the percentage of positively stained malignant cells among Lymphoscintigraphy was performed 24 hours before surgery in all the total number of tumour cells assessed. A Ki-67 cut-off point of 20% these patients and the radioactive axillary SLN was intraoperatively was defined to separate low from high proliferation grade. [15]. Tumors localized by means of a gamma probe. SLNs were analyzed during were classified according to the St. Gallen in 2013 guidelines [16]. surgery using TIC to detect axillary metastasis. An axillary node dissection was carried out whenever macrometastases were detected by Statistical analysis TIC in the SLN. All surgical procedures were performed by two expert breast surgeons. Statistical analyses were performed using R software (version 3.0.3). Quantitative data are reported as mean ± standard deviation (SD) Touch imprint cytology technique and median (range). Qualitative variables are expressed as number of patients and percentages. We evaluated the performance of TIC The technique used to perform TIC analysis was the same computing sensitivity (SN), specificity (SP), positive predictive value as described elsewhere [11]. The SLN harvested by the surgeon (PPV) and negative predictive value (NPV). Every diagnostic parameter was immediately sent to the cytopathologist, who was aware of (SN, SP, PPV, NPV) is reported with confidence interval (C.I.) at 95%. the examination to perform. The SLN was then isolated from the surrounding fat and divided. One surface of the nodal section was used Results to prepare a cellular smear, scraping it with a slide and then smearing this material on to a second slide. The second slide was fixed in 95% Between January 2015 and December 2016, 343 patients (338 (99%) alcohol, stained with hematoxylin and eosin and then used to detect females and 5 (1%) males) underwent breast surgery and SLN TIC for possible metastatic cells. Each section of each SLN retrieved was used clinically node-negative invasive breast cancer. to prepare touch imprint slides (Figure 1). Patient and tumor characteristics Post-operative staging Patient’s median age was 66 (33-92 years). As reported in Table 1, most Breast cancers stage was defined according to the American patients