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Accuracy of Intraoperative Frozen Section Analysis of Lymph Nodes in Women Undergoing Axillary Sampling for Treatment of Breast Cancer: Single Institution Audit
Abstract
Background:
Axillary lymph node (LN) positivity is an important prognostic factor in breast cancer. Almost 30% clinically node negative (cN0) early breast cancers have positive nodes on pathology, wherein an axillary dissection is done as a second stage surgery. Intra operative frozen section (FS) potentially avoids redo surgery.
Materials and methods:
We performed a retrospective audit for the false negative rate of intraoperative FS, from 2014 to 2018. All cN0 women undergoing upfront surgery, who underwent low axillary sampling (LAS) with FS were included.
Results:
Of 22,854 breast cancer cases, 2230 underwent LAS, of which 877 were node positive. Intraoperative FS was negative in 1423/2230 (63.81%) cases, of which 71/1423 (4.98%) were false negative, and came positive on final histopathology report (HPR). These 71 women had a median of 5 nodes (mean 4.85) dissected on FS (range 1-12) with a median 1 (mean 1.3) node positive (range 1-6) on HPR. The sensitivity of FS was 91.89% (95% CI, 89.89-93.62), with a negative predictive value of 95.01% (95% CI, 93.84-95.97), accuracy of 96.73% (95% CI, 95.90-97.43) and false negative rate 4.98%. On logistic regression analysis, micrometastasis (Odds ratio (OR) 7.76, 95% CI, 3.49-17.25, P < .001) lobular histology (OR 2.50, 95% CI, 1.007-6.223, P = .04) and nodes dissected (OR 1.18, 95% CI, 1.07-1.30, P = .001) were associated with higher false negative FS, and extra nodal extension (OR 0.32, 95% CI, 0.18-0.57, P ≤ .001) with lower false negative FS.
Conclusion:
The high concordance between intraoperative FS and definitive histology, suggests it's routine use for Sentinel lymph node/LAS LN can help avoid a second surgery.
... In light with this not re-assuring reports, our assessments indicated 59.3% sensitivity and 47.8% specificity for US based on permanent pathology as the gold standard. Currently, FS is one of the most frequently used methods for identifying involved sentinel LNs during BC surgery owing to the high concordance between FS and permanent pathology 47 . In a recent retrospective study, the sensitivity and accuracy of FS was reported 91.89% and 96.73%, in the evaluation of 2230 LNs, respectively 47 . ...
... Currently, FS is one of the most frequently used methods for identifying involved sentinel LNs during BC surgery owing to the high concordance between FS and permanent pathology 47 . In a recent retrospective study, the sensitivity and accuracy of FS was reported 91.89% and 96.73%, in the evaluation of 2230 LNs, respectively 47 . While our study's findings align with previous research in terms of favorable sensitivity, it's essential to acknowledge the drawbacks of FS pathology. ...
... While our study's findings align with previous research in terms of favorable sensitivity, it's essential to acknowledge the drawbacks of FS pathology. These encompass challenges in accurately detecting micrometastasis and tumors with lobular histopathology, as well as factors such as cost, time consumption, and the necessity for an experienced pathologist 47,48 . Regarding the costs, the price of each head probe of ELS system is about 3 dollars, which could be used for each patient. ...
Lymph node (LN) status is an essential prognostic factor in breast cancer (BC) patients, with an important role in the surgical and therapeutic plan. Recently, we have been developed a novel system for real-time intra-operative electrical LN scanning in BC patients. The ELS scores were calibrated by pathological evaluation of the LNs. Herein, we evaluated the efficacy of ELS in a prospective study for non-chemo-treated breast cancer patients. This is a prospective study in which ELS scores are blind for pathologists who declare the clearance or involvement of LNs based on permanent pathology as the gold standard. ELS and frozen-section (FS) pathology results were achieved intra-operatively, and samples were sent for the permanent pathology. The score of ELS did not affect the surgeons’ decision, and the treatment approach was carried out based on FS pathology and pre-surgical data, such as imaging and probable biopsies. Patients were recruited from October 2021 through November 2022, and 381 lymph nodes of 97 patients were included in the study. In this study we recruited 38 patients (39.2%) with sentinel lymph node biopsy (SLNB) and 59 patients (60.8%) with ALND. Of the 381 LNs scored by ELS, 329 sentinel LNs underwent routine pathology, while others (n = 52) underwent both FS and permanent pathology. ELS showed a sensitivity of 91.4% for node-positive patients, decreasing to 84.8% when considering all LNs. Using ROC analysis, ELS diagnosis showed a significant AUC of 0.878 in relation to the permanent pathology gold standard. Comparison of ELS diagnosis for different tumor types and LN sizes demonstrated no significant differences, while increasing LN size correlated with enhanced ELS sensitivity. This study confirmed ELS’s efficacy in real-time lymph node detection among non-chemo-treated breast cancer patients. The use of ELS’s pathological scoring for intra-operative LN diagnosis, especially in the absence of FS pathology or for non-sentinel LN involvement, could improve prognosis and reduce complications by minimizing unnecessary dissection.
The incidence of breast cancer is increasing rapidly in urban India due to the changing lifestyle and exposure to risk factors. Diagnosis at an advanced stage and in younger women are the most concerning issues of breast cancer in India. Lack of awareness and social taboos related to cancer diagnosis make women feel hesitant to seek timely medical advice. As almost half of women develop breast cancer at an age younger than 50 years, breast cancer diagnosis poses a huge financial burden on the household and impacts the entire family. Moreover, inaccessibility, unaffordability, and high out-of-pocket expenditure make this situation grimmer. Women find it difficult to get quality cancer care closer to their homes and end up traveling long distances for seeking treatment. Significant differences in the cancer epidemiology compared to the west make the adoption of western breast cancer management guidelines challenging for Indian women. In this article, we intend to provide a comprehensive review of the management of breast cancer from diagnosis to treatment for both early and advanced stages from the perspective of low-middle-income countries. Starting with a brief introduction to epidemiology and guidelines for diagnostic modalities (imaging and pathology), treatment has been discussed for early breast cancer (EBC), locally advanced, and MBC. In-depth information on loco-regional and systemic therapy has been provided focusing on standard treatment protocols as well as scenarios where treatment can be de-escalated or escalated.
Sentinel node biopsy (SNB) may be a decision-making tool for function preservation surgery, including radical trachelectomy and ovary preservation in the treatment of cervical and endometrial cancer. The intraoperative diagnosis is important for guiding treatment decisions for patients with these conditions. Three hundred seventy-one patients with cervical and endometrial cancer received SNB with an intraoperative frozen section analysis and imprint cytology. The sentinel node was cut in half, parallel to the longest axis, to obtain the maximum section area. After performing imprint cytology, one half was used to create a frozen section. The specimen was cut at 2-mm intervals into 5-μm-thick sections, which were subjected to hematoxylin and eosin staining. The diagnostic accuracy of intraoperative frozen section analyses and imprint cytology was compared to the final pathological diagnosis. Among 951 detected sentinel nodes, 51 nodes were found to be positive in the final pathological diagnosis. The sensitivity of a frozen section analysis, imprint cytology and the combination of the two modalities was 76.5%, 72.6%, and 92.2%, respectively. The specificity of a frozen section analysis and imprint cytology was 100%. The negative predictive value of a frozen section analysis and imprint cytology was 98.7% and 98.5%, respectively. In these settings, the accuracy of the frozen section analysis and imprint cytology in the evaluation of SNB specimens was considered acceptable; however, the sensitivity of the combined approach was higher in comparison to when a frozen section analysis or imprint cytology was performed alone.
Background
Intraoperative evaluation of the axillary sentinel lymph node (SLN) in patients with breast carcinoma reduces the need of re-operations in cases where an axillary completion lymph node dissection (CLND) is indicated. Different methods have been used to determine the SLN status intraoperatively, e.g. frozen section histology (FS) and touch imprint cytology (TIC). The sensitivity of intraoperative TIC examination on SLN is not consistent between different studies and varies according to different tumor histologic subtypes, tumor size and the age of the patient. The aim of this study was to describe the specificity and sensitivity of TIC and to compare TIC sensitivity in the different histological subtypes of breast carcinoma.
Methods
A retrospective review was performed of 1227 consecutive clinically node negative breast cancer patients treated with sentinel lymph node biopsy (SLNB) with intraoperative TIC between the years 2003 and 2008. The SLN was bisected and stained using the May-Grünwald-Giemsa method and immunocytochemically with the antibody MNF-116.
Results
The overall sensitivity of the TIC test was 68.6% and the specificity was 99.8%. There was no statistically significant difference between the detection of SLN metastases from ductal carcinoma versus lobular carcinoma. The sensitivity improved over the period of the study.
Conclusion
TIC is highly specific with an acceptable overall sensitivity. The sensitivity increased under the period of the study and it was higher in cases with larger size of the primary tumor. There was no difference in TIC sensitivity between the different histological subtypes.
Background:
If treatment of the axilla is indicated in patients with breast cancer who have a positive sentinel node, axillary lymph node dissection is the present standard. Although axillary lymph node dissection provides excellent regional control, it is associated with harmful side-effects. We aimed to assess whether axillary radiotherapy provides comparable regional control with fewer side-effects.
Methods:
Patients with T1-2 primary breast cancer and no palpable lymphadenopathy were enrolled in the randomised, multicentre, open-label, phase 3 non-inferiority EORTC 10981-22023 AMAROS trial. Patients were randomly assigned (1:1) by a computer-generated allocation schedule to receive either axillary lymph node dissection or axillary radiotherapy in case of a positive sentinel node, stratified by institution. The primary endpoint was non-inferiority of 5-year axillary recurrence, considered to be not more than 4% for the axillary radiotherapy group compared with an expected 2% in the axillary lymph node dissection group. Analyses were by intention to treat and per protocol. The AMAROS trial is registered with ClinicalTrials.gov, number NCT00014612.
Findings:
Between Feb 19, 2001, and April 29, 2010, 4823 patients were enrolled at 34 centres from nine European countries, of whom 4806 were eligible for randomisation. 2402 patients were randomly assigned to receive axillary lymph node dissection and 2404 to receive axillary radiotherapy. Of the 1425 patients with a positive sentinel node, 744 had been randomly assigned to axillary lymph node dissection and 681 to axillary radiotherapy; these patients constituted the intention-to-treat population. Median follow-up was 6·1 years (IQR 4·1-8·0) for the patients with positive sentinel lymph nodes. In the axillary lymph node dissection group, 220 (33%) of 672 patients who underwent axillary lymph node dissection had additional positive nodes. Axillary recurrence occurred in four of 744 patients in the axillary lymph node dissection group and seven of 681 in the axillary radiotherapy group. 5-year axillary recurrence was 0·43% (95% CI 0·00-0·92) after axillary lymph node dissection versus 1·19% (0·31-2·08) after axillary radiotherapy. The planned non-inferiority test was underpowered because of the low number of events. The one-sided 95% CI for the underpowered non-inferiority test on the hazard ratio was 0·00-5·27, with a non-inferiority margin of 2. Lymphoedema in the ipsilateral arm was noted significantly more often after axillary lymph node dissection than after axillary radiotherapy at 1 year, 3 years, and 5 years.
Interpretation:
Axillary lymph node dissection and axillary radiotherapy after a positive sentinel node provide excellent and comparable axillary control for patients with T1-2 primary breast cancer and no palpable lymphadenopathy. Axillary radiotherapy results in significantly less morbidity.
Funding:
EORTC Charitable Trust.
Sentinel node biopsy (SNB) was initially conceived as excision of the first station axillary lymph node(s) (LN) identified by radioactive and/or blue dye uptake. The definition was subsequently enlarged to also include palpable lymph nodes in the vicinity of sentinel node(s) (SN). We reasoned that the excision of this combination of nodes might be best achieved by sampling the lower axilla.
Each patient underwent low axillary sampling (LAS) and identification of SN in the excised specimen followed by complete axillary lymph node dissection (ALND). LAS was defined as excision of all fibrofatty tissue overlying the second digitation of serratus anterior below the intercostobrachial nerve and was carried out following a pre-operative injection of radioactive colloid and an intra-operative injection of blue dye. Blue and/or hot nodes (B&/HN) in the dissected tissue and remaining axilla, along with any palpable nodes within the sampled tissue, were defined as SN. The primary endpoint of the study was to compare false negative rates (FNR) of SN with that of LAS in predicting axillary LN status (NCT00128362).
The study was performed between March 2004 and December 2011 in 478 women with clinically node negative axilla. On histopathological evaluation the median tumor size was 2.5 cm and axillary nodal metastases were found in 34.1% of patients. The FNR of SNB (12.7%, 95% CI 8.1-19.4) and LAS (10.5%, 95% CI 6.6-16.2) were not significantly different (p = 0.56). The FNR of B&/HN alone, without palpable nodes, (29.0%, 95% CI 22.5-36.6) was significantly inferior to those of SNB (p = 0.0007) and LAS (p = 0.0003).
LAS is as accurate as SNB in predicting axillary LN status in women with clinically node negative operable breast cancer. Confining SNB procedure to excision of B&/HN, significantly increases the risk of leaving behind metastatic lymph nodes in the axilla. LAS is an effective and low cost procedure that minimizes axillary surgery and can be implemented widely. Registry Name: Clinicaltrials.gov. Registration Number: NCT00128362.
To investigate the long-term survival rate of node-positive (pN+) breast cancer treated by locoregional therapy alone, we made an attempt to identify all such patients followed up for at least 15 years after treatment in a defined geographical area (city of Turku, Southwestern Finland) and time period (1945-79) using the files of the local hospitals and the Finnish Cancer Registry. The clinical and autopsy records and histological slides of 1172 women diagnosed with breast cancer in the city were reviewed. From this cohort we identified 339 women with unilateral node-positive breast cancer treated with locoregional therapy without systemic adjuvant therapy. The relative survival rate of the cohort compared with the general female population matched for age and year of follow-up was calculated. The 15- and 30-year survival rates corrected for known intercurrent deaths were 26% (95% CI, 21-31%) and 21% (16-26%) respectively, and the relative survival rates 23% and 21% respectively. None of the patients with pN2 disease survived for 15 years, whereas the 30-year corrected survival rate in pN1 disease was 24% (18-30%). Women with pT1N1M0 cancer had as high as 59% (43-75%) 15-year survival rate corrected for intercurrent deaths. A trend for improving survival was found by the decade of diagnosis. The results indicate that a considerable proportion of women with pN1 breast carcinoma treated with locoregional therapy alone become 30-year survivors and are probably cured. Adequate locoregional treatment is mandatory in the care of node-positive breast cancer.
To evaluate aspects of the current practice of sentinel lymph node (SLN) pathology in breast cancer via a questionnaire based survey, to recognise major issues that the European guidelines for mammography screening should address in the next revision.
A questionnaire was circulated by mail or electronically by the authors in their respective countries. Replies from pathology units dealing with SLN specimens were evaluated further.
Of the 382 respondents, 240 European pathology units were dealing with SLN specimens. Sixty per cent of these units carried out intraoperative assessment, most commonly consisting of frozen sections. Most units slice larger SLNs into pieces and only 12% assess these slices on a single haematoxylin and eosin (HE) stained slide. Seventy one per cent of the units routinely use immunohistochemistry in all cases negative by HE. The terms micrometastasis, submicrometastasis, and isolated tumour cells (ITCs) are used in 93%, 22%, and 71% of units, respectively, but have a rather heterogeneous interpretation. Molecular SLN staging was reported by only 10 units (4%). Most institutions have their own guidelines for SLN processing, but some countries also have well recognised national guidelines.
Pathological examination of SLNs throughout Europe varies considerably and is not standardised. The European guidelines should focus on standardising examination. They should recommend techniques that identify metastases > 2 mm as a minimum standard. Uniform reporting of additional findings may also be important, because micrometastases and ITCs may in the future be shown to have clinical relevance.
The study aimed to evaluate intraoperative immunohistochemistry (IHC) staining of sentinel nodes in primary breast cancer surgery. We analysed retrospectively 1209 consecutive sentinel node procedures and compared the rate of late positive metastases in sentinel node biopsy (SNB) and the duration of the surgical procedures before (n=706) and after (n=503) introducing intraoperative IHC on frozen section. We also did a cost analysis. Intraoperative IHC staining led to a lowering of the late positive SNB rate. Introducing IHC gave a decrease in the late positive rate from 93 to 52% (p<0.0001) for isolated tumour cell metastasis, from 56 to 36.4% (p<0.02) for micrometastasis, and from 16 to 5% (p<0.01) for macrometastasis. The surgical procedures were slightly prolonged for lumpectomies but not for mastectomies after introducing intraoperative IHC staining. The cost analysis showed an overall cost saving of approximately 40%. In conclusion, intraoperative IHC staining of the SNB lowered the late positive rate and gave an overall cost saving.
The ACOSOG Z0011 study, heralded as a “practice changing” trial, suggested that women with T1–2 breast cancer with 1–2 SLN+, undergoing breast conservation therapy, need not be offered further ALND. However, whether these results are applicable to all women in the Indian setting, it remains debatable. A retrospective audit of all cN0 operated from 2013 to 2018 was conducted. We analyzed the percentage of additional LN positive (LN+) in the ALND group and compared it to the ACOZOG Z11 trial. Of the 2350 cN0 with EBC who underwent LAS, 687 (29%) had positive lymph nodes on final histopathology. Five hundred ninety-seven (86.9%) patients had 1–2 LN+, 40 (5.8%) patients had 3 LN+, and 50 (7.3%) had 4 or more nodes positive. Demographic features in the ACOSOG Z11 are different from those in our study, looking at ACOZOG Z11 versus our cohort—median pT 1.7 cm versus 3 cm, 45% micrometastasis versus 99.16% macrometastasis, and 28–30% grade 3 tumors versus 73.7%. In our cohort 31.82% of the 1–2 LN positive had additional LN+ on ALND. Keeping in mind the difference in clinicopathological features between our cohort and that of ACOZOG Z0011 and that 31.82% of women had additional LN+ on ALND, it may not be appropriate to apply the results of the ACOSOG Z0011 trial directly to our general population. Possibly, only a select subset of patients who match the trial population of the ACOSOG Z11 could be offered observation of the axilla and validated nomograms can be used to identify high-risk patients.
Importance
The results of the American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) trial were first reported in 2005 with a median follow-up of 6.3 years. Longer follow-up was necessary because the majority of the patients had estrogen receptor–positive tumors that may recur later in the disease course (the ACOSOG is now part of the Alliance for Clinical Trials in Oncology).
Objective
To determine whether the 10-year overall survival of patients with sentinel lymph node metastases treated with breast-conserving therapy and sentinel lymph node dissection (SLND) alone without axillary lymph node dissection (ALND) is noninferior to that of women treated with axillary dissection.
Design, Setting, and Participants
The ACOSOG Z0011 phase 3 randomized clinical trial enrolled patients from May 1999 to December 2004 at 115 sites (both academic and community medical centers). The last date of follow-up was September 29, 2015, in the ACOSOG Z0011 (Alliance) trial. Eligible patients were women with clinical T1 or T2 invasive breast cancer, no palpable axillary adenopathy, and 1 or 2 sentinel lymph nodes containing metastases.
Interventions
All patients had planned lumpectomy, planned tangential whole-breast irradiation, and adjuvant systemic therapy. Third-field radiation was prohibited.
Main Outcomes and Measures
The primary outcome was overall survival with a noninferiority hazard ratio (HR) margin of 1.3. The secondary outcome was disease-free survival.
Results
Among 891 women who were randomized (median age, 55 years), 856 (96%) completed the trial (446 in the SLND alone group and 445 in the ALND group). At a median follow-up of 9.3 years (interquartile range, 6.93-10.34 years), the 10-year overall survival was 86.3% in the SLND alone group and 83.6% in the ALND group (HR, 0.85 [1-sided 95% CI, 0-1.16]; noninferiority P = .02). The 10-year disease-free survival was 80.2% in the SLND alone group and 78.2% in the ALND group (HR, 0.85 [95% CI, 0.62-1.17]; P = .32). Between year 5 and year 10, 1 regional recurrence was seen in the SLND alone group vs none in the ALND group. Ten-year regional recurrence did not differ significantly between the 2 groups.
Conclusions and Relevance
Among women with T1 or T2 invasive primary breast cancer, no palpable axillary adenopathy, and 1 or 2 sentinel lymph nodes containing metastases, 10-year overall survival for patients treated with sentinel lymph node dissection alone was noninferior to overall survival for those treated with axillary lymph node dissection. These findings do not support routine use of axillary lymph node dissection in this patient population based on 10-year outcomes.
Trial Registration
clinicaltrials.gov Identifier: NCT00003855
Breast cancer treatment has a long, fascinating history. Multimodality therapy utilizes surgery, systemic therapy and radiation. The role of surgical axillary staging in breast cancer continues to evolve. Secondary to randomized, controlled trials, sentinel lymph node biopsy is the standard for surgical staging in patients with a clinically negative axilla. Traditionally, when sentinel nodes revealed metastases, a complete axillary lymph node dissection was performed. Recently however, the value of complete axillary dissection is being challenged.
PATIENTS AND METHODS: Patients with breast cancer and clinically negative axillary were recruited for sentinel lymph node biopsy (SLNB). All nodes were examined by intraoperative FS and underwent further paraffin sectioning.
Many sentinel lymph node biopsies (SLNBs) are evaluated intraoperatively by frozen section, which may impact the need for further axillary dissection (AD). However, the need for AD in patients with small metastases has been recently called into question, meaning that frozen SLNB may be unnecessary. Furthermore, frozen section can compromise tissue for further study. At our institution, we grossly evaluate all SLNB and freeze half of the node. Here, we evaluate the frozen SLNB discrepancy rate using this method, focusing on cause of discrepancy and need for further surgery. We reviewed surgical pathology records for all breast cancer resections with frozen section of SLNB examined from 2003 to 2012. For cases with a frozen section discrepancy, we compiled clinicopathologic data. In total, 1,940 cases involved frozen section evaluation of SLNB. In 95 cases (4.9 % of total cases, 23.8 % of positive node cases), the SLNB was called negative on frozen but positive on final examination (false negatives). The majority of missed metastases are isolated tumor cells or micrometastases. A trend was observed toward fewer patients receiving completion AD after a discrepant frozen SLNB in the later years of the study. The protocol of freezing half of a SLNB is a reasonable method, with results similar to or better than other studies. The main adverse outcome is the need for separate AD; however, additional positive nodes are uncommon. The trend of fewer patients getting additional AD after a discrepant frozen SLNB suggests that clinicians may be using this information differently recently.
Background:
Current guidelines recommend full axillary lymph node dissection (ALND) whenever the SLN is positive for metastases. In our institute, we aim to complete surgery in a single setting and base the decision for ALND on the intraoperative FS analysis of the SLN. In this study, we evaluate the efficacy this practice in terms of the accuracy of FS analysis, patient recall rate, and additional time required for FS analysis.
Materials and methods:
Retrospective review was performed of 586 patients who underwent SLN biopsy at our institution from January 1, 2006 to December 31, 2010. Intraoperative FS analysis was routinely performed in all cases with a preoperative diagnosis of invasive breast cancer and in selected cases of ductal carcinoma in situ according to surgeon preference.
Results:
The SLN was positive for metastases in 123 (22.7%) patients; this was identified on FS analysis in 107 patients. FS analysis had a sensitivity of 87.0% and specificity of 100% and resulted in a patient recall rate of 3%. Micrometastasis accounted for most of the false negative FS results. These deposits were mostly detected only on deeper sectioning of the permanent sections of the SLN. An invasive lobular histology and lymphovascular invasion were found to be independent predictors of a false negative FS on multivariate analysis (P < .01). Intraoperative FS did not significantly prolong operating times.
Conclusion:
Intraoperative FS analysis is an accurate and efficient means of rapid SLN assessment and allows ALND to be completed in a single setting.
Intra-operative frozen section plays an important role in the management of surgical patients and yet it must be used prudently to avoid the indiscriminate usage of this important technique. As it is subjected to many limitations in comparison to the paraffin embedded tissue sections, this review aims to highlight the important concepts and principle of intra-operative frozen section consultation as well as discussing the limitations of this technique. This will then allow the endusers of this technique to be more informed and more selective in their decisions when requesting for a frozen section report.
Sentinel lymph node (SLN) biopsy has become the standard of care for breast carcinoma management, as it precludes the negative morbid effects-including decreased shoulder range of motion, lymphedema, and paresthesias-of unnecessary axillary lymph node dissection. However, the method of pathologic evaluation of the lymph node has been scrutinized to obtain the greatest sensitivity, specificity, and negative predictive value, ultimately for the benefit of the patient. This retrospective study analyzed 488 biopsies completed by two surgeons and read by multiple pathologists affiliated with Pathologists Biomedical Laboratories. When metastatic disease was not grossly obvious, analysis of the SLN began with touch imprint cytology and, if necessary, a frozen section analysis. On the subsequent day, three levels of the SLN were analyzed with hematoxylin and eosin stain and immunohistochemistry with cytokeratin AE1-3 and the appropriate control. Touch imprint cytology and/or frozen section analysis (where applicable) correctly identified 78 of 89 macrometastases, with a sensitivity of 88%, specificity of 100%, and negative predictive value of 97%. Sensitivity was 72% for micrometastases and 60% for isolated tumor cells, each with 100% specificity. In conclusion, the sensitivity and specificity of SLN biopsy at our institution compares with the higher end of percentages reported in the literature.
Accurate intraoperative pathologic examination of sentinel lymph nodes (SLNs) has been an important tool that can reduce the need for reoperations in patients with SLN-positive breast cancer. The objective of the current study was to determine the accuracy of intraoperative frozen section (IFS) of SLNs during breast cancer surgery.
The authors retrospectively reviewed the records of 326 patients with breast cancer who underwent IF analysis of SLNs at a single institution. Then, they conducted a meta-analysis that included 47 published studies of IFS of SLNs in patients with breast cancer.
Hematoxylin and eosin (H&E) staining revealed metastasis in SLNs in 99 patients (30.4%), including 61 patients with macrometastasis (MAM) (>2 mm) (the MAM group) and 38 patients with micrometastasis (Mi) or isolated tumor cell (ITC) deposits (the Mi/ITC group). The overall sensitivity of the institutional series was 60.6% (60 of 99 patients), and overall specificity was 100% (227 of 227 true negatives). The sensitivity of IFS was significantly lower in the Mi/ITC group (28.9%) than in the MAM group (80.3%; P < .0001). According to the meta-analysis of published studies and data from the author's institution (47 studies, for a total of 13,062 patients who underwent SLN dissection with IFS of SLNs), the mean sensitivity was 73%, and the mean specificity was 100%. The mean sensitivity was 94% for the MAM group and 40% for the Mi/ITC group.
IFS of SLNs was more reliable for detecting MAM than for detecting Mi/ITC deposits. It lacked sufficient accuracy to rule out Mi/ITC deposits.
A population-based study was performed to assess the likelihood of axillary lymph node metastases in patients with clinically negative lymph nodes, according to patient age, tumor size and site, estrogen receptor status, histologic type and mode of detection. Data were obtained from the population-based Eindhoven Cancer Registry. During the period 1984-1997, 7680 patients with invasive breast cancer were documented, 6663 of whom underwent axillary dissection. Of the 5125 patients who were known to have clinically negative lymph nodes and underwent axillary dissection, 1748 (34%) had positive lymph nodes at pathological examination. After multivariate analysis, histologic type, tumor size, tumor site and the number of lymph nodes in the axillary specimen remained as independent predictors of the risk of nodal involvement (P < 0.001). Lower risks were found for patients with medullary or tubular carcinoma, smaller tumors, a tumor in the medial part of the breast and patients with less than 16 nodes examined. This study gives reliable estimates of the risk of finding positive lymph nodes in patients with a clinically negative axilla. Such information is useful when considering the need for axillary dissection and to predict the risk of a false-negative result when performing sentinel lymph node biopsy.
The aim of the study was to evaluate total hospital costs of three different sentinel node biopsy (SNB) protocols compared to those of diagnostic axillary lymph node dissection (ALND).
The study included 237 consecutive breast cancer patients who underwent SNB with frozen section diagnosis. The sequence of the treatment procedures for each patient was recorded. The sequences of treatment procedures for the same patients were evaluated using three hypothetical scenarios: diagnostic ALND, SNB without frozen section diagnosis and SNB as day case surgery prior to the breast operation. The total hospital costs were calculated in all protocols.
The hospital costs per patient were 3750euro;. The hospital costs per patient would have been 3020euro; when using the ALND model, 4087euro; had the frozen section not been applied and 4573euro; using 'SNB as day case surgery' model. The costs with or without frozen section diagnosis would have been equal with a threshold false negative rate of 35%.
SNB seems to be associated with higher hospital costs than diagnostic ALND. Frozen section diagnosis seems to be worthwhile as long as the false negative rate is <35%.
Although many questions regarding sentinel lymph node (SLN) biopsy in breast cancer have been answered by observational studies and, increasingly, by prospective trials, the role of intraoperative SLN assessment remains a matter of debate. Here we report in detail the results of intraoperative SLN assessment by frozen section (FS), with particular attention to variations in sensitivity and yield by histologic subtype, by tumor size, and by other clinicopathologic parameters.
Five thousand two hundred ninety-eight consecutive patients with clinical stage T1-3N0 invasive breast carcinoma had SLN biopsy with intraoperative FS at Memorial Sloan Kettering Cancer Center between 1996 and 2004. We report the results of FS by sensitivity (the proportion of all positive SLN detected by FS) and by yield (the proportion of all FS procedures in which the FS was positive).
The sensitivity of FS was 61% overall, was higher for invasive duct (ID) than for invasive lobular (IL) cancers (62% vs. 52%; P = 0.006), and was marginally lower for favorable subtypes (46%; P = 0.26). The yield of FS was 21% overall, with no difference between ID and IL cancers (22% vs. 21%; P = 0.49), and with a substantially lower yield for favorable subtypes (3%; P < 0.001). The yield of FS increased with tumor size for ID and IL cancers (P < 0.001), but not for favorable subtypes. For both ID and IL cancers, the sensitivity and yield of FS were significantly higher with younger patient age, increasing tumor size, and lymphovascular invasion. The yield of FS was <10% for all patients with ID or IL tumors < or =1 cm in size who were older than 60 years of age. Among all FS-positive patients, only 45% were identified by the first FS, whereas 91% were cumulatively identified by the first, second, or third FS.
For patients with ID and IL cancers, the overall sensitivity of FS is >50%, but the yield of FS is <10% for individuals > or =60 years of age with T1a/b tumors. Intraoperative FS may not be worthwhile for this low-yield subset, especially for patients with invasive breast cancer of favorable type.
Axillary sentinel lymph node biopsy (SLNB) has been adopted as a suitable alternative to traditional level I and II axillary dissection in the management of clinically node-negative (N0) breast cancers. There are two current techniques used to identify the sentinel node(s): radiopharmaceutical, technetium sulfur colloid, and isosulfan blue dye (used in the United States) and technetium-labeled albumin and patent blue dye (used in Europe). (The labeled albumin is not U.S. Food and Drug Administration [FDA] approved in the United States.) SLNB to replace axillary dissection should only be performed by surgeons and patient management teams with appropriate training and experience. Although both radiocolloid and blue dye are used together by most surgeons, and training should be in both techniques, some experienced surgeons use one or the other almost exclusively. In addition, surgical pathologists must recognize the need to examine these small specimens with great care, using a generally adopted protocol. Imprint cytology or frozen sections may be used, followed by additional sections for light microscopy. Immunochemical staining with cytokeratin or other techniques to identify "submicroscopic" metastasis is often used, but the results should not be used to influence clinical decisions with respect to adjuvant therapy. "Failed" SLNB implies the surgeon's failure to identify the sentinel nodes, in which case a complete dissection is performed. A "false-negative" SLNB implies the finding of metastasis in the excised sentinel nodes by light microscopy after a negative frozen section examination. Whether a false-negative SLNB mandates completion axillary dissection is controversial, with clinical trials currently under way to answer this question. Although SLNB was initiated to accompany breast-conserving treatment, it is equally useful in patients undergoing mastectomy. It is more difficult to perform with mastectomy. When using blue dye only, SLNB may require a separate incision because of time constraints between injection and identification of the blue-stained nodes; radiocolloid usually does not. Completion axillary dissection after false-negative SLNB is more difficult after mastectomy. SLNB is a useful procedure that may save 70% of women with clinically negative (N0) axillae and all of those with pathologically negative axillae from the morbidity of complete axillary dissection. Ideally the sentinel nodes should be able to identified in more than 95% of patients, with a false-negative rate of less than 5%. Until these rates can be achieved consistently, however, surgeons should not abandon traditional axillary dissection.