Sentinel Lymph Node Involvement Research Articles

Primary diffuse large B-cell lymphoma of the uterus – A case report

Extranodal non-Hodgkin’s lymphoma (NHL) constitutes one fifth to one third of all cases of NHL. Secondary lymphomatous involvement of the female genital tract (FGT) is not rare and is often seen in disseminated disease; however, primary NHL of the FGT is extremely rare. The uterine corpus is only third to the ovaries and uterine cervix as a site for primary NHL of the FGT. Differentiation between primary and secondary involvement of FGT organ by a haematolymphoid neoplasm relies upon the localisation versus dissemination of the disease at time of diagnosis. We report a case of a 71-years-old lady with primary diffuse large B-cell lymphoma (DLBCL) of the uterine corpus. The histology showed a diffuse infiltrate of large atypical discohesive cells associated with multinucleated tumour cells and brisk mitosis. A panel of immunohistochemical stains showed results consistent with the diagnosis of DLBCL made on routine stains. There was only one involved sentinel node, and radiologically there was no evidence of other involved sites by lymphoma. Designation of the lymphoma as primary to the FGT is clinical and having appropriate imaging studies of the patient is vital for this purpose.

Sentinel lymph node melanoma metastases: Assessment of tumor burden for clinical prediction of outcome in the first Multicenter Selective Lymphadenectomy Trial (MSLT-I)

PurposeAs clinical management decisions in patients with Stage III melanoma have become more complex, precise pathologic characterization of sentinel lymph node (SLN) metastases has become critical to guide management. The extent of SLN involvement correlates with risk of adverse outcomes, but reported methods of disease quantification vary. We examined SLN metastases from patients participating in an international clinical trial and compared several methods of tumor burden quantification. MethodsSLNs from 146 node-positive patients in the first Multicenter Selective Lymphadenectomy Trial (MSLT-I) were centrally-reviewed and characterized by number of tumor-positive nodes, percent nodal area tumor replacement, maximum dimension of largest metastasis, tumor penetrative depth, number of tumor foci, metastasis microanatomic location, and extracapsular extension. These data were analyzed for correlation with non-SLN metastasis and melanoma-specific survival (MSS). ResultsThe median number of tumor-involved SLNs was 1. The median maximum metastasis dimension was 1.11 mm. Median SLN area involvement was 1.5%. Tumor burden measures were highly correlated with each other. Factors associated with non-SLN metastasis by univariable analysis were primary tumor ulceration and extent of metastases. Tumor thickness, ulceration, non-SLN metastasis and multiple measures of SLN tumor burden were significantly related to MSS on univariable analysis. After multivariable adjustment, number of involved SLNs (p = 0.05) and percent nodal area tumor replacement (p = 0.02) were independent predictors of MSS. ConclusionCentral review of MSLT-I pathology indicates that primary tumor and SLN tumor characteristics predict non-SLN metastasis and MSS. Percent nodal involvement was more powerfully prognostic than the more commonly used maximum dimension of largest metastasis.

Histopathological growth distribution of ductal carcinoma in situ: tumor size is not "one size fits all".

Ductal carcinoma in situ (DCIS) is a group of preinvasive breast neoplasms. Studies have shown excellent survival among patients with lumpectomy-amenable disease. Patients requiring mastectomy have been less well characterized. We aim to characterize this cohort and identify whether growth distribution pattern is associated with sentinel lymph node involvement at time of surgery or subsequent development of metastatic disease. Patients were identified using local cancer registry data and were chart reviewed using electronic medical records. Growth pattern was classified as unifocal, multifocal, or diffuse. Chi-squared, Analysis of Variance (ANOVA), and Kaplan-Meier analyses were performed. Two hundred and twenty-six patients were identified with median age at diagnosis 49 and follow up 7.1 years. 42 had unifocal, 51 had multifocal and 20 had diffuse lesions. 3/20 patients with diffuse type lesions developed subsequent distant metastatic disease, while none of the patients with unifocal or multifocal lesions did. 1/20 patients with diffuse and 2/51 with multifocal disease had sentinel lymph node involvement (SLNI) at surgery. Tumor extent was not associated with sentinel lymph node involvement or distant metastatic disease (P=0.2, Kaplan-Meier analysis) but growth pattern was (P=0.01). It was also associated on Kaplan-Meier with development of distant metastatic disease alone (P=0.01). Patients with diffuse growth pattern DCIS were more likely to have SLNI or development of distant metastatic disease. Our findings suggest that patients with diffuse type lesions are at greater risk of metastatic disease and therefore breast cancer death from DCIS. Optimal therapy for these patients will need further elucidation.

Melanoma trials that defined surgical management.

Treatment of regional lymph nodes in melanoma has been controversial for more than a century. A series of clinical trials evaluating elective lymph node dissection and then sentinel lymph node biopsy have helped define the current standard of care. These trials resulted in increasingly selective application of surgical intervention for regional lymph nodes in melanoma. First by focusing on optimal candidates for elective lymph node dissection and then by identifying patients through sentinel lymph node biopsy. The current standard of sentinel lymph node biopsy for appropriately selected patients and nodal observation for many patients, even with involved sentinel nodes is both more accurate in staging and much less morbid than what came before.

Sentinel node involvement with or without completion axillary lymph node dissection: treatment and pathologic results of randomized SERC trial

Based on results of clinical trials, completion ALND (cALND) is frequently not performed for patients with breast conservation therapy and one or two involved sentinel nodes (SN) by micro- or macro-metastases. However, there were limitations despite a conclusion of non-inferiority for cALND omission. No trial had included patients with SN macro-metastases and total mastectomy or with >2 SN macro-metastases. The aim of the study was too analyze treatment delivered and pathologic results of patients included in SERC trial. SERC trial is a multicenter randomized non-inferiority phase-3 trial comparing no cALND with cALND in cT0-1-2, cN0 patients with SN ITC (isolated tumor cells) or micro-metastases or macro-metastases, mastectomy or breast conservative surgery. We randomized 1855 patients, 929 to receive cALND and 926 SLNB alone. No significant differences in patient’s and tumor characteristics, type of surgery, and adjuvant chemotherapy (AC) were observed between the two arms. Rates of involved SN nodes by ITC, micro-metastases, and macro-metastases were 5.91%, 28.12%, and 65.97%, respectively, without significant difference between two arms for all criteria. In multivariate analysis, two factors were associated with higher positive non-SN rate: no AC versus AC administered after ALND (OR = 3.32, p < 0.0001) and >2 involved SN versus ≤2 (OR = 3.45, p = 0.0258). Crude rates of positive NSN were 17.62% (74/420) and 26.45% (73/276) for patient’s eligible and non-eligible to ACOSOG-Z0011 trial. No significant differences in patient’s and tumor characteristics and treatment delivered were observed between the two arms. Higher positive-NSN rate was observed for patients with AC performed after ALND (17.65% for SN micro-metastases, 35.22% for SN macro-metastases) in comparison with AC administered before ALND.

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.

How accurate is frozen section pathology compared to permanent pathology in detecting involved margins and lymph nodes in breast cancer?

BackgroundFrozen section (FS) pathology has multiple limitations, and different institutions report variable experiences with the use of FS for diagnosis of tumor involvement. We aimed to compare the FS accuracy with that of permanent pathology (gold standard) regarding marginal involvement and lymph node status using data from the largest breast cancer registry in Iran.MethodsIn this retrospective study, women who had both FS and permanent pathology reports were included. The two pathology reports were cross compared with regard to the involvement of tumor margins and sentinel lymph nodes.ResultsOverall, 2786 patients entered the study. Mean age of patients was 48.96±11.44 years. A total of 1742 margins were analyzed. Accordingly, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FS pathology for detection of involvement of involved margins were 78.49%, 97.63%, 65.1%, and 98.7%, respectively. The accuracy and area under the curve (AUC) for FS pathology were 96.61% and 0.73 (95% CI: 0.64–0.831), respectively.A total of 1702 sentinel lymph node biopsies were assessed. Sensitivity, specificity, PPV, and NPV, of FS pathology for detection of lymph node involvement, were 87.1%, 98%, 95.5%, and 93.3%, respectively. Accuracy and AUC of FS for diagnosis of involved lymph nodes were 94.1% and 0.926 (95% CI: 0.909–0.942), respectively.ConclusionFrozen pathology is a suitable method for identifying involved sentinel lymph nodes in patients with breast cancer, but this method has a less than optimum efficacy for detecting and confirming marginal involvement.

Sentinel node biopsy for diagnosis of lymph node involvement in endometrial cancer.

Sentinel node biopsy for diagnosis of lymph node involvement in endometrial cancer.

In-depth proteomics analysis of sentinel lymph nodes from individuals with endometrial cancer

SummaryEndometrial cancer (EC) is one of the most common gynecological cancers worldwide. Sentinel lymph node (SLN) status could be a major prognostic factor in evaluation of EC, but several prospective studies need to be performed. Here we report an in-depth proteomics analysis showing significant variations in the SLN protein landscape in EC. We show that SLNs are correlated to each tumor grade, which strengthens evidence of SLN involvement in EC. A few proteins are overexpressed specifically at each EC tumor grade and in the corresponding SLN. These proteins, which are significantly variable in both locations, should be considered potential markers of overall survival. Five major proteins for EC and SLN (PRSS3, PTX3, ASS1, ALDH2, and ANXA1) were identified in large-scale proteomics and validated by immunohistochemistry. This study improves stratification and diagnosis of individuals with EC as a result of proteomics profiling of SLNs.

Potential Impact of the Z0011 Trial on the Omission of Axillary Dissection: A Retrospective Cohort Study.

To evaluate the number of patients with early-stage breast cancer who could benefit from the omission of axillary surgery following the application of the Alliance for Clinical Trials in Oncology (ACOSOG) Z0011 trial criteria. A retrospective cohort study conducted in the Hospital da Mulher da Universidade Estadual de Campinas. The study population included 384 women diagnosed with early-stage invasive breast cancer, clinically negative axilla, treated with breast-conserving surgery and sentinel lymph node biopsy, radiation therapy, chemotherapy and/or endocrine therapy, from January 2005 to December 2010. The ACOSOG Z0011 trial criteria were applied to this population and a statistical analysis was performed to make a comparison between populations. A total of 384 patients underwent breast-conserving surgery and sentinel lymph node biopsy. Of the total number of patients, 86 women underwent axillary lymph node dissection for metastatic sentinel lymph nodes (SNLs). One patient underwent axillary node dissection due to a suspicious SLN intraoperatively, thus, she was excluded from the study. Among these patients, 82/86 (95.3%) had one to two involved sentinel lymph nodes and met the criteria for the ACOSOG Z0011 trial with the omission of axillary lymph node dissection. Among the 82 eligible women, there were only 13 cases (15.9%) of lymphovascular invasion and 62 cases (75.6%) of tumors measuring up to 2 cm in diameter (T1). The ACOSOG Z0011 trial criteria can be applied to a select group of SLN-positive patients, reducing the costs and morbidities of breast cancer surgery.

Relationship between type 2 diabetes mellitus and markers of cutaneous melanoma aggressiveness: an observational multicentric study in 443 patients with melanoma.

Some studies have suggested a relationship between type 2 diabetes mellitus (T2DM) and increased incidence of melanoma. Efforts are under way to identify preventable and treatable factors associated with greater melanoma aggressiveness, but no studies to date have examined the relationship between T2DM and the aggressiveness of cutaneous melanoma at diagnosis. To explore potential associations between T2DM, glycaemic control and metformin treatment and the aggressiveness of cutaneous melanoma. We conducted a cross-sectional multicentric study in 443 patients diagnosed with cutaneous melanoma. At diagnosis, all patients completed a standardized protocol, and a fasting blood sample was extracted to analyse their glucose levels, glycated haemoglobin concentration and markers of systemic inflammation. Melanoma characteristics and aggressiveness factors [Breslow thickness, ulceration, tumour mitotic rate (TMR), sentinel lymph node (SLN) involvement and tumour stage] were also recorded. The mean (SD) age of the patients was 55·98 (15·3) years and 50·6% were male. The median Breslow thickness was 0·85 mm. In total, 48 (10·8%) patients were diagnosed with T2DM and this finding was associated with a Breslow thickness > 2 mm [odds ratio (OR) 2·6, 95% confidence interval (CI) 1·4-4·9; P = 0·004)] and > 4 mm (OR 3·6, 95% CI 1·7-7·9; P = 0·001), TMR > 5 per mm2 (OR 4·5, 95% CI 1·4-13·7; P = 0·009), SLN involvement (OR 2·3, 95% CI 1-5·7; P = 0·038) and tumour stages III-IV (vs. I-II) (OR 3·4, 95% CI 1·6-7·4; P = 0·002), after adjusting for age, sex, obesity, alcohol intake and smoking habits. No significant associations emerged between glycated haemoglobin levels, metformin treatment and melanoma aggressiveness. T2DM, rather than glycaemic control and metformin treatment, is associated with increased cutaneous melanoma aggressiveness at diagnosis.

Abstract PS1-53: Does the axilla surgical management for limited sentinel lymph nodes involvement vary between total mastectomy and breast-conserving surgery

Abstract Purpose: The ACOSOG Z0011 study demonstrated that axillary lymph node dissection (ALND) can be safely omitted in patients with one to two positive sentinel lymph node (SLN) who underwent breast-conserving surgery (BCS) with planned whole-breast irradiation. This study aimed to analysis the surgical management in patients with one to two positive SLNs, and further evaluate the rates of non-sentinel lymph node (non-SLN) metastasis between patients receiving BCS or total mastectomy (TM). Methods: We performed a retrospective analysis of patients with early breast carcinoma from the Shanghai Jiao Tong University-Breast Cancer Database (SJTU-BCDB) between 2011 to 2018. The inclusion criteria were (1) cT1-2N0M0 invasive breast cancer, (2) aged ≥18 years at diagnosis, (3) received surgical treatment for the primary tumor and the axilla, (4) had one to two positive SLNs, (5) no history of previous or concurrent malignant disease, and (6) no neoadjuvant therapy. Patients were classified into the BCS and TM groups. Time trends of ALND rates were analyzed with Chi-square tests. And the rates of non-SLN metastasis between BCS and TM groups were also analyzed with Chi-square tests. Multivariable logistic regression was used to determine factors influencing the completion of ALND and non-SLN metastasis. And Kaplan-Meier estimator and log-rank tests were used to analysis the recurrence-free survival (RFS) between SLNB alone and SLNB+ALND arms. Results: Of the 891 patients enrolled, 586 (65.8%) received TM and 305 (34.2%) received BCS. Between 2011 and 2018, the completion of ALND for 1-2 positive SLN decreased from 100% to 72.7% (P &amp;lt;0.001). And the rate of ALND was significantly higher in the TM group compared with the BCS group (n = 541, 92.3% vs n = 195, 63.9%; P &amp;lt;0.001).Earlier year of diagnosis (P &amp;lt;0.001), primary mastectomy (P &amp;lt;0.001), SLN positive-total ratio &amp;gt;50% (P =0.001), and SLN macro-metastasis (P &amp;lt;0.001) were all independently associated with a higher probability of completing ALND. Among the 736 patients undergone ALND, the rates of non-SLN metastasis were significantly higher in the TM group, compared to the BCS groups (TM: n = 170, 31.4% vs BCS: n = 46, 23.6%; P =0.044). The multivariable regression analysis indicated that non-SLN metastasis was significantly associated with SLN positive-total ratio &amp;gt;50% (OR=3.43, 95%CI 2.28-5.17; P &amp;lt;0.001), Her-2 positive disease (OR=1.63, 95%CI 1.09-2.46; P =0.019), and pT2-3 disease (OR=1.46, 95%CI 1.01-2.09; P =0.042). However, surgery of the breast was not independently associated with the rate of non-SLN metastasis (P =0.090). After a median follow-up time of 31.9 months (range, 1.0-96.5 months), there were no significant difference in RFS between the SLNB alone and SLNB+ALND arms, regardless of the surgery of the breast (TM group: Log-rank P = 0.910; BCS group: Log-rank P =0.840). Conclusion: There is an increasing trend toward omitting ALND in patients with one to two positive SLNs. Compared with the patients undergone BCS, the rate of non-SLN metastasis was significantly higher in patients undergone TM. However, the omission of ALND had limited influence on disease outcome among those patients received TM. Citation Format: Weiqi Gao, Xiaosong Chen, Kunwei Shen. Does the axilla surgical management for limited sentinel lymph nodes involvement vary between total mastectomy and breast-conserving surgery [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-53.

Women Could Avoid Axillary Lymph Node Dissection by Choosing Breast-Conserving Therapy Instead of Mastectomy.

The ACOSOG Z0011 trial showed that completion axillary lymph node dissection (cALND) can be safely omitted for some patients with T1-2 clinically node-negative breast cancer with one to two involved sentinel lymph nodes (SLNs) treated with breast-conserving therapy (BCT). There is little evidence for the safety of omitting cALND for mastectomy-treated patients. Consequently, cALND is often recommended for sentinel node-positive patients treated with mastectomy. The aim of this study is to determine the proportion of patients who could avoid cALND by choosing BCT instead of mastectomy at a tertiary cancer center. All T1-2 clinically node-negative breast cancer patients treated with BCT or mastectomy between 2012 and 2017 with metastases in the SLN(s) were selected from a prospectively maintained database. Clinical factors and outcomes were evaluated between the two groups. Differences were compared using Wilcoxon rank-sum test, chi-square test or Fisher's exact test as appropriate. Significance was set at the 0.05 level for all analyses. A total of 306 patients were included, 199 (65.0%) of whom were treated with BCT and 107 (35.0%) with mastectomy. Patients treated with mastectomy were more often treated with cALND compared with those treated with BCT (71.0% versus 26.6%, p < 0.0001). Overall, 52 of the mastectomy patients (68.4%) could have avoided cALND if they had chosen BCT. Patients treated with mastectomy are more likely to receive cALND than those treated with BCT. Axillary management should be addressed during discussion of primary tumor therapy, and cALND may be avoided when patients choose BCT instead of mastectomy.

Regional lymph node metastases in cutaneous melanoma: a single-center analysis from southeast europe

Sentinel lymph node biopsy is the standard of care for nodal staging in clinically node-negative melanoma patients. Our goal was to present 10-year results of sentinel lymph node biopsy at our institution and to evaluate the clinicopathologic factors as potential predictors of sentinel lymph node and non-sentinel lymph node metastatic involvement in patients with cutaneous melanoma. We have analyzed clinicopathologic and lymphoscintigraphic characteristics in 420 patients with cutaneous melanoma who underwent sentinel lymph node biopsy between 2010 and 2019. In addition, we have examined the results of group of patients with positive sentinel lymph node biopsy undergoing complete lymph node dissection. The overall detection rate of sentinel lymph node biopsies was 97.1%, of which 18.8% was metastatic. Drainage to one regional basin was seen in 345 patients (83.1%) and to multiple drainage regions in 71 patients (17%). In-transit lymph nodes were detected in 20 patients. On univariate logistic regression analysis, male gender, primary tumor thickness with nodular histology, acral location, presence of ulceration, and the number of nodes harvested were significantly associated with sentinel lymph node biopsy status (p < 0.05). On multivariate analysis, the Breslow thickness was the only independent predictor of sentinel lymph node biopsy status. The metastases in non-sentinel lymph node found in 26 patients with positive sentinel lymph node (35.6%) correlated on univariate, as well as on multivariate logistic regression, with tumor subtype and number of sentinel lymph node harvested. In addition to the well-established primary tumor thickness as a predictor of sentinel lymph node biopsy positivity, we observed acral location and nodular melanoma subtype to significantly enhance the risk of metastases in sentinel lymph node(s). Primary tumor histology and number of nodes harvested were the only statistically significant variables predicting the non-sentinel lymph node status on multivariate analysis. Lymphoscintigraphy imaging characteristics were not significantly associated with sentinel lymph node status.

The design and fabrication of nanoengineered platinum needles with laser welded carbon nanotubes (CNTs) for the electrochemical biosensing of cancer lymph nodes.

A new biosensor for detecting cancer involved sentinel lymph nodes has been developed via the electrochemical tracing of fatty acid oxidation as a distinct metabolism of malignant cells invading lymph nodes (LNs). The system included integrated platinum needle electrodes that were decorated by carbon nanotubes (as hydrophobic agents) through laser-assisted nanowelding. It was applied to record the dielectric spectroscopy data from LN contents via electrochemical impedance spectroscopy. The system was applied for dielectric spectroscopy of LN contentsviaelectrochemical impedance approach. The reduced lipid content of involved LNs, due to fat metabolism by invasive cancer cells, would decrease the charge transfer resistance (RCT) of the LNs with respect to their normal counterparts. Multi-walled carbon nanotubes (MWCNTs) with superhydrophobic properties were used to enhance the interaction of Pt needle electrodes with the lipidic contents of lymph nodes. This is the first time that a fatty acid metabolism-based sensing approach has been introduced to detect involved LNs. Moreover, a novel electrode decorating method was applied to enhance the interfacial contact of this lipid detection probe (LDP). In order to avoid doubt about the biocompatibility of ferrocyanide, [Fe(CN)6]4- and ferricyanide, [Fe(CN)6]3-, a biocompatible injectable metal ion-based material, ferric carboxymaltose, was selected and applied as the electrolyte for the first time. Rabbit LNs were tested using the LDP in the animal model phase. The system was then used in vitro on 122 dissected human LNs in the operating room. Calibration of the results showed an excellent match between the dielectric response of the LDP (known as charge transfer resistance (RCT)) and the final pathological diagnoses. The LDP may have a promising future after further clinical investigations for intra-operative distinction between normal and cancerous LNs.

The uterine pathological features associated with sentinel lymph node metastasis in endometrial carcinomas.

BackgroundIn recent years, sentinel lymph node excision and ultrastaging have been performed in endometrial carcinomas to obtain information about lymph node status, avoiding unnecessary complete pelvic and paraaortic lymphadenectomy. The purpose of this retrospective study was to provide a comprehensive evaluation of the pathological features of endometrial carcinomas and their significance in association with sentinel lymph node involvement.MethodsPatients with endometrial carcinomas, preceded by sentinel lymph node mapping, were classified into Group-I and Group-II with negative and positive involvement, respectively. The pathological features, associated with sentinel lymph node involvement, were statistically analyzed, including determination of test performance parameters.ResultsAmong 70 patients who had undergone hysterectomy and sentinel lymph node excision, 61 had carcinoma and 9 had atypical hyperplasia. There were 50 patients in Group-I and 10 in Group-II. In Group-II, the significant pathological features were: 1) lower uterine segment involvement (100%), 2) an average tumor size of ≥5 CM, 3) lymphovascular invasion (50%), 4) cervical stromal invasion (40%), and 5) depth of myometrial invasion of ≥50% (50%). The incidences of these pathological features were significantly less in Group-I. Statistical analyses singled out “lower uterine segment involvement” as the most important feature.ConclusionsWe have identified five pathological features which are associated with sentinel lymph node involvement. Since lower uterine segment involvement has occurred in all cases of the Group-II cohort, we recommend FIGO and other organizations that determine staging rules should consider whether tumors that involve the lower uterine segment should be staged as higher than “1a”, if the findings in this small series are confirmed by other studies. The results of this study may guide pathologists and oncologists in the diagnostic and therapeutic approaches to management of endometrial carcinomas.

Nodal Recurrence Rates for Melanoma Patients with ≥1 mm Sentinel Lymph Node Involvement in the Era of Adjuvant Immunotherapy

Nodal Recurrence Rates for Melanoma Patients with ≥1 mm Sentinel Lymph Node Involvement in the Era of Adjuvant Immunotherapy

Clinical significance of extranodal extension in sentinel lymph node positive breast cancer

The precise stage of lymph node (LN) metastasis is a strong prognostic factor in breast cancers, and sentinel lymph node (SLN) is the first station of nodal metastasis. A number of patients have extranodal extension (ENE) in SLN, whereas the clinical values of ENE in SLN in breast cancers are still in exploration. The aim of our study was to evaluate the predictive and prognostic values of ENE in SLN in breast cancers, and to investigate the feasibility of ENE to predict non-SLN metastasis, nodal burden, disease free survival (DFS) and overall survival (OS) in clinical practice. 266 cases of primary invasive breast cancer (cT1-2N0 breast cancer) underwent SLN biopsy and axillary lymph node dissection (ALND) between 2008 and 2015 were extracted from the pathology database of Fudan University Shanghai Cancer Center. ENE in SLN was defined as extension of neoplastic cells through the lymph-nodal capsule into the peri-nodal adipose tissue, and was classified as no larger than 2 mm and larger than 2 mm group. The associations between ENE and clinicopathological features, non-SLN metastasis, nodal burden, DFS, and OS were analyzed. In the 266 patients with involved SLN, 100(37.6%) were positive for ENE in SLN. 67 (25.2%) cases had ENE no larger than 2 mm in diameter, and 33(12.4%) had ENE larger than 2 mm. Among the clinicopathological characteristics, the presence of ENE in SLN was associated with higher pT and pN stages, PR status, lympho-vascular invasion. Logistic regression analysis indicated that patients with ENE in SLN had higher rate of non-SLN metastasis (OR4.80, 95% CI 2.47–9.34, P < 0.001). Meanwhile, in patients with SLN micrometastasis or 1–2 SLNs involvement, ENE positive patients had higher rate of non-SLN metastasis, comparing with ENE negative patients (P < 0.001, P = 0.004 respectively). The presence of ENE in SLN was correlated with nodal burden, including the pattern and number of involved SLN (P < 0.001, P < 0.001 respectively), the number of involved non-SLN and total positive LNs (P < 0.001, P < 0.001 respectively). Patients with ENE had significantly higher frequency of pN2 disease (P < 0.001). For the disease recurrence and survival status, Cox regression analysis showed that patients with ENE in SLN had significantly reduced DFS (HR 3.05, 95%CI 1.13–10.48, P = 0.008) and OS (HR 3.34, 95%CI 0.74–14.52, P = 0.092) in multivariate analysis. Kaplan–Meier curves and log-rank test showed that patients with ENE in SLN had lower DFS and OS (for DFS: P < 0.001; and for OS: P < 0.001 respectively). Whereas no significant difference was found in nodal burden between ENE ≤ 2 mm and > 2 mm groups, except the number of SLN metastasis was higher in patients with ENE > 2 mm. Cox regression analysis, Kaplan–Meier curves and log-rank test indicated that the size of ENE was not an independent factor of DFS and OS. Our study indicated that ENE in SLN was a predictor for non-SLN metastasis, nodal burden and prognosis in breast cancers. Patients with ENE in SLN had a higher rate of non-SLN metastasis, higher frequency of pN2 disease, and poorer prognosis. Patients with ENE in SLN may benefit from additional ALND, even in SLN micrometastasis or 1–2 SLNs involvement patients. The presence of ENE in SLN should be evaluated in clinical practice. Size of ENE which was classified by a 2 mm cutoff value had no significant predictive and prognostic values in this study. The cutoff values of ENE in SLN need further investigation.

Sentinel lymph node biopsy should be considered for clinically node-negative breast cancer regardless of BRCA1/2 mutation status.

BackgroundBRCA1/2 mutations lead to an elevated risk of breast cancer. None involved in whether BRCA1/2 mutation status will affect the first decision-making of sentinel lymph node (SLN) biopsy or not for clinically node-negative breast cancer. We retrospectively investigated whether BRCA1/2 mutation status influenced SLN involvement rate and survival outcomes after sentinel lymph node biopsy (SLNB) for Chinese clinically node-negative breast cancer patients.MethodsPatients who underwent SLNB at initial were enrolled and divided according to BRCA1/2 mutation status. Germline DNA for BRCA1/2 testing was derived from blood samples. SLN involvement rate and clinicopathological characteristics were analyzed using the Chi-square test. Kaplan–Meier univariate and multivariate Cox regression analysis was performed to compare survival between groups.ResultsAccording to BRCA1/2 mutation test criteria, 156 Chinese women receiving initial SLNB with clinically node-negative breast cancer were selected—thirty-one patients identified as BRCA1/2 mutation carriers and 102 as non-carriers were enrolled. Non-carriers seemed to be with a more advanced TNM stage (P<0.01) compared to the non-carrier group. Once SLN involved, the patient will receive axillary lymph node dissection in which BRCA1/2 mutation did not increase the rate (P=0.73). Disease-free survival (DFS) (P=0.48) and recurrence-free survival (RFS) (P=0.79) are comparable between groups, even after adjustment for clinicopathological characteristics, systemic treatment, and surgical management of breast [DFS, hazard ratio (HR) =1.63, confidence interval (CI): 0.48–5.54, P=0.43; RFS, HR =0.75, CI: 0.14–3.89, P=0.73].ConclusionsSLNB should be considered for clinically node-negative breast cancer regardless of BRCA1/2 status.

Diagnostic value of frozen section examination of sentinel lymph nodes in early-stage cervical cancer at the time of ultrastaging

ObjectivesWe aimed to assess the diagnostic value of frozen-section pathologic examination (FSE) of sentinel lymph nodes (SLN) in patients with early-stage cervical cancer. MethodsTwo French prospective multicentric database on SLN biopsy for cervical cancer (SENTICOL I and II) were analysed. Patients with IA to IIA1 2018 FIGO stage, who underwent SLN biopsy with both FSE and ultrastaging examination were included. Results and discussionBetween 2005 and 2012, 313 patients from 25 centers fulfilled the inclusion criteria. Metastatic involvement of SLN was diagnosed in 52 patients (16.6%). Macrometastases, micrometastases and isolated tumor cells (ITCs) were found in 27, 12 and 13 patients respectively. Among the 928 SLNs analysed, FSE identified 23 SLNs with macrometastases in 20 patients and 5 SLNs with micrometastases in 2 patients whereas no ITCs were identified. Ultrastaging of negative SLNs by FSE found macrometastases, micrometastases and ITCs in additional 7, 11 and 17 SLNs. Ultrastaging increased significantly the rate of patients with positive SLN from 7% to 16.6% (p < 0.0001).The sensitivity and the negative predictive value of FSE were 42.3% and 89.7% respectively or 56.4% and 94.1% if ITCs were excluded. False-negative cases were more frequent with tumor size ≥ 20 mm (OR = 4.46, 95%IC = [1.45–13.66], p = 0.01) and preoperative brachytherapy (OR = 4.47, 95%IC = [1.37–14.63], p = 0.01) and less frequent with patients included in higher volume center (>5 patients/year) (OR = 0.09, 95%IC = [0.02–0.51], p = 0.01). ConclusionsFSE of SLN had a low sensitivity for detecting micrometastases and ITCs and a high negative predictive value for SLN status. Clinical impact of false-negative cases has to be assessed by further studies.