Intraoperative sentinel lymph node evaluation in patients with node-positive breast cancer status post neoadjuvant systemic therapy - An institutional experience

Recent studies have shown the feasibility and utility of sentinel lymph node (SLN) biopsy in patients with biopsy proven node-positive breast cancer after neoadjuvant chemotherapy. We reviewed our experience in intraoperative SLN evaluation in such cases and its effect on axillary management. A retrospective analysis of breast cancer patients (2015–2018) with a biopsy-proven positive axillary lymph node, who received neoadjuvant systemic therapy and underwent intraoperative SLN assessment was performed. Intraoperative SLN assessment results were compared with final pathology. Its accuracy and effect on axillary management is summarized. We identified 106 patients with positive axillary lymph node and neoadjuvant systemic therapy between the ages of 28 and 75 years who had SLN biopsy and lumpectomy (33) or mastectomy (73). Three or more SLNs were identified in 91 cases (86 %). The previously biopsied lymph node was identified as one of the sentinel lymph nodes in 93 cases (88 %). There is a high concordance rate between frozen section diagnosis and final diagnosis on sentinel lymph nodes. No false positive case and seven false negative frozen section diagnosis cases (diagnosed as negative on frozen section and positive on permanent sections) were identified. False-negative frozen section diagnosis correlated with low-volume nodal disease and obscuring tumor bed changes. Almost half of the positive lymph nodes were converted to negative after neoadjuvant chemotherapy. SLN biopsy with intraoperative frozen section evaluation after neoadjuvant systemic therapy in node-positive patients is an effective way to minimize axillary surgery.     

乳腺癌非前哨淋巴结转移的预测

目的 :预测非前哨淋巴结 (non SLN)转移 ,以筛选出转移局限于前哨淋巴结 (SLN)的乳腺癌患者。方法 :采用99mTc SC作为示踪剂 ,对 95例乳腺癌患者行前哨淋巴结活检 ,对乳腺癌非前哨淋巴结转移进行单因素和多因素分析。结果 :95例患者中成功发现 91例患者有SLN (95 8% ) ,其中 85例患者SLN能准确反映腋窝淋巴结的病理状况 (93 4% )。临床肿块大小(P =0 0 2 8)、肿瘤分级 (P =0 0 40 )和原发灶cyclinD1蛋白 (P =0 0 17)的表达与non SLN转移显著相关。而Logistic多因素分析证实 ,临床肿块大小、肿瘤分级为独立的预测非前哨淋巴结转移的因子。结论 :可根据临床病理学特征 ,筛选出乳腺癌转移只局限于前哨淋巴结的患者 ,也存在免除腋窝淋巴结清扫的可能性     

Reliability of intraoperative frozen section and imprint cytological investigation of sentinel lymph nodes in breast cancer

AIMS: The sentinel lymph node procedure enables selective targeting of the first draining lymph node, where the initial metastases will form. A negative sentinel node (SN) predicts the absence of tumour metastases in the other regional lymph nodes with high accuracy. This means that in the case of a negative SN, regional lymph node dissection is no longer necessary. Besides saving costs, this will prevent many side-effects of lymph node dissection. The aim of this study was to evaluate the reliability of intraoperative cytological and frozen section investigation of the SN to detect metastases. This would allow the axillary lymph node dissection to be performed in the same session as the SN procedure and the excision of the primary tumour in case of a positive SN. METHODS AND RESULTS: Seventy-four SNs were detected by gamma probe detection of nanocolloid and visual localization of Patent Blue accumulations in 54 women with stage T1-2N0M0 invasive breast cancer. The identified SN were immediately investigated by frozen section and imprint cytological investigation. Diagnoses were confirmed on the paraffin material, and in case of negative frozen section and paraffin haematoxylin and eosin sections, skip sections and immunohistochemistry were performed. Thirty-one SNs (42%) contained metastases, of which 27 were detected by the frozen section procedure (sensitivity 87%). There were no false positives (specificity 100%). The sensitivity of the imprints was 62% with a specificity of 100%. When evaluating the data per patient, for the frozen section procedure the sensitivity was 91% and the specificity 100%, and for the imprints, the sensitivity was 63% and the specificity 100%. There were no SNs in which the imprints showed metastases and the frozen section did not. CONCLUSIONS: Intraoperative frozen section analysis is a reliable procedure by which a high percentage of sentinel lymph node metastases can be detected in breast cancer patients without false positive results. This allows the surgeon to perform an immediate axillary lymph node dissection in case of positive SNs. In up to 10% of cases, the final paraffin sections will reveal micrometastases that were not detected by the frozen section, and in these patients axillary lymph node dissection will have to be performed in a second session. The imprint method is significantly less sensitive than the frozen section but may be used as an alternative when frozen section is not possible.     

Assessment of sentinel lymph nodes for breast cancer

Sentinel lymph node biopsy is standard of care for assessment of lymph node stage in early breast cancer in patients with clinically negative nodes. The limited clinical significance of low volume axillary metastatic disease has led to changes in surgical management of the axilla with a shift away from routine axillary lymph node dissection if the sentinel lymph node is found to contain metastatic tumour. This has led to a decrease in the use of intraoperative assessment of sentinel nodes. Specimen handling and histological assessment of sentinel lymph nodes is described, with the emphasis on identification of macrometastatic disease defined as metastases greater than 2 mm. Routine levels and/or cytokeratin immunohistochemistry is not recommended. The increasing use of neoadjuvant chemotherapy and growing evidence that sentinel lymph node biopsy is safe and accurate in this setting, including in patients with proven node positive disease, has resulted in new challenges in the interpretation of these specimens.     

Intraoperative evaluation of sentinel lymph nodes for metastatic breast carcinoma by imprint cytology.

BACKGROUND: The increasing utilization of lymphatic mapping techniques for breast carcinoma has made intraoperative evaluation of sentinel lymph nodes attractive. Axillary lymph node dissection can be performed during the initial surgery if the sentinel lymph node is positive, potentially avoiding a second operative procedure. At present the optimal technique for rapid sentinel lymph node assessment has not been determined. Both frozen sectioning and intraoperative imprint cytology are used for rapid intraoperative sentinel lymph node evaluation at many institutions. The purpose of this study is to evaluate experience with imprint cytology for intraoperative evaluation of sentinel lymph nodes in patients with breast cancer. METHODS: A retrospective review of the intraoperative imprint cytology results of 678 sentinel lymph node mappings for breast carcinoma was performed. Sentinel nodes were evaluated intraoperatively by either bisecting or slicing the sentinel node into 4 mm sections. Imprints were made of each cut surface and stained with H&E and/or Diff-Quik. Permanent sections were evaluated with up to four H&E stained levels and cytokeratin immunohistochemistry. Intraoperative imprint cytology results were compared with final histologic results. Results: The sensitivity of imprint cytology was 53%, specificity was 98%, positive predictive value was 94%, negative predictive value was 82% and accuracy was 84%. The sensitivity for detecting macrometastases (more than 2mm) was significantly better than for detecting micrometastases (相似文献   

Assessing second echelon lymph nodes during sentinel lymph node biopsy: can we have more accurate axillary treatment for breast cancer patients?

Sentinel lymph node biopsy (SLNB) is the standard treatment for breast cancer patients with clinically negative axilla. For patients with positive sentinel lymph nodes, axillary lymph node dissection (ALND) was required. However, approximately a half of the SLNs-positive patients were found to have clear axillary lymph nodes after ALND, indicating that they had received unnecessary ALND without therapeutic benefit. Therefore, we propose a hypothesis for solution of this clinical problem. We defined the second echelon lymph nodes (SELNs) as those nodes receiving lymphatic drainage directly from the SLNs. For patients with positive-SLNs, SELNs can be biopsy and assessed. If SELNs are negative, no more ALND was needed in these patients even if their SLNs are positive. If our hypothesis were confirmed to be true, we can tailored our axillary treatment to more breast cancer patients, avoiding unnecessary ALND and its complications.     

Histolopathologic approach to direct the management of the axilla in early breast cancer patients

Screening mammography improved early detection of breast cancer and since then, the percentage of patients with node involvement is declining. Sentinel lymph node biopsy (SLNB), although helpful in the diagnostic armamentarium of these patients, has consequential limitations. In these patients, moreover, lymphatic invasion (LI) is of utmost importance to determine the risk of local recurrence. To find an adjuvant histologic approach to assist in pre‐operative analysis of the patient's risk for having LI and thus sentinel ± non‐sentinel axillary lymph node metastasis, one hundred and twenty patients with early invasive duct carcinoma without axillary lymph node metastasis were evaluated. Logistic regression predictive models were built from 80 patients and validated in the remaining 40 patients. The final stepwise multi‐regression analysis identified four sensitive models. In the validation group, model 1 [applicable to tumors grade 3 having micropapillary differentiation (MPD)] correctly identified 92.31% of patients with LI and confirmed LI [positive predictive value (PPV) = 83%], but with moderate sensitivity. Model 2 [applicable to tumors without MPD], model 3 [applicable to tumors grade 1/2], and model 4 [applicable to tumors grade 1/2 having no MPD] all had moderate PPV and a high negative predictive value (NPV) rendering these models reliable negative tests. However, as they had high sensitivity, positive results confirm the presence of LI. Patient with tumors grade 3 and MPD might need SLNB and/or axillary lymph node dissection (ALND). Patients having tumors grade 1/2, size <2 cm, and no MPD nor extensive retraction artifact, SLNB and/or ALND could be omitted. In tumors grade 1/2 (model 2) and those without MPD (model 3), the proposed models are reliable negative tests rather than a definitive positive one.     

Accuracy of lymph nodes cell block preparation according to ultrasound features in preoperative staging of breast cancer

To analyse the correlation between axillary ultrasonography (US), cell block (CBs) preparation, and histological diagnosis of lymph nodes from patients with primary breast cancer with the intention to assess the accuracy of cell block (CB) technique in preoperative staging. We tested a series of 26 patients who underwent axillary cell blocks from ultrasound guided fine‐needle aspiration with histologic follow‐up (axillary lymph nodes dissection). The specificity of axillary cell block was 100% vs. 14% for axillary ultrasound and the sensitivity was 73% for axillary cell block and 87% for axillary ultrasound. The positive and negative predictive values of cell block were respectively, 100 and 78%. Based on these results, we concluded that CB preparation was a feasible and specific technique to evaluate axillary lymph nodes status of patients with primary invasive breast cancer. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Intraoperative sentinel lymph node evaluation: Optimizing surgical pathology practices in an era of changing clinical management

Axillary lymph node status is an independent prognostic indicator in breast cancer. Intraoperative identification of metastatic carcinoma in sentinel lymph nodes may allow for concurrent axillary lymph node dissection at the time of primary tumor excision. A retrospective review of patients undergoing primary breast cancer excision with sentinel lymph node sampling was performed. Sensitivity and specificity of imprint cytology (touch prep) with and without the incorporation of gross evaluation was determined using permanent section results as the gold standard. Five hundred sixteen lymph nodes were analyzed by imprint cytology in 213 patients, and 203 lymph nodes were analyzed in 74 patients incorporating gross examination. Sensitivity and specificity for the detection of macrometastases by touch prep alone were 60% and 99% respectively with 4 patients undergoing same-day axillary dissection for only micrometastatic disease. False negative causes included lack of transfer of malignant cells in 8 cases and misinterpretation of tumor cells in 6 cases. Incorporating gross examination in the modified protocol resulted in reduced sensitivity of 38%, but achieved the desired 100% specificity and positive predictive value. Imprint cytology alone did not reliably distinguish between micro- and macrometastatic disease. Gross assessment combined with imprint cytology allows for improved assessment of volume of axillary disease, but is an insensitive technique.     

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.     

Sentinel node biopsy as an indicator for pelvic nodes dissection in early stage cervical cancer

The purpose of this study was to investigate the feasibility of sentinel node frozen biopsy to minimize the extensive pelvic lymph nodes dissection in early stage cervical cancer patients on the basis that the risk of skip metastasis to the paraaortic area is negligible. Twenty-six patients with early stage cervical cancer were enrolled in this study. Technetium-99m colloid albumin (Tc(99m)) was injected intradermally around the tumor for allowing preoperative lymphoscintigraphy and intraoperative hand-held gama probe detection of seninel nodes. For visual detection, isosulfan blue dye was injected into the peritumoral sites before peritoneal opening. Postoperative morbidity and negative predictive value were the endpoints of this study. The 26 patients, ranging in age from 32 to 71 yr, underwent intraoperative sentinel nodes mapping. All the patients underwent complete pelvic lymph nodes dissection including para-aortic nodes. There was one case with positive non-sentinel nodes despite the negative sentinel node by frozen biopsy (negative predictive value, 95.2%). This new technique of sentinel node mapping is safe and simple to perform. Further clinical trials using the combination of Tc(99m) and isosulfan blue dye are warranted and this technique will make a true advance for less aggressive management of patients with early stage cervical cancer.     

Sentinel lymph node biopsy in breast cancer: creating controversy and defining new standards

Sentinel lymph node (SLN) biopsy is an exciting and promising new addition to surgical management and pathologic evaluation of breast cancer. Sentinel nodes are more likely to contain metastases than nonsentinel nodes providing an opportunity to more accurately stage breast cancer patients. In the future, surgical management of the axilla may be approached as a staged procedure, perhaps eliminating axillary dissection in SLN-negative patients, should clinical trials demonstrate the safety of this approach. The advent of SLN biopsy has propelled an old question back to the forefront of clinical investigation: do occult metastases in lymph nodes have prognostic, predictive, and clinical significance? This article provides one opinion and a review on the pathology and future of SLN biopsy in breast cancer. Practicing pathologists will need to stay abreast of the issues and facts in order to participate in the debate and shape the future of pathologic management of sentinel nodes.     

乳腺癌保乳根治术并腔镜下腋窝淋巴结廓清术应用

目的探讨乳腺癌保乳根治术并腔镜下腋窝淋巴结廓清术的效果及安全性。方法2003年8月至2006年8月在中国医科大学附属盛京医院第一微创外科住院的5例乳腺癌（年龄38～61岁,平均年龄51岁）行保乳根治术并腔镜下腋窝淋巴结廓清术患者,对其资料进行回顾分析。结果5例乳腺癌患者行保乳根治术并腔镜下腋窝淋巴结廓清术均获成功,所有切除乳腺标本经术中冰冻病理证实切缘肿瘤细胞阴性。平均手术时间150min,术中及术后均无并发症发生。结论保乳根治术并腔镜下腋窝淋巴结廓清术治疗乳腺癌能够达到良好的手术效果且更安全。     

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.     

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.     

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.     

Evaluation of sentinel lymph nodes in breast cancer

Sentinel lymph node biopsy is an accurate method for the detection of axillary metastases in cases of breast carcinoma and is of value as a replacement for axillary dissection. There is variation, however, in the methods and protocols used for the histopathological evaluation of sentinel lymph nodes, standardisation of which will be required if results of sentinel lymph node analysis are to be used to stratify patients into prognostic groups. The significance of micrometastases, isolated tumour cells (ITCs) and the value of immunohistochemistry are also matters for further definition. In this Expert Opinion we present reviews from two authors, providing American and European perspectives on the approach to sentinel lymph node evaluation.     

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.     

Factors affecting metastases to non-sentinel lymph nodes in breast cancer

AIMS: Because sentinel lymph node (SLN) biopsy for breast cancer has become well established, one of the challenges now is to determine which patients require a completion axillary dissection following a positive SLN biopsy. METHODS: A prospective database of patients who underwent SLN biopsy for invasive breast cancer from July 1999 to November 2002 (n = 180) was analysed. Fifty four patients (30%) had one or more positive SLN, and all underwent a completion axillary dissection. This subgroup was further analysed to delineate which factors predicted non-SLN metastasis. RESULTS: Twenty six of the 54 patients with a positive SLN had additional metastases in non-SLNs. Significant variables that predicted non-SLN metastasis included extranodal extension (odds ratio (OR), 17.399; 95% confidence interval (CI), 1.69 to 178.96) and macrometastasis within the SLN (OR, 6.985; 95% CI, 1.291 to 37.785). CONCLUSIONS: In patients with invasive breast cancer and a positive SLN, extranodal extension or macrometastasis within the SLN were both independent predictors of non-SLN involvement.     

The value of cytokeratin immunohistochemistry in the evaluation of axillary sentinel lymph nodes in patients with lobular breast carcinoma

BACKGROUND: Cytokeratin immunohistochemistry (IHC) reveals a higher rate of occult lymph node metastases among lobular carcinomas than among ductal breast cancers. IHC is widely used but is seldom recommended for the evaluation of sentinel lymph nodes in breast cancer patients. Objective: To assess the value of cytokeratin IHC for the detection of metastases in sentinel lymph nodes of patients with invasive lobular carcinoma. METHODS: The value of IHC, the types of metastasis found by this method, and the involvement of non-sentinel lymph nodes were analysed in a multi-institutional cohort of 449 patients with lobular breast carcinoma, staged by sentinel lymph node biopsy and routine assessment of the sentinel lymph nodes by IHC when multilevel haematoxylin and eosin staining revealed no metastasis. RESULTS: 189 patients (42%) had some type of sentinel node involvement, the frequency of this increasing with increasing tumour size. IHC was needed for identification of 65 of these cases: 17 of 19 isolated tumour cells, 40 of 64 micrometastases, and 8 of 106 larger metastases were detected by this means. Non-sentinel-node involvement was noted in 66 of 161 cases undergoing axillary dissection. Although isolated tumour cells were not associated with further lymph node involvement, sentinel node positivity detected by IHC was associated with further nodal metastases in 12 of 50 cases (0.24), a proportion that is higher than previously reported for breast cancer in general. CONCLUSIONS: IHC is recommended for the evaluation of sentinel nodes from patients with lobular breast carcinoma, as the micrometastases or larger metastases demonstrated by this method are often associated with a further metastatic nodal load.