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 in breast carcinoma by imprint cytology,frozen section and rapid immunohistochemistry

Sentinel lymph nodes (SLN) isolated in 40 patients of breast carcinoma (stage T₁/T₂) were evaluated intraoperatively by imprint cytology and frozen section. Rapid immunohistochemistry (IHC) was done in cases where both imprint smears and frozen sections were negative for any metastatic tumor deposits. The results of these different techniques were compared with postoperative paraffin sections taken as “Gold Standard.” Nottingham modification of Bloom Richardson scoring system was used for grading the tumors. Further, the correlation of the SLN status with tumor size, grade, and lymphovascular invasion was studied. The sensitivity, specificity, and overall accuracy of imprint cytology were 91.7, 100, and 95% respectively, and those of the frozen section were 95.8, 100, and 97.5% respectively. Examination of multiple serial sections improved the sensitivity and overall accuracy of frozen section. Results of intraoperative rapid IHC were equivalent to final paraffin sections. Histological grade and lymphovascular invasion were in direct correlation with SLN metastasis (P < 0.05). The risk of lymphovascular invasion increased from 22.2% in grade I tumors to 85.7% in grade III tumors. SLN biopsy is a reliable method to evaluate the status of the axillary lymph nodes. Imprint cytology can be used reliably where the facility of frozen section is not available. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Intraoperative imprint cytology of sentinel lymph nodes in breast cancer: initial experience and lessons learnt in establishing a new practice

AIMS: The initial 18 months experience of performing intraoperative imprint cytology for patients with breast cancer undergoing sentinel lymph node biopsy is described for a single institution. The learning process is compared with published results from institutions with many years of experience in order to assess progress in reaching those ideal results, and the methodology used by these institutions is reviewed. METHODS: A retrospective review was undertaken of the intraoperative imprint cytology results from 103 patients with breast cancer (yielding a total of 170 lymph nodes) who underwent imprint cytology of their sentinel lymph node. The intraoperative imprint cytology results were compared with the final histopathological results. Details regarding the primary tumour characteristics and metastatic deposit size were recorded. RESULTS: The sensitivity for imprint cytology was 31.1%, with a specificity of 100% and overall accuracy of 77.8%. The sensitivity for detecting macrometastases (>2 mm diameter) was 61.9% and the sensitivity for micrometastases (<2 mm diameter) and including isolated tumour cells was 4.2%. CONCLUSIONS: The differences in sensitivity in comparison with many studies in the literature are multifactorial, and include technical aspects, such as the methodology used in the final histopathological and intraoperative evaluation of the sentinel lymph nodes, interpretative difficulties, and much lower case numbers. Furthermore, these numbers represent early experience and methods to improve sensitivity and overall accuracy are detailed in this paper.     

影响乳腺癌前哨淋巴结数目的临床病理特征分析

目的分析影响乳腺癌前哨淋巴结数目的相关因素,探讨最佳的前哨淋巴结活检值。方法回顾性分析2007年1月-2011年12月中国医学科学院肿瘤医院乳腺癌前哨淋巴结活检病例578例。采用Logistic回归模型分析前哨淋巴结数目与临床病理特征的相关性。结果全组女性,平均年龄49.9(21～90)岁。总共获得2 222枚前哨淋巴结,平均每例3.8枚(1～15)。淋巴结转移率17.8%(103/578),转移组和无转移组淋巴结数目无差异。单因素分析显示,术式、显像方法和体质指数影响前哨淋巴结数目(P<0.05)。多因素分析中,单纯乳房切除、联合显像、BMI≤30者前哨淋巴结较多(P<0.05)。前哨淋巴结限于5枚时,转移病例检出率100%。18.7%(108/578)病例不必继续送检淋巴结,298枚淋巴结免于切除。结论乳腺癌前哨淋巴结活检数量受到显像方法、乳腺术式和体质指数的影响,5枚前哨淋巴结可能是一个比较合适的参考标准。     

Intraoperative cytologic evaluation of sentinel lymph nodes in patients with breast carcinoma by scrape preparation

Intraoperative evaluation of sentinel lymph nodes (SLNs) in patients with breast carcinoma allows surgeons to complete axillary lymph node dissection in one procedure if any SLN shows metastasis. The accuracy of intraoperative pathological diagnosis is critical for decision-making. The purpose of this study was to evaluate our rapid intraoperative cytologic diagnosis of SLN through comparing with the final surgical pathologic diagnosis of the corresponding lymph nodes. A total of 454 SLNs from 159 consecutive female patients with a preoperative diagnosis of breast carcinoma over 3-year period were included in this study. After gross examination of each bisected lymph node, a scrape preparation was prepared for each submitted lymph node and was stained by the rapid Papanicolaou method. The intraoperative cytologic diagnosis was compared with the final surgical pathologic diagnoses. The overall sensitivity of intraoperative cytology was 52.5% with specificity of 100%. There were 17 false-negative cases. Of them, six nodes had isolated tumor cells, seven nodes had micrometastasis (0.2-2 mm), and four nodes had macrometastasis (>2 mm). There were no interpretive errors identified. The size of metastasis and tumor grade appeared to be significant factors in detecting metastasis by cytology. In addition, subsequent non-SLN involvement was 9% in patients with micrometastasis versus 50% in patients with macrometastasis (P < 0.05). Our study shows that the intraoperative cytologic evaluation of SLNs in breast carcinoma is a reasonably accurate method. The majority of false-negative cases were due to micrometastasis and isolated tumor cells.     

本院5年来乳腺癌前哨啉巴结活检报告

目的探讨乳腺癌前哨淋巴结活检技术的可行性和前哨淋巴结的组织学状况能否准确预告腋淋巴结的状况。方法使用美蓝染色和或^99mTc-SC同位素示踪法对我院收治的108例乳腺癌患者进行前哨淋巴结活检。结果108例患者中有95例成功确定前哨淋巴结，检出率88％，其中关蓝组为87S（S5／98），美蓝与核素联合组全部检出（100S）。40岁以下的妇女检出率明显高于40岁以上的妇女（P〈0．05），而假阴性率有显著性增高。97例浸润性癌（包括导管癌和腺癌）中假阴性率为22％，但当使用免疫组化检查法以后，假阴性率下降至14％。结论前哨淋巴结活检技术在临床是可行的，绝大多数前哨淋巴结可以比较准确地反映其余腋窝淋巴结的组织学特点。美蓝染色和／或^99mTc-SC同位素示踪法结合应用是较好的选择方法。     

Angiogenesis and mast cells in human breast cancer sentinel lymph nodes with and without micrometastases

AIMS: An increasing number of mast cells have been reported in angiogenesis associated with solid and haematopoietic tumours. Data concerning the number of mast cells in neoplastic lymph nodes and their relationship with microvessel density are controversial. The aim was to correlate the extent of angiogenesis with the number of mast cells reactive with tryptase in biopsy specimens of sentinel lymph nodes with and without micrometastases obtained from patients with breast cancer. METHODS AND RESULTS: Specimens from sentinel lymph nodes obtained from 80 patients (40 with and 40 without micrometastases) were investigated immunohistochemically by using anti-CD31 and anti-tryptase antibodies. Angiogenesis, measured as microvessel counts, increased in parallel with the number of tryptase-positive mast cells and their values were significantly higher in lymph nodes with micrometastases compared with those without. CONCLUSIONS: Tryptase-positive mast cells may contribute, at least in part, to angiogenesis occurring in sentinel lymph nodes with micrometastases from patients with breast cancer.     

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.     

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     

The flow cytometric DNA index can predict the presence of lymph node metastases in invasive ductal breast carcinoma

Axillary lymph node (LN) dissection is an important staging procedure for invasive ductal breast carcinoma (IDC), but causes elevated morbidity. Reliable preoperative prediction of metastases is at present not possible. We investigated whether flow cytometric analysis of primary IDC can correctly predict the presence of LN metastases at the time of primary diagnosis. In 341 primary IDC, DNA index (DI) in absolute values, S-phase fraction (SPF), size of the primary tumor, tumor grade (G), estrogen/progesterone receptors (ER/PR) expression and age were analysed and correlated with the axillary LN status with the aim of correctly predicting the LN status. No predictive value was identified for S-phase fraction (SPF), tumor grade, or ER/PR expression. The DI correlated statistically with LN status in all patients. A practically useful association was, however, only observed in 37 women aged 45-58 years with an IDC >2 cm diameter: a DI >1.44 predicted the presence of LN metastases at the time of operation with a specificity of 100% and a sensitivity of 89%, a negative predictive value of 91% and a positive predictive value of 100%. Determination of the absolute values of the DI may be a useful adjunct to sentinel LN preparation when predicting the axillary LN status and may spare some women the morbidity associated with axillary LN dissection.     

Eight-year experience with the intraoperative frozen section examination of sentinel lymph node biopsy for breast cancer in a North-Italian university center

Sentinel lymph node biopsy (SLNB) completely changed the impact of breast surgery on patients psycho-physical wellness, reducing morbidity associated with complete axillary lymph node dissection (CALND) while granting an adequate breast cancer staging. We reviewed our experience with the SLNB in a University Clinic. We collected data about all breast cancer patients submitted to SLNB from 2002 to 2010, and analyzed them with R (version 2.15.2), considering significant p<0.05. We performed 615 SLNBs on 607 patients, with a mean age of 59.86 (±10.76). Sentinel node detection rate resulted 99,7%, with a mean number of biopsied nodes of 1.64 (±0.67), axillary localization in 98% of cases, and negative intraoperative histological finding in the 86.2% of cases. Prevalence of ITCs, micrometastasis, macrometastasis and pericapsular metastasis resulted respectively 0.6%, 4.9%, 7.5% and 8.8%. Among women who received CALND, mean number of examined nodes was 16.36 (±6.19) and mean number of metastatic non-sentinel nodes was 0.97 in case of micrometastasis, 2.65 in case of macrometastasis, and up to 9.88 when pericapsular invasion was described. To conclude, our data confirm the role of nodal metastasis size in the prediction of non-sentinel node involvement, but further studies are required in order to better assess the role of ITCs and micrometastasis in the diagnostic and therapeutic management of breast cancer, with the final aim to reduce the surgical complications of axilla demolition when unnecessary.     

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.     

Intramammary lymph nodes: Cytologic findings and implications for fine-needle aspiration cytology diagnosis of breast nodules

The recognition of intramammary lymphoid proliferations is important because smears of these proliferations would be judged as insufficient by several of the published criteria for specimen adequacy. Alternatively, some might be confused with medullary carcinoma of the breast or adenocarcinomas with a “single-cell” pattern. We found 19 intramammary lymphoid proliferations in a series of 887 fine-needle aspirates of palpable breast nodules. Six were lymphomas and 13 were benign intramammary lymph nodes. Smear cellularity ranged from scant to high, but in all cases, lymphocytes dominated the cell population. The cytology of intramammary lymph nodes and lymphoma did not differ from those occurring at other sites. Diagn. Cytopathol. 1997;17:223–229. © 1997 Wiley-Liss, Inc.     

乳腺癌术中前哨淋巴结169枚印片细胞学诊断分析

目的探讨印片细胞学检查在乳腺癌术中前哨淋巴结诊断的价值,提高术中快速诊断的准确率。方法对67例乳腺癌患者的169枚前哨淋巴结同时进行术中冷冻切片检查及印片细胞学检查,与术后石蜡切片诊断对比分析。结果以淋巴结枚数为单位,169例术中前哨淋巴结冷冻切片确诊163例,确诊率96.45%;印片细胞学确诊162例,确诊率95.86%;两者联合诊断,共同确诊166例,确诊率98.22%。结论乳腺癌术中前哨淋巴结印片细胞学检查与冷冻切片检查相结合有互补作用,联合应用可提高术中前哨淋巴结诊断准确率。     

Use of intraoperative stereomicroscopy for preventing loss of metastases during frozen sectioning of sentinel lymph nodes in breast cancer

Aims:  Optimal detection of metastases in sentinel lymph nodes (SLN) remains controversial. To determine the reliability of intraoperative frozen sections, SLN protocol with one frozen section was compared with macroscopic SLN evaluation with consecutive complete SLN embedding.
Methods and results:  SLN from 135 consecutive breast cancer patients were analysed under a sereomicroscope. Frozen sections were performed in suspicious or clearly involved SLN on cut surface. One control group ( n  = 143) underwent one intraoperative frozen section on each SLN. The second control group ( n  = 90) was subjected to stereomicroscopy and one intraoperative frozen section on each SLN. A conventional SLN protocol with cytokeratin immunohistochemistry was performed postoperatively in all cases. All groups were statistically comparable. In the study group metastases were suspected in 21 SLN (16%) under the stereomicroscope and all were confirmed histologically. The negative SLN rate was significantly lower in the study group than in the main control group (47% versus 64%, P  = 0.008), suggesting loss of metastases during frozen sections. More macrometastases were detected in the study group (30% versus 15%, P  = 0.006); there were no differences in isolated tumour cells or micrometastases. The false-negative rate was significantly lower in the control groups (29% versus 13% and 12%, P  = 0.001).
Conclusions:  Frozen sections potentially lead to loss or reduced size of metastatic deposits in SLN. Avoiding intraoperative frozen sections on grossly inconspicuous SLN may therefore be justified.     

Adenoid cystic carcinoma of the breast: a case with axillary lymph node metastasis

A breast tumour with proven lymph node metastasis is conclusively characterized as an adenoid cystic carcinoma using immunocytochemistry and electron microscopy. The majority of tumour cells showed certain of the characteristic features of myoepithetial cells while the pseudocystic spaces contained large amounts of reduplicated basal lamina. A small proportion of tumour cells, however, showed epithelial differentiation with the formation of true lumina.     

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.