Occult metastases in sentinel nodes of 200 patients with operable breast cancer

Background:Up to 30% of patients with operable breast cancer and negative regional lymph nodes experience disease recurrence within 10 years. Serial sectioning and immunohistochemical staining of these nodes have revealed 9% to 30% occult metastases.Methods:Sentinel nodes from 200 patients with T1 and T2 invasive breast carcinoma were step-sectioned at 2- to 3-mm intervals, fixed in 10% formalin, and embedded in paraffin. Sections were taken from the face of the blocks and stained with hematoxylin and eosin (H&E). The blocks were then cut completely, and sections at .25-mm intervals were stained with cytokeratin and examined.Results:Tumor metastases were found in 34 patients when the sentinel nodes were examined at 2- to 3-mm intervals and in an additional 51 patients when the nodes were sectioned in their entirety at .25-mm intervals and stained with cytokeratin, bringing the total number of patients with metastases to 85. Of the 51 patients whose metastases were detected by 2- to 3-mm sectioning and cytokeratin staining, 27 had isolated tumor cells and 24 had clusters of innumerable malignant cells, all of which were visualized and confirmed by H&E staining of the adjacent sections.Conclusions:Histologic examination of sentinel nodes of patients with invasive breast cancer sectioned at 2- to 3-mm intervals and stained with H&E significantly underestimates nodal metastases. Sectioning of the entire sentinel nodes at .25-mm intervals and staining with cytokeratin detects metastases as either isolated cells or as clusters.     

Factors influencing the number of sentinel lymph nodes identified in patients with breast cancer

BACKGROUND: Although the sentinel lymph node (SLN) is defined as the first node draining a tumor, multiple nodes are often identified. Few SLNs are required for adequate staging; removal of more may be unnecessary. The objective of this study was to determine factors influencing the number of SLN identified. METHODS: The University of Louisville Breast Sentinel Lymph Node Study was used to determine correlates of identifying greater than 4 SLNs by using univariate and multivariate analyses. RESULTS: An SLN was identified in 3,882 of 4,131 patients (94%). The median number of SLN identified was 2 (range 1-18); 90% had < or = 4 SLNs identified. Palpable tumors, surgeon inexperience, and dermal injection were associated with greater than 4 SLNs identified. All 3 of these factors remained significant on multivariate analysis. CONCLUSIONS: Palpable tumors often have greater than 4 SLNs identified, and the use of intradermal injection increases this probability.     

乳腺癌前哨淋巴结检测的临床研究

目的通过前哨淋巴结(sentinel lymph node,SLN)活检,了解前哨淋巴结是否能反映乳腺癌腋窝淋巴结转移情况,从而决定是否行腋窝淋巴结清扫(axillary lymph node dissection,ALND). 方法 47例T1、T2、T3临床检查腋窝淋巴结无肿大的乳腺癌患者,术前30 min于乳腺肿块周围腺体注射蓝色染料,术中取蓝染的SLN病理检查,术后将病理检查结果与腋窝淋巴结转移情况进行比较分析. 结果 47例中5例未见淋巴结及淋巴管蓝染,其余42例找到腋窝淋巴结608个,阳性18例168个,阴性24例440个;SLN共78个,阳性16例29个,阴性26例49个.SLN的检出率89.4%,准确性95.2% ,特异性100%,敏感性88.9%,假阴性率11.1%,假阳性率0. 结论 SLN活检反应腋窝淋巴结的肿瘤转移状况,可以用于术中确定是否行ALND.     

Recurrence rates in breast cancer patients with false-negative intraoperative evaluation of sentinel lymph nodes

Background

Intraoperative identification of sentinel lymph node (SLN) metastases in breast cancer patients results in synchronous axillary lymph node dissection. We examined the effect of false-negative SLN biopsy on breast cancer treatments and recurrence rate.

Methods

Patient and tumor characteristics, intraoperative and final SLN biopsy results, and treatments of patients with and without recurrence were compared.

Results

Recurrence rates for patients with true-positive SLN biopsy (9%) were significantly higher than rates for false-negative SLN biopsy patients (2%). Recurrence rates were significantly higher for patients with primary tumors greater than 2 cm, positive lymph nodes greater than 2 mm, and tumors with negative hormone receptors, and varied with treatment extent.

Conclusions

Patients with greater amounts of disease in the breast and axilla required more treatment and had a higher recurrence rate. False-negative SLN evaluation occurred more commonly in patients with less lymph node metastasis and was not associated with an increased recurrence rate.     

乳腺癌前哨淋巴结微转移的研究

目的：提高乳腺癌前哨淋巴结（SLN）病理诊断的准确性，为手术彻底切除肿瘤提供依据。方法：应用亚甲蓝生物染色的方法确定60例Ⅰ、Ⅱ期乳腺癌SLN并活检，44（73．3％）例SLN取材成功。每一枚SLN均进行冰冻病理切片、石蜡病理和角蛋白Keratinl9（CK-19）逆转录聚合酶链反应（RT—PCR）检测。结果：44例SLN冰冻病理切片、石蜡病理切片和CK-19诊断的灵敏度和特异度分别是77．8％和100．0％、88．9％和100．0％、100．0％和82．9％，诊断符合率分别为95．5％、97．7％和86．4％，诊断指数分别为0．778、0．889和0．829。结论：CK-19检测可进一步提高乳腺癌SLN微转移的检出率，提高SLN活检的准确性。但CK-19检测与冰冻病理病理检查联合应用可提高诊断的准确率和临床的可操作性。     

Stage migration with sentinel node biopsy in breast cancer

Background

Axillary staging provides the single most important piece of prognostic information in breast cancer patients. This retrospective study was performed to document the phenomenon of stage migration.

Methods

Of 392 patients, 5 (1%) failed identification of sentinel lymph nodes (SLNs) and therefore underwent axillary lymph node dissection (ALND). Four patients (80%) had metastatic lymph nodes, 302 (77%) patients had negative SLNs, 47 (15%) underwent ALND, 85 (22%) had positive SLNs, 11 (13%) received adjuvant radiation treatment to the axilla, and 74 (87%) underwent completion ALND.

Results

The median (quartiles) follow-up period was 29 months (19-46 mo). Twenty of 392 (5%) patients had disease relapse; 2 of which were local (.5%) and the rest were systemic. Earlier relapse was related significantly to lymph node status, tumor grade, and tumor size. SLN-negative patients who did not receive ALND had a relapse rate of 2.3% (6 of 256) compared with 0% in those who were truly negative based on confirmatory ALND. SLN-positive patients who did not receive ALND had a 9% (1 of 11) relapse rate.

Discussion

The stage-matched pattern of relapse between SLN biopsy and ALND patients revealed lower relapse rates in SLN biopsy-staged patients, documenting the stage migration phenomenon.     

Accuracy of intraoperative imprint cytology of sentinel lymph nodes in breast cancer

BACKGROUND: In breast cancer treatment, immediate completion of axillary lymph node dissection (ALND) can be performed if the intraoperative sentinel lymph node (SLN) examination is positive. This study evaluates the accuracy of intraoperative imprint cytology (IC) for detecting SLN metastases. METHODS: Pathology reports from 385 SLN biopsy examinations were reviewed retrospectively. The SLNs were serially sectioned perpendicular to the long axis and IC was performed intraoperatively. The SLNs then were formalin-fixed for permanent sections. Final pathology was compared with the intraoperative IC results. RESULTS: The sensitivities for IC detection of N0(i+) (n = 36), N1mi (n = 24), and N1a-3a (n = 65) metastases were 0%, 4%, and 74%, respectively. The specificity was 100%. CONCLUSIONS: Final pathology identified 89 (23%) patients with N1 or greater disease. IC allowed 49 (55%) of these patients to undergo synchronous completion of ALND. No unnecessary completion ALNDs were performed. The sensitivity of IC decreased with decreasing size of the metastasis.     

原发性乳腺癌患者非哨兵淋巴结转移预测因素的研究

目的探讨原发性乳腺癌患者哨兵淋巴结活检(SLNB)后，哨兵淋巴结(SN)转移者非哨兵淋巴结(NSN)转移相关的临床及组织学因素。方法252例确诊为原发性乳腺癌患者SLNB后行腋窝淋巴结清扫，所有的腋窝淋巴结(SN及NSN)均行常规组织学检查。应用X^2检验分析年龄，肿瘤大小，肿瘤位置，病理类型，受体状态和SN转移数目与NSN转移的关系。结果SLNB成功率94％，假阴性率7．4％。随着原发肿瘤的增大，NSN转移的可能性增加：T1a T1b期肿瘤NSN转移率为0；T1c期为42％；T2期为87％。只有1个SN转移的患者NSN转移率明显低于多个SN转移的患者(27％vs46％)。结论NSN转移的可能性随着原发肿瘤的增大和多个SN转移而增加，而患者的年龄，肿瘤的位置，病理类型和受体状态不影响NSN转移的可能性。     

Intraoperative identification of sentinel lymph nodes by near-infrared fluorescence imaging in patients with breast cancer

We present a novel method for sentinel lymph node (SLN) identification by fluorescence imaging that provides a high detection rate and a low false-negativity rate. Twenty-five breast cancer patients with tumors less than 3 cm in diameter were enrolled. A combination of indocyanine green and indigo carmine was injected subdermally in the areola. Subcutaneous lymphatic channels draining from the areola to the axilla were immediately showed by fluorescence imaging. After incising the axillary skin near the point of disappearance of the fluorescence, the SLN was dissected under fluorescence guidance. In all patients, the lymphatic channels and SLN were successfully visualized. The mean number of fluorescent SLN and blue-dyed SLN were 5.5 and 2.3. Eight patients were found to have lymph node metastases pathologically. All of them were recognized by fluorescence imaging. This method is feasible and safe for intraoperative detection of SLN allowing real-time observation without any need for training.     

Selective intraoperative consultation for the evaluation of sentinel lymph nodes in breast cancer

BACKGROUND: Routine intraoperative evaluation of sentinel lymph nodes (SLNs) in breast cancer suffers from lack of sensitivity and consumes both time and resources. Failure to perform immediate consultation requires node-positive patients to return for delayed dissection. METHODS: We sought to determine whether selective use of intraoperative pathology consultation (IOC), based on the surgeon's clinical suspicion for metastases, would be accurate, avoid unnecessary consultations, and have a similar rate of delayed axillary dissection. We performed a retrospective chart review of two cohorts of clinically node-negative patients with invasive breast cancer undergoing axillary lymph node dissection (ALND). Selective pathology evaluation was performed in the study group and mandatory evaluation in the control group. RESULTS: The axillary basins of 327 patients undergoing routine IOC were compared with those of 91 patients in whom selective IOCs were requested. Twenty-eight consultations (31%) were obtained in the selective group. Selective consultation changed intraoperative management in 11 of 28 patients (39%) compared to 46 of 327 (14%) in the routine group (P = 0.005). The mean SLN metastasis size was 9.6 mm compared to 1.5 mm in patients in whom consultation was deferred (P = 0.003). The need for delayed ALND (17% vs. 14%) was similar in both groups, and was determined by occult metastases that were not detected by either method. CONCLUSIONS: Selective use of IOC detects the majority of SLN macrometastases, avoids consultation that does not alter intraoperative management, and is not associated with an increased need for delayed ALND.     

Biology of lymphatic metastases in breast cancer: Lessons learned from sentinel node biopsy

Background The evolution of sentinel node biopsy has placed new emphasis on the biology of lymphatic metastases in breast cancer. If radiocolloid mimics the migration of tumor cells, the nodes with the most uptake should also be the most likely to harbor metastatic cells. We attempted to correlate the frequency of metastatic disease to the greatest gamma uptake and to clarify the physiology of breast lymphatic drainage. Methods Data were collected from 152 patients undergoing sentinel node biopsy from January 1997 to June 1999. Localization was by injection of unfiltered^99mTc-labeled sulfur colloid. Sentinel nodes were identified with an intraoperative gamma counter and the 10% rule. A completion level I/II axillary dissection was performed in all patients. Results Fifty-four of 152 patients were positive for metastatic disease. There were no falsenegative sentinel nodes. In 46 (85%) of 54 cases, the node with the highest uptake was positive for metastatic disease. In the remaining eight (15%) cases, another node with a lower gamma count was positive. Conclusions The sentinel node with the highest uptake is not the one that contains metastatic disease in 15% of cases. This may reflect variations in lymphatic channels or technical variations in colloid properties and injection technique.     

The use of touch preparation for the evaluation of sentinel lymph nodes in breast cancer

Background

This study was undertaken to evaluate the accuracy of touch preparation (touch prep) in the evaluation of sentinel lymph nodes (SLNs).

Methods

We performed a retrospective review of 402 breast cancer patients who underwent SLN biopsy.

Results

A SLN was identified in 381 patients. Of 61 patients with a true positive result, 59 underwent axillary node dissection, and in 22 the SLN was the only node with metastases. Thirty-six (9.44%) had at least 1 false negative result. Twenty-five with a false negative results were due to macrometastases, with 17 (2.4%) false negatives occurring in patients with invasive ductal and 6 (5.5%) in those with invasive lobular histology, P = .04. Touch prep had an overall sensitivity of 62.89% and specificity of 98.94%.

Conclusions

Touch prep for the evaluation of SLNs in breast cancer compares favorably to reported results for frozen section. False negative findings are more likely with micrometastases and invasive lobular histology.     

乳腺癌淋巴结微小转移状态下前哨与非前哨淋巴结免疫细胞的改变

目的观察乳腺癌淋巴结微小转移状态下前哨淋巴结(SLN)与非前哨淋巴结(Non- SLN)免疫细胞密度的改变。方法53例符合研究标准的女性乳腺癌患者按SLN不同转移状态分为阴性、游离肿瘤细胞及微转移3组。从各组随机选择6对SLN和Non-SLN与DC-LAMP,CD68,CD123,Foxp3抗体行免疫组织化学染色,半定量评估染色细胞密度改变;所有SLN和Non-SLN蜡块切片均行与DC-LAMP抗体免疫反应的免疫组织学检查以确认成熟树突状细胞(DC)。蔡司图像分析系统定量分析每个淋巴结DC-LAMP阳性细胞的相对密度(DC-LAMP阳性细胞面积/淋巴结面积)。Wicoxon检验和Mann-Whitney检验分别用于DC-LAMP阳性细胞的相对密度的组内和组间比较。结果DC-LAMP阳性细胞密度改变显著。组内比较显示阴性组和微转移组SLN内DC-LAMP阳性细胞平均密度较Non-SLN高(P<0.05);组间比较显示微转移组SLN和Non-SLN内DC-LAMP阳性细胞密度较阴性组显著升高(P<0.05)。结论SLN和Non-SLN内DC-LAMP 细胞平均密度在淋巴结肿瘤转移形成早期发生改变,揭示SLN在肿瘤与引流淋巴结免疫相互作用中起重要作用。     

Intramammary sentinel lymph node in patients with breast cancer: Report of four cases

To analyze breast cancer patients with intramammary sentinel lymph node, we reviewed T1-T2N0 breast cancer patients who underwent sentinel lymph node mapping using radioisotope methods. Intramammary sentinel lymph (ISN) nodes were detected in 4 of 166 patients. Three of four ISNs were present in completely different quadrants of the breast from those of primary lesions. Although two patients had no involved nodes, including ISNs, the remaining two with T2 tumor had metastasis of ISNs alone with resulting upstaging. We should keep in mind the presence of intramammary SN in regions apart from the primary tumor, particularly when performing breast conservative surgery.     

Intraoperative touch imprint cytology of axillary sentinel nodes for breast cancer: A series of 355 procedures

Aims

Our objective was to evaluate intraoperative sentinel node touch imprint cytology (IOSNTI) for breast cancer. Three hundred and fifty-five patients with invasive breast cancer (pT1 N0, lobular or ductal subtype) were included in our study. IOSNTI consists of touching glass slides to the surfaces of interest after gently pressing the spatially localized specimen, taken according to predetermined conditions, in order to perform a final histological examination consisting of H&;E and immunohistochemical staining.

Results

The total sensitivity (Se) of IOSNTI was 36% and 15% of patients with nodal metastasis went undetected during the intraoperative examination. Sensitivity was significantly lower for the oldest patients (aged over 57 years: 25%), small tumors (smaller than 12 mm: 23.3%), lobular subtypes (8.3%), in the absence of vascular emboli (33%) and for detection of micrometastases (10%).

Discussion

This simple, fast and relatively inexpensive method could be combined with intraoperative molecular biology methods in populations in which cytology is less efficient and produces negative results.     

前哨淋巴结阳性乳腺癌非前哨淋巴结转移的情况分析

目的探讨前哨淋巴结（SLN）阳性乳腺癌患者的临床病理特征与非前哨淋巴结（NSLN）转移的关系。 方法回顾性分析2010年1月至2016年1月中山大学附属第一医院500例行前哨淋巴结活检（SLNB）的临床分期为T_1-2N₀M₀期乳腺癌患者资料,其中病理检查确诊SLN阳性、随后行腋窝淋巴结清扫（ALND）的乳腺癌患者共89例,总结其临床、病理因素的特征及其对腋窝NSLN转移的影响因素进行单因素及多因素Logistic分析。 结果SLN阳性率为17.8%（89/500）,49.4%（44/89）出现NSLN转移。单因素分析显示,NSLN转移与原发肿瘤分期、脉管浸润、SLN阳性数、SLN阳性率相关（χ²=4.062、36.084、7.003、10.889,P=0.044、<0.001、0.030、0.004）。进一步多因素Logistic回归分析显示,脉管浸润、SLN阳性率是NSLN转移的独立预测因子（OR=46.142,95%CI：11.821~258.472,P<0.000 1;OR=10.482,95%CI：2.564~51.312,P=0.002）。 结论SLN阳性的乳腺癌患者,其原发肿瘤分期、肿瘤是否多发、脉管浸润、SLN阳性数、SLN转移率与腋窝NSLN转移相关。其中,脉管浸润及SLN阳性率≥0.5是SLN阳性乳腺癌患者腋窝NSLN转移的独立预测因子。     

Accuracy of intraoperative touch imprint cytologic analysis of sentinel lymph nodes in breast cancer

BACKGROUND: Eliminating full axillary dissection (AD) in the face of negative sentinel lymph nodes (SLN) has become increasingly popular. We sought to evaluate the accuracy of intraoperative touch imprint cytology in detecting clinically significant metastatic involvement of the SLN. METHODS: Retrospective review of intraoperative cytology and final hematoxylin-eosin stain evaluation of sentinel nodes examined in a community hospital from 1997 to 2002. RESULTS: During that period 1,585 patients underwent axillary dissection; 380 had SLN identification with 142 patients undergoing intraoperative cytologic evaluation of 446 SLNs. Fourteen patients with negative intraoperative cytology had involvement of a SLN on final hematoxylin-eosin examination, for a sensitivity of 75%, specificity of 100%, negative predictive value of 95%, and a false negative rate of 4.9%. In all but 1 case the metastasis was microscopic and measured 2 mm or less. Seven patients went on to completion axillary dissection (50%) with no additional nodal involvement found. CONCLUSIONS: Intraoperative touch imprint cytology is accurate in predicting clinically significant SLN pathology. Although the false negative rate in this series was 4.9%, in all but 1 case it represented micrometastatic disease that may not necessarily require completion axillary dissection.     

The likelihood of additional nodal disease following a positive sentinel lymph node biopsy in breast cancer patients: validation of a nomogram

BACKGROUND: Sentinel lymph node (SLN) biopsy examination is the current modality for evaluating the axilla in breast cancer patients. A nomogram has been developed to predict the likelihood of non-SLN metastases after a positive SLN biopsy examination. The purpose of this study was to validate the nomogram in a community breast center. METHODS: A prospective database was used to identify breast cancer patients with a positive SLN biopsy examination who underwent a completion axillary lymph node dissection. The nomogram was used to calculate the probability of having non-SLN involvement, and was compared with the observed numbers. RESULTS: The observed incidence of non-SLN involvement showed excellent correlation with the nomogram predicted probability (chi-square test statistic = 5.87; P = .83). CONCLUSIONS: Predicting the risk of additional nodal metastases allows the surgeon and patient to make an individualized decision regarding the need for completion axillary lymph node dissection.     

Feasibility and reliability of sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer patients with positive axillary nodes at initial diagnosis: An up-to-date meta-analysis of 3,578 patients

PurposeNeoadjuvant chemotherapy (NACT) is increasingly adopted in the therapy of breast cancer (BC) patients with positive axillary nodes (cN+), but the reliability and feasibility of sentinel lymph node biopsy (SLNB) following NACT are still controversial. The objective of the present study is to conduct an updated meta-analysis on this issue.MethodsA literature search was performed using PubMed, Cochrane, Embase, and Web of Science to identify papers published from January 1, 2000 to October 22, 2020 to research SLNB after NACT in BC patients. Studies that met the quality standard were enrolled for this meta-analysis.ResultsA total of 3578 participants from 27 trials were included in this meta-analysis. The pooled estimate of the identification rate (IR) for SLNB was 91 %, and the false negative rate (FNR) was 15 %. The pooled negative prediction value (NPV), accuracy, specificity, and sensitivity were 82 %, 89 %, 97 %, and 85 %, respectively. In subgroup analysis, the application of dual mapping could clearly decrease the FNR. The FNR was significantly high in the luminal types, and it declined as more sentinel lymph nodes (SLNs) were removed.ConclusionSLNB following NACT is now technically feasible for BC with cN+. However, it must be emphasized that the FNR is unacceptable high.     

Intraoperative identification of suspicious palpable lymph nodes as an integral part of sentinel node biopsy in patients with breast cancer

Purpose Despite the sensitivity and accuracy of sentinel lymph node biopsy (SLNB), the number of false negative (FN) results is still relatively high, which has prompted much investigation. We studied the effectiveness of the biopsy of suspicious palpable lymph nodes (LNs) in reducing the number of FN results. Methods We reviewed the medical records of 865 breast cancer patients who underwent successful SLNB at a single institution. After excising the blue-stained or radioactive nodes, all suspicious palpable LNs that were not either blue-stained or radioactive were also excised. Results Sampling of a suspicious palpable LN was done in 342 (39.5%) of the 865 patients. The average number of suspicious palpable nodes was 1.9. The suspicious nodes harbored metastasis in 19 of the 342 patients. Both blue-stained and radioactive metastatic SLNs were found in 8 patients, whereas the palpable nodes were the only ones involved in the other 11. LN involvement was identified solely by biopsy of a suspicious palpable LN in 11 (6.5%) of 170 patients with SLN metastasis (6.5%). Conclusion Biopsy of a suspicious palpable LN should be done as part of SLNB to reduce the number of FN results of SLNs in breast cancer patients.