Use of Intraoperative Frozen Section to Assess Final Tumor Margin Status in Patients Undergoing Surgery for Oral Cavity Squamous Cell Carcinoma

Abstract

ImportanceMethods of assessing final margin status in patients undergoing surgery for oral cavity squamous cell carcinoma, such as intraoperative frozen section histopathology (IFSH) taken from the tumor bed, may have limitations in accuracy.ObjectiveTo evaluate the accuracy and implications of using IFSH samples to assess tumor bed margins in patients undergoing surgery for oral cavity squamous cell carcinoma (SCC).Design, Setting, and ParticipantsThis cross-sectional study included 1257 patients who underwent surgery for oral cavity SCC between January 1, 2000, and December 31, 2015, at an academic cancer center. A total of 4821 IFSH samples were examined from 1104 patients (87.8%) who had at least 1 IFSH sample. Institutional practice is to harvest margins for IFSH from the tumor bed. Statistical analysis was performed from August 1, 2021, to April 4, 2022.Main Outcomes and MeasuresSensitivity and specificity were calculated for IFSH samples of margins compared with the permanent pathology samples of the same tissue and for IFSH compared with the final tumor specimen histopathology (FTSH). Results were classified using a binary method, with histopathologic reports interpreted as either negative (including negative or atypia or dysplasia) or positive (including carcinoma in situ, suspicious, or positive).ResultsA total of 1257 patients met the inclusion criteria, including 709 men (56.4%), with a median age of 62 years (IQR, 52-73 years); 1104 patients (627 men [56.8%]; median age, 62 years [IQR, 52-72 years]) had IFHS samples. For IFSH relative to permanent sections of the IFSH tissue, sensitivity and specificity of IFSH were high (sensitivity, 76.5% [95% CI, 67.5%-85.5%]; specificity, 99.9% [95% CI, 99.8%-100%]), with discordant results in 24 of 4821 total specimens (0.5%). Final specimen margins were positive in 11.7% of patients (147 of 1257). Compared with FTSH, the sensitivity of IFSH for defining margin status was 10.8% (95% CI, 5.8%-15.8%), and the specificity was 99.1% (95% CI, 98.8%-99.4%). The rate of discordance was 4.0% (171 of 4284 specimens) between IFSH and FTSH.Conclusions and RelevanceThe findings of this cross-sectional study suggest that IFSH is accurate compared with permanent pathologic characteristics of the same tissue, but less reliable at assessing final margin status on the tumor specimen. Despite a high specificity, the sensitivity of IFSH compared with FTSH is low, which may be associated with the inherent inability of tumor bed IFSH margin analysis to accurately account for the 3-dimensional association of tumor margins with the periphery of the specimen and the overall low rate of positive final tumor margins. Although tumor bed IFSH is widely used in the management of oral cavity cancer, this study suggests that there are limitations of this modality in assessing the final surgical margin status.

Ultrasound‐guided resection for squamous cell carcinoma of the buccal mucosa: A feasibility study

“…Frozen section analysis is a routinely used technique in daily clinical practice. However, this technique is prone to false negatives because only a tiny fraction of the specimen is evaluated 17,34 . In addition, the evidence to support this commonly used technique is lacking 35 …”

“…Unfortunately, this method has low sensitivity in predicting close or positive margins due to sampling and interpretation errors. [15][16][17] An intraoperative imaging modality is needed to assess margin status and adjust the resection plane if necessary to obtain a higher percentage of clear margins (≥5 mm). A study by de Koning et al showed a significant improvement of adequate resection margins in tongue cancer when using intraoperative ultrasound (US).…”

“…When in doubt, a surgeon may use frozen sections for intraoperative feedback. Unfortunately, this method has low sensitivity in predicting close or positive margins due to sampling and interpretation errors 15–17 …”

“…Unfortunately, this method has low sensitivity in predicting close or positive margins due to sampling and interpretation errors. 15 , 16 , 17 …”

Moving Forward After Gaining Hard-won Experience Through the COVID-19 Pandemic

“…JAMA Otolaryngology–Head and Neck Surgery has published several studies that were presented at the 2022 AHNS meeting. These include a study examining the relationship between tumor bed–sourced frozen sections and final pathological margins, which showed poor correlation between the two. Another study examined the results of checkpoint inhibition outside of clinical trials .…”