Axillary sentinel lymph node examination in breast carcinoma.

OBJECTIVE: To evaluate whether the type of pathologic examination of breast sentinel nodes (frozen section, step sections, and immunoperoxidase staining) results in different percentages of nodes positive for metastatic disease. DESIGN: Twenty-eight consecutive patients with breast sentinel node biopsies were evaluated by step-sectioning the sentinel node(s) along with performing immunoperoxidase stains for low-molecular-weight cytokeratin and epithelial membrane antigen. SETTING AND PARTICIPANTS: The patients were from a university hospital and large private hospital. MAIN OUTCOME MEASURES: The results of the step sections and immunoperoxidase stains were compared with routine examination, that is, intraoperative frozen section along with a single hematoxylin-eosin slide. RESULTS: Nine cases were positive by routine evaluation, 10 by step sections, and 11 by immunoperoxidase staining. CONCLUSIONS: The large, multi-institutional studies of sentinel node utility must take into account the surgical pathology methods used to evaluate these specimens so that uniform techniques, which reliably predict the status of the axillary nodes, can be instituted at all institutions that use this procedure.     

Intraoperative examination of the sentinel lymph node for breast carcinoma staging.

Intraoperative pathologic examination of the sentinel lymph node (SLN) draining a primary breast carcinoma allows an SLN-positive patient to undergo complete axillary lymphadenectomy as part of the same surgical procedure. However, the optimal technique for rapid SLN assessment has not been determined. We reviewed our results with imprint cytology (IC) and frozen section (FS) examination of SLNs from 278 patients. Compared with H&E-stained paraffin sections, IC and FS had an overall accuracy of 93.2%. The false-reassurance rate (false-negative results/all negative results) was 8.4%. It correctly identified 98% of macrometastases but only 28% of micrometastases. There were no false-positive results. Compared with paraffin-section cytokeratin immunohistochemistry results, the IC-FS false-reassurance rate increased to 25.8%. The false-reassurance rate decreased with smaller primary tumor size (T1 vs T2/3) and ductal type, smaller diameter of the SLN (< or = 2.0 cm), and greater pathologist experience. IC combined with 2-level FS reliably identifies SLN macrometastases but commonly fails to detect SLN micrometastases. If SLN micrometastasis is used to determine the need for further lymphadenectomy, more sensitive intraoperative methods will be needed to avoid a second operation.     

Intra-operative examination of the sentinel node in breast cancer

Intra-operative sentinel node analysis allows immediate progression to axillary clearance in patients with node positive breast cancer and reduces the need for re-operation. Despite this, intra-operative sentinel node analysis is infrequently performed in Ireland. We report our experience using this technique. Sentinel node biopsy was performed in 47 consecutive patients with symptomatic T1-T2 clinically node negative breast cancer. Sentinel nodes were examined intra-operatively by frozen section and imprint cytology and definitive histological assessment was performed on paraffin-embedded tissue. The sentinel node was identified in 46 (98%) patients. Twelve patients had axillary metastases. The sensitivity of intra-operative analysis in identifying nodal metastases was 92%. False negative rate was 8%, negative predictive value 97%, and specificity 100%. Intra-operative analysis of the sentinel node allowed re-operation to be avoided in 92% of patients with axillary node metastases. In our experience this technique can be readily introduced with reliable outcomes.     

Update on sentinel node pathology in breast cancer

Pathologic examination of the sentinel lymph nodes (SLNs) in patients with breast cancer has been impacted by the publication of practicing changing trials over the last decade. With evidence from the ACOSOG Z0011 trial to suggest that there is no significant benefit to axillary lymph node dissection (ALND) in early-stage breast cancer patients with up to 2 positive SLNs, the rate of ALND, and in turn, intraoperative evaluation of SLNs has significantly decreased. It is of limited clinical significance to pursue multiple levels and cytokeratin immunohistochemistry to detect occult small metastases, such as isolated tumor cells and micrometastases, in this setting. Patients treated with neoadjuvant therapy, who represent a population with more extensive disease and aggressive tumor biology, were not included in Z0011 and similar trials, and thus, the evidence cannot be extrapolated to them. Recent trials have supported the safety and accuracy of sentinel lymph node biopsy (SLNB) in these patients when clinically node negative at the time of surgery. ALND remains the standard of care for any amount of residual disease in the SLNs and intraoperative evaluation of SLNs is still of value for real time surgical decision making. Given the potential prognostic significance of residual small metastases in treated lymph nodes, as well as the decreased false negative rate with the use of cytokeratin immunohistochemistry (IHC), it may be reasonable to maintain a low threshold for the use of cytokeratin IHC in post-neoadjuvant cases. Further recommendations for patients treated with neoadjuvant therapy await outcomes data from ongoing clinical trials. This review will provide an evidence-based discussion of best practices in SLN evaluation.     

乳腺癌前哨淋巴结活检的方法和临床意义

在乳腺癌根治术中，腋窝淋巴结清扫的主要目的是：切除可能的转移病灶，指导进一步的辅助治疗。但近年的生物医学研究证实，乳腺癌从发生起即是全身性的疾病，早期乳癌的手术范围大小对病人预后影响不大；Fendas对24740例病人的腋窝淋巴结研究也证实，腋淋巴结的总转移率不足50％，小于1cm的浸润性乳癌，淋巴结浸润率仅为3％～7％，原位导管癌淋巴结浸润率仅约0％～1％。因此，专业论著中强调的乳腺癌进     

Axillary lymph node status in carcinoma of the breast

In this prospective study, axillary clearance specimens from consecutive routine mastectomies and wide excisions for carcinoma were divided into three segments by sutures in the theatre: apical (furthest from the tumour), mid and basal (nearest to the tumour) segments. Each specimen was then randomized to either formalin or Carnoy's fixation. Following fixation, lymph nodes were dissected from each of the three segments, sectioned once through the hilum, and examined microscopically. There was a significant (P less than 0.05) difference in the total number and number of reactive lymph nodes harvested from Carnoy's compared with formalin-fixed material. The number of nodes containing metastatic carcinoma was not significantly different (P = 0.64). In several cases, involved apical segment lymph nodes were found with no involvement of the proximal groups; this observation may have serious implications for the procedure of proximal lymph node sampling in the surgical management of breast cancer. It is suggested that clearing of axillary contents with Carnoy's fixative does not provide any additional information of clinical significance, although it may allow the pathologist to identify lymph nodes rapidly.     

The role of sentinel lymph node biopsy in the management of breast cancer

Axillary nodes status is the best single predictor of disease outcome in patients with breast cancer; presence ofaxillary node metastasis (ANM) reduces the patient's 5-year survival by 28-40%. However, ANM is seen in only 40% of all breast cancer and furthermore since axillary lymph node dissection (ALND) is associated with significant morbidity, sentinel lymph node biopsy (SLNB) seems to be a good alternative for nodal staging in breast cancer. Pathologically negative sentinel lymph node (SLN) is able to predict the absence of metastasis to the remainder of the regional lymph node basin with a very high degree of certainty. This article presents a systematic detailed review of the existing studies on SLNB in relation to the following parameters: sensitivity and accuracy of the different techniques used; pathologic evaluation of SLN; clinical and pathological factors affecting SLN status and role of SLNB in different clinical situations related to breast cancer management. We have also included brief mention of our experience at UMass from a pathological perspective in this review article.     

乳腺癌前哨淋巴结活检术中不同染色淋巴结与肿瘤转移的关系

目的探讨乳腺癌前哨淋巴结活检术(SLNB)中不同染色情况的淋巴结与肿瘤转移的关系。方法选择我院2014年1月至2018年1月行前哨淋巴结活检的乳腺癌患者92例,以亚甲蓝为示踪剂,根据92例乳腺癌患者SLNB中淋巴结染色情况的不同分为无染色组、完全染色组和染色不均组,病理检测3组患者淋巴结的肿瘤转移情况并作比较。结果92例乳腺癌SLNB共取得淋巴结256枚,平均每例患者2.8枚,无染色组(80枚)肿瘤转移率为13.8%,完全染色组(112枚)肿瘤转移率为43.8%,染色不均组(64枚)肿瘤转移率为62.5%,3组间肿瘤转移率差异有统计学意义(P<0.05)。结论乳腺癌SLNB中染色不均的淋巴结最易出现肿瘤转移,其次为完全染色的淋巴结,染色淋巴结附近看到的未染色淋巴结也有肿瘤转移的可能,宜一并切除送检,有利于降低假阴性率。     

Cytokeratin immunohistochemical validation of the sentinel node hypothesis in patients with breast cancer

No standard method for handling and histopathologic examination of the sentinel node (SN) exists. We hypothesized that a focused examination of all nodes with serial sectioning and cytokeratin immunohistochemical staining would confirm the SN as the node most likely to harbor metastasis. Intraoperative lymphatic mapping and sentinel lymphadenectomy using blue dye and (99m)technetium-labeled sulfur colloid were performed. All nodes were stained with H&E. All tumor-free nodes underwent additional sectioning and staining with H&E and an immunohistochemical stain. Routine H&E examination detected SN metastases in 27.6% of cases. Occult SN metastases were identified in 12.7% of cases. None of the 724 non-SNs examined contained occult metastases. The SN false-negative rate was zero. This study confirms histopathologically that the SN has biologic significance as the axillary node most likely to harbor metastatic tumor Standardization of the handling, sectioning, and staining of the SN is necessary as lymphatic mapping and sentinel lymphadenectomy become integrated into the care of patients with breast cancer     

Strategies for optimizing pathologic staging of sentinel lymph nodes in breast cancer patients

Due to the extensive pathologic evaluation of the sentinel lymph node (SLN), micrometastases are frequently observed. If micrometastases are clinically relevant, the histopathologic examination of SLNs should be sensitive enough to detect them. The probability of detecting micrometastases was calculated when examining the SLN according to the current Dutch pathology protocol and strategies evaluated to optimize the chance of detection. The dimensions of 20 consecutive axillary SLNs in patients with cT1-2N0 breast cancer were measured. In a mathematical model, the probability of detecting micrometastases in a SLN was calculated. Similarly, strategies to optimize the probability of detecting micrometastases were explored. When applying the pathology guidelines, the calculated probability to detect a micrometastasis was 18% for a 200-microm micrometastasis and 69% for a 2.0-mm metastasis in a median sized SLN. To detect the smallest micrometastasis in a median-sized SLN with a 95% probability, the interval between the sections must be decreased to 200 microm, and 20 levels from both halves must be examined. Given a prognostic significance of micrometastases, our current pathology guidelines are not sensitive enough. The number of sections should be increased, while the interval between cuts should be no more than 200 microm.     

乳腺癌前哨淋巴结相关的临床病理问题

乳腺癌是全球女性发病率最高的恶性肿瘤,其手术方式从最初的乳腺癌根治术到改良根治术,并进一步发展至目前的保乳治疗,极大地提高了患者的生活质量.腋窝淋巴结转移是乳腺癌最重要的预后指标,通过确定淋巴结转移情况可对乳腺癌进行分期,从而确定患者的治疗方案.但传统的腋窝淋巴结清扫(axillary lymph node dissection,ALND)可造成患者上肢水肿、疼痛、手臂运动功能受损和肩部僵硬等,影响其生活质量.近年来,ALND正逐渐被乳腺癌前哨淋巴结(sentinel lymph node,SLN)活检所取代.SLN活检在国内的逐步推广也对病理工作者提出了新的要求,因此本文就乳腺癌SLN的临床病理相关问题进行介绍.     

乳腺癌前哨淋巴结相关的临床病理问题

乳腺癌是全球女性发病率最高的恶性肿瘤,其手术方式从最初的乳腺癌根治术到改良根治术,并进一步发展至目前的保乳治疗,极大地提高了患者的生活质量.腋窝淋巴结转移是乳腺癌最重要的预后指标,通过确定淋巴结转移情况可对乳腺癌进行分期,从而确定患者的治疗方案.但传统的腋窝淋巴结清扫(axillary lymph node dissection,ALND)可造成患者上肢水肿、疼痛、手臂运动功能受损和肩部僵硬等,影响其生活质量.近年来,ALND正逐渐被乳腺癌前哨淋巴结(sentinel lymph node,SLN)活检所取代.SLN活检在国内的逐步推广也对病理工作者提出了新的要求,因此本文就乳腺癌SLN的临床病理相关问题进行介绍.     

hMAM在乳腺癌前哨淋巴结中的表达及其临床意义分析

探讨人乳腺球蛋白(human mammary globulin,hMAM)在乳腺癌前哨淋巴结(sentinel lymph node,SLN)中的表达及其临床意义。RT-PCR检测20例乳腺癌组织及正常淋巴结组织中hMAM的表达;SLN定位后通过RT-PCR与常规病理检测SLN转移情况,并进行比较;分析SLN转移与临床病理的关系。乳腺癌组织中有18例过表达,表达率为90.0%,而正常淋巴结中hMAM不表达,两者差异有统计学意义(P<0.01)。常规病理检查转移率为50.98%,RT-PCR法检测的阳性率提高到70.59%,RT-PCR法比常规病理检测的检出率高19.61%,两者之间差异显著(χ2=38.28,P<0.01)。SLN无转移组、微转移组、转移组与肿瘤位置、ER表达及病理类型之间差异均不显著(P>0.05)。hMAM可作为辅助判断SLN是否转移的标志。     

乳腺癌前哨淋巴结活检术中保留肋间臂神经的可行性

目的:探讨乳腺癌前哨淋巴结活检术(sentinel lymph node biopsy,SLNB)中保留肋间臂神经(intercostobrachial nerve,ICBN)的可行性.方法:回顾性分析乳腺癌前哨淋巴结活检术患者184例,其中50例行保留ICBN的SLBN,134例行切除ICBN的SLBN.比较两组的手术时间、出血量、清扫淋巴结数目及术后切口合并症;记录SLNB后术侧上臂和腋窝疼痛及感觉异常情况及转归.结果:保留ICBN组与非保留组比较,手术时间、出血量、淋巴结清扫数目及术后切口合并症比较差异无统计学意义.保留组及非保留组术侧上臂、腋窝的疼痛及感觉情况发生率近3天差异无统计学意义.而腋窝及上臂内侧区皮肤感觉异常术后0.5~3个月比较差异有统计学意义,且术后3个月非保留组的患侧腋窝及上臂内侧区皮肤感觉异常的缓解率较差,差异有统计学意义.结论:乳腺癌SLNB中保留ICBN的术式不增加手术难度,可减少患者术后术侧腋窝及上臂疼痛、感觉异常的发生率,能保持患者术后高质量的生活,保留ICBN的乳腺癌SLNB是安全可行的.     

Lymphangiogenesis in breast cancer is associated with non-sentinel lymph node metastases in sentinel node positive patients

Axillary lymph node dissection (ALND) is not suggested in breast cancer patients with negative sentinel lymph node (SLN) biopsies, and SLN is the only positive node in 40-70% of the remaining cases. To distinguish a subgroup in which ALND would be omitted, we investigated the role of lymphangiogenesis in primary breast cancer as a risk factor for distal lymph node involvements in patients with positive SLNs. 86 patients were included in this study. The frequency of proliferative lymphatic endothelial cells (LECP%) was evaluated in each specimen after immunohistochemical double staining for D2-40 and Ki-67. Larger primary tumor size, increased number of positive SLNs, lymphatic vessel invasion and LECP% were significantly associated with non-SLN metastases in the univariate analysis, but only LECP% retained significance in the multivariate model. A positive correlation between LECP% and lymphatic vessel invasion was also revealed. Our study confirmed the important role of lymphangiogenesis in tumor spread, and suggested that LECP% is a promising predictor for additional axillary lymph node involvements.