Presence Of Sentinel Lymph Node Metastasis Research Articles

Ultrasonographic Algorithm for the Assessment of Sentinel Lymph Nodes That Drain the Mammary Carcinomas in Female Dogs.

Simple SummaryMammary neoplasms are one of the most common oncological diseases diagnosed in female dogs. Their staging also involves the evaluation of the sentinel lymph nodes that drain these tumors. Since non-invasive diagnosis is an important requirement in both human and veterinary medicine, by using simple and available ultrasound techniques, our study proposes a non-invasive assessment of the status of sentinel lymph nodes of the tumoral mammary glands. The algorithm consists of B-mode ultrasound, Doppler technique, contrast-enhanced ultrasound (CEUS), and real-time elastography. Diagnostic performance was established for each technique. The highest accuracy in identifying metastases in sentinel lymph nodes was given by the elasticity score followed by the short/long-axis ratio and resistivity index. CEUS had the same accuracy as the Doppler examination. By assigning a score to each parameter of the mentioned techniques and summing up these scores, we obtained a high accuracy of metastasis detection in sentinel lymph nodes (92.2%). This algorithm for examining the status of sentinel lymph nodes that uses simple and widely available techniques in the current practice can be extremely useful to practitioners for staging mammary malignant tumors in female dogs, leading to the right treatment decision.The status of sentinel lymph nodes (SLNs) is decisive in staging, prognosis, and therapeutic approach. Using an ultrasonographic examination algorithm composed of B-mode, Doppler technique, contrast-enhanced ultrasound (CEUS) and elastography, this study aimed to determine the diagnostic performance of the four techniques compared to histopathological examination. 96 SLNs belonging to 71 female dogs with mammary gland carcinomas were examined. After examinations, mastectomy and lymphadenectomy were performed. Histopathological examination confirmed the presence of metastases in 54 SLNs. The elasticity score had the highest accuracy—89.71%, identifying metastases in SLNs with 88.9.9% sensitivity (SE) and 90.5% specificity (SP), ROC analysis providing excellent results. The S/L (short axis/long axis) ratio showed 83.3% SE and 78.6% SP as a predictor of the presence of metastases in SLN having a good accuracy of 81.2%. On Doppler examination, the resistivity index(RI) showed good accuracy of 80% in characterizing lymph nodes with metastases versus unaffected ones; the same results being obtained by CEUS examination. By assigning to each ultrasonographic parameter a score (0 or 1) and summing up the scores of the four techniques, we obtained the best diagnostic performance in identifying lymph node metastases with 92.2% accuracy. In conclusion, the use of the presented algorithm provides the best identification of metastases in SLNs, helping in mammary carcinoma staging and appropriate therapeutic management.

Sentinel lymph node biopsy in acral melanoma: A Korean single-center experience with 107 patients (2006-2018).

Sentinel lymph node biopsy (SLNB) of primary cutaneous melanoma as an important staging method has not been popularly undertaken in Korea and only a few studies with small patient numbers have been published. We examined the clinical feasibility and overall outcomes of SLNB in acral melanoma (AM) of Korean in Kyungpook National University Hospital (KNUH) over the past 13 years. SLNB in AM patients during 2006-2018 were analyzed retrospectively for sentinel lymph node (SLN) harvesting rate, positivity rate, positivity-relevant overall survival (OS) and disease-free survival (DFS), and its side effects. A total of 109 AM patients who underwent SLNB were enrolled. Harvested nodes were identified from 107 patients and SLN harvesting rate was 98.2%. The mean Breslow thickness (±standard deviation) was 3.38 ± 3.03mm, and the proportion of ulcerated melanomas was 64%. Twenty-two (20.6%) had a tumor-positive SLN and, among them, 82% (18/22) underwent immediate complete lymph node dissection (CLND). The metastasis-positive nodal basin after CLND was detected in 16.7% of cases (3/18). Tumor-negative SLN cohorts showed significantly better OS and DFS than tumor-positive ones (P=0.006 and P<0.001 for each). Two side effects, one seroma and one lymphocele, were observed without major sequelae. SLNB, crucial management of melanoma, proved its efficacy to predict patients' prognosis and could be performed successfully and safely in Korean AM patients by interdisciplinary cooperation between dermatology and other surgical departments. SLN(-) showed significantly better OS and DFS than SLN(+). Significant risk factors for DFS were Breslow thickness, the presence of ulceration and the presence of SLN metastasis. SLNB should be encouraged in order to stage melanoma accurately and direct the proper management in Korean AM.

Identification of novel, immune-mediating extracellular vesicles in human lymphatic effluent draining primary cutaneous melanoma

ABSTRACTEpithelial tumors including melanoma often first metastasize to regional, sentinel lymph nodes (SLN). Thus, the presence of SLN metastases is a critical prognostic factor of survival. Prior to metastasis, accumulating evidence suggests the SLN is immunologically compromised; however, the process by which pre-metastatic niche formation occurs remains unknown. In this prospective study, freshly dissected, afferent lymphatic fluid was obtained during SLN biopsy in three patients with primary cutaneous melanoma. Lymphatic extracellular vesicles (L-EV) were visualized by transmission electron microscopy and proteomic cargo profiled by mass spectrometry. Flow cytometry assessed L-EV effects on autologous dendritic cell maturation in vitro. Immunogold electron microscopy and immunohistochemistry visualized expression of EV cargo within the primary tumor and SLN. Lymphatic extracellular vesicles from each afferent lymphatic channel demonstrated inhibition of autologous dendritic cell maturation. Proteomic profiling identified 81 peptides shared among the L-EV preparations including a signature of 18 immune-modulating proteins including previously established inhibitor of dendritic cell maturation, S100A9. Immunohistochemistry and immunogold electron microscopy confirmed S100A9 tracking along the lymphatic path, from keratinocytes in the primary tumor to sub-capsular macrophages in the SLN. Our findings suggest L-EV cargo may serve as early mediators of tumor-induced immune subversion in regional lymph nodes, by preceding malignant cells and trafficking within the lymphatic vasculature to harbor the first pre-metastatic niche.

Minimal prognostic significance of sentinel lymph node metastasis in patients with cT1\u20132 and cN0 breast cancer

BackgroundThe prognostic value of sentinel lymph node (SLN) metastases may be minimized by the limited disease burden of lymph node metastases and tailoring adjuvant therapy based on breast cancer biology. The aim of this study is to assess the prognostic significance of SLN metastasis in patients with cT1–2N0M0 breast cancer.Patients and methodsBetween January 2006 and December 2015, 582 patients underwent SLN biopsy for cT1–2N0M0 breast cancers. cN0 was essentially diagnosed by ultrasound sonography. The prognostic values of SLN metastases were retrospectively evaluated.ResultsAmong 582 patients with cT1–2N0M0 breast cancer, 111 patients (19.1%) were positive for SLN metastasis, including 39 cases (6.7%) of micrometastasis and 72 cases (12.4%) of macrometastases. The median size of SLN metastasis was 3.0 mm (range 0.2–16 mm, mean 4.1 mm). In log-rank test, presence of SLN metastasis was not associated with breast cancer recurrence (p = 0.21); 5-year and 10-year recurrence-free survival (RFS) were 93.0% and 96.5%, and 93.0% and 90.4% in the SLN-positive and SLN-negative groups, respectively. In the propensity score matching cohort (n = 178), there was no significant difference in RFS between the SLN-positive and SLN-negative groups (p = 0.90). In Cox regression analysis, a continuous value of Ki67 expression was a significant prognostic factor (HR 1.03; 95% CI 1.01–1.05, p = 0.017).ConclusionSLN metastasis has a minimal impact on RFS for patients with cT1–2N0M0 breast cancer in the modern medical era. A proliferation marker is a better factor for poor prognosis than the presence of SLN metastases in this population.

Abstract P1-01-10: Sentinel lymph node-II biopsy in breast cancer: A novel method to accurately predict non-sentinel axillary lymph node status

Abstract Background: In breast cancer patients, axillary lymph node dissection (ALND) is recommended in the presence of sentinel lymph node metastasis (SLNM). However, in 50-70% of patients, SLN is the only site affected by metastasis and thus majority of these patients are exposed to risk of morbidity of ALND without any benefit. Z011 trial suggests avoiding ALND in early breast cancer patients with isolated SLNM. However, this trial results are not applicable to women with advanced T-stage, multiple SLNM, and the presence of lympho-vascular or peri-capsular invasion. This prospective study aims to analyze whether SLN-II biopsy would help in accurate prediction of non sentinel axillary metastases in the presence of metastatic SLN-I. Methods: After IRB approval, 65 patients with biopsy proven breast cancer underwent SLN biopsy using a standard technique. After identification of the SLN-I, 0.1 cc of methylene blue dye was injected into SLN-I, and the lymphatic channels were traced to identify SLN-II station. ALND was performed in the presence of SLNM. After a pathologic examination, the sensitivity and specificity of SLN-II and the concordance rate between SLN-I, SLN-II and the axilla were calculated to determine the accuracy of SLN-II in identifying the non-sentinel axillary metastasis. Results: A total of 65 breast cancer patients underwent SLN-I and SLN-II biopsy. Average number of SLN-I harvested was 1.7 (range 1-5) and that of SLN-II was 1.4 (range 1-4). Metastases to SLN-I were identified in 12 (18.5%) patients. Upon ALND, only 3 (25%) patients had higher axillary metastasis whereas in 9 patients (75%), axilla had no metastasis. SLN-II predicted the presence (3 of 3) or absence (9 of 9) of axillary metastases with 100% accuracy. The sensitivity, accuracy, false negative rate and negative predictive value of SLN-I in identifying higher axillary metastasis were 92.3%, 98.5%, 7.7% and 98% respectively, whereas same metrics for SLN-II were 100%, 100%, 0% and 100% respectively. Utility of different sentinel lymph node stations in determining axillary metastasesTestTrue positiveTrue negativeFalse negativeSLN-I12521SLN-II4610ALND390 Thus in the presence of SLN-I metastasis, SLN-II accurately identified axillary involvement 100% of the times. One patient was associated with a skip SLN-II metastasis. In this patient SLN-I was negative, however non-sentinel metastases were noted upon ALND. Comparitive analysis of SLN-I and SLN-II in determining axillary metastasisTestSensitivityFNRNPVAccuracyNLRSLN-I12/13 (92.3%)1/13 (7.7%)52/53 (98%)64/65 (98.5%)77%SLN-II4/4 (100%)0%61/61 (100%)65/65 (100%)100%NLR: negative likelihood ratio, NPV, negative predictive value Conclusions: This study demonstrates that in breast cancer patients with SLN-I metastases, SLN-II biopsy is feasible and accurately predicts the higher axillary lymph node status in terms of either the presence or absence of metastasis. In other words, in patients with SLN-I metastasis, a negative SLN-II rules out higher axillary metastasis, whereas the presence of the SLN-II metastasis was associated with further axillary metastasis. Thus, ALND can be avoided in women with isolated SLN-I metastasis but absent SLN-II involvement. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-10.

Role of sentinel lymphadenectomy in thin cutaneous melanomas with positive deep margins on initial biopsy

Breslow thickness (BRES) on initial melanoma biopsy determines need for sentinel lymph node (SLN) biopsy. In presence of positive deep margins, BRES is indeterminate. We hypothesized that thin (BRES <0.76 mm) melanomas with positive deep margins and thicker melanomas (BRES 0.76-2.0 mm) have statistically similar risk of SLN metastasis. Retrospective review was performed of adult patients undergoing wide excision plus SLN biopsy for melanoma from 01/2004 to 05/2010. Group 1 (BRES <0.76 mm and positive deep margins) was compared to Group 2 (BRES 0.76-2.0 mm, regardless of margin status). Primary outcome was presence of SLN metastasis. 260 patients were eligible, 72 (28%) in Group 1 and 188 (72%) in Group 2. Average age was 57 years, with 120 (46%) females. SLNs were positive in 6/72 (8.3%) patients in Group 1 and 17/188 (9.0%) patients in Group 2 (P=0.86). The two groups were not statistically different by multivariate analysis (P=0.49). In multivariate model, Clark's level IV (P=0.009) was only predictive factor of SLN metastasis. Melanoma patients with thin BRES but positive deep margins carry risk of SLN metastasis similar to patients with thicker melanomas. Positive deep margins should be considered in decision to perform SLN biopsy. Clark's level IV was significantly associated with SLN metastasis.

P3-07-36: Predicting Sentinel Lymph Node Metastasis of a Chinese Breast Cancer Population: Assessment of an Existing Nomogram and a New Predictive Nomogram.

Abstract Background: The Memorial Sloan-Kettering Cancer Center (MSKCC) developed a nomogram to predict the presence of sentinel lymph node (SLN) metastasis in breast cancer patients. In our study, The MSKCC nomogram performance for prediction of SLN metastases was assessed in Chinese breast cancer population. A new model (Shanghai Cancer Center Nomogram, SCC nomogram ) was developed with clinically relevant variables and possible advantages. Methods: Data were collected from 771 patients with successful SLN biopsy who were treated during March 2005 to June 2010. Touch imprint cytology (TIC) and serial section with H&amp;E staining were performed routinely on each sentinel node. 580 SLN biopsy procedures from March 2005to November 2009were used as training group to validate the MSKCC nomogram and assessed with multivariable logistic regression to predict the presence of SLN metastasis in breast cancer. The predictive accuracy of MSKCC nomogram was assessed by calculating the area under the receiver-operating characteristic (ROC) curve (AUC). The SCC nomogram was created from the logistic regression model. The new model was subsequently applied to 191 sequential SLN biopsies from January 2010 to June 2010 as the validation group. Results: It was shown that age, tumor size, tumor type, histological grade, lymphovascular invasion and neural invasion was correlated with the probability of SLN metastasis by univariate analysis (P&amp;lt;0.05). By multivariate analysis, tumor size, histological grade and lymphovascular invasion were identified as independent predictors of SLN metastasis. The SCC nomogram was then developed with four variables associated with SLN metastasis: age, tumor size, histological grade and lymphovascular invasion. The new model was accurate and discriminating, with AUC of 0.773 when applied to the validation group, as compared to the MSKCC nomogram with AUC of 0.754 in the modeling group. The trend of actual probability in various decile groups was comparable to the predicted probability. For predicted probability cut-off points of 7% and 15%, the false-negative rates of SCC nomogram were 0% and 8.1%. Conclusion: As far as we know, this is the first study designed to evaluate the MSKCC nomogram and develop a new nomogram in Chinese early breast cancer population. Compared to the MSKCC nomogram, the SCC nomogram was developed with similar AUC but less variables and lower false-negative rates for low-probability subgroups. It could provide a more acceptable clinical accessory in the preoperative discussion with patients, especially in the very low risk of patients. For those patients, the SCC nomogram could be used to safely avoid a SLN procedure, thereby reducing postoperative morbidity, whereas the rate could be as high as 7% in the literature. Although the SCC nomogram that predicts metastasis of breast cancer in the sentinel lymph node performed well in Chinese breast cancer population, it is imperfect. The SCC nomogram was developed and validated in the single instite. The SCC model should be validated in different patient groups before it is demonstrated to be reproducible and would be applied widely. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-36.

The Numbers of FoxP3+ Lymphocytes in Sentinel Lymph Nodes of Breast Cancer Patients Correlate With Primary Tumor Size but Not Nodal Status

Regulatory T cells, lymphocytes marked by expression of the transcription factor Forkhead Box Protein P3 (FoxP3), inhibit the activation of tumor-specific T cells in tumor-draining lymph nodes. Immunohistochemical analyses of sentinel lymph nodes (SLNs) from 104 breast cancer patients showed a significant association (p = .0028, Pearson correlation) between the number of FoxP3+ cells and the size of primary breast invasive ductal carcinoma. In contrast, there was no correlation between the number of FoxP3+ cells and the presence of SLN metastases, or other clinicopathological parameters. These results suggest the presence of an immune suppressive environment in SLNs of larger tumors.

Abstract 870: Candidate SNPs in angiogenesis and lymphangiogenesis and risk of cutaneous melanoma

Abstract Background: Currently, a combination of clinical and pathologic features are used to predict patient outcome in localized melanoma including age, sex, and tumor location, ulceration and Breslow depth. The presence or absence of metastasis in the local draining (sentinel) lymph node (SLN) as determined by SLN biopsy is considered the most accurate method for staging localized melanoma and is the most important predictor of recurrence and survival in patients with clinically node-negative melanoma. Additional biomarkers are needed to improve prediction models and target therapies to individual patients. Among the most promising candidate biomarkers are genes affecting lymph/angiogenesis which are thought to play a critical role in the development and progression of melanoma. We investigated whether single nucleotide polymorphisms (SNPs) in the lymph/angiogenesis pathway are associated with risk of SLN metastasis and mortality in patients with invasive melanoma of the skin. Methods: We examined risk of SLN metastasis and melanoma-related death in relation to 290 candidate and tagging SNPs in 26 lymph/angiogenesis genes in patients referred to the Moffitt Cancer Center between 1999 and 2008 for wide local excision and SLN staging of a primary invasive melanoma of the skin. Genotypes by the Illumina Goldengates in lymph/angiogenesis pathway genes were compared in a total of 177 patients with pathologically documented SLN metastasis and 375 patients negative for nodal metastasis, of whom a total of 41 (23%) and 19 (5%) patients, respectively, died from systemic disease. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the risk of SLN metastasis in relation to examined genotypes adjusting for age and gender. Proportional hazards regression was used to estimate age and gender-adjusted hazard ratios (HR) for melanoma-related death. Results: A total of 17 variant alleles in 8 lymph/angiogenesis genes including COL18A1, ELAVL1, FLT1, HSPG2, PDGFD, PIK3CA, NFRSF1b and VEGFA were associated with presence of SLN metastasis. An additional 17 SNPs in 10 genes including 4 genes associated with SLN metastasis (COL18A1, ELAVL1, PDGFD, PIK3CA), CXCL12, EGFR, FGFR4, IL10, NOS3, and PDPN were associated with survival. Carriers of the variant allele in COL18A1 rs728142 (minor allele frequency: 25%) were at increased risk of SLN metastasis (per allele OR: 1.33; 95% CI: 1.00-1.77; p trend =0.05) and melanoma-related death (per allele HR: 1.57; 95% CI: 1.06-2.33; p trend =0.03). Conclusion: Results from this exploratory analysis suggest that genetic variation in the lymphangiogenesis pathway may influence melanoma aggressiveness and patient outcome. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 870. doi:10.1158/1538-7445.AM2011-870

Sentinel Lymph Node Biopsy in Breast Cancer: An Analysis of the Maximum Number of Nodes Requiring Excision

Sentinel lymph node biopsy (SNB) is now the standard of care in assessment of patients with clinically staged T1-2, N0 breast cancers. This study investigates whether there is a maximum number of sentinel lymph nodes (SLN) that need to be excised without compromising the false-negative (FN) rate of this procedure. Data were prospectively collected for 319 patients undergoing SNB between February 2001 and December 2006 at our institution. This data were analysed, both in terms of the order of SLN retrieval and relative isotope counts of the SLNs, in order to determine the maximum number of SLNs that need to be retrieved without increasing the FN rate. Furthermore, we investigated the relationship between SLN blue dye concentration and the presence of SLN metastases. The SLN identification rate was 97% with no false-negative cases amongst patients undergoing simultaneous axillary clearance historically during technique validation. In patients with SLN metastases, excision of the first 4 SLNs encountered results in the identification of a metastatic SLN in all cases. Although the majority (86%) of SNB metastases are in the hottest node, the SLN containing the metastasis is in the first 4 hottest nodes in 99% of patients with nodal metastases. The remaining 1% of SLN metastases were identified by blue dye. There was no statistically significant association between the SLN blue dye concentration and the presence of SLN metastases. A policy to remove a maximum of four blue and/or hot SLNs along with any palpably abnormal lymph nodes does not result in an increased false-negative rate of detection of SLN metastases.

Impact of HER2 Status on Risk of Sentinel Node Metastasis: An Independently Validated Multivariable Model.

Abstract Purpose The presence of axillary lymph node metastases is dictated by tumor biology and is a strong prognostic indicator in breast cancer. We have previously published a user-friendly nomogram that provides a risk estimate for sentinel lymph node (SLN) metastasis in women with breast cancer (Bevilacqua et al. 2007, J Clin Oncol 25: 3670). At that time, HER2 testing was not uniformly performed, but is now standard of care. The purpose of this study was to determine if the addition of HER2 status or grouping of patients by molecular subtype improves the prediction of SLN metastasis.Patients and Methods: The ability of clinical and pathologic features to predict the presence of SLN metastasis in patients presenting with clinically node negative invasive breast cancer, was assessed with multivariable logistic regression (MVA) for 4723 sequential SLN biopsy procedures with known ER, PR, and HER2 from 1996 to 2004. HER2 status was defined as positive if IHC=3+ and/or FISH≥2. The modeling (n=3297) and validation (n=1426) groups were identified by simple random sampling. Two models were created using the modeling population: one included ER, PR, and HER2 as separate variables and one combined these markers into 4 subtypes defined as: Luminal A-like=ER or PR +, HER2 −; Luminal B-like=ER or PR +, HER2 +; HER2-like=ER and PR −, HER2 +; Basal-like=ER and PR −, HER2 −. The validation group was used to assess the calibration (intercept, slope, Emax, Eavg) and discrimination (AUC, area under the receiver operating curve) of the models.Results: In addition to age, tumor size, tumor type, lymphovascular invasion, tumor location, and multifocality, subtype was found to be an independent predictor of SLN metastasis on MVA (p=0.003). The Basal-like subtype was associated with a significantly lower risk of SLN metastasis (compared with referent Luminal A-like subtype, OR=0.58). HER2 alone was not found to be an independent predictor of SLN metastasis (p=0.56), while ER and PR remained significant (p=.05, p=.02). Compared to our previous model without HER2, the AUC was slightly decreased by the addition of either HER2 or subtype into the model, but the calibration was slightly improved (Table 1). DiscriminationCalibrationModelAUCInterceptSlopeEmaxEavgPrevious Model0.735- 0.0440.8690.0390.020Mew model with HER20.733- 0.0030.8890.0270.019New model with subtype0.731- 0.0010.8870.0270.020Table 1: Discrimination and calibration measures comparing the new model (with HER2 alone or subtype) with the previously published model (without HER2 or subtype).Conclusion: The addition of subtype, defined by combining HER2 status with ER and PR, slightly increases the calibration of the new model but does not increase its discrimination compared to the previous model. Breast tumor subtype is a significant independent predictor of risk of SLN metastasis, with basal-like subtype having a lower risk of SLN metastasis. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1004.

Tumor and lymph node lymphangiogenesis—impact on cancer metastasis

The extent of lymph node (LN) metastasis is a major determinant for the staging and the prognosis of most human malignancies and often guides therapeutic decisions. Although the clinical significance of LN involvement is well documented, little has been known about the molecular mechanisms that promote tumor spread via lymphatic vessels to sentinel and distal LN and beyond. However, recent discoveries have identified novel lymphatic-specific markers, and the newly discovered lymphangiogenesis factors vascular endothelial growth factor-C (VEGF-C) and VEGF-D were found to promote tumor-associated lymphatic vessel growth in mouse tumor models, leading to enhanced tumor spread to sentinel LN. Our recent findings indicate that VEGF-A also acts as a potent tumor lymphangiogenesis factor that promotes lymphatic tumor spread. VEGF-A overexpressing primary tumors induced sentinel LN lymphangiogenesis even before metastasizing and maintained their lymphangiogenic activity after metastasis to draining LN. Our recent studies showed that primary human melanomas that later metastasized were characterized by increased lymphangiogenesis and that the degree of tumor lymphangiogenesis can serve as a novel predictor of LN metastasis and overall patient survival, independently of tumor thickness. Tumor lymphangiogenesis also significantly predicted the presence of sentinel LN metastases at the time of surgical excision of the primary melanoma. Together, these findings suggest that tumor lymphangiogenesis actively contributes to cancer dissemination, that blockade of lymphatic vessel growth might inhibit tumor metastasis to LN, and that the extent of tumor-associated lymphangiogenesis could serve as a novel, prognostic parameter for the metastatic risk of human cancers.

Correlation Between Concordance of Tracers, Order of Harvest, and Presence of Metastases in Sentinel Lymph Nodes With Breast Cancer

There are various methods for the detection of sentinel lymph nodes (SLNs) in breast cancer by using a combined method with blue dye and radioisotope (RI) tracers. The purpose of the study was to reveal any correlation between concordance of the tracers and the order of harvest with the presence of metastases in SLNs. The outcomes were reviewed in 408 cases with stage 0 to II breast cancer; the combined method was used in which blue dye and RI were injected subcutaneously around the tumor. The radioactivity and blue staining in each harvested SLN were checked. In 330 cases (81%), SLNs contained both blue dye and RI tracers (blue-hot cases), and in 42 (10%) and 31 (8%) cases, the SLNs contained only the blue stain (blue-only cases) and only RI (hot-only cases), respectively. The overall metastatic rate was 25% on a patient basis. Blue-only cases had a higher rate (42%) of metastasis than hot-only cases (14%). The rate of nodes containing both blue dye and RI gradually decreased from the first SLNs harvested to the third SLNs harvested. The rate of nodes containing RI only increased with the number harvested, and there was not so much change in the rate of nodes containing blue only. These data suggest that RI tracer could detect a wide range of SLNs and that the blue dye tracer could efficiently detect SLNs with metastasis. The combined methods compensates for the deficiencies of each method and thus will probably help to prevent missing SLNs.

Intraoperative cytologic examination of breast sentinel lymph nodes: test utility and patient impact.

The sentinel lymph node (SLN) procedure is a method for ascertaining the axillary lymph node status in patients with breast cancer. Intraoperative examination of the SLN may be important, because a positive result directs surgery to a complete axillary lymph node dissection. Intraoperative cytologic examination (IOCE) is a method of intraoperative evaluation, although little data are available regarding the sensitivity of the method with respect to tumor size and the size of the SLN metastasis. All SLN cases for the years 1997-2002 at Magee-Womens Hospital were tabulated for primary breast carcinoma size, IOCE result, final histologic result, and size of the SLN metastasis. All SLNs had IOCE with touch imprints. Scrape SLN preparations and frozen sections were strongly discouraged. There were 748 SLN cases comprising 1576 SLNs that had IOCE, and there were 247 true positive SLN cases comprising 522 SLNs. Of the 247 true positive SLN cases, 111 had a positive IOCE (111/247; 45% sensitivity overall) and there were 136 false negatives. Of the 247 cases, 164 were SLN micrometastases < or =2.0 mm in size, and 44 (27%) of these were detected by IOCE, while the remaining 120 cases were false negative. Of the 83 SLN macrometastases (>2.0 mm), 66 (80%) were detected by IOCE, with 17 false negatives. In this series, 15 cases (2%) were given the IOCE diagnosis of atypical/defer, and all of these permanent sections were histologically positive. There were five IOCE-positive cases that were histologically negative. Of the 164 SLNs with micrometastases < or =2.0 mm, 17.6% (29/164) were < or =0.5 mm (6/29 [21.4%] were IOCE positive), 5.5% (9/164) were 0.51-1.0 mm (3/9 [33%] were IOCE positive), and 3.6% (6/164) were 1.1-2.0 mm (2/6 [33%] were IOCE positive). There were 83 SLNs with macrometastases larger than 2.0 mm, and 66/83 (80%) were detected by IOCE. In this group, 22% (18/83) were 2.1-5.0 mm (8/18 [44.4%] were IOCE positive) and 57.8% (48/83) were larger than 5.0 mm (41/48 [85%] were IOCE positive). The mean primary breast tumor size was 15.4 mm, with a mean SLN tumor size of 1.4 mm. There was a significant correlation with tumor size and the presence of SLN metastasis, and a significant correlation with tumor size and size of the SLN metastasis. There was a significant t correlation of primary tumor size and positive IOCE, with the group of negative IOCE cases having a mean tumor size of 14 mm and the positive IOCE group having a mean tumor size of 22 mm. The overall sensitivity of the method was 45%, specificity 99%, positive predictive value 0.99, and negative predictive value 0.80. Sensitivity of the IOCE procedure based on SLN tumor size is as follows: < or =0.5 mm, 21.4%; 0.51-1.0 mm, 33%; 1.1-2.0 mm, 33%; 2.1-5.0 mm, 44.4%; and >5.0 mm, 85%. Primary tumor size correlates with a positive SLN status and size of the SLN metastasis. Most false-negative IOCEs are due to micrometastases. Positive IOCE cases had a significantly larger SLN metastasis size (mean 8.0 mm) than the false-negative IOCE group (mean 1.4 mm). The IOCE of SLNs has a high negative predictive value, but this is a poor test for the detection of micrometastases, as this group accounts for the majority of false-negative IOCEs of breast SLNs.