Can Methylene Blue Only Be Used in Sentinel Lymph Node Biopsy for Breast Cancer?

Sentinel lymph node biopsy (SLNB) has become an accepted standard of care to stage the axilla for clinically node-negative early stage breast cancer. In experienced hands, studies have shown an acceptable rate of identification of the sentinel lymph node (SLN) with blue dye only. Lymphazurin is occasionally associated with severe allergic reaction, including anaphylaxis and death. The use of methylene blue alone as a method of identifying the SLN in breast cancer has been reported once previously in the literature. Methylene blue may be an acceptable alternative with fewer deleterious side effects. Medical records of patients, who underwent sentinel node mapping between September 2003 and March 2005 by two surgeons at an academic medical center were reviewed. SLN mapping was performed by periareolar injection of 5 cc of 1% methylene blue. All patients with positive SLNs underwent completion axillary node dissection. During the study period, 141 consecutive patients with clinically node-negative axillas and without evidence of inflammatory breast cancer underwent SLNB with injection of methylene blue only. A SLN was identified in 136 of 141 patients (96.5%). Thirty-three of 136 SLNs (24%) harbored metastatic disease. No cases of anaphylaxis were noted. In experienced hands, methylene blue alone is a highly sensitive method of detecting SLNs. Avoiding the greater frequency of allergic reactions seen with lymphazurin is an important advantage of methylene blue.     

Is Blue Dye Indicated for Sentinel Lymph Node Biopsy in Breast Cancer Patients With a Positive Lymphoscintigram?

Background The use of isosulfan blue dye in sentinel node biopsy for breast cancer has been questioned because of its risk of allergic reaction. We hypothesized that blue dye could be safely omitted in the subgroup of patients who have evidence of successful sentinel node localization by lymphoscintigraphy.Methods A retrospective review of patients with breast cancer and sentinel node biopsy was conducted. Information was collected on lymphoscintigraphy results, use of blue dye, and intraoperative and pathologic findings of sentinel nodes.Results We identified 475 patients with breast cancer who underwent 478 sentinel node biopsies. Both dye and isotope were given in 418 cases, of which 380 had a positive lymphoscintigram. In 5 of the 380 cases with a positive lymphoscintigram, the sentinel nodes obtained were blue but not hot, for a 1.3% marginal benefit of dye in the technical success of the procedure. Sentinel nodes positive for metastasis were found in 102 of 380 cases; in 3 cases, the only positive sentinel node was blue but not hot. Omission of the blue dye tracer would have increased the false-negative rate of the sentinel node procedure by approximately 2.5%.Conclusions Even in sentinel node biopsy cases with a positive lymphoscintigram, the use of blue dye is beneficial for both improving the technical success of the procedure and reducing the false-negative rate of the procedure. Because the marginal benefits of dye justify its routine use, strategies to minimize the toxicity of blue dye are warranted.Published by Springer Science+Business Media, Inc. © 2005 The Society of Surgical Oncology, Inc.     

Implementation of Sentinel Lymph Node Biopsy with Blue Dye Outside a Specialized Center: Can We Improve Quality Assurance?

Implementation of sentinel lymph node biopsy (SLNB) outside a specialized center requires adequate quality control and quality assurance for optimal patient care. We examine the model of a supervising breast cancer unit in improving quality assurance in the treatment of breast cancer patients. A total of 76 SLNBs followed by level I/II axillary dissection were performed in the general hospital by using patent blue V alone. Patient selection, technical information, documentation, pathologic examination of the sentinel lymph node (SLN), and surgical training were provided by the supervising breast cancer unit. In 73 of 76 SLNBs, identification of the sentinel node was successful. The false-negative rate was 2.7% and the accuracy was 98.6%. The results of the procedure in the general hospital were comparable with the results of the supervising breast cancer unit. The model of a supervising breast cancer unit seems to accelerate surgeons' learning curve and may provide support for appropriate application of the SLNB in a wider number of nonspecialized centers.     

Macroscopic Quality Control Improves the Reliability of Blue Dye–Only Sentinel Lymph Node Biopsy in Breast Cancer

Background: One of the problems of sentinel lymph node (SLN) biopsy is the risk of false negatives. At the Institut Curie, to reduce the false-negative rate, we have developed a histological quality control of the SLN performed by blue dye alone, which consists of verification of the SLN blue stain by the pathologist.Methods: A total of 324 patients underwent an SLN biopsy procedure with patent blue dye only followed by an immediate axillary dissection. Initially, SLNs were checked to ensure that they were blue by macroscopic examination. Finally, a search for immunohistochemistry micrometastasis was performed.Results: In 277 (85.5%) of 324 patients, an SLN was identified by the surgeon. After standard examination, the false-negative rate was 11.1% (10 of 90). After macroscopic checking of the 197 negative SLNs, 167 of the 197 were confirmed blue, and there were 5 false negatives, which brought the false-negative rate down to 5.6% (5 of 90). Sixty SLNs out of the 167 confirmed blue SLNs were then proved to be immunohistochemically micrometastatic, and there were 3 false negatives, giving a final false-negative rate of 2.2% (2 of 90; P = .002).Conclusions: In this series, the procedure of pathologic analysis of the SLN has resulted in a significant reduction of the false-negative rate.     

Can Sentinel Lymph Node Biopsy Be Omitted in Patients With Favorable Breast Cancer Histology?

Background The widespread use of sentinel lymph node biopsy (SLNB) to replace axillary dissection has broadened the indications for axillary staging in breast cancer. Recent studies have demonstrated a finite risk of lymphedema and sensory morbidity associated with SLNB. We undertook this study to determine whether SLNB could be omitted in clinically node-negative patients with favorable-histology breast cancer.Methods We conducted a retrospective review of a prospective database of SLNBs performed at Memorial Sloan-Kettering Cancer Center from 1996 to 2003 to determine the incidence of lymph node metastases by histological subtype. For the favorable subtypes, the patients age, tumor size, estrogen receptor status, lymphovascular invasion, nuclear grade, and histological grade were compared by nodal status to determine their predictive value.Results A total of 196 cases with favorable breast cancer subtypes were identified with a 4.1% (8 of 196) sentinel lymph node (SLN) positivity rate. Each of the histological subtypes included patients with positive SLNs, with the exception of adenoid cystic (n = 4) and secretory (n = 1) breast carcinoma, which were quite rare in our series. When compared by nodal status, the patients age, tumor size, estrogen receptor status, lymphovascular invasion, nuclear grade, and histological grade failed to predict those with positive SLNs.Conclusions Patients with favorable breast cancer histology have a small risk of axillary SLN metastases. The use of SLNB in these patients should be individualized, taking into consideration the small incidence of axillary metastases and the risks and benefits associated with the SLN procedure.     

Sentinel Lymph Node Biopsy for Melanoma: How Many Radioactive Nodes Should be Removed?

Background: Sentinel lymph node (SLN) biopsy has become a standard method of staging patients with cutaneous melanoma. Sentinel lymph node biopsy usually is performed by intradermal injection of a vital blue dye (isosulfan blue) plus radioactive colloid (technetium sulfur colloid) around the site of the tumor. Intraoperative gamma probe detection has been shown to improve the rate of SLN identification compared to the use of blue dye alone. However, multiple sentinel nodes often are detected using the gamma probe. It is not clear whether these additional lymph nodes represent true sentinel nodes, or second-echelon lymph nodes that have received radiocolloid particles that have passed through the true sentinel node. This analysis was performed to determine the frequency with which these less radioactive lymph nodes contain metastatic disease when the most radioactive, or hottest, node does not.Materials and Methods: In the Sunbelt Melanoma Trial, 1184 patients with cutaneous melanoma of Breslow thickness 1.0 mm or more had sentinel lymph nodes identified. Sentinel lymph node biopsy was performed by injection of technetium sulfur colloid plus isosulfan blue dye in 99% of cases. Intraoperative determination of the degree of radioactivity of sentinel nodes (ex vivo) was measured, as well as the degree of blue dye staining.Results:Sentinel nodes were identified in 1373 nodal basins in 1184 patients. A total of 288 of 1184 patients (24.3%) were found to have sentinel node metastases detected by histology or immunohistochemistry. Nodal metastases were detected in 306 nodal basins in these 288 patients. There were 175 nodal basins from 170 patients in which at least one positive sentinel node was found and more than one sentinel node was harvested. Blue dye staining was found in 86.3% of the histologically positive sentinel nodes and 66.4% of the negative sentinel nodes. In 40 of 306 positive nodal basins (13.1%), the most radioactive sentinel node was negative for tumor when another, less radioactive, sentinel node was positive for tumor. In 20 of 40 cases inding a positive sentinel node other than the hottest node.Conclusions: If only the most radioactive sentinel node in each basin had been removed, 13.1% of the nodal basins with positive sentinel nodes would have been missed. It is recommended that all blue lymph nodes and all nodes that measure 10% or higher of the ex vivo radioactive count of the hottest sentinel node should be harvested for optimal detection of nodal metastases.Preliminary findings presented at the annual meeting of the Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999.     

Sentinel Lymph Node Detection for Breast Cancer: Which Patients Are Best Suited for the Patent Blue Dye Only Method of Identification?

Background: The objectives of this study were, first, to define the preoperative criteria for using solely the blue dye method and, second, to decrease its operator dependence in predicting axillary lymph node status.Methods: Two hundred fifty-three women consecutively identified with operable breast cancer underwent sentinel lymph node (SLN) detection by the patent blue dye method followed by completion axillary lymph node dissection. A standard pathological examination was performed for all SLN. Then, a pathological color quality assessment (PCQA), which checked for the presence of the blue dye, was performed on the paraffin blocks of the nonmetastatic SLN. Six preoperative identifiable variables likely to influence the detection rate were examined.Results: The surgical detection (sd) rate was 84% (213 of 253) and the PCQA rate was 73% (185 of 253). Only breast size (sd, P = .0005; PCQA, P = .0007) and body mass index 30 (sd, P = .005; PCQA, P = .0007) were significant for SLN identification. Multivariate analysis revealed two independent factors influencing SLN identification: breast size (sd, P = .0001; PCQA, P = .002) and the timing of injection—injection prior to lumpectomy (sd, P =.04).Conclusions: The optimal patient features for identifying the SLN by the patent blue dye method are small or medium-sized breasts, low body fat, and that the procedure is carried out prior to tumor excision. The PCQA offers a useful second assessment of the surgically removed SLN, introducing an independent element of quality control.     

A Longitudinal Comparison of Arm Morbidity in Stage I–II Breast Cancer Patients Treated with Sentinel Lymph Node Biopsy,Sentinel Lymph Node Biopsy Followed by Completion Lymph Node Dissection,or Axillary Lymph Node Dissection

Background  

Long-term shoulder and arm function following sentinel lymph node biopsy (SLNB) may surpass that following complete axillary lymph node dissection (CLND) or axillary lymph node dissection (ALND). We objectively examined the morbidity and compared outcomes after SLNB, SLNB + CLND, and ALND in stage I/II breast cancer patients.     

99mTc–Evans Blue Dye for Mapping Contiguous Lymph Node Sequences and Discriminating the Sentinel Lymph Node in an Ovine Model

Background The aim of this study was to investigate the potential of ^99mTc–Evans blue for discriminating the sentinel lymph node in multitiered lymph node sequences by using an ovine model. ^99mTc–Evans blue is an agent that has both radioactive and color signals in a single dose. Previous studies in smaller animal models suggested that this agent could have advantages over the dual-injection technique of radiocolloid/blue dye. Methods Doses of ^99mTc–Evans blue (∼ 21 MBq) containing Evans blue dye (approximately 4 mg) were administered to the hind limbs or fore limbs of sheep to map the lymphatic drainage patterns, validate its ability to identify the sentinel lymph node, and examine the reproducibility of the technique. The study protocol was repeated with ^99mTc–antimony trisulfide colloid and Patent Blue V dye. After the operative exposure, lymph nodes were identified with the gamma probe and then excised and analyzed for radioactivity (percentage of injected dose) and blue color. Results After the administration of ^99mTc–Evans blue, all lymph nodes harvested (35 of 35) in either short chains or long basins were hot and blue. The sentinel lymph nodes concentrated more radioactivity than the second-tier nodes to the extent of 2:1 to 215:1. For radiocolloid/Patent Blue V, the ratios were lower, at 2:1 to 3:1. Conclusions ^99mTc–Evans blue was found to better discriminate the sentinel lymph node than ^99mTc–antimony trisulfide colloid/Patent Blue V in variable multitier lymph node anatomy, and it is an agent that promises to have positive clinical applications.     

Desmoplastic Melanoma: Is There a Role for Sentinel Lymph Node Biopsy?

Background

The utility of sentinel lymph node biopsy (SLNB) for desmoplastic melanoma (DM) is debated. We describe a large single-institution experience with SLNB for DM to determine clinicopathologic factors predictive of SLN metastasis.

Methods

Retrospective review identified 205 patients with DM who underwent SLNB from 1992 to 2010. Clinicopathologic characteristics were correlated with SLN status and outcome.

Results

Median age was 66 years, and 69 % of patients were male. Median Breslow thickness was 3.7 mm. In 128 cases (62 %), histologic subtype data was available; 61 cases (47.7 %) were mixed and 67 cases (52.3 %) were pure DM. A positive SLN was found in 28 cases (13.7 %); 24.6 % of mixed and 9 % of pure DM had SLN metastases. Multivariable analysis demonstrated that after controlling for age, histologic subtype correlated with SLN status [odds ratio: 3.0 for mixed vs pure, 95 % confidence interval: 1.1–8.7; p < .05]. Completion lymph node dissection was performed in 24 of 28 positive SLN patients with 16.7 % of cases having additional nodal disease. After a median follow-up of 6.3 years, 38 patients developed recurrence and 61 patients died. Positive SLN patients had a significantly higher risk of melanoma-related death compared with negative SLN patients (p = .01).

Conclusions

The overall risk for SLN metastasis for DM is 13.7 % and is significantly higher for mixed (24.6 %) compared with pure (9.0 %) DM. We believe that these rates are sufficient to justify consideration of SLNB for both histologic variants, especially since detection of SLN disease appears to predict a higher risk for melanoma-related death.     

Does the Method of Biopsy Affect the Incidence of Sentinel Lymph Node Metastases?

More detailed examination of the sentinel lymph node (SLN) in breast cancer has raised concerns about the clinical significance of micrometastases, specifically isolated tumor cells detected only through immunohistochemical (IHC) staining. It has been suggested that these cells do not carry the same biologic implications as true metastatic foci and may represent artifact. A retrospective institutional review board-approved review was conducted on clinically node-negative breast cancer patients who underwent SLN biopsy (SLNB) between 1997 and 2003. Retrospective analysis of tumor characteristics and the method of the initial diagnostic biopsy were correlated with the presence and nature of metastatic disease in the SLN. Of 537 SLNBs, 123 (23%) were hematoxylin-eosin (H&E) positive. SLN positivity strongly correlated with tumor size (p<0.001) and tumor grade (p=0.025), but not with the method of biopsy (needle versus excisional biopsy). Prior to July 2002, we routinely evaluated H&E-negative SLNs with IHC (n=381). Of the 291 H&E-negative patients, 26 had IHC-only detected micrometastases (9%). The likelihood of detecting IHC-only metastases did not correlate with tumor size or grade, but was significantly higher in patients undergoing excisional biopsy than core needle biopsy. While the method of biopsy has no demonstrable effect on the likelihood of finding metastases in the SLN by routine serial sectioning and H&E staining, it may significantly impact the likelihood of finding micrometastases by IHC. IHC should not be used routinely in the evaluation of the SLN and caution should be used when basing treatment decisions (completion axillary lymph node dissection or adjuvant therapy) on IHC-only detected micrometastases.     

Does Blue Dye Contribute to Success of Sentinel Node Mapping for Breast Cancer?

Background

We sought to evaluate the utilization of blue dye in addition to radioisotope and its relative contribution to sentinel lymph node (SLN) mapping at a high-volume institution.

Methods

Using a prospectively maintained database, 3,402 breast cancer patients undergoing SLN mapping between 2002 and 2006 were identified. Trends in utilization of blue dye and results of SLN mapping were assessed through retrospective review. Statistical analysis was performed with Student t test and chi-square analysis.

Results

2,049 (60.2%) patients underwent mapping with dual technique, and 1,353 (39.8%) with radioisotope only. Blue dye use decreased gradually over time (69.8% in 2002 to 48.3% in 2006, p < 0.0001). Blue dye was used significantly more frequently in patients with lower axillary counts, higher body mass index (BMI), African-American race, and higher T stage, and in patients not undergoing skin-sparing mastectomy. There was no difference in SLN identification rates between patients who had dual technique versus radiocolloid alone (both 98.4%). Four (0.8%) of 496 patients who had dual mapping and a positive SLN had a blue but not hot node as the only involved SLN. None of these four had significant counts detected in the axilla intraoperatively. Nine (0.4%) of 2,049 patients who had dual mapping had allergic reactions attributed to blue dye.

Conclusions

Blue dye use has decreased with increasing institutional experience with SLN mapping. In patients with adequate radioactive counts in the axilla, blue dye is unlikely to improve the success of sentinel node mapping.

     

Is Axillary Lymph Node Dissection Necessary After Sentinel Lymph Node Biopsy in Patients with Mastectomy and Pathological N1 Breast Cancer?

Background

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial reported that axillary lymph node dissection (ALND) did not change the recurrence and overall survival (OS) rates in patients with lumpectomy and one to two positive nodes detected by sentinel lymph node biopsy (SLNB). The aim of this study was to determine whether patients with mastectomy and pathological N1 disease found by SLNB could forego ALND.

Materials and Methods

This is a retrospective study of 214 patients diagnosed with primary invasive breast cancer who were treated by mastectomy and lymph node staging surgery (SLNB or ALND) at the Revlon/UCLA Breast Center between January 2002 and December 2010. Patients with pathological N1 disease were separated by their first nodal surgery into SLNB (subgroups: observation, radiation, and additional ALND with or without radiation) and ALND groups (subgroups: ALND with or without radiation).

Results

After a median follow-up of 43.6 months, the OS and systemic relapse-free survival (RFS) rate of the radiation group and additional ALND group were significantly better than the observation group (p = 0.031 and 0.046, respectively). Human epidermal growth factor receptor 2 (HER2) expression was found to predict OS and patients’ age, histological grade and HER2 expression predicted systemic recurrence. Compared with the SLNB group, pain (p = 0.021) and lymphedema (p = 0.043) occurred more frequently in the ALND group.

Conclusion

Radiation was as effective as ALND in patients with mastectomy and N1 disease for OS and RFS rates, yet radiation after SLNB had fewer side effects than ALND. SLNB followed by radiation could replace ALND in patients with mastectomy and pathological N1 breast cancer identified by SLNB.