Non-sentinel Node Research Articles

Intratumor expanded T cell clones can be non-sentinel lymph node derived in breast cancer revealed by single-cell immune profiling

BackgroundSentinel lymph nodes (LNs) are regarded as key immune surveillance sites in cancer wherein mature dendritic cells present tumor-derived antigens to prime and activate T cells, which then migrate to the tumor site. However, it is unclear whether the tumor-specific T cells can be elicited within the tumor independent of the sentinel LNs.MethodsWe performed an integrative analysis of gene expression profiles of 65,285 cells and T cell receptor sequences of 15,831 T cells from 5 paired primary breast tumors and sentinel LNs to identify where clonal T cells come from and the characteristics of those clonal T cells.ResultsThe proportion of clonal T cells was higher in the primary tumors compared with the sentinel LNs, whereas all expanded clones identified in the sentinel LN were also present in the primary tumors. In contrast, 10.91% of the expanded clones in the primary tumors were not found in the sentinel LNs. These novel intratumoral T cell clones were characterized by high tissues retention capacity (CXCR6 +ITGAE+) and a distinct coinhibitory pattern (CD39 +NKG2A+) compared with the expanded T cell clones common to both sites. Furthermore, multiplex immunofluorescence imaging showed the presence of tertiary lymphoid structures (TLS) in the primary breast tumors wherein the activated cytolytic T cells were concentrated, indicating its possible role in eliciting non-sentinel LN-derived T cell clones.ConclusionsOur study revealed expanded intratumor non-sentinel LN derived T cell clones located in the TLS, which points to the need for exploring the role of TLS in antitumor immunity.

Prediction of Non-sentinel Lymph Node Metastasis by One-step Nucleic Acid Amplification of Sentinel Lymph Nodes in Luminal Breast Cancer

背景:近年，早期乳癌の周術期治療はsubtypeで個別化され，大規模試験によりSLN転移陽性でも腋窩郭清省略が示唆された．また，luminal乳癌のリンパ節転移が1-2個ならば化学療法省略傾向にある．しかし，リンパ節転移数は補助療法決定の重要因子であり，SLN以外の腋窩リンパ節（non-SLN）に転移があれば，補助療法が不十分となりうる．当院はSLNを術中OSNA法で判定してきたが，転移陽性SLNのTTL（total tumor load）がnon-SLN転移を予測すると報告され，luminal乳癌のSLNのTTLとnon-SLN転移を後ろ向きに検討した．方法:対象は2012年5月～2021年6月にOSNA法でSLN陽性と判定され腋窩郭清へ移行したER陽性でHER2陰性の83例．TTL cut off値2.1×104 copies/μLでの2群のnon-SLN転移を解析した．結果:83例中non-SLN転移陽性は11例で，TTL高値群は有意にnon-SLN転移発生率が高かった（P=0.00854）．結語:Luminal乳癌においてTTLはnon-SLN転移を予測する可能性が示された．

Distribution pattern and pathologic analysis of metastatic sentinel and non-sentinel lymph nodes in lymphatic basin dissection for clinical T2/T3 oral cancer with clinical N0 status

ObjectiveThe localization pattern of metastatic sentinel lymph node (SN) and non-SNs and pathologic analysis of metastatic lymph nodes in SN lymphatic basin dissection (SLBD) were investigated in patients with cT2/T3cN0 oral squamous cell carcinoma (OSCC). MethodsThis prospective multicenter trial involved 10 institutions nationwide in Japan. A total of 57 patients were enrolled. The lateral neck was divided into 5 lymphatic basins. The lymphatic basin containing SNs was defined as the SN lymphatic basin.All patients underwent SLBD with backup selective neck dissection (I-III) combined with primary tumor removal. When SNs were found outside of levels I-III, including in the contralateral neck, SLBD was performed by removing the compartments containing SNs separately. SN metastasis was classified as isolated tumor cells (ITCs), micrometastasis, or macrometastasis. ITCs are defined as a lesion no larger than 0.2 mm in largest dimension and are classified as pN0. ResultsSN metastasis was observed in 22 cases. All metastatic lymph nodes, including false-negative cases, were detected in the SN lymphatic basin. Isolated tumor cells in the SNs did not affect prognosis, whereas micrometastasis tended to have poor prognosis.After adjusting for other risk factors, a positive SN remained a significant predictor of poor 5-year overall survival in pT2-4 OSCC. ConclusionSLBD for intraoperative SN biopsy is a sufficient therapeutic procedure and is valuable for determining pathologic nodal stage in OSCC. SN positivity was demonstrated to be an independent predictor of poor prognosis in patients with pT2-4 disease undergoing SLBD with backup selective neck dissection (I-III).

A Novel Predictive Nomogram including Serum Lipoprotein a Level for Nonsentinel Lymph Node Metastases in Chinese Breast Cancer Patients with Positive Sentinel Lymph Node Metastases.

Background We developed a new nomogram combining serum biomarkers with clinicopathological features to improve the accuracy of prediction of nonsentinel lymph node (SLN) metastases in Chinese breast cancer patients. Methods We enrolled 209 patients with breast cancer who underwent SLN biopsy and axillary lymph node dissection. We evaluated the relationships between non-SLN metastases and clinicopathologic features, as well as preoperative routine tests of blood indexes, tumor markers, and serum lipids, including lipoprotein a (Lp(a)). Risk factors for non-SLN metastases were identified by logistic regression analysis. The nomogram was created using the R program to predict the risk of non-SLN metastases in the training set. Receiver operating characteristic (ROC) analysis was applied to assess the predictive value of the nomogram model in the validation set. Results Lp(a) was significantly associated with non-SLN metastasis status. Compared with the MSKCC model, the predictive ability of our new nomogram that combined Lp(a) level and clinical variables (pathologic tumor size, lymphovascular invasion, multifocality, and positive/negative SLN numbers) was significantly greater (AUC: 0.732, 95% CI: 0.643–0.821) (C-index: 0.703, 95% CI: 0.656–0.791) in the training cohorts and also performed well in the validation cohorts (C-index: 0.773, 95% CI: 0.681–0.865). Moreover, the new nomogram with Lp(a) improved the accuracy (12.10%) of identification of patients with non-SLN metastases (NRI: 0.121; 95% CI: 0.081–0.202; P = 0.011). Conclusions This novel nomogram based on preoperative serum indexes combined with clinicopathologic features facilitates accurate prediction of risk of non-SLN metastases in Chinese patients with breast cancer.

Clinicopathologic models predicting non-sentinel lymph node metastasis in cutaneous melanoma patients: Are they useful for patients with a single positive sentinel node?

Background and ObjectivesOf clinically node‐negative (cN0) cutaneous melanoma patients with sentinel lymph node (SLN) metastasis, between 10% and 30% harbor additional metastases in non‐sentinel lymph nodes (NSLNs). Approximately 80% of SLN‐positive patients have a single positive SLN.MethodsTo assess whether state‐of‐the‐art clinicopathologic models predicting NSLN metastasis had adequate performance, we studied a single‐institution cohort of 143 patients with cN0 SLN‐positive primary melanoma who underwent subsequent completion lymph node dissection. We used sensitivity (SE) and positive predictive value (PPV) to characterize the ability of the models to identify patients at high risk for NSLN disease.ResultsAcross Stage III patients, all clinicopathologic models tested had comparable performances. The best performing model identified 52% of NSLN‐positive patients (SE = 52%, PPV = 37%). However, for the single SLN‐positive subgroup (78% of cohort), none of the models identified high‐risk patients (SE > 20%, PPV > 20%) irrespective of the chosen probability threshold used to define the binary risk labels. Thus, we designed a new model to identify high‐risk patients with a single positive SLN, which achieved a sensitivity of 49% (PPV = 26%).ConclusionFor the largest SLN‐positive subgroup, those with a single positive SLN, current model performance is inadequate. New approaches are needed to better estimate nodal disease burden of these patients.

Melanoma sentinel lymph node biopsy and completion lymph node dissection: A regional hospital experience

Completion lymph node dissection (CLND) following positive sentinel lymph node biopsy (SLNB) for cutaneous melanoma is a topic of controversy. The second Multicenter Selective Lymphadenectomy Trial (MSLT-II) suggested no survival benefit with CLND over observation amongst patients with a positive SLNB. The findings of the MSLT-II may have limited applicability to our high-risk population where nodal ultrasound and non-surgical melanoma treatment is rationed. In this regional, retrospective study, we reviewed primary melanoma, SLNB and CLND histopathological reports in the Bay of Plenty District Health Board (BOPDHB) across a 10-year period. The primary outcomes measured were size of sentinel lymph node metastases and non-sentinel node (NSN) positivity on CLND for patients with a positive SLNB. In the 157 SLNB identified, the mean sentinel lymph node metastatic deposit size was larger in BOPDHB compared with MSLT-II (3.53 vs 1.07/1.11mm). A greater proportion of BOPDHB patients (54.8%) had metastatic deposits larger than 1mm compared with MSLT-II (33.2/34.5%) and the rate of NSN involvement on CLND was also higher (23.8% vs 11.5%). These findings indicate that the BOPDHB is a high-risk population for nodal melanoma metastases. Forgoing CLND in the context of a positive SLNB may place these patients at risk.

Sentinel Lymph Node Staging with Indocyanine Green for Patients with Cervical Cancer: The Safety and Feasibility of Open Approach Using SPY-PHI Technique.

(1) Background: Sentinel lymph node staging (SLN) with indocyanine green (ICG) in cervical cancer is the standard of care in most national and international guidelines. However, the vast majority of relevant studies about the safety and feasibility of this method are conducted on minimally invasive surgery; (2) Methods: This study is a retrospective analysis of a retrospective collected database of 76 consecutive patients with cervical cancers, who were operated laparoscopically (50%), or laparotomy (50%). Sentinel nodes were defined as the ICG-positive pelvic nodes in the first and second echelons. False negative cases were defined as positive non-sentinel lymph nodes despite successful sentinel mapping or failed mapping bilaterally by per-patient assessment or unilaterally by pelvic sidewall assessment; (3) Results: Regardless of the approach (open or laparoscopic), the SLN technique achieved a total sensitivity, specificity, and negative predictive value (NPV) of 94.7%, 98.6%, and 94.7%, respectively in the entire sample. The bilateral detection rate was as high as 93.4% with identical results in both approaches. The sensitivity and NPV for SNL in open surgery was found to be similar to minimal access surgery; (4) Conclusions: ICG and SPY-PHI technique is a reliable tool to detect sentinel lymph nodes in cervical cancer during laparotomy.

Is Sentinel Lymph Node Biopsy for Breast Cancer with Cytology-Proven Axillary Metastasis Safe? A Prospective Single-Arm Study.

The purpose of this study was to evaluate pathologic lymph node metastasis in breast cancer with cytology-proven axillary metastasis. This study was designed prospectively. We performed axillary lymph node dissections (ALND) after lymphatic mapping by near-infrared (NIR) fluorescence imaging with Indocyanine Green (ICG). We evaluated 72 breast cancer patients with cytology-proven axillary metastasis by curative surgery at the Samsung Medical Center between May of 2016 and December of 2017. Among the 72 patients with cytology-proven axillary metastasis, 14 of 39 patients (35.9%) with one or two sentinel lymph nodes containing metastases were metastasized to post-sentinel lymph node. Thirteen of fourteen patients had additional non-sentinel lymph node metastases, seven of thirteen patients also had additional level II lymph node metastases, and one patient had only one additional level II lymph node metastasis. Of T1 or T2 stage patients, 10 of 33 patients (30.3%) with one or two sentinel lymph nodes containing metastases were metastasized to post-sentinel lymph node. Even in patients without SLN metastasis, 50% of the patients had at least three LN metastases, and 40% in the T1 or T2 stage patients. Sentinel lymph node biopsy without ALND might be not safe for patients with cytology-proven axillary metastasis.

Siglec-15 Is an Immune Suppressor and Potential Target for Immunotherapy in the Pre-Metastatic Lymph Node of Colorectal Cancer.

Lymph node metastasis indicates a poor prognosis in colorectal cancer. To better understand the underlying mechanisms of lymph node metastasis, we analyzed transcriptome characteristics of the pre-metastatic lymph node, a putative microenvironment favorable for the seeding and proliferation of cancer cells. Thus, we tried to compare and elucidate the transcriptional and immune characteristics of sentinel lymph nodes (SNs) with matched non-sentinel lymph nodes (NSNs) in colorectal cancer patients. In this study, a total of 38 pairs of SNs and NSNs were collected, in which 26 pairs of non-metastatic lymph nodes were subjected to RNA-seq and bioinformatics analysis for the gene expression profiles. There were 16 differentially expressed genes between SNs and NSNs being identified, including 9 upregulated and 7 downregulated genes in SN. Gene Ontology (GO) classification analysis revealed that the differentially expressed genes were mainly involved in leukocyte differentiation, chemokine secretion, and immune system regulation. In the meantime, gene set enrichment analysis (GSEA) showed that immune-related signaling pathways, such as transforming growth factor beta (TGF-β) signaling and tumor necrosis factor alpha (TNF-α)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, were enriched in NSN, while cell proliferation–related signaling pathways were enriched in SN, including MYC signaling and G2M checkpoint signaling. We further identified SIGLEC15 as a top upregulated gene in SN. However, RNAscope assay showed that SIGLEC15 was not largely co-expressed with M2 macrophage marker CD163. We then selected eight pairs of lymph nodes for further cytological studies. Flow cytometry analysis revealed that Siglec-15 was expressed on all myeloid cell subsets. The relative expression of SEGLEC15 (SN/NSN) was correlated with the microsatellite instability (MSI) status in colorectal cancer patients. Further studies found that small interfering ribonucleic acid (siRNA)-mediated silencing of SLGLEC15 can enhance the anti-tumor function of T cells, as indicated by cytokine release analysis. In conclusion, we presented here a first report on the gene expression profiling of the pre-metastatic lymph node in colorectal cancer. The findings in this study suggest that SIGLEC15 plays an important role in SN immunosuppression. SEGLEC15 silencing could be a therapeutic strategy for restoring T cell function in tumor SNs.

Development of a prediction model based on LASSO regression to evaluate the risk of non-sentinel lymph node metastasis in Chinese breast cancer patients with 1\u20132 positive sentinel lymph nodes

This study aimed to develop an intraoperative prediction model to evaluate the risk of non-sentinel lymph node (NSLN) metastasis in Chinese breast cancer patients with 1–2 positive sentinel lymph nodes (SLNs). The clinicopathologic data of 714 patients with 1–2 positive SLNs were investigated. Univariate and multivariate analyses were performed to identify the risk factors of NSLN metastasis. A new mathematical prediction model was developed based on LASSO and validated in an independent cohort of 131 patients. The area under the receiver operating characteristic curve (AUC) was used to quantify performance of the model. Patients with NSLN metastasis accounted for 37.3% (266/714) and 34.3% (45/131) of the training and validation cohorts, respectively. A LASSO regression-based prediction model was developed and included the 13 most powerful factors (age group, clinical tumour stage, histologic type, number of positive SLNs, number of negative SLNs, number of SLNs dissected, SLN metastasis ratio, ER status, PR status, HER2 status, Ki67 staining percentage, molecular subtype and P53 status). The AUCs of training and validation cohorts were 0.764 (95% CI 0.729–0.798) and 0.777 (95% CI 0.692–0.862), respectively. We presented a new prediction model with excellent clinical applicability and diagnostic performance for use by clinicians as an intraoperative clinical tool to predict risk of NSLN metastasis in Chinese breast cancer patients with 1–2 positive SLNs and make the final decisions regarding axillary lymph node dissection.

Analysis of sentinel lymph node biopsy and non-sentinel lymph node metastasis in invasive ductal and invasive lobular breast cancer: a nationwide cross-sectional study (CSBrS-001).

BackgroundInformation regarding the implementation of sentinel lymph node biopsy (SLNB) in invasive lobular carcinoma (ILC) is scarce, and whether ILC patients with 1–2 positive sentinel lymph nodes (SLNs) can be omitted from axillary lymph node dissection (ALND) remains controversial. This study aimed to compare involvement of SLNs and non-SLNs between patients with invasive ductal carcinoma (IDC) and ILC.MethodsWe retrospectively collected the clinical and pathological data of invasive breast cancer patients from 37 medical centers in China from January 2018 to December 2018. The number of resected SLNs, positive rate of SLNs, and non-SLNs metastasis were compared between patients with IDC and ILC.ResultsA total of 6,922 patients were included, comprising 6,650 with IDC (96.1%) and 272 with ILC (3.9%). No difference was observed in the number of resected SLNs between patients with IDC and ILC (IDC: 4.0±1.9 vs. ILC: 3.9±1.6, P=0.352). The positive rate of SLNs was significantly higher in patients with IDC than that in patients with ILC (19.3% in IDC vs. 12.9% in ILC, P=0.008). The difference in positive rate of SLNs between IDC and ILC was mainly attributed to macro-metastasis. For patients with positive SLNs who received ALND, and those with 1–2 positive SLNs, the metastatic rate of non-SLNs in the ILC group was higher than that in the IDC group (for patients with positive SLNs: 50.0% in ILC vs. 39.9% in IDC, P=0.317; for patients with 1–2 positive SLNs: 45.4% in ILC vs. 34.8% in IDC, P=0.366), but the differences were not statistically significant.ConclusionsPatients with ILC had similar number of resected SLNs and lower positive rate of SLNs compared to those with IDC. In participants with 1–2 positive SLNs, the ILC group had an increased tendency for non-SLNs metastasis compared with the IDC group. Surgeons may need to be more cautious about omitting ALND for ILC patients with 1–2 positive SLNs.

Non-Sentinel Lymph Node Detection during Sentinel Lymph Node Biopsy in Not-Complete-Lymph-Node-Dissection Era: A New Technique for Better Staging and Treating Melanoma Patients.

Sentinel lymph node biopsy has been demonstrated to be an effective staging procedure since its introduction in 1992. The new American Joint Committee on Cancer (AJCC) classification did not consider the lack of information that would result from the less usage of the complete lymph node dissection as for a diagnostic purpose. Thus, this makes it difficult the correct staging and would leave about 20% of the further positive non-sentinel lymph nodes in the lymph node basin. In this paper, we aim to describe a new surgical technique that, combined with single-photon emission computed tomography-computed tomography (SPECT-CT), allows for better staging of melanoma patients. This is a prospective study that includes 104 patients with cutaneous melanoma. Sentinel lymph node biopsy was offered according to the AJCC guideline. Planar lymphoscintigraphy was performed in association with SPECT-CT, identifying and removing all non-biologically “excluded” lymph nodes, guiding the surgeon’s hand in detection and removal of lymph nodes. Even if identification and removal of non-sentinel lymph nodes is unable to increase overall survival, it definitely gives better disease control in the basin. With a “classic” setting, the risk of leaving further lymph nodes out of the sentinel lymph node procedure is around 20%, thus, basically, the surgical sentinel lymph node of first and second lymph nodes would have therapeutic value and complete lymph node dissection classically performed.

A Pilot Study for the Validation of Sentinel Lymph Node Biopsy with Indocyanine Green Fluorescence Method in Early Endometrial Cancer at Fundacion Jimenez Diaz University Hospital

Background: Sentinel Lymph Node Biopsy is a technique developed to predict lymphatic involvement in patients with early endometrial cancer, decreasing the morbimortality associated with routine systematic lymphadenectomy and improving quality of life. Main Objective: To determine the detection rate and negative predictive value of the Sentinel Lymph Node Biopsy by Immunofluorescence in patients with early endometrial cancer. Methods: A descriptive observational study in patients with early endometrial cancer (FIGO stage I-II) for all histological types and grades, who underwent the Sentinel Lymph Node by immunofluorescence Technique, between June 2019 and March 2020 at the Fundación Jiménez Díaz University Hospital. We used indocyanine green powder for injection, with a concentration of 25 milligrams (mg). We proceeded to dissolve it in 10 cubic centimeters (cc) of distilled water to. After which, we injected 2 cc of the prepared solution into the cervix at the 3 and 9 o’clock positions at a depth of 1 centimeter. Results: Eighteen patients were included, analysing a total of 26 sentinel nodes: 24 pelvic and 2 paraortic; and a total of 273 lymph nodes (sentinel and non-sentinel nodes): 83 right pelvic, 86 left pelvic and 104 paraortic. All nodes were negative for metastasis. Global and bilateral detection rates were 77.78% and 50% respectively. The Negative Predictive Value and sensitivity were 100%. No significant difference in morbimortality was found between performing only Sentinel Lymph Node technique or systematic lymphadenectomy, but the association with quality of life was significant, with better results for those who only underwent the sentinel lymph node technique versus systematic lymphadenectomy (0% vs 77%). Conclusion: The global and bilateral detection rates of the Sentinel Lymph Node Technique by immunofluorescence were 77.78% and 50% respectively, obtaining a Negative Predictive Value and Sensitivity of 100%. Sentinel Node Biopsy is a valid technique to predict lymphatic affectation in early endometrial cancer, with lower morbimortality than systematic lymphadenectomy.

Predictors of positive axillary non-sentinel lymph nodes in breast cancer patients with positive sentinel lymph node biopsy after neoadjuvant systemic therapy

AimTo assess the rate of positive non-sentinel lymph nodes (non-SLNs) after neoadjuvant systemic therapy (NAST) in breast cancer (BC) following positive sentinel lymph node biopsy (SLNB). Materials and methodsFrom institutional database, 265 consecutive patients receiving NAST for cT1-3, any N, M0 BC between 2001 and 2018 were identified. Patients presented clinically negative axilla before surgery and were candidate for SLNB. Following metastatic SLNB, completion axillary lymph node dissection (AxLND) was performed. Non-SLNs rate was investigated using multivariate (MV) logistic regression models. The distribution of non-SLNs across the axilla was observed. ResultsPositive non-SLNs were found in 62.3% of cases and showed no correlation with SLN metastasis size. At MV, statistically significant variables associated with non-SLNs were older age (p = 0.025), clinically positive lymph nodes (p = 0.002), SLN extracapsular extension (ECE, p = 0.001), and higher ratio of positive SLNs/total SLNs (p = 0.016).ECE and higher nodal ratio were independent predictors of III axillary level positivity. By categorizing patients in intermediate- and high-risk groups using the study variables, positive non-SLNs were found in the range of 23–56% across the three axillary levels, rates which did not support radiotherapy volume de-escalation. The III axillary level lower involvement (6.3%) was better identified with the RAPCHEM trial criteria based on the ypN status after AxLND. ConclusionsInvolved non-SLNs rate following positive SLNB after NAST is nearly double the rate observed after primary surgery, supporting some intervention on the axilla. If AxLND is limited to I and II level, the involvement of the III level up to 31% of the cases seems to require some additional treatment, while the omission in selected cases needs further investigation.

Models for Predicting Sentinel and Non-sentinel Lymph Nodes Based on Pre-operative Ultrasonic Breast Imaging to Optimize Axillary Strategies

Axillary strategy decisions have become more complex and controversial in considering minimally traumatic therapy instead of sentinel lymph node biopsy, axillary lymph node dissection or regional nodal irradiation for people with breast cancer. The purpose of this study was to noninvasively predict sentinel lymph node (SLN) and non-sentinel lymph node (NSLN) status based on pre-operative sonographic and clinicopathologic features to determine optimal decisions regarding axillary therapy. In total, 701 patients with breast cancer from two independent centers were retrospectively analyzed. The SLN model (SLNM) for predicting SLN status and the NSLN model (NSLNM) for predicting NSLN status were trained based on a training set using the random-forest algorithm, and their performance was validated using an independent external test set. A receiver operating characteristic curve was drawn to obtain the area under the curve, which was used to assess performance. The area under the curve for the SLNM in the training and test, respectively, was 94.2% and 83.0%, and for the NSLNM, 99.5% and 92.7%. The SLNM and NSLNM accurately predicted that 61.46% (319/519) and 17.53% (91/519), respectively, of our participants were non-metastatic. The overall benefit of the three models was 78.99% in our participants. The two models for predicting SLN and NSLN status showed excellent application potential in optimizing axillary strategies.

Diagnostic accuracy of frozen section and patterns of nodal spread in high grade endometrial cancer: a secondary analysis of the SENTOR prospective cohort study

<h3>Objectives:</h3> Recent studies have shown that sentinel lymph node (SLN) biopsy accurately detects nodal metastases in patients with high-grade endometrial cancer (EC). SLN biopsy has the potential to replace complete lymphadenectomy for surgical staging in patients with high-grade EC, provided that an SLN algorithm is followed (side-specific pelvic and para-aortic lymphadenectomy for non-mapped hemipelves). The aim of this study was to define the accuracy of intraoperative frozen section for the detection of metastases in SLN biopsy and describe the pattern of lymph node (LN) spread in patients with high-grade EC. <h3>Methods:</h3> We performed a secondary analysis of clinicopathologic data from the SENTOR prospective cohort study evaluating SLN node biopsy at 3 designated cancer centres in Toronto, Canada (ClinicalTrials.gov ID: NCT01886066). Patients with clinical stage I high-grade EC (grade 3 endometrioid, serous, clear cell, carcinosarcoma, undifferentiated, or mixed tumors) undergoing laparoscopic or robotic primary hysterectomy were enrolled. The primary outcome was sensitivity of frozen section of the SLN specimen, compared to a standardized ultrastaging protocol. Secondary outcomes included the pattern and characteristics of LN spread. <h3>Results:</h3> There were 126 patients with high-grade EC with median age 66 years (range: 44-86) and median BMI 26.9 kg/m² (range: 17.6-49.3). Frozen section was performed on surgical specimens from 212 hemipelves; SLNs were identified in 202 specimens (95.7%) and fatty tissue alone was identified in 10 specimens (4.7%). Of the 202 hemipelves in which SLNs were identified, 24 were positive for metastatic disease. Frozen section correctly identified only 12, yielding a sensitivity of 50% (12/24, 95% CI 29.6-70.4) and negative predictive value of 94% (178/202, 95% CI 89-96.5). A total of 24 patients had LN metastases: 16 (13%) had isolated pelvic metastases, 7 (6%) had both pelvic and para-aortic metastases and 1 (0.8%) had an isolated para-aortic metastasis. All para-aortic metastases (n=8) occurred in non-sentinel LNs, among patients with serous (n=5), carcinosarcoma (n=2), and dedifferentiated (n=1) histology. One patient with isolated para-aortic metastases (carcinosarcoma, p53 abnormal) did not have a mapped SLN, but was identified by the SLN algorithm. Nodal metastases occurred in 10% of patients (3/30) with grade 3 endometrioid histology (all pelvic), compared to 33% of patients (15/46) with serous histology (10 pelvic alone, 5 pelvic and para-aortic). <h3>Conclusions:</h3> Intraoperative frozen section of SLNs in high-grade EC patients has poor sensitivity. However, frozen section may still be beneficial to confirm the presence of nodal tissue and ensure adherence to an SLN algorithm, including complete pelvic and para-aortic lymphadenectomy for non-mapped hemipelves. Because isolated para-aortic metastases are rare, para-aortic lymphadenectomy may be omitted in patients in which SLNs were successfully mapped to the pelvis.

False-negative frozen section of sentinel nodes in early breast cancer (cT1-2N0) patients

BackgroundSentinel lymph node biopsy (SLNB) is the standard approach for the axillary region in early breast cancer patients with clinically negative nodes. The present study investigated patients with false-negative sentinel nodes in intraoperative frozen sections (FNSN) using real-world data.MethodsA case–control study with a 1:3 ratio was conducted. FNSN was determined when sentinel nodes (SNs) were negative in frozen sections but positive for metastasis in formalin-fixed paraffin-embedded (FFPE) sections. The control was defined as having no metastasis of SNs in both frozen and FFPE sections.ResultsA total of 20 FNSN cases and 60 matched controls from 333 SLNB patients were enrolled between April 1, 2005, and November 31, 2009. The demographics and intrinsic subtypes of breast cancer were similar between the FNSN and control groups. The FNSN patients had larger tumor sizes on preoperative mammography (P = 0.033) and more lymphatic tumor emboli on core biopsy (P < 0.001). Four FNSN patients had metastasis in nonrelevant SNs. Another 16 FNSN patients had benign lymphoid hyperplasia of SNs in frozen sections and metastasis in the same SNs from FFPE sections. Micrometastasis was detected in seven of 16 patients, and metastases in nonrelevant SNs were recognized in two patients. All FNSN patients underwent a second operation with axillary lymph node dissection (ALND). After a median follow-up of 143 months, no FNSN patients developed breast cancer recurrence. The disease-free survival, breast cancer-specific survival, and overall survival in FNSN were not inferior to those in controls.ConclusionsPatients with a larger tumor size and more lymphatic tumor emboli have a higher incidence of FNSN. However, the outcomes of FNSN patients after completing ALND were noninferior to those without SN metastasis. ALND provides a correct staging for patients with metastasis in nonsentinel axillary lymph nodes.

Sentinel node tumor burden in cutaneous melanoma. Survival with competing risk analysis and influence in relapses and non-sentinel node status: retrospective cohort study with long follow-up in a Spanish population.

Several authors have studied the potential of sentinel lymph node (SLN) tumor burden as prognostic factor but the microscopic classifications used in different study groups were variable. We examined the prognostic role of tumor burden in SLN on melanoma specific-survival and competing causes of death. We also analysed clinical and histological factors as predictors of disease relapses and additional non sentinel lymph node (NSLN) metastases. We included all patients with cutaneous melanoma that underwent SLN biopsy between 2002 and 2012 at Complejo Hospitalario de Navarra (Spain). The study end-points were death due to melanoma, melanoma relapse and involvement of NSLN. We used Fine-Gray test for competing risk analysis. A logistic regression model was performed to predict the risk of involvement of NSLN. Between 2002 and 2012, there were 348 patients who underwent SLN biopsy in our centre (308 were eligible for the study). 26.9% patients positive SLN. 88 patients died during the follow-up period and 66 (75%) died from melanoma. The 5-year cumulative incidence of melanoma death was 15.33% (95 % CI 15.25-15.42). The cumulative probability of death from melanoma was associated with gender, histological subtype, Breslow thickness, mitotic rate, ulceration and SLN tumor burden. In multivariable analysis, Breslow thickness and SLN tumor burden remained as independent prognostic factors. SLN tumor burden appears to be an important prognostic factor. It is very important reporting these characteristics in pathological reports. More prospective studies would be necessary to analyze these variables and to be able to make recommendations in management of melanoma patients.

Clinical relevance of a degree of extracapsular extension in a sentinel lymph node in breast cancer patients: a single-centre study

In some breast cancer (BC) patients, an examination of lymph nodes dissected during sentinel lymph node biopsy (SLNB) demonstrates a presence of metastatic lesions and extracapsular extension (ECE) in a SLN. This study aimed to evaluate clinical relevance of ECE in BC patients. This is a retrospective analysis of 891 patients with cancer metastases to SLN, referred to supplementary axillary lymph node dissection (ALND), hospitalized between Jan 2007 and Dec 2017. Clinical and epidemiological data was evaluated. Long-term treatment outcomes were analysed. In 433 (48.6%) patients, cancer metastases were limited to the SLN (group I), in 61 (6.8%) patients the SLN capsule was exceeded focally (≤ 1 mm—group II). In 397 (44.6%) patients, a more extensive ECE was found (> 1 mm—group III). Metastases to non-sentinel lymph nodes (nSLNs) were diagnosed in 27.0% patients from group I, 44.3% patients from group II and in 49.6% patients from group III. No statistically significant differences were observed in long-term treatment outcomes for compared groups. The presence of ECE is accompanied by a higher stage of metastatic lesions in the lymphatic system. The differences in this respect were statistically significant, when compared to the group of ECE(−) patients. ECE, regardless of its extent, did not impact the long-term treatment results. ECE remains an indication for supplementary ALND and for other equivalent cancer treatment procedures, regardless of ECE size.

Prevalence of extracapsular extension in metastatic sentinel lymph nodes in breast cancer

IntroductionAxillary lymph node involvement is recognized as a key prognostic factor for invasive breast cancer. Retrospective analyzes have shown that extracapsular extension (ECE) is correlated with negative prognostic factors in this neoplasia. Objectiveto evaluate the measurement of ECE and its relationship with the number of affected non-sentinel lymph nodes, as well as to investigate the association between ECE with other clinical and pathological prognostic factors. MethodsThis is a cross-sectional observational study carried out from January 2015 to June 2019, at the Breast Surgical Oncology service of Liga Contra o Cancer (LIGA), in Natal, Brazil. A total of 150 patients were included in the study and were divided into three groups: absence of ECE, ECE less than or equal to 2 mm and ECE greater than 2 mm. ResultsThe mean age was 58 years for the group with ECE and 57 years for the group without ECE. Most of the patients were mixed race (66.7%), had no family history of breast cancer (64%) and underwent quadrantectomy (64.5%). Regarding the characteristics of the disease, most presented a histological report compatible with Invasive Carcinoma of the non-special type (IC NST) (87.5%), histological grade II (52.7%), negative Lymphovascular invasion (LVI) (52.7%), Tumor Size T1 (<2.0 cm) (52%) and Luminal B molecular subtype (36.7%). Regarding sentinel lymph nodes: 103 patients (68.7%) had ECE and 1 positive sentinel lymph node was identified in most cases. There was a statistically significant association between the presence of ECE and of being mixed race (p = 0.03), between ECE and LVI (p = 0.05) and between ECE and a greater number of positive non-sentinel lymph nodes (p < 0.001). ConclusionOur study showed that ECE> 2 mm is associated with increased axillary nodal load compared to groups without ECE and ECE ≤ 2 mm in sentinel node biopsy in patients who met the Z0011 criteria.