Accurate Nodal Staging Research Articles

PD32-08 CHOLINE PET/CT SCAN FOR THE DETECTION OF NODAL RELAPSES OF PROSTATE CANCER AFTER BIOCHEMICAL RECURRENCE: RESULTS FROM A MULTICENTRIC STUDY

INTRODUCTION AND OBJECTIVES: Recently, Glu-NH-CONH-Lys-(Ahx)-[(68)Ga(HBED-CC)] as a novel 68Gallium-labelled ligand of the prostate-specific membrane antigen (68Ga-HBEDPSMA) has been introduced for the diagnostic evaluation of prostate cancer (PCa) patients. The aim of this study was to evaluate the accuracy of preoperative 68Ga-HBED-PSMA PET with the results of postoperative histological findings after radical prostatectomy (RP) and pelvine template lymph node (LN) dissection with regard to metastatic LN involvement. METHODS: 92 consecutive patients with intermediate to highrisk PCa patients were included. All patients received 68Ga-HBEDPSMA PET hybrid imaging prior to surgery. Pelvine template LN dissection was performed according to 8 predefined anatomical fields. In all patients LN involvement was evaluated in a blinded fashion according to a 5-point scale (1 1⁄4 metastatic; 2 1⁄4 probably metastatic; 3 1⁄4 equivocal; 4 1⁄4 probably benign; 5 1⁄4 benign) on a patientand field-based manner and correlated to postoperative histological analysis. RESULTS: Due to lacking PSMA expression of the primary tumor 4 patients were excluded from further analysis. In total, 20 patients showed metastatic LN. 68Ga-HBED-PSMA PET detected 15 out of 20 patients with histological proven metastatic LN (sensitivity: 75.0%) and correctly classified all 68 patients without histological evidence of LN metastases (specificity: 100%; accuracy 94.3%; PPV: 100%; NPV: 93.2%). 5 patients without evidence of metastatic LN on imaging showed only small metastases in single LN (3 patients with one positive LN, 2 patients with two LN). In total, 470 anatomical fields could be analysed (52 with LN metastases). Sensitivity, specificity, accuracy, PPV and NPV for the field-based analysis were calculated as 73.1%, 98.6%, 95.7%, 86.4% and 96.7%, respectively. CONCLUSIONS: 68Ga-HBED-PSMA PET hybrid imaging shows a high sensitivity as well as superb specificity and accuracy for lymph node staging in intermediate to high-risk PCa patients and might replace current standard imaging (sole MRI, CT or PET using FDG or choline-based tracers) in the future.

Year in review 2014: Lung cancer, pleural diseases, respiratory infections and tuberculosis, bronchoscopic intervention and imaging.

Year in review 2014: Lung cancer, pleural diseases, respiratory infections and tuberculosis, bronchoscopic intervention and imaging.

Topographic distribution and characteristics of normal gastric regional lymph nodes on diffusion-weighted magnetic resonance imaging.

Current lack of recognition of normal gastric regional lymph nodes (GRLNs) and inherent defect of morphological imaging limit the accuracy of preoperative nodal (N) staging of gastric cancer. To map the distribution of normal GRLNs and evaluating the characteristics of GRLNs with diffusion-weighted imaging (DWI) in healthy population. Forty-nine enrolled healthy volunteers were divided into two age groups and underwent conventional magnetic resonance imaging (MRI) and DWI examinations. The characteristics of GRLNs in 14 regional stations, including short axis diameter (SD), short-to-long axis diameter ratio (SLR), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC), were recorded and compared between age groups and among different stations. The normal GRLNs were mainly distributed in station 7 in both age groups, followed by stations 3, 8, and 9. The SLR was lower in the young group than in the old group (P = 0.034) while SD, SNR, CNR, and ADC were significantly higher in the young group compared to the old group, P = 0.045, 0.041, 0.037, and 0.042, respectively. SD was different among stations in both age groups (P = 0.002, 0.001), especially bigger in station 8, and the SNRs and CNRs of stations 8 and 9 were relatively high in the old group (P = 0.031, 0.035), while there was no difference in ADC value. Better understanding of the appearances of normal GRLNs on conventional MRI and DWI may help to build more appropriate imaging criteria for GRLN assessment in gastric cancer.

Combined Evaluation of FDG-PET/CT and CT Imaging Characteristics of Cervical Lymph Nodes to Increase the Interpretation Accuracy for Nodal Metastatic Involvement in Head and Neck Cancer

Rationale and objectives: Accurate staging of regional lymph nodes in patient with head and neck squamous cell carcinoma (HNSCC) has important therapeutic and prognostic implications. The objective of this study was to assess qualitative and quantitative imaging characteristics of cervical lymph nodes on FDG PET/CT and contrast enhanced CT (CECT), either alone or in cross-modality combinations, for more accurate diagnosis of nodal metastatic involvement in HNSCC patients who had hypermetabolic cervical lymph nodes on PET/CT imaging. Materials and methods: Lymph nodes were evaluated using quantitative PET/CT parameters (SUVmax, SUVmean, metabolic tumor volume, total lesion glycolysis) and qualitative and quantitative CT parameters (shape, margin, focal hypoattenuation, fatty hilum, short axis, long axis, volume, eccentricity factor). A subset analysis was performed on FDG-avid lymph nodes that lacked imaging findings suggestive of extracapsular spread or necrosis. Statistical outcomes included sensitivity, specificity, accuracy, positive likelihood ratio, and odds ratio. Results: In the full cohort (174 nodes), the most malignancy specific parameters were ill-defined margin and focal hypoattenuation, and the most accurate variables included SUVmax, SUVmean, ill-defined margin, short axis, and focal hypoattenuation. On multivariate analysis, ill-defined margin, short axis measurement, and SUVmax independently predicted nodal metastasis. In the subgroup of smaller lymph nodes without ill-defined margin or focal hypoattenuation (100 nodes), round shape was among the most accurate and specific criteria for malignancy. Cross-modality combination criteria with SUVmax and shape, eccentricity factor, or long to short axis ratio resulted in statistically significant improvements in specificity and accuracy for lymph node metastasis. Conclusion: A combined evaluation strategy using individual PET/CT and CECT characteristics in cross modality combinations, particularly SUVmax with round shape on axial imaging or with loss of eccentricity, can improve diagnostic accuracy of malignant nodal involvement in the evaluation of indeterminate cervical lymph nodes for malignancy.

Imaging sentinel lymph nodes.

As the technique of sentinel lymph node (SLN) biopsy has evolved over the last 22 years, it has become increasingly evident that accurate SLN imaging is vital to allow surgical removal of only the true SLN(s) and not other nodes. Identifying the lymphatic collectors draining a tumor site and following them to the draining SLNs defines which nodes need to be removed for careful histologic examination. Current technology allows the exact location of each SLN to be defined. This allows the full benefits of SLN biopsy to be achieved, that is, highly accurate lymph node staging with minimal morbidity. In melanoma and breast cancer, the current practice of preoperative lymphoscintigraphy (LS) using peritumoral injections of tracer or injection adjacent to an excision biopsy site with dynamic imaging to visualize the lymphatic collectors and delayed imaging including single-photon emission computed tomography/computed tomography gives the best results. This information informs the surgical approach and allows rapid excision of the SLNs at surgery.In patients with visceral tumors where the primary cancer site is difficult to access, it appears that using fluorophores that are fluorescent under near-infrared light, injected during surgery, is evolving as the preferred technique.

The International Association for the Study of Lung Cancer Lymph Node Map: A Radiologic Atlas and Review.

Accurate lymph node staging of lung cancer is crucial in determining optimal treatment plans and predicting patient outcome. Currently used lymph node maps have been reconciled to the internationally accepted International Association for the Study of Lung Cancer (IASLC) map published in the seventh edition of TNM classification system of malignant tumours. This article provides computed tomographic illustrations of the IASLC nodal map, to facilitate its application in day-to-day clinical practice in order to increase the appropriate classification in lung cancer staging.

Detection of micro-metastases by serial sectioning and immuno-histochemical validation of sentinel nodes in patients with breast carcinoma

Background Examination of sentinel lymph node (SLN) biopsy can give accurate nodal staging for breast cancer and assist in the management of patients. Serial sectioning and immuno-histochemical (IHC) staining of SLN can improve detection of micro-metastases. Methods Twenty-five patients with clinically node-negative breast cancer were recruited. A combination of radiotracer and blue-dye were used for identification of SLN. The nodes were thinly sliced and embedded. Serial sectioning and immuno-histochemical staining against AE1/3 were done if initial H&E sections were negative. Results Three cases (12%) had no tumour at initial H&E sections but tumour was found at serial levels and with IHC validation. These were micro-metastases of less than 2 mm diameter. Four other cases with macro-metastases were found at initial H&E sections of the SLN. Three false negative cases had axillary nodal (ALN) metastases with no tumour in the SLN despite levelling and IHC staining. Discussion and conclusion Thin slicing of tissue and serial sectioning improved the detection of micro-metastases. However, immuno-histochemical validation did not additionally increase the sensitivity of detection. The presence of ALN metastases without SLN involvement could be due to discontinuous or skip metastases to non-sentinel nodes or poor technique resulting in missed detection of the SLN.

Sentinel lymph node biopsy and nodal ultrastaging in colorectal cancer.

The tumor status of the regional lymph nodes is the most important prognostic indicator in colorectal cancer (CRC), as it is in other solid tumors. Sentinel lymph node biopsy (SLNB), which has profoundly impacted the treatment of melanoma and breast cancer, has been applied in CRC in an attempt to improve nodal staging accuracy. The challenge lies in identifying patients who have tumor-negative nodes but are at high risk of regional or distant failure and therefore may benefit from adjuvant chemotherapy. Because standard pathological analysis of lymph nodes may incorrectly stage colon cancer, multiple studies have investigated nodal ultrastaging based on identification and immunohistochemical and/or molecular assessment of the sentinel node. This review focuses on the technique of SNLB, its feasibility and validity, and the controversies that remain regarding the clinical significance of nodal ultrastaging in CRC.

Characteristics of the patients with colorectal cancer: epidemiologic study or pathology report-based study.

Dear Editor, In the Iranian Red Crescent Medical Journal issue published in June 2013, I read with great interest the article entitled “Frequency of all types of colorectal tumors in the patients referred to selected hospitals in Tehran”, by Golfam et al. (1). The authors briefly and incompletely reviewed the pathologic characteristics of the patients with colorectal cancer referring to two educational hospitals of Tehran University of Medical Sciences. They explored any association between the patients’ demographic characteristics (sex and age) and the tumor characteristics (location and differentiation). Nonetheless, some important pathologic data, including the type of surgery, surgical margin status, total number of identified lymph nodes, number of positive lymph nodes, presence of lymphatic-vascular and perineural invasion, presence of obstruction and/or perforation, and primary tumor stage, have been missed. These pathologic characteristics are important indicators for defining accurate tumor and lymph node staging and predicting the prognosis (2, 3). Furthermore, the findings of this study were influenced by an institutional referral bias. Higher male/female ratio (1.9:1) and higher proportion of rectal location (60%) are the examples of institutional referral biases in comparison to large national reports (4-7). Therefore, this is an incomplete pathology report-based study rather than an epidemiologic one.

Quality indicators for EUS.

EUS has become integral to the diagnosis and staging of GI and mediastinal mass lesions and conditions. EUS-guided FNA (EUS-FNA) allows the endoscopist to obtain tissue or fluid for cytologic and chemical analysis, adding to the procedure's utility. Furthermore, the recent development of EUS-guided core biopsy techniques enables his-tologic sampling in selected cases and for obtaining tissue for molecular analysis in neoadjuvant and palliative settings. The clinical effectiveness of EUS and EUS-FNA depends on the judicious use of these techniques.

Endoscopic Ultrasonography for Tumor Node Staging and Vascular Invasion in Pancreatic Cancer: A Meta-Analysis

Background/Aims: The accurate staging of pancreatic cancer (PanCa) is crucial in the development of a stage-specific treatment plan for PanCa patients. We aimed to perform a meta-analysis of endoscopic ultrasonography (EUS) in the tumor node (TN) staging and evaluation of vascular invasion in PanCa. Methods: A meta-analysis of diagnostic accuracy parameters was performed to evaluate the EUS-based TN staging, and vascular invasion by PanCa was compared to the results of intraoperative staging or to the histopathology of resected specimens. Results: Twenty studies with 726 PanCa cases were identified from 281 articles. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 0.72, 0.90, 6.27, 0.28, and 24.69, respectively, for T1-2 staging and 0.90, 0.72, 3.58, 0.16, and 24.69, respectively, for T3-4 staging. The overall sensitivity, specificity, PLR, NLR, and DOR were 0.62, 0.74, 2.54, 0.51, and 6.67, respectively, for N staging (positive vs. negative) and 0.87, 0.92, 7.16, 0.20, and 56.19, respectively, for vascular invasion. The area under the curve was 0.90, 0.90, 0.79, and 0.94 for T1-2 staging, T3-4 staging, N staging, and vascular invasion, respectively. Conclusions: EUS is a reliable and accurate diagnostic tool for the TN staging and evaluation of vascular invasion in PanCa. The nodal staging accuracy using EUS is less satisfactory. i 2014 S. Karger AG, Basel

PB.5. Accuracy of axillary nodal staging on MRI of the breasts: correlation with ultrasound of the axilla and histopathology findings

Ultrasound (US) is routinely used for preoperative staging of the axilla in women with breast cancer but this has limitations with variable sensitivities published in the literature. Magnetic resonance imaging (MRI) of the breasts is frequently performed for preoperative staging of the breasts, and the axilla can be visualised on these scans. The aim of this study is to assess the accuracy of axillary nodal staging on MRI of the breasts.

Preoperative chemoradiation therapy decreases the number of lymph nodes resected during esophagectomy.

This study aimed to analyze the effect of preoperative chemoradiation on the adequacy of lymph node dissection. Patients with esophageal cancer treated with esophagectomy by the same surgeon between 2004 and 2011 were reviewed. Specimens were examined by the same pathologist. Patients were grouped into two depending on the type of treatment received. Forty-seven patients with curative esophagectomy were included in the study. Twenty patients had preoperative chemoradiation followed by surgery and 27 had surgery alone. Open and hybrid esophagectomy approaches were used. The average number of lymph nodes dissected was 16 ± 10 (1-39). There was a significant decrease in the number of lymph nodes examined in patients with preoperative chemoradiotherapy in comparison to surgery alone (p = 0.001). Median length of stay was 12 days. R0 resection rate was 96%. The median survival was 36.3 months, with a 42% 5-year survival. Seven patients (25%) had complete pathologic response following chemoradiation. No significant difference was recorded in terms of disease recurrence (p = 0.3). While morbidity was higher in the preoperative therapy group with 30 day mortality of 10%, type of surgical approach does not seem to influence the number of lymph nodes dissected (p = 0.7). Preoperative chemoradiation decreases the number of harvested lymph nodes following esophagectomy regardless of the surgical technique used. The optimum number of lymph nodes currently recommended to be dissected for accurate nodal staging and survival needs revision in this group of patients.

Preoperative mediastinal lymph node staging for non-small cell lung cancer: 2014 update of the 2007 ESTS guidelines.

Accurate preoperative staging and restaging of mediastinal lymph nodes in patients with potentially resectable non-small cell lung cancer (NSCLC) is of paramount importance. In 2007, the European Society of Thoracic Surgeons (ESTS) published an algorithm on preoperative mediastinal staging integrating imaging, endoscopic and surgical techniques. Over the last years more evidence of the different mediastinal staging technique has become available. Therefore, a revision of the ESTS guidelines was needed. In case of CT-enlarged or PET-positive mediastinal lymph nodes, tissue confirmation is indicated. Endosonography (EBUS/EUS) with fine needle aspiration is the first choice (when available) since it is minimally invasive and has a high sensitivity to rule in mediastinal nodal disease. If negative, surgical staging with nodal dissection or biopsy is indicated. Video-assisted mediastinoscopy is preferred over mediastinoscopy. The combined use of endoscopic staging and surgical staging results in the highest accuracy. When there are no enlarged lymph nodes on CT and when there is no uptake in lymph nodes on PET or PET-CT, direct surgical resection with systematic nodal dissection is indicated for tumors ≤3 cm located in the outer third of the lung. In central tumors or N1 nodes, preoperative mediastinal staging is indicated. The choice between endoscopic staging with EBUS/EUS and fine needle aspiration or video-assisted mediastinoscopy depends on local expertise to adhere to minimal requirements for staging. For tumors larger than 3 cm, preoperative mediastinal staging is advised, mainly in adenocarcinoma with high SUV uptake.

Intra-arterial methylene blue injection into ex vivo colorectal cancer specimens improves lymph node staging accuracy: a randomized controlled trial.

A randomized controlled trial was carried out to study the effect of a recently proposed technique of ex vivo intra-arterial methylene blue injection of the surgical specimen removed for colorectal cancer on lymph node harvest and staging. Between May 2012 and February 2013, 100 consecutive colorectal cancer resection specimens in a single institution were randomly assigned to intervention (methylene blue injection) and control (standard manual palpation technique) groups before formalin fixation. The specimen was then examined by the histopathologist for lymph nodes. Both groups were similar for age, sex, site of tumour, operation and tumour stage. In the intervention group, a higher number of nodes was found [median 23 (5-92) vs. 15 (5-37), P < 0.001], with only one specimen not achieving the recommended minimum standard of 12 nodes [1/50 (2%) vs. 8/50 (16%), P = 0.014]. However, there was no upstaging effect in the intervention group [23/50 (46.0%) vs. 20/50 (40.0%); P = 0.686]. With a significantly lower number of nodes harvested in rectal cancer, the positive effect of the intervention was particularly observed in the patients who underwent preoperative neoadjuvant radiotherapy [median 30 nodes (12-57) vs. 11 (7-15); P = 0.011; proportion of cases with < 12 nodes 0/5 vs. 5/8 (62.5%), P = 0.024]. Ex vivo intra-arterial methylene blue injection increases lymph node yield and can help to reduce the number of cases with a lower-than-recommended number of nodes, particularly in patients with rectal cancer having neoadjuvant treatment. The technique is easy to perform, cheap and saves time.

Clinical nodal staging scores for prostate cancer: a proposal for preoperative risk assessment

Background:Pelvic lymph node dissection in patients undergoing radical prostatectomy for clinically localised prostate cancer is not without morbidity and its therapeutical benefit is still a matter of debate. The objective of this study was to develop a model that allows preoperative determination of the minimum number of lymph nodes needed to be removed at radical prostatectomy to ensure true nodal status.Methods:We analysed data from 4770 patients treated with radical prostatectomy and pelvic lymph node dissection between 2000 and 2011 from eight academic centres. For external validation of our model, we used data from a cohort of 3595 patients who underwent an anatomically defined extended pelvic lymph node dissection. We estimated the sensitivity of pathological nodal staging using a beta-binomial model and developed a novel clinical (preoperative) nodal staging score (cNSS), which represents the probability that a patient has lymph node metastasis as a function of the number of examined nodes.Results:In the development and validation cohorts, the probability of missing a positive lymph node decreases with increase in the number of nodes examined. A 90% cNSS can be achieved in the development and validation cohorts by examining 1–6 nodes in cT1 and 6–8 nodes in cT2 tumours. With 11 nodes examined, patients in the development and validation cohorts achieved a cNSS of 90% and 80% with cT3 tumours, respectively.Conclusions:Pelvic lymph node dissection is the only reliable technique to ensure accurate nodal staging in patients treated with radical prostatectomy for clinically localised prostate cancer. The minimum number of examined lymph nodes needed for accurate nodal staging may be predictable, being strongly dependent on prostate cancer characteristics at diagnosis.

Invited Commentary

Invited Commentary

Invasive techniques in diagnosis and staging of lung cancer

Aim-Background During the staging process of lung cancer, accurate mediastinal lymph node staging is one of the more important factors to affect patient outcome. Accurate staging of the disease is important not only in determining prognosis but also in deciding the optimal treatment plan. The most significant treatment decision is establishing which patients can benefit from surgical resection and which should receive chemotherapy, radiation, or both. This paper reviews indications and current data regarding minimally invasive approaches for diagnosis and staging of lung cancer. In addition, current advances in diagnostic endoscopy for lung cancer will be reviewed.

Internal Mammary Sentinel Lymph Node Biopsy: Minimally Invasive Staging and Tailored Internal Mammary Radiotherapy

Internal mammary lymph node (IMLN) metastasis has a similar prognostic importance as axillary lymph nodal involvement in breast cancer patients. Even though TNM staging has incorporated the internal mammary sentinel lymph node biopsy (IM-SLNB) concept since the 6th edition of the American Joint Committee on Cancer, IMSLNB has not been performed routinely and has remained a subject of discussion. In fact, accurate staging could not be achieved by depending on the status of the axillary sentinel lymph node alone, which might lead to under-stage and under-treatment. The recent studies of Caudle et al. and Gnerlich et al. showed again that IM-SLNB was a minimally invasive technique for the efficient evaluation of the status of internal mammary sentinel lymph nodes (IMSLN) with high safety and feasibility. Gnerlich et al. reported no complications in their study, and Caudle et al. found only two intraoperative surgical complications, but both were resolved smoothly. In our current study, there is no pneumothorax on postoperative chest radiography and no postoperative bleeding. IM-SLNB had made a more accurate lymph node staging and improved the decision making of the adjuvant radiotherapy of the IMLN, and even adjuvant systemic therapy in some cases. Caudle et al. suggested that IM-SLNB should be performed in patients who revealed IM-SLN drainage by preoperative lymphoscintigraphy. Even though the success rate of IM-SLNB has reached 72–100 %, the visualization rate of IM-SLN was low (mean 13 %; range 0–37 %), which has been the restriction for both clinical study and daily practice of IM-SLNB to date. In the retrospective analysis of Caudle et al., only 71 cases (8.8 %) of 808 patients (from 1998 to 2011) underwent IM-SLNB according to preoperative lymphoscintigraphy. In order to improve the preoperative visualization rate of IM-SLN, we established a modified technology, which could significantly improve the preoperative visualization rate of the IM-SLN (70.2 %, 203/289, the latest data). With the combination of the intraoperative c-probe, the detection rate of IM-SLN could reach 77.2 % (223/289; p 0.05). The algorithm of our study is shown in Figs. 1 and 2. In the study, all patients who determined IMLN map ? (hotspot on lymphoscintigraphy and/or detected intraoperative cprobe) underwent IM-SLNB. We found the site of IMSLNs concentrated in the second and third intercostal space (85.4 %, 176/206). The involvement rate of IM-SLN was 8.8 % (17/193) when the axillary lymph nodes (ALN) were negative, and 23.3 % when the ALN were positive. These results were in accordance with the form study of extended radical mastectomy, which could reflect the accuracy of IM-SLNB indirectly. The IMLN metastases related significantly to the status of ALN. In the study of Veronesi et al., IMLN were positive in 29.1 % of patients with ALN metastases and only 9.1 % with negative ALN (p 0.001). Gnerlich et al. also confirmed that the number of the positive ALN was the only independent predictor of IM-SLN metastases. Similarly, Caudle et al. showed that 91 % (10/11) of patients with IM-SLN metastases were ALN positive. Current research of SLNB (both axillary and internal mammary) was limited to patients with clinically negative ALN. As IMLN metastases are Society of Surgical Oncology 2014

Histologic evaluation of sentinel and non-sentinel axillary lymph nodes in breast cancer by multilevel sectioning and predictors of non-sentinel metastasis.

Sentinel lymph node (SLN) provides accurate nodal staging for breast cancer. This technique has been introduced in Siriraj Hospital since 1998. The goal of this study is to assess its accuracy in predicting the state of the axilla, and compare the results of standard examination and multilevel sectioning. A retrospective analysis of 195 breast cancer patients who underwent both SLN biopsy (using dye alone as the lymphatic mapping) and axillary node dissection during 1998-2002 were analyzed. All slides including SLNs and the non-SLNs (NSLNs) were reviewed and multilevel study was performed on all SLNs and NSLNs [four levels of hematoxylin-eosin (HE) at 200 µm interval and keratin stains on the first and fourth levels]. Of 195 patients, 30% of cases were SLN-positive (32 NSLN-positive and 27 NSLN-negative). Additional study could detect positive axillary nodes 10.8% (4 SLN-positive and 5 NSLN-positive) more than standard HE stain. The false negative rate increased from 20.3% to 24.1%. The concordance between SLN and NSLN statuses was 89.7%. The sensitivity was 75.9%. By multivariate analysis, the significant predictors for axillary node metastasis were tumor size of more than 2.2 cm, histologic type of invasive ductal carcinoma (IDC), not otherwise specified (NOS) and lymphovascular invasion (LVI). By univariable analysis, the significant predictors of NSLN metastasis after positive-SLN were outer location of the tumor, LVI and perinodal extension. In conclusion, use of multilevel and immunohistochemistry increased detection of positive-SLNs. Caution should be kept in accepting SLN biopsy using peritumoral dye technique alone as the procedure for staging due to a high false-negative rate. The concordance rate of 89.7% confirmed the reliability of SLN. Outer location of tumor, LVI and perinodal extension is significant predictors of positive-NSLN after positive-SLN.