Frozen Section Analysis Of Margins Research Articles

Abstract PO2-23-01: Selective cavity margin shaving: effective method to maintain balance between cosmesis and negative margin in breast conserving surgery

Abstract Background: Breast conserving surgery (BCS), which became the mainstay of breast cancer surgery, both cosmesis and margin negativity are significant issues. Firstly, it is well known that negative resection margin is crucial for reducing local recurrence after BCS. Therefore, there has been numerous attempts to secure negative margin, such as specimen mammography, frozen section margin analysis, and cavity margin shaving. Regarding cosmesis, wider excision to secure negative margin could disrupt cosmesis especially in Asian patients with relatively smaller breast, and minimizing excision volume is necessary for optimal cosmetic outcome. Our center adopted the concept of selective cavity margin shaving (SCMS) to achieve negative margin while optimizing cosmetic result. Method: 606 female patients with non-metastatic, unilateral breast cancer were prospectively collected and underwent BCS with SCMS from October, 2012 to December, 2020. The medical record was retrospectively reviewed, and we assessed positive margin rate and local recurrence. During BCS, the surgeon excised gross margin of 1~2cm around the cancer, and assessed the proximity of the margin through gross examination. If sufficient margin was not obtained, cavity shaving was performed in the close margin, while shaving from retrieved specimen was conducted on the sufficient margin side. Additionally, circumferential margin frozen analysis was carried out, and further excision was performed until a negative margin was achieved or when only focal DCIS involvement remained. Result: The mean ± SD age of the patients was 52.47 ± 9.92 years and mean follow-up period was 59.98 ± 26.59 months. 56 patients (9.24%) received neoadjuvant chemotherapy. 123 patients (20.29%) got positive margin for invasive cancer or DCIS in frozen section margin analysis and 97 patients (16.01%) underwent intraoperative re-excision. There was discordance between frozen and permanent section margin analysis in 48 patients (7.92%), and 7 patients (1.16%) underwent post-operative re-excision operation. Local recurrence occurred in 11 patients (1.82%), which is significantly lower compared to previously reported outcomes after BCS. Presence of lympho-vascular invasion, neoadjuvant chemotherapy, and margin involvement of invasive cancer in permanent section analysis were strongly related with local recurrence. Conclusion: In conclusion, SCMS and frozen section margin analysis demonstrated low positive margin rate and reduced re-excision rate. The local recurrence was also lower compared to conventionally reported rate after BCS. Selective cavity margin shaving is an oncologically safer and effective surgical method with minimized cosmetic deformity. Table 1. Baseline patient characteristics Table2. Univariate and multivariate analysis of factors associated with local recurrence Table2. Univariate and multivariate analysis of factors associated with local recurrence by Cox proportional hazard model. Citation Format: Dabin Kim, Zisun Kim, Sung Mo Hur, Cheol wan Lim. Selective cavity margin shaving: effective method to maintain balance between cosmesis and negative margin in breast conserving surgery [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-23-01.

A Novel Technique for Intraoperative Assessment of Surgical Margin Using Lugols Iodine and Frozen Section Methods in Oral Squamous Cell Carcinoma

Surgery is considered to be the primary mode of treatment of head and neck malignancies and the ultimate aim of surgical resection is to obtain a tumor-free margin. No uniform criteria to define a clear surgical margin exist among practicing surgeons. This study intends to find the adequacy of surgical margin marking intraoperatively by Lugol’s iodine solution considering the frozen section method for oral squamous cell carcinoma (OSCC). Intraoperative staining with Lugol’s iodine and Frozen section analysis of margins of the surgical bed was negative in anterior, superior, and inferior specimens in all the cases, except in one case (4.3%), a posterior margin was found to be positive (unstained) for tumor. The chi-square value of the Lugol’s stained margins following resection of the tumor and negative results of frozen section analysis of the same was found to be statistically significant with the P value <0.001. Hence, we conclude that Lugol’s iodine helps in obtaining a clear surgical margin intra-operatively where inter-surgeons bias/judgment errors regarding safe margin can be avoided, especially in cases where the frozen section is not feasible.

Frozen sections in head and neck surgery and the impact of intraoperative analysis on final resection margins: An institutional study

Frozen section (FS) analysis is an indispensable tool for intraoperative patient management.To assess the utilisation of head and neck FS analysis, with a particular focus on the concordance rate between the intraoperative FS margin analysis and the final FFPE results. Additionally, to determine whether FS analysis had any impact on intraoperative patient management.Lastly, to determine the impact of the FS analysis on the final margin status of resection specimens. Histopathology reports from January 2015 to December 2018 were reviewed at Pretoria Oral and Dental Hospital to analyse all FS requests involving the head and neck region. Captured data was analysed to determine the concordance rate, discordance rate, and FS deferral rates, with correlations performed using the Chi-square test. Eighty-two frozen section cases were reviewed with a total of 312 FS tissue sections performed. The majority (73%) of the FS requests were from the Maxillofacial and Oral Surgery (MFOS) department for the assessment of surgical margins. The FS-FFPE concordance and discordance rates were at 97.5% and 2.4% respectively, with a deferral rate of 1.2%. Additional surgical margins were only received in 16 of the 26 cases with positive margins on intraoperative FS analysis. There was no statistically significant correlation between intraoperative FS positive margin status and advanced pathological T staging. The concordance rate between intraoperative FS margin analysis and final FFPE results were within an acceptable range. In a significant number of cases, the intraoperative FS margin analysis did not influence further surgical management.

Analysis of Esophagectomy Margin Practice and Survival Implications

The objective of this study was to determine how thoracic surgeons manage intraoperative esophagectomy positive margins and how these decisions may relate to overall survival and progression-free survival in esophageal cancer. A survey was sent to thoracic surgeons to understand the management of intraoperative positive esophagectomy margins. Primary data at two high-volume esophageal cancer institutions from 1994 to 2017 were retrospectively reviewed to identify patients who had intraoperative positive frozen section margins during esophagectomy. Patient characteristics and survival data were collected and analyzed. Overall survival and progression-free survival were assessed using a Cox model. Eighty-five percent of thoracic surgeons responding to a survey reported the utilization of frozen pathologic evaluation during esophagectomy with attempts at re-resection to achieve negative margin. Our esophagectomy database identified 94 patients with intraoperative positive margins. Of those re-resected (n= 67, 63%), 44 patients (46.8%) were converted to R0 resections. overall survival was improved for patients in the R0 group (13 months) vs R+ group (3.4 months, P= .04). Progression-free survival was also improved between the R0 group (8.6 months) and the R+ group (2.2 months, P= .03). In a multivariable analysis for progression-free survival, margin status was an independent predictor of survival (hazard ratio 3.13, P= .03). From a thoracic surgery survey, 85% of surgeons use intraoperative frozen section margin analysis to guide surgical decision making during an esophagectomy. Analyzing patients with a positive margin discovered during esophagectomy suggests that esophageal cancer patients who can undergo re-resection to a negative margin have increased progression-free survival. The final margin appears to be related to progression-free survival.

Intraoperative Frozen Section Analysis for the Excision of Nonmelanoma Skin Cancer: A Single-center Experience

INTRODUCTION: Recurrence rates for nonmelanoma skin cancers (NMSCs) following Mohs’ micrographic surgery (MMS) are consistently lower than standard surgical excision. However, variations in the availability of MMS, waiting times, and costs continue to affect patient preference between treatment modalities. Furthermore, MMS commonly requires delayed reconstruction leading to additional surgeries that increases the risk of adverse outcomes. To achieve curative resection while ensuring optimal cosmetic outcomes, plastic surgeons may utilize intraoperative frozen section-guided excision to forego extensive or delayed reconstruction. METHODS: Patients presenting with NMSCs undergoing wide local excision using intraoperative frozen section margin analysis (IFSA) at our institution from October 2008 to November 2016 were retrospectively reviewed. Analyzed data included IFSA results, final permanent section histopathology, number of resections required for clear margins, and recurrence rates. Excisions were performed by 1 of 3 plastic surgeons and analyzed by 1 of 8 pathologists. RESULTS: A total of 171 patients and 204 lesions were included in the study. Mean patient age was 72 years. Operative reports demonstrated that 79.9% of margins were clear after one excision. The remaining 20.1% of cases with residual positive margins after primary excision were identified using IFSA and were re-excised until negative margins were achieved. Of the 20.1%, a total of 11.8% required a second excision and 8.3% required ≥3 excisions. Intraoperative frozen section results revealed 1 false-positive case representing a rate of 0.49% and 5 false-negative results leading to a rate of 2.45%. Fifteen patients had local recurrence; a rate of 7.35%. Frozen section sensitivity was 89.79% and specificity was 99.35%. The positive predictive value was 97.78% with a negative predictive value of 96.85%. Patients had a mean follow-up of 39 months. CONCLUSION: The resection results and recurrence rate of NMSCs excised at our institution are comparable to national trends using standard surgical excision. The findings suggest that standard surgical excision using intraoperative frozen section analysis is a safe and effective alternative to MMS.

Positive fresh frozen section margins as an adverse independent prognostic factor for local recurrence in oral cancer patients.

To access 1) the value of further surgical resection (completion surgery) in cases with a positive intraoperative margin analysis, and 2) whether cancers that undergo completion surgery following positive intraoperative margin analysis with subsequent negative margins should be considered true margin-negative (R0) resections in terms of adjuvant treatment planning. Retrospective analysis of patients with primary oral cancer. One hundred and fifty-one patients underwent primary surgical resection of oral squamous cell carcinoma with intraoperative margin examination. In all cases for which frozen section margin analysis was positive, an extended resection was performed. Only patients with clear final margins were included in the study. The intraoperative analysis of surgical margins revealed that cancer-free margins were achieved in 123 cases (81.5%). In 28 specimens (18.5%), the surgical margins were positive. Local recurrence was observed in 28 (18.5%) patients, whereas regional recurrence developed in 30 (19.9%) patients. Factors significantly (P < 0.05) increased the risk of local recurrence: advanced stage of the disease (III/IV), node N-positive status, lymphovascular invasion and positive fresh frozen surgical margins. On multivariate analysis, only positive fresh frozen surgical margins remained significant independent adverse factors. Our study demonstrates that positive fresh frozen margins, regardless of re-resection to R0 status, could be a powerful adverse factor that determines an aggressive nature of the tumor. This feature should be taken into consideration in adjuvant treatment planning. The greatest impact this could have is in borderline clinical situations for which the indication for adjuvant treatment may be questionable. 4. Laryngoscope, 128:1093-1098, 2018.

Assessment of frozen section margin analysis during olfactory neuroblastoma surgery.

1) assess the performance of the intraoperative frozen section procedure to correctly classify biopsies obtained during olfactory neuroblastoma (ONB) surgery; 2) define the relationship between posttest probabilities and pretest probabilities from frozen section analysis; and 3) review incorrectly classified specimens. Study of diagnostic accuracy. We searched our institution's pathology database for patients who had ONB surgery between January 1, 2000 and November 16, 2012. We only included patients who had a definitive diagnosis of ONB prior to surgery and frozen sections obtained during surgery. All frozen sections in this study had corresponding permanent sections available to serve as a gold standard. This database was analyzed to obtain classification statistics. The confidence intervals for classification performance were obtained using the bootstrap sampling method. Confidence intervals for posttest probability curves were derived using the Taylor series expansion. Finally, we obtained and reviewed the slides from ambiguous or incorrect reads. A total of 459 specimens from 33 patients were analyzed. We found the following performance characteristics: sensitivity: 0.89 (0.81, 0.94); specificity: 0.96 (0.94, 0.98); accuracy: 0.95 (0.92, 0.96); likelihood ratio positive: 24.4 (14.5, 44.1); prevalence: 0.20 (0.17, 0.25); positive predictive value: 0.86 (0.78, 0.92); and negative predictive value: 0.97 (0.95, 0.99). Histopathologic review revealed that crush artifacts and inadequate specimen size were major sources of incorrect reads. We found frozen section assessment of ONB specimens to be an excellent tool for the assessment of intraoperative margins. NA. Laryngoscope, 127:1735-1741, 2017.

Economic Implications of Widespread Expansion of Frozen Section Margin Analysis to Guide Surgical Resection in Women With Breast Cancer Undergoing Breast-Conserving Surgery.

In the current health care environment, cost effectiveness is critically important in policy setting and care of patients. This study performed a health economic analysis to assess the implications to providers and payers of expanding the use of frozen section margin analysis to minimize reoperations for patients undergoing breast cancer lumpectomy. A health care economic impact model was built to assess annual costs associated with breast lumpectomy procedures with and without frozen section margin analysis to avoid reoperation. If frozen section margin analysis is used in 20% of breast lumpectomies and under a baseline assumption that 35% of initial lumpectomies without frozen section analysis result in reoperations, the potential annual cost savings are $18.2 million to payers and $0.4 million to providers. Under the same baseline assumption, if 100% of all health care facilities adopted the use of frozen section margin analysis for breast lumpectomy procedures, the potential annual cost savings are $90.9 million to payers and $1.8 million to providers. On the basis of 10,000 simulations, use of intraoperative frozen section margin analysis yields cost saving for payers and is cost neutral to slightly cost saving for providers. This economic analysis indicates that widespread use of frozen section margin evaluation intraoperatively to guide surgical resection in breast lumpectomy cases and minimize reoperations would be beneficial to cost savings not only for the patient but also for payers and, in most cases, for providers.

Diagnostic accuracy and utility of intraoperative microscopic margin analysis of gastric and esophageal adenocarcinoma.

Positive resection margins are amongst the strongest predictors of cancer-related mortality for adenocarcinoma of the stomach and esophagus. Although intraoperative pathology consultation with frozen section of margins can predict final permanent section pathology, the accuracy of this approach is not known. We sought to determine the diagnostic accuracy of frozen section margin analysis in esophagogastric adenocarcinoma and the impact that it had on surgical therapy. Patients with resection of esophagogastric adenocarcinoma at a single centre from 1998 to 2008 were identified. Clinicopathologic data were collected. Frozen section results were compared to permanent section assessment, and sensitivity, specificity, positive, and negative predictive values were calculated. Patients with positive margins by frozen section were reviewed to assess the impact on surgical decision-making. Of 220 patients who underwent surgery for adenocarcinoma of the esophagus and stomach (esophagus: 34/220, EGJ: 106/220, stomach 80/220), 56% had an intraoperative consultation. Of these 122 patients, 66% underwent frozen section. All errors on frozen section occurred on the interpretation of the proximal margin. The diagnostic accuracy of frozen section at the proximal margin was 93% with sensitivity=67%, specificity=100%, positive predictive value=100%, and negative predictive value=91%. Signet ring cells were present in 83% of false-negative readings. Surgical management was altered in 10 of the 13 of patients who had a true positive frozen section and 9 of these patients were converted to R0 resections. Although very specific, negative results on frozen section require greater caution when signet ring cells are present. For esophagogastric adenocarcinoma, frozen section alters management and may increase the rate of complete resection.

Assessment of the Performance of Frozen Section Margin Analysis during Esthesioneuroblastoma Surgery

Assessment of the Performance of Frozen Section Margin Analysis during Esthesioneuroblastoma Surgery

The Utility of Frozen Section Margin Analysis in Transoral Robotic Surgery

Objective: Determine the benefit of frozen section margin analysis on oncologic specimens resected via Transoral Robotic Surgery (TORS). Method: A retrospective, single institution chart review of 150 consecutive patients with upper aerodigestive tract malignancies who underwent Transoral Robotic Surgery with intraoperative frozen section margin analysis between April 2007 and November 2010. Results: A total of 105 of the 150 cases were found to have negative tumor margins on initial tumor extripation. None of these patients were found to have delayed positive margins on permanent section analysis. Forty-five patients were found to have 1 or more positive margins on frozen section analysis following initial tumor, and/or tumor margin resection. These positive margins were all re-resected until frozen section pathology was consistent with tumor free margins (no evidence of CIS or invasive carcinoma). Of the 45 patients who underwent re-resection of initial tumor involved margins, 2 were found to have positive margin disease on permanent section pathology. Conclusion: Frozen section margin analysis is a critical intraoperative tool in Transoral Robotic Surgery that accurately accesses margin free tumor resection. This technique allows for a single operative encounter consisting of initial tumor biopsy with rapid diagnosis, followed by immediate complete primary tumor resection with synchronous neck dissection when oncologically indicated.

Frozen section analysis of margins for head and neck tumor resections: reduction of sampling errors with a third histologic level

Frozen section analysis is an essential tool for assessing margins intra-operatively to assure complete resection. Many institutions evaluate surgical defect edge tissue provided by the surgeon after the main lesion has been removed. With the increasing use of transoral laser microsurgery, this method is becoming even more prevalent. We sought to evaluate error rates at our large academic institution and to see if sampling errors could be reduced by the simple method change of taking an additional third section on these specimens. All head and neck tumor resection cases from January 2005 through August 2008 with margins evaluated by frozen section were identified by database search. These cases were analyzed by cutting two levels during frozen section and a third permanent section later. All resection cases from August 2008 through July 2009 were identified as well. These were analyzed by cutting three levels during frozen section (the third a ‘much deeper’ level) and a fourth permanent section later. Error rates for both of these periods were determined. Errors were separated into sampling and interpretation types. There were 4976 total frozen section specimens from 848 patients. The overall error rate was 2.4% for all frozen sections where just two levels were evaluated and was 2.5% when three levels were evaluated (P=0.67). The sampling error rate was 1.6% for two-level sectioning and 1.2% for three-level sectioning (P=0.42). However, when considering only the frozen section cases where tumor was ultimately identified (either at the time of frozen section or on permanent sections) the sampling error rate for two-level sectioning was 15.3 versus 7.4% for three-level sectioning. This difference was statistically significant (P=0.006). Cutting a single additional ‘deeper’ level at the time of frozen section identifies more tumor-bearing specimens and may reduce the number of sampling errors.

Extramammary Paget’s Disease

I read with interest the article by Pierie and coauthors concerning extramammary Paget’s disease. I noted their results in 33 cases of a 42% recurrence rate and 52% incidence of positive margins on permanent sections. They claimed that “one would not expect intraoperative frozen section analysis of margins to substantially reduce the incidence of microscopically positive margins on permanent sections.” I would like to point out a study by Stacy and colleagues of Atlanta, GA, that showed that intraoperative frozen sections of margins in patients with extramammary Paget’s disease of the vulva did reduce the need for subsequent operations. They reported on 13 consecutive cases of vulvar Paget’s disease. In a group of eight patients having Paget’s disease not involving the anal mucosa, the extent of disease was completely defined by frozensection margins. Additional intraoperative resections were necessary in five of the eight. None had residual involvement on permanent sections and none had recurrences in 3 to 8 years of followup. A second group of two patients had frozen sections to define some, but not all, of the margins. Both had positive perineal margins on permanent sections. One required two subsequent revisions after 3 years of followup, and the other was free of disease during 9 years of followup. A third group of three patients all had anal mucosal involvement, and all had associated mucinous adenocarcinoma of the rectum. Frozen section actually discovered the presence of one of the three carcinomas. After appropriate radical operations, all three were alive and free of disease between 2 and 9 years of followup. I worked with the Atlanta group from 1976 to 1984. Since 1979, I have used intraoperative frozen sections to evaluate margins and to define the extent of surgery necessary. In my experience, this minimizes recurrences of Paget’s disease of the vulva. I believe that frozen sections for margins at the time of wide local excision is both indicated and mandatory. This lesion always extends beyond its gross margin. Although a 2-cm margin is usually adequate, many times it is not. I believe that the high recurrence rate quoted by Pierie and colleagues is not from the multifocal nature of Paget’s disease, but rather from inadequate surgery and inadequate margins. Between 1984 and 2002, I personally operated on 15 women with Paget’s disease of the vulva. Five had a partial vulvectomy, one had a hemivulvectomy, seven had a simple complete bilateral vulvectomy, and two had an extended radical vulvectomy with pedicle flap reconstruction. In all cases, frozen section evaluation of the margins was used to determine the extent of resection required and to try to ensure that such patients would not require subsequent anesthesia and operations for extramammary Paget’s disease. Disease recurred in 2 of 15 patients (13%). Both had been treated with extended radical vulvectomy because the disease had initially spread beyond the vulva. One recurred on the mons at 8 months, and one at the vaginal margin 16 months later. They remained free of disease after wide local excisions with a followup of 6 years and 1 year, respectively. In my opinion, women with Paget’s disease of the vulva should be referred to a gynecologic oncologist for appropriate surgical management.

The Role of Frozen Section Analysis of Margins during Breast Conversation Surgery

Purpose. The role of frozen section analysis during breast conversation surgery is undefined. Assessment of margins using eprmanent section evaluation is the standard method of ensuring complete tumor excision. If the margin is positive, however, surgical re-excision is necessary to reduce the likelihood of subsequent local recurrence. Therefore, biopsy of the surgical cavity with immediate pathological evaluation during lumpectomy was performed to evaluate the effect on local recurrence, the number of re-excisions, and cosmesis. Patients and Methods. One hundred sixty patients underwent attempted lumpectomy with frozen section margin determination. One hundred forty patients were available for long-term follow-up (mean = 57 months, median = 46 months). All patients underwent attempted breast conservation surgery, which consisted of tumorectomy with excision of a greater than 1-cm rim of grossly normal tissue. Tumor margins were obtained by intraoperative biopsy with frozen section analysis of the lumpectomy cavity walls. Results. In 21 patients (15%), frozen section analyses (FSA) revealed positive margins, resulting in immediate re-excision. In seven of these patients (%), margins were persistetly positive, and these patients therefore underwent mastectomy. Fourteen patients were successfully re-excised to a negative margin. The sensitivity and specificity of FSA were 91% and 100%, respectively. Five percent of patients definitively managed by lumpectomy with FSA of margins recurred locally. The mean cosmesis score after radiotherapy was 7.0 out of a possible 10, correlating with a good to excellent result. Discussion. The accuracy of FSA, low recurrence rate, avoidance of reoperation, and good cosmesis indicate that intraoperative frozen section analysis should be adopted as a safe and effective method of margin analysis during breast conservation surgery.

Technical considerations for prophylactic mastectomy in patients at high risk for breast cancer

A study of 5 patients and 10 mastectomy specimens was performed to identify the extent of surgery necessary to completely remove all breast tissue in patients having prophylactic mastectomies. A standard total mastectomy performed for breast cancer was shown to frequently leave breast tissue within the superficial pectoralis major muscle and the lower skin flap. Frozen section analysis of margins was found to be essential to clear the axillary extension of the breast and lower skin flap in particular. The value of more extensive surgery to remove all glandular elements of the breast in the high-risk patient remains to be demonstrated.