Non-sentinel lymph node involvement in patients with breast cancer and sentinel node micrometastasis; too early to abandon axillary clearance

AIMS: It has been suggested that patients with T1-2 breast tumours and sentinel node (SLN) micrometastases, defined as foci of tumour cells smaller than 2 mm, may be spared completion axillary lymph node dissection because of the low incidence of further metastatic disease. To gain insight into the extent of non-sentinel lymph node (n-SLN) involvement, SLNs and complementary axillary clearance specimens in patients with SLN micrometastases were examined. METHODS: A set of 32 patients with SLN micrometastases was selected on the basis of pathology reports and review of SLNs. Five hundred and thirteen n-SLNs from the axillary clearance specimens were serially sectioned and analysed by means of immunohistochemistry for metastatic disease. Lymph node metastases were grouped as macrometastases (> 2 mm), and micrometastases (< 2 mm), and further subdivided as isolated tumour cells (ITCs) or clusters. RESULTS: In 11 of 32 patients, one or more n-SLN was involved. Grade 3 tumours and tumours > 2 cm (T2-3 v T1) were significantly associated with n-SLN micrometastases as clusters (grade: odds ratio (OR), 8.3; 95% confidence interval (CI), 1.4 to 50.0; size: T2-3 tumours v T1: OR, 15; 95% CI, 2.18 to 103.0). However, no subgroup of tumours with regard to size and grade was identified that did not have n-SLN metastases. CONCLUSIONS: In patients with breast cancer and SLN micrometastases, n-SLN involvement is relatively common. The incidence of metastatic clusters in n-SLN is greatly increased in patients with T2-3 tumours and grade 3 tumours. Therefore, axillary lymph node dissection is especially warranted in these patients. However, because n-SLN metastases also occur in T1 and low grade tumours, even these should be subjected to routine axillary dissection to achieve local control.     

Paracortical axillary sentinel lymph node ectopic breast tissue

Benign glandular inclusions in axillary lymph nodes are uncommon, and their presence in axillary sentinel lymph nodes is exceptionally rare. The possibility of over-staging due to misinterpretation of glandular inclusions as metastatic carcinoma is a concerning issue. We present a 54-year-old female with high grade ductal carcinoma in-situ undergoing simple mastectomy with sentinel lymph node biopsy. Permanent sections of the sentinel lymph node revealed scarce naked small glands without surrounding stroma scattered in the paracortex in the superficial level. Deeper levels showed glands spanning a much larger area (2 mm), with bland ducts and tubules separated by abundant stroma. The myoepithelial layer was visible and was immunohistochemically confirmed. A final diagnosis of benign ectopic breast tissue within an axillary sentinel lymph node was rendered. Previous studies described axillary sentinel lymph nodes with glandular inclusions separated by stroma or subcapsular in location. It has been suggested that paracortical location and absence of stroma are characteristics of metastasis. As demonstrated in our report, benign inclusions may be paracortical and lack surrounding stroma. We recommend that glandular inclusions should be a diagnostic consideration for cases in which paracortically located naked glands do not histologically resemble the corresponding primary tumor.     

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。     

超声对乳腺癌腋下淋巴结转移状态评估价值的研究进展

超声技术作为术前评估乳腺癌腋下淋巴结转移(axillary lymph node metastasis,ALNM)状态最常用的方法,可通过二维灰阶图像、血流表现、弹性成像、超声造影等手段根据淋巴结的形态、纵横比、皮质状态、淋巴门表现、血流情况等指标预测淋巴结转移与否.但超声技术受众多影响因素如腋下淋巴结的大小、位置、腋窝深度、医师经验、超声仪器分辨率不同等的限制,其检出率及准确率仍未达到令人满意的水平.因此,如何提高超声对乳腺癌ALNM的评估效能成为亟需解决的问题.     

Prediction of nonsentinel lymph node metastasis in sentinel node-positive breast carcinoma

The incidence of nonsentinel (NSN) lymph node metastases in patients with a tumor-positive sentinel (SN) lymph node varies greatly from 20% to 70% in the published literature. Current practice is that most patients with a positive SN (micro- and macrometastases) undergo a complete axillary dissection. However, it has been shown by other investigators that a large number of patients with a positive SN do not necessarily need a complete axillary dissection. In this analysis, we reviewed the pathology slides from 58 patients who had undergone SN and axillary node dissection. The tumor size, histologic parameters, receptor (estrogen and progesterone), and HER-2neu oncoprotein expression were noted. Student t test and Fisher exact test were used for statistical analysis. Of 58 patients, 19 (32.7%) had NSN metastases. Primary tumor size (P < .002), size of SN metastatic tumor (P < .03), and the presence of extracapsular tumor extension (P < .0001) were associated significantly with NSN metastases. We have shown in this study that it would be possible to predict the NSN status based on primary tumor size, size of SN metastatic tumor, and presence of SN extracapsular tumor extension.     

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.     

血浆D-二聚体水平与乳腺癌腋窝淋巴结转移的相关性研究

目的：探讨血浆D–二聚体水平与乳腺癌腋窝淋巴结转移的关系,为预测乳腺癌腋窝淋巴结转移状态提供依据。方法：选取乳腺癌患者73例(乳腺癌组),乳腺良性疾病患者36例(良性疾病组)及健康体检女性50例(正常对照组),均检测D–二聚体水平,并结合患者临床及病理资料(肿瘤大小、病理分型、是否淋巴结转移、淋巴结转移个数、激素受体、癌基因等)进行综合分析。结果：乳腺癌组血浆D–二聚体水平明显高于其他两组,差异有统计学意义(P<0.01);乳腺良性疾病组与正常对照组D–二聚体水平比较,差异无统计学意义(P>0.05);腋窝淋巴结转移阳性患者D–二聚体水平高于腋窝淋巴结转移阴性患者,差异有统计学意义(P<0.01);肿瘤大小、病理类型、血浆D–二聚体水平与腋窝淋巴结转移个数显著相关(P<0.01);原发肿瘤的病理类型、血浆D–二聚体水平是腋窝淋巴结转移的危险因素(OR =7.464、6.470);血浆D–二聚体水平诊断乳腺癌腋窝淋巴结转移时的ROC曲线下面积(area under concentration-time,AUC)为0.689,以0.455μg/mL为最佳诊断分界点,灵敏度为52.3%,特异度为86.2%。结论：血浆D–二聚体水平与乳腺癌腋窝淋巴结转移状态及转移个数有关,其对判断乳腺癌腋窝淋巴结转移状态有一定临床价值。     

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     

乳腺癌患者妊娠次数与腋窝淋巴结转移的关系研究

目的探讨乳腺癌患者妊娠次数与腋窝淋巴结转移之间的关系。方法171例乳腺癌患者按妊娠次数分为妊娠1次，2次及2次以上共3组。统计该3组患者各自发生腋窝淋巴结转移的患者比例及发生转移的腋窝淋巴结在所检测的淋巴结中的比例，应用X2检验分析不同组别间腋窝淋巴结转移阳性患者比例的差异，阳性转移淋巴结比例之间的差异，从而探讨乳腺癌患者的妊娠次数与其腋窝淋巴结转移例数及转移个数之间的关系。结果妊娠1次、妊娠2次及妊娠2次以上组发生腋窝淋巴结转移的比例分别为34．78％、50％、64．10％。随妊娠次数增加，发生腋窝淋巴结转移的比例逐渐增高。其中妊娠2次以上患者组发生腋窝淋巴结转移的比例明显高于妊娠1次患者组发生腋窝淋巴结转移的比例（64．10％掷34．78％），2者相比差异有显著性（P：0．012）。妊娠1次、妊娠2次及妊娠2次以上组腋窝淋巴结发生转移的比例分别为44．58％、44．18％、52．97％。妊娠2次以上患者组腋窝淋巴结发生转移的比例明显高于妊娠2次患者组腋窝淋巴结发生转移的比例（52．97％协44．18％），2者相比差异有显著性（P=0．025）。但妊娠1次组腋窝淋巴结发生转移的比例与妊娠2次组及妊娠2次以上组相比，差异均无显著性（P=0．948，P=0．167）。结论妊娠次数较少的患者组发生腋窝淋巴结转移的比例相对较小，发生转移的腋窝淋巴结数目也相对较少。乳腺癌患者的妊娠次数与乳腺癌的腋窝淋巴结转移有关。乳腺癌患者的妊娠次数对判断乳腺癌患者的腋窝淋巴结转移有一定的意义。     

Evaluation of axillary sentinel lymph node biopsy by immunohistochemistry and multilevel sectioning in patients with breast carcinoma

BACKGROUND: Axillary lymph node dissection for evaluation of the presence or absence of metastatic disease is the single most important prognostic factor for patients with newly diagnosed primary breast cancer. Recently, sentinel lymph node (SLN) biopsy is being investigated as an alternative to the evaluation of the entire axilla. We evaluated whether the application of multilevel sectioning and immunohistochemistry in SLNs will increase the accuracy of detection of metastatic deposits. METHODS: Between October 1998 and July 1999, 38 patients with breast carcinoma (25 ductal, 5 lobular, 4 tubular, and 4 mixed ductal and lobular) underwent successful SLN biopsy followed by complete axillary node dissection. Sentinel lymph nodes were localized with a combination of isosulfan blue dye and radionuclide colloid injection. Frozen sections and permanent sections of SLNs were examined. All negative SLNs were examined for micrometastases by 3 additional hematoxylin-eosin (H&E)-stained sections and immunohistochemistry with the cytokeratins AE1/AE3. RESULTS: Sentinel lymph nodes were successfully identified surgically in 38 (93%) of 41 patients. There was a 97% correlation between the results of the frozen sections and the permanent H&E-stained sections. Twelve (32%) of 38 patients showed evidence of metastatic disease in their SLN by routine H&E staining. In 7 (58%) of 12 patients with positive nodes, the sentinel node was the only positive node. The 26 patients with negative SLN examination by H&E were further analyzed for micrometastases; 5 (19%) were found to have metastatic deposits by immunohistochemistry. Of these patients, 2 were also converted to node positive by detection of micrometastatic disease by examination of the additional H&E levels. CONCLUSIONS: Sentinel lymph nodes can be accurately identified in the axilla of breast cancer patients. Evaluation of SLNs provides reliable information representative of the status of the axilla in these patients. Immunohistochemistry and, to a lesser degree, detailed multilevel sectioning are able to further improve our ability to detect micrometastatic disease in SLNs of breast cancer patients.     

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.     

Intraoperative frozen section examination of axillary sentinel lymph nodes in breast cancer

The study presents the results from intraoperative frozen section assessment of axillary sentinel lymph nodes (SLNs) in breast cancer. Routine histological frozen sections from one level were used, two sections stained with haematoxylin and eosin. Immunohistochemistry for cytokeratins was applied to the permanent SLN paraffin sections only. Axillary dissection was performed on all SLN-positive cases regardless of the size of the metastatic deposits. With a detection rate of 83%, 272 patients entered the study over a period of 46 months. A total of 61 cases were SLN positive by frozen section analysis. The paraffin sections gave an additional 23 SLN-positive cases. The false-negative rate for frozen sections was then 27% (23/84). Micrometastases were found in 28 of 84 cases, and macrometastases in 56. The false-negative rate of frozen sections for micrometastases was 71% (20/28), and for macrometastases 5% (3/56). A total of 73% (61/84) of the patients underwent axillary surgery as a one-step procedure.     

乳腺癌前哨淋巴结术中分子诊断的临床实用性初探

目的 探讨GeneSearchTM乳腺淋巴结检测试剂盒(以下简称GeneSearch)在乳腺癌前哨淋巴结(SLN)术中诊断的临床实用性.方法 对复旦大学附属肿瘤医院2009年2月至6月诊治的88例乳腺癌患者行SLN活检.首先垂直长轴将所得淋巴结切成数块厚约2 mm的组织块,对各切面进行术中细胞印片后,奇数号组织块用于术后连续切片检查,偶数号组织块采用GeneSearch进行检测,应用即时荧光定量逆转录聚合酶链反应检测SLN中CK19和乳腺球蛋白表达的Ct值.将GeneSearch以术后连续切片的诊断为准,与术中细胞印片、术后连续切片的病理结果分别进行比较.结果 88例共获得225枚SLN,其中宏转移淋巴结27枚,微转移淋巴结9枚,阴性淋巴结189枚(其中5枚为孤立肿瘤细胞).从切割淋巴结开始到最终形成报告,GeneSearch耗时范围为35～45 min(平均40 min).基于淋巴结数目,GeneSearch与术后连续切片的总体符合率为95.6%(215/225),其检测敏感度为86.1%(31/36),均高于术中细胞印片[分别为94.7%(213/225)和72.2%(26/36)].SLN转移灶大小与CKl9和乳腺球蛋白的Ct值存在统计学相关性(P＜0.01).结论 GeneSearch用于SLN术中诊断时,其检测敏感度高于术中细胞印片,达到比较满意的效果,但在应用中仍存在一些问题.