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Background: In cervical cancer, presence of lymph-node macrometastases (MAC) is a major prognostic factor and an indication for adjuvant treatment. However, since clinical impact of micrometastases (MIC) and isolated tumor-cells (ITC) remains controversial, we sought to identify a cut-off value for the metastasis size not associated with negative prognosis. Methods: We analyzed data from 967 cervical cancer patients (T1a1L1-T2b) registered in the SCCAN (Surveillance in Cervical CANcer) database, who underwent primary surgical treatment, including sentinel lymph-node (SLN) biopsy with pathological ultrastaging. The size of SLN metastasis was considered a continuous variable and multiple testing was performed for cut-off values of 0.01-1.0 mm. Disease-free survival (DFS) was compared between N0 and subgroups of N1 patients defined by cut-off ranges. Results: LN metastases were found in 172 (18%) patients, classified as MAC, MIC, and ITC in 79, 54, and 39 patients, respectively. DFS was shorter in patients with MAC (HR 2.20, P = 0.003) and MIC (HR 2.87, P < 0.001), while not differing between MAC/MIC (P = 0.484). DFS in the ITC subgroup was neither different from N0 (P = 0.127) nor from MIC/MAC subgroups (P = 0.449). Cut-off analysis revealed significantly shorter DFS compared to N0 in all subgroups with metastases ≥0.4 mm (HR 2.311, P = 0.04). The significance of metastases

Purpose: Factors affecting local outcome were evaluated in patients with clinically node-positive (cN+) breast cancer at diagnosis, who underwent sentinel lymph node biopsy (SLNB) alone after neoadjuvant chemotherapy (NAC). Methods: Between 2004 and 2018, 303 cytopathology-proven cN (+) patients in a multicentric registry, who received NAC and underwent SLNB alone were analysed. All patients had regional nodal irradiation. Results: Median age was 46 (23-70). Of those, 211 patients had ypN0 disease (69.6%), whereas 92 pa-tients had ypN (+) disease including 19 (20.6%) isolated tumor cells (ITC), 33 micrometastases (35.9%) and 40 macrometastases (43.5%). At a median follow-up of 36 months (24-172), one patient (0.3%) with macrometastatic SLN was found to have locoregional recurrence as chest wall and supraclavicular LN metastases at the 60th month. Five-year disease-free survival (DFS) and disease specific survival (DSS) rates were 87% and 95%, respectively. Patients with cT3/4 (HR = 2.41, 95% CI; 1.14-5.07), non-luminal molecular pathology (HR = 2.60, 95% CI, 1.16-5.82), and non-pCR in the breast (HR = 2.11, 95% CI, 0.89-5.01) were found to have an increased HR compared to others in 5-year DFS. However, no dif-ference could be found between ypN0 and ypN ITC and micrometastasis (HR = 1.23, 95% CI, 0.44-3.47), whereas there was a slight increase in HR of patients with ypN macrometastasis versus ypN0 (HR = 1.91, 95% CI, 0.63-5.79). Conclusion: ALND could be avoided in meticulously selected cN (+) patients who underwent SLNB after NAC having breast and/or nodal pCR, cT1-2, or low volume residual nodal disease with luminal pa-thology, as long as axillary radiotherapy is provided. (c) 2021 Published by Elsevier Ltd., Istanbul Breast Society, This project has been supported by the Istanbul Breast Society.

Detection of nodal micrometastasis (tumor size: 0.2–2.0 mm) is challenging for pathologists due to the small size of metastatic foci. Since lymph nodes with micrometastasis are counted as positive nodes, detecting micrometastasis is crucial for accurate pathologic staging of colorectal cancer. Previously, deep learning algorithms developed with manually annotated images performed well in identifying micrometastasis of breast cancer in sentinel lymph nodes. However, the process of manual annotation is labor intensive and time consuming. Multiple instance learning was later used to identify metastatic breast cancer without manual annotation, but its performance appears worse in detecting micrometastasis. Here, we developed a deep learning model using whole-slide images of regional lymph nodes of colorectal cancer with only a slide-level label (either a positive or negative slide). The training, validation, and testing sets included 1963, 219, and 1000 slides, respectively. A supercomputer TAIWANIA 2 was used to train a deep learning model to identify metastasis. At slide level, our algorithm performed well in identifying both macrometastasis (tumor size > 2.0 mm) and micrometastasis with an area under the receiver operating characteristics curve (AUC) of 0.9993 and 0.9956, respectively. Since most of our slides had more than one lymph node, we then tested the performance of our algorithm on 538 single-lymph node images randomly cropped from the testing set. At single-lymph node level, our algorithm maintained good performance in identifying macrometastasis and micrometastasis with an AUC of 0.9944 and 0.9476, respectively. Visualization using class activation mapping confirmed that our model identified nodal metastasis based on areas of tumor cells. Our results demonstrate for the first time that micrometastasis could be detected by deep learning on whole-slide images without manual annotation.

Objective This study evaluated diagnostic accuracy of intraoperative sentinel lymph node (SLN) frozen section examination and scrape cytology as a possible solution for management of SLN positive patients. Study design Clinically early-stage endometrial cancer patients who underwent SLN algorithm and intraoperative SLN examination were analyzed. Findings were compared with final pathology results and diagnostic accuracy of frozen section and scrape cytology were evaluated. Results Of the 208 eligible patients, 100 patients (48 %) had frozen section examination and 108 (52 %) had scrape cytology of the SLN. Intraoperative examination and final pathology were negative for metastasis in 187/208 (90 %) cases. The rest 21 cases had metastatic SLNs according to final pathology. 12 of 21 (57 %) metastases were classified as macrometastasis. Intraoperative examination of SLNs correctly identified 13 cases (true positive) and missed 8 cases (false negative). Five of 8 false negative cases had micrometastasis or isolated tumor cells. Considering identification of macrometastasis, sensitivity and negative predictive value were 85.71 % and 98.94 %, respectively, for the frozen section and 60.00 % and 98.15 %, respectively, for the scrape cytology. Conclusion Frozen section examination of SLN has higher sensitivity in detecting macrometastasis compared to scrape cytology and it could help the surgeon in decision for further lymphadenectomy intraoperatively.

Objective To identify predictors of extensive lymphatic dissemination and distant recurrences in node-positive endometrial cancer (EC). Methods Clinicopathologic data were collected of patients who had fully staged EC with at least 1 positive lymph node. Permanent sections of metastatic lymph nodes were reviewed; metastases were characterized according to size (≤2 mm and >2 mm) and location in the lymph node (intra- vs extracapsular). Risk of occurrence of multiple pelvic and para-aortic lymph node dissemination was calculated by combining risk factors identified at multivariate analysis. Results Of 96 patients, 85 had positive pelvic nodes, of whom 71 (83.5%) had high-volume metastases. In the presence of both macrometastasis in the pelvic basin (odds ratio [OR], 13.42; [95% CI, 2.44–73.83]) and uterine serosal involvement of the tumor at final pathologic evaluation (OR, 11.84 [95% CI, 1.22–115.11]), multiple pelvic node dissemination occurred in 91.7% of cases (vs 7.7% in the absence of both). Concomitant presence of pelvic macrometastasis, lymphovascular space invasion (LVSI), and extracapsular invasion led to 85.7% occurrence of para-aortic involvement (vs 11.1% if no factors present). LVSI was independently associated with nonvaginal recurrences (hazard ratio, 2.62 [95% CI, 1.33–5.16]). Conclusions Presence of high-volume metastases in the pelvic lymph nodes is associated with concomitant presence of multiple positive pelvic nodes, as well as para-aortic node involvement. LVSI is associated with both para-aortic node involvement and occurrence of nonvaginal relapses. In this era of sentinel lymph node mapping, these factors may help predict the extent of lymphatic dissemination in EC.

An application of FTIR spectroscopic imaging for the identification and visualization of early micrometastasis from breast cancer to lungs in a murine model is shown. Spectroscopic and histological examination is focused on lung cross-sections derived from animals at the early phase of metastasis (early micrometastasis, EM) as compared to healthy control (HC) and late phase of metastasis (advanced macrometastasis, AM) using murine model of metastatic breast cancer with 4T1 cells orthotopically inoculated. FTIR imaging allows for a detailed, objective and label-free differentiation and visualization of EM foci including large and small micrometastases as well as single cancer cells grouped in clusters. An effect of the EM phase on the entire lung tissue matrix as well as characteristic biochemical profiles for HC and advanced macrometastasis were determined from morphological and spectroscopic points of view. The extraordinary sensitivity of FTIR imaging toward EM detection and discrimination of AM borders confirms its applicability as a complementary tool for the histopathological assessment of the metastatic cancer progression.

Background Sentinel lymph node (SLN) biopsy is the current prognostic tool for clinically node-negative breast cancer patients. If the SLN reveals macrometastasis, axillary lymph node dissection (ALND) is recommended. However, the use of ALND in patients with micrometastasis is debated. The objective of this study was to assess the utilization of ALND in the treatment of micrometastatic breast cancer. Methods An IRB approved, retrospective study of a pooled dataset of breast cancer patients with micrometastatic disease on SLN biopsy was performed. Patients diagnosed from 1999-2016 were identified via query of a single-institution National Comprehensive Cancer Network (NCCN) breast cancer database as well as a prospective tumor board. Results A total of 91 patients were diagnosed with micrometastatic nodal disease. The median age at diagnosis was 56 y (range: 31-85); median follow-up time was 47 mo (range: 0-203 mo). 42/91(46.2%) patients had ALND of which 37/42 (88.1%) were a second operation; 3/42(7.1%) patients had additional positive nodes found at ALND. 44/91 (48.4%) patients received radiation. 7/91 (7.7%) patients had a recurrence, 5/7 local, including one axillary (2.1%; patient declined ALND). Conclusions Given that the risk of lymphedema after ALND ranges between 20%-53%, the morbidity of ALND may far exceed the likelihood of detecting further nodal involvement in women with micrometastatic disease: 7.1% in this series.

Background Recent clinical trials have shown that axillary lymph node dissection can be omitted even with positive sentinel nodes (SN) unless the patient undergoes total mastectomy without irradiation. The aim of our study was to identify predictive factors for non-SN metastasis among patients with solitary or multiple breast cancer treated with total mastectomy. Patients and Methods Clinically node-negative breast cancer patients with pathologically node-positive disease treated with total mastectomy and axillary dissection after SN biopsy were retrospectively analyzed. Significant pathologic predictive factors for positive non-SN metastasis were also examined. Results There were 47 multiple and 143 solitary breast cancer patients. Pathologic diagnosis demonstrated that smaller invasion size but larger tumor size, including adjacent noninvasive cancer, was observed in multiple breast cancer. The number of involved SNs and the rate of non-SN metastasis were similar between the multiple and solitary groups. Regarding predictive factors for non-SN metastasis, lymphatic invasion and SN macrometastasis were significant factors in the solitary group, and pathologic invasion size > 2 cm was the only significant factor in the multiple group. Conclusion Larger pathologic invasion size was important for predicting non-SN metastasis in multiple breast cancer.

Background Z0011 study suggests patients with minimal disease do not require axillary clearance. Exclusions include T3 tumours, mastectomy or neoadjuvant treatment. This study assessed the utility of pre-operative US-guided core biopsy of axillary nodes and its correlation with nodal macrometastases. Methods 247 women with breast cancer outside Z0011 criteria were reviewed retrospectively. Sensitivity and specificity of pre-operative axillary ultrasound and core biopsy compared to final histology was assessed by contingency tables. Results 75/247 patients had macrometastases. Ultrasound-axilla was 72% sensitive and 77% specific in predicting macrometastasis. The positive (PPV) and negative predictive value (NPV) was 58% and 86.4% respectively. Core-biopsy of axilla node, was 92.6% sensitive and 66.7% specific in detecting macrometastasis. PPV and NPV 79.4% and 86.7% respectively. Conclusion Positive pre-operative ultrasound-guided core biopsy accurately predicts macroscopic involvement of axillary nodes. Selected patients outside Z0011 parameters can proceed to axillary clearance without sentinel node biopsy or risking overtreatment.

Aim To assess the influence of time on the reliability of sentinel lymph node biopsy (SLNB) in breast cancer patients with previous excisional biopsy (EB), analyzing both the sentinel lymph node detection and the lymph node recurrence rate. Materials and methods Thirty-six patients with cT1/T2 N0 breast cancer and previous EB of the lesion underwent a lymphoscintigraphy after subdermal periareolar administration of radiocolloid, the day before SLNB. Patients were classified into two groups, one including 12 patients with up to 29 days elapsed between EB and SLNB (group A), and another with the remaining 24 in which time between both procedures was of 30 days or more (group B). Scintigraphic and surgical detection of the sentinel lymph node, histological status of the sentinel lymph node and of the axillary lymph node dissection, if performed, and lymphatic recurrences during follow-up, were analyzed. Results Sentinel lymph node visualization at the lymphoscintigraphy and surgical detection was 100% in both groups. Histologically, three patients showed macrometastasis in the sentinel lymph node, one from group A and two from group B. None of the patients, not even those with malignancy of the sentinel lymph node, relapsed after a medium follow-up of 49.5 months (24–75). Conclusion Time elapsed between EB and SLNB does not influence the reliability of this latter technique as long as a superficial injection of the radiopharmaceutical is performed, proving a very high detection rate of the sentinel lymph node without evidence of lymphatic relapse during follow-up.

Background The management of the axilla in the presence of positive sentinel lymph node (SLN) remains controversial. Many centres forgo completion axillary lymph node dissection (cALND) in the presence of micrometastatic disease. The American College of Surgeons Oncology Group (ACOSOG) Z0011 trialists argue for extending this to macrometastasis. The aim of this study was to correlate tumour burden in SLNs with that in the residual lymph node basin to determine the likelihood of residual disease in patients with micro- and macrometastasis in the SLN. Methods Patients who underwent cALND following a positive SLN were analysed for histopathological features of the primary tumour and burden of axillary disease. Results Of 155 patients, 115 (74%) had macrometastases and 40 (26%) micrometastases in the SLNs. Residual axillary disease was detected in 55/155 (35%) patients with macrometastases and 4/40 (10%) with micrometastases. Generally, with increasing size of metastasis in the SLN there was an increasing risk of further disease in residual lymph nodes. Logistic regression analysis showed increased odds ratios for further disease for all groups when compared with the Conclusion Patients may be advised to forgo cALND where the SLN contains isolated tumour cells or micrometastasis. Recommendations for proceeding to cALND can be based on the size of metastasis in the SLN, which relates to the risk of further disease in the residual axillary lymph nodes and subsequent regional recurrence.

Background With the advent of taxanes and targeted agents in neoadjuvant chemotherapy (NACT) for breast cancer, the rates of pathologic complete response (pCR) have been steadily increasing. One of the roles of surgery in these women is to serve the purpose of a biopsy to confirm or negate a pCR. Methods We conducted a prospective validation study. Women who had undergone a titanium clip placement followed by neoadjuvant chemotherapy (NACT), and achieved a complete/near complete clinical and radiological response were included. Eligible women underwent an MRI of the breast followed by a US guided core biopsy (CNB) of the tumour bed. The CNB was compared with the final histopathology report after definitive surgery. Results 65 patients were recruited in this study, of whom 75% had T1/2 tumours and 39 women had hormone negative tumours. The overall rate of pCR in the breast (BrpCR) was 42%. Among women with BrpCR, only one patient had residual disease in the axilla (macrometastasis). The mean number of CNB of the tumour bed after NACT was 4. The accuracy of CNB in predicting BrpCR was 69%, with a false negative rate (FNR) of 14.8%. In a pre-planned sub-group analysis of hormone negative tumours, the FNR was 9.5%. No untoward side effects were observed in any of the patients. Conclusions Ultrasound guided CNB of the tumor bed was useful in predicting BrpCR, especially in hormone negative tumours, with an FNR of 9.5%. Increasing the number of cores in the biopsy or changing the imaging modality could help in improving the accuracy of this method. Clinical trial identification CTRI/2018/01/011122. Legal entity responsible for the study The authors. Funding Hyderabad Cancer Foundation. Disclosure All authors have declared no conflicts of interest.

Background Intraoperative frozen section (IFS) examination of sentinel lymph nodes (SLN) is useful in selecting patients with invasive breast cancer for immediate axillary lymph node dissection. However, whether IFS evaluation of the SLNs in ductal carcinoma in situ (DCIS) of the breast has any value has not been previously assessed. Methods Clinicopathologic data from patients with DCIS who underwent resection with SLN biopsy (2004-2010) were collected to assess the sensitivity, specificity, and accuracy of IFS, and its impact on axillary management. Results A total of 267 patients with DCIS underwent resection with SLN biopsy and IFS evaluation. Preoperative pathology was DCIS (n = 231), DCIS with microinvasion (n = 24), and DCIS with other lesions (n = 12). Fifty-two (19.5%) patients had invasive breast cancer on final pathology. SLN metastases were identified in 13 (4.8%) patients; however, only 4 (1.5%) were IFS positive. IFS examination was negative in 263 (98.5%) patients. Among patients with SLN metastases, the most common pattern of metastases was either micrometastasis (n = 6) or immunohistochemistry-positive individual tumor cells (n = 4), whereas 3 patients had a macrometastasis. IFS examination was falsely negative in 9 of these 13 patients for a false-negative rate of 69.3%, and a sensitivity and specificity of 31% and 100% respectively. Nine of the 13 patients underwent axillary lymph node dissection and only 1 patient had further axillary metastasis. Conclusions SLN metastases in DCIS is rare and most commonly involves SLN micrometastasis or immunohistochemistry-positive individual tumor cells. SLN IFS evaluation in DCIS has a low yield and sensitivity, and can be safely omitted to reduce operative duration and cost.

Objective The one-step nucleic acid amplification (OSNA) assay can assess an entire lymph node and detect clinically relevant metastases quantified based on cytokeratin 19 (CK19) mRNA copy number. The OSNA assay of all sentinel lymph nodes (SNs) and non-sentinel nodes (non-SNs) allows for the accurate measurement of tumour burden in either situation. We aim to reveal the usefulness of the OSNA assay regarding the prediction of non-SN metastasis. Methods The subjects consisted of 185 breast cancer patients who underwent axillary dissection after a metastatic SN biopsy and whose SNs and non-SNs were examined using the OSNA whole-node assay between 2009 and 2011. The non-SN tumour burden was classified as macrometastasis (CK19 mRNA ⩾5000 copies/μl) or micrometastasis (250–5000 copies/μl). The relationship between SN and non-SN tumour burdens and predictors of non-SN metastasis were investigated. Results Among these 185 patients, 38 patients (20.5%) had macrometastasis and 58 (31.4%) had micrometastasis only in the non-SNs. Non-SN macrometastasis rates increased in direct proportion to the SN copy number: approximately 5% in patients with SNs with 250–500 copies; 20%, 500–5000 copies and 30%, ⩾5000 copies. However, non-SN micrometastasis rates were approximately 30% regardless of the SN copy number. In multivariate analyses, the mean SN copy number, number of macrometastatic SN and lymphovascular invasion were significant for identifying non-SN macrometastases. Conclusions The SN tumour burden quantified using the OSNA assay predicts non-SN metastases. A novel mathematical model to predict the non-SN tumour burden can be generated using the results of the OSNA assay.

International audience; BACKGROUND: Pure Tubular Carcinoma (PTC) of the breast is a rare histological subtype of invasive breast cancer characterized by a low rate of lymph node involvement. Currently there is no consensus on less surgical axillary node staging according to this histological subtype. METHODS: We performed a retrospective multi-institutional study. Inclusion criteria were PTC, sentinel lymph node detection (SLND) and conservative breast surgery. RESULTS: From January 1999 to December 2006, 234 patients were included in the study from 9 institutions. The median pathological tumor size was 9.59 (1-22) mm. SLN were successfully detected in 98% (229/234) of patients. Among the 234 patients, a macrometastasis was found in 6 cases (2.5%), micrometastasis in 15 cases (6.4%), and isolated cells in 2 cases (0.8%). In the case of patients with SLND macrometastasis, half of them had macrometastasis in the complementary axillary lymphadenectomy, and none in the case of SLN only micrometastasis or isolated cells. Of the 122 patients with a pathological tumor size 10 mm) was the only parameter significatively linked to the risk of lymph node involvement (p = 0.007). CONCLUSION: In a large multi-institutional series with SLND, we have shown that the risk of axillary lymph node involvement in PTC is very low. In the case of PTC

Although the metastatic rate of cutaneous squamous cell carcinoma (SCC) is low, detailed examination for the presence of micro- and macrometastasis of lymph nodes is crucial in avoiding the devastating outcomes and in planning appropriate treatment. Cutaneous SCC of the head and neck can spread to parotid lymph nodes, cervical lymph nodes, or both, depending on the location of the primary tumor. Therefore, clinical and radiologic evaluation of the parotid and neck should be performed in patients with cutaneous SCC. Optimal treatment of metastatic cutaneous SCC of the head and neck should consist of complete surgical resection with adjuvant radiotherapy.

Background We evaluated the usefulness of axillary ultrasound (US) in patients with core biopsy–proven ductal carcinoma in situ (DCIS). Methods Preoperative axillary US, fine-needle aspiration (FNA), and sentinel lymph node (SLN) data from women with DCIS were reviewed. Results Eighty-two women with DCIS underwent axillary US. In 16 women (19.5%) US was abnormal; however, FNA was negative in all cases. Sixty-one women (74%) underwent SLN surgery; 2 were positive for macrometastasis (3%) and 1 had isolated tumor cells. None of them had an abnormal US. Axillary US did not change the management in any of the cases. Conclusions Axillary US and FNA did not change the management in any of the 82 cases. In women with a core biopsy diagnosis of DCIS, positive nodes are uncommon and unlikely to be detected by axillary US. Routine preoperative axillary US is not recommended for pure DCIS on core biopsy.

In a significant proportion of patients, the sentinel lymph node (SLN) is the only involved axillary node. The goal of the present study was to identify predictive factors associated with a positive SLN and with a positive non-SLN in patients in whom axillary lymph node dissection (ALND) was performed.Data was reviewed for patients with T1-2 invasive breast cancer who underwent SLN biopsy with or without axillary dissection in a single institution between July 2000 and May 2010. The SLNs were examined by serial sectioning and HE staining, and by cytokeratin immunostaining in suspicious cases.Of 332 patients with SLNB, 134 had SLN positivity, and 116 of them further underwent completion axillary dissection. Patients with T2 tumors (OR=3.2; 95% CI, 1.74-5.58), or tumors with lymphovascular invasion (OR=8.0; 95% CI, 4.44-14.27), or invasive ductal cancer (OR=2.92; 95% CI, 1.1-8.0) were more likely to have a positive SLN. In patients with ALND, the non-SLN involvement rates were 10%, 11.5% and 50% in patients with isolated tumor cells (ITC), micrometastasis and macrometastasis, respectively. Finding of ITC or micrometastasis in SLNs (OR=0.28; 95% CI, 0.08-0.99) or presence of extracapsular invasion (ECI) in SLN (OR=0.24; 95% CI, 0.09-0.67) were the predictive factors of not having a non-SLN metastasis in logistic regression analysis.These findings suggest further axillary surgery can be best omitted in patients with micrometastasis while validation of nomograms including factors such as ECI are still needed to be studied in patients with macrometastasis.

Objectives Sentinel lymph node (SLN) biopsy is a surgical procedure proposed in early cervical cancer. This technique yields the potential interest to reduce the morbidity of complete lymphadenectomy, which could then be performed only in case of positive SLN. Intraoperative examination has a major per-operative role in predicting nodal involvement and preventing a second step procedure. The aim of this study was to assess the diagnostic value of intraoperative examination with frozen section (FS) or imprint cytology (IC) of SLNs in early cervical cancer. Methods Prospective study in 7 centers (01/2005–06/2007) including patients with stage IA1 and lymphovascular space involvement to IB1 cervical cancer (squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma). SLNs were detected with a combined method (Tc99m+blue dye) and then removed laparoscopically. Intraoperative examination (FS or IC) was not systematically performed but recommended in case of macroscopical nodal enlargement in 5 centers. Results of intraoperative examination were compared with final histology performed by Hematoxylin–Eosin–Safran staining and immunohistochemistry. The diagnostic value of intraoperative examination was calculated. Results One hundred and thirty-nine patients were analyzed in the study. The combined detection rate was 97.8% per patient, with 454 detected SLNs. One hundred and two patients (73.4%) had an intraoperative examination (97 patients with FS and 5 with IC). Among patients with intraoperative examination, 5 SLNs were positive (all with macrometastasis at final histology), as compared with 22 metastatic nodes at final result. The 17 false negative SLNs were: 4 macrometastasis, 4 micrometastasis and 9 isolated tumor cells. Sensitivity of the intraoperative examination per node was 20.7% [95%CI: 7.8%–45.4%] and the negative predictive value 93.0% [95%CI: 89.0%–95.9%]. Conclusions Intraoperative examination of SLNs by FS and IC has a poor diagnostic value. This is mainly related to micrometastasis and isolated tumor cells, which are not detected by intraoperative techniques. Other techniques, like new molecular assays, should be investigated to improve intraoperative assessment of SLNs.

Introduction: The aim of this study is to validate the predictive value of the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and the Tenon score system in our sentinel lymph node (SLN)-positive series, and to define their actual usefulness when applied to the subgroup of patients with micrometastasis in SLN. Patients and Methods: The study population consisted of 95 patients: 68 with macrometastasis and 27 with micrometastasis in the SLN. The predicted probability of non-SLN metastasis was calculated for each patient by using a computerized model from the MSKCC Web site. Furthermore, we have applied the Tenon score to our dataset. The receiver operating charac- teristic (ROC) curves were drawn and the areas under the curve (AUCs) were calculated to assess the discriminative power of the nomograms. The ROCs and relative AUCs were calculated both for all the patients in the study and for 2 subgroups. Results: The AUC for the entire study population was 0.720 in MSKCC nomogram: and 0.754 in Tenon nomogram. In 68 patients with macrometastasis in SLN, the AUC was 0.760 in MSKCC nomogram and 0.707 in Tenon score. Micrometastasis in SLN were found in 27 patients: AUC was 0.595 in MSKCC nomogram and 0.734 in Tenon score. Conclusion: In our results the MSKCC nomogram did not provide a reliable predictive model for identi- fying patients with low risk of non-SLN metastasis in the event of micrometastasis in SLN. Our validation study shows that the Tenon score is more accurate and useful in patients with micrometastasis in SLN.

Aim The study of the sentinel node has made it possible to obtain more comprehensive knowledge about the extent of axillary involvement in breast cancer. It has also decreased the surgical morbidity associated to the surgical examination of the axilla. The systematic use of immunohistochemical staining and molecular biology techniques improves the ability to detect the presence of micrometastasis or isolated tumor cells in a significant number of cases when this is the only sign of the lymph node extension of the disease. The possibility of avoiding complete axillary lymphadenectomy in those patients who are only affected by micrometastasis is proposed because of the low incidence of further involvement of the remaining lymph nodes. Material and method 159 patients diagnosed of stage T1 or T2 breast cancer, in which the sentinel node had been identified by scintigraphy and intraoperative localization, were included in the study. Complete axillary lymphadenectomy was performed when micro- or macrometastases were found in the sentinel node, in order to determine the degree of axillary involvement. Results A total of 40 patients (25%) showed infiltration of the sentinel node. This infiltration was only by micrometastasis in 17 of them (10.7%). Of these 17 patients, only 2 (11.8%) showed macrometastasis in the lymphadenectomy. In the remaining subjects, the final staging reached after the sentinel node study was not modified. Conclusion It is possible to speculate that, in the future, axillary dissection can be avoided in those patients diagnosed of micrometastasis in the sentinel node, pending the conclusions of the on-going multicenter studies.

The detection of papillary microcarcinomas of the thyroid is increasing due to frequent use of ultrasound and fine-needle aspiration biopsy. Although most of the papillary microcarcinomas remain quiescent and follow an indolent clinical course, some behave aggressively and metastasize early, giving rise to clinically significant disease. There have been few studies concerning factors predictive of lymph node metastasis in papillary microcarcinomas. We analyzed the expression of S100A4, cyclin D1, p27 and MUC1, the presence of the BRAF V600E mutation and the clinicopathological features of the tumors, including patient age, tumor size (>or=5 vs

Background In curative colorectal cancer surgery, radical lymph node dissection is essential for staging and decision-making for adjuvant treatment. Purpose The aims of the study were to analyse to what extent sentinel lymph node dissection (SLND) in colorectal cancer could upstage N0 patients and how lymphatic mapping could demonstrate micrometastatic disease. Patients and methods In a prospective study, patients were selected by CT scanning, avoiding bulky disease and distant metastasis. When standard staining (HE) was negative, micrometastases were searched for by immunohistochemistry (cytokeratin 11, CEA and Ca19-9 antibodies). Micrometastatic lymph nodes were classified N+(i). Results Detection of sentinel lymph nodes was successful in 48 out of 52 colorectal cancer patients. Among the 44 M0 patients, 22 were N0 (i−) and 22 were N+ (13 with standard HE procedure, three were N+ (macrometastasis) with the SN as the only positive node and six patients had 1–4 micrometastatic SN (N+(i)). An overall potential upstaging of 9/44 could be considered after SLND. With a mean follow-up of 48 months survival, analysis showed that disease-specific survival of the group of six N+(i) patients was intermediate between the group of 22 N0 (i−) patients and the group of 16 N+ patients. Conclusion SLND may improve the detection of metastasis in conventionally bivalved nodes. Further studies could assess if micrometastatic disease detected in SN could be integrated into the risk factors for stage II patients in order to consider adjuvant chemotherapy.

Purpose: Sentinel lymph node–positive (SLN+) patients who are unlikely to have 4 or more involved axillary nodes might be treated with less extensive regional nodal radiation. The purpose of this study was to define possible predictors of having 4 or more involved axillary nodes. Methods and Materials: The records of 224 patients with breast cancer and 1 to 3 involved SLNs, who underwent completion axillary dissection without neoadjuvant chemotherapy or hormonal therapy were reviewed. Factors associated with the presence of 4 or more involved axillary nodes (SLNs plus non-SLNs) were evaluated by Pearson chi-square test of association and by simple and multiple logistic-regression analysis. Results: Of 224 patients, 42 had involvement of 4 or more axillary nodes. On univariate analysis, the presence of 4 or more involved axillary nodes was positively associated with increased tumor size, lobular histology, lymphovascular space invasion (LVSI), increased number of involved SLNs, decreased number of uninvolved SLNs, and increased size of SLN metastasis. On multivariate analysis, the presence of 4 or more involved axillary nodes was associated with LVSI, increased number of involved SLNs, increased size of SLN metastasis, and lobular histology. Conclusions: Patients with 1 or more involved SLN, LVSI, or SLN macrometastasis should be treated to the supraclavicular fossa/axillary apex if they do not undergo completion axillary dissection. Other SLN+ patients might be adequately treated with less extensive radiation fields.

The object of this paper was to investigate lipoplastic lymphadenopathy in superficial locations with ultrasound. We selected 110 patients with a total number of 247 nodes with a central hyperechoic area extended for more than one third of the transverse diameter. We considered gender, age, body mass index (BMI), and associated disease such as thyroid disorders and diabetes. For each lymph node, we measured the long:short axis ratio and the parenchyma:fat (P:F) ratio. Differences between mean P:F ratio in diabetic and nondiabetic patients were significant (p=0.045). Mean P:F ratio was negatively related to BMI (r=0.62, p=0.015) and age (r=0.54, p=0.024). All of the nodes examined with a mean P:F ratio

The decision whether to proceed with complete axillary node dissection based on sentinel node status is clear for patients with negative or macrometastatic disease. However, the course of action based on sentinel node micrometastasis remains controversial. We reviewed 358 cases from 6/1999 to 7/2003. All sentinel nodes were evaluated at three levels by frozen section, touch preparation, and scrape preparation. Micrometastasis was defined as tumor deposits between 0.2 and 2 mm. Size, grade, and lymphvascular invasion of the primary tumor, as well as number, status, size of metastatic disease, and presence of extranodal capsular extension of sentinel and nonsentinel nodes were recorded. Of the 358 cases, 89 had positive sentinel nodes, 29 of which represented micrometastases. Only one (3%) of the 29 cases contained a nonsentinel node with macrometastasis. In 60 of the 89 cases sentinel nodes contained macrometastases. Of these, 38 cases (63%) had metastatic tumor in nonsentinel nodes. Intraoperative consult was performed in 53 of the 89 cases with positive sentinel nodes. Only 1 of the 19 (5%) intraoperative consult cases with micrometastatic sentinel nodes had positive nonsentinel nodes, while 21 of 34 (62%) of macrometastatic sentinel nodes at intraoperative consult had tumor in nonsentinel nodes. No single variable studied discriminated between micro- vs macrometastatic disease. At intraoperative consult, macrometastatic disease was present in all three diagnostic preparations, while diagnostic material in micrometastatic sentinel nodes was usually present in only one modality. This analysis suggests that the risk of finding tumor in nonsentinel nodes differs significantly between cases with micro (3%)- vs macro (63%)-metastatic disease in sentinel nodes. This holds true for cases assessed by intraoperative consult. Considering the known morbidity of complete axillary dissection, assessments of risk vs benefit of undertaking this procedure should be performed on a case-by-case basis in patients with sentinel node micrometastases.

The aim was to identify a subset of breast cancer patient with positive sentinel nodes (SNs) for whom secondary axillary clearance would be unnecessary.Between March 1999 and May 2001, 288 patients with T0-T2 breast cancer less than 3cm in diameter had SN detection either by a colorimetric method or using a combined technique. SNs were stained with haematoxylin and eosin (HE). For all negative SNs, serial sections and immunochemistry (IHC) were performed. All patients with positive SNs underwent a complete axillary lymph node dissection. One hundred and twenty patients were SN positve.Non-sentinel node positivity (NSNP) was closely associated with the size of the tumour (14.3%, 54.1% and 51.8% for pT1a-b, pT1c and pT2 tumours respectively) and with the size of the SN metastasis: 15.9% IHC detected micrometastasis, 33.3% and 78.8% micro- and macrometastasis detected with HE staining respectively. NSNP was found in 24.0% and 42.8% of patients with pT1c breast cancer and with micrometastasis detected by IHC and HE staining. The node positivity rate reached 81.1% for pT1c lesions with macrometastasis in the SN. For the patients with pT2 breast cancer, these rates were 12.5% (IHC), 28.5% (HE) 91.1% (macrometastasis).We are unable to isolate precisely a subset of patients for whom total axillary lymph node dissection would be unnecessary. A subset of 14 small tumours (1cm diameter) demonstrated micrometastases in the SN without NSNP.

Background The Oncotype Dx® recurrence score (RS) assay quantifies the risk of distant recurrence (rDR) and its use has increased despite the lack of prospective studies. Methods This is a cross-sectional study of consecutive patients (PTS) from our Institution with histologically confirmed invasive breast cancer (IBC) who underwent surgery with curative intent and in whom Oncotype Dx (ODx) was performed. The main objectives were to compare (1) the predicted rDR by RS and Adjuvant! (2) Risk allocation by RS and St Gallen Criteria and (3) the agreement between histological grading (HG) and RS. Results From October/2006 to April/2012, 105 PTS with ER positive IBC were evaluated. Median age: 55y. Sixty-eight (64.8%) were EC IA; axillary lymph node involvement was seen in 25 PTS (14 micro and 11 macrometastasis). The rDR by RS was low in 64 PTS (60.9%), intermediate in 34 (32.4%) and high in 7 (6.7%). According to Saint Gallen, 12 (12%), 68 (68%) and 20 PTS (20%) were classified as low, intermediate and high risk, respectively, among 100 classifiable PTS. There was no statistically significant agreement between risk allocation by RS and Saint Gallen criteria (Kappa coefficient = -0.043; p = 0.401). Ki-67 data was available for 89 PTS: Conclusions We found no statistically significant agreement between Oncotype Dx®, the Saint Gallen criteria, Adjuvant!Online, or Ki-67. However, a potential association between HG and RS was noted. The rDR may be overestimated by clinicopathological-based classifications Disclosure All authors have declared no conflicts of interest.

Objective To determine the identification and the percentage of the false negative of the sentinel nodes in patients with early breast cancer Hospital La Linea, during the period 2007 to 2010. Methods We collect fifty patients with early breast cancer, without clinical and ultrasonographic involvement of axillary nodes, from November 2007 to September 2010. We use the vital dye in the first twenty patients, and the combined technique with vital dye and albumin labeled with technetium 99 in the other thirty patients. The site of injection for patients who use blue dye was the subdermal near to the tumor, and to the patients who use the technetium was the periareolar technique. The sentinel node biopsy was examined during the surgery. The sentinel node was cut through its long axis and then with fine cuts of 250 microns, with freezing technique. The axillary dissection was completed in the first seventeen patients, and in the remaining patients we performed total axillary dissection if the sentinel node was positive for metastasis. Results Sentinel nodes were identified in 49 of 50 patients (98%), procedures. The only case where we did not identify the sentinel node was a patient in the combined technique. The percentage of nodes identified in the patients with vital dye was one sentinel node, and in the patients who use technetium the percentage was two sentinel nodes. The false negative rate was 8% (4 patients), in three of them we found a micrometastasis in the final examination, in the other one we found a macrometastasis. This cases of false negative in the sentinel node biopsy occurred at the beginning of the study. Pathologists acquired a learning curve for sentinel node examination, and practiced subsequently fine cuts in the intraoperative examination of the sentinel node. Conclusion This experience indicates that intraoperative examination of sentinel node biopsy is crucial for staging of the axilla. The rate of identification of sentinel node is excellent and with the use of the technetium the technique is more accurate. The improvement in the learning curve about the intraoperative examination of the sentinel node biopsy has decreased our rates of false negatives. Disclosure All authors have declared no conflicts of interest.