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Assessment of the feasibility of frozen sections for the detection of spread through air spaces (STAS) in pulmonary adenocarcinoma


Spread through air spaces (STAS) is reportedly associated with worse prognosis in sublobar resections of lung adenocarcinoma. Recently, it was proposed that STAS detected on frozen sections can be an indication for lobectomy instead of sublobar resection. We undertook this study to evaluate the reliability of STAS assessment on frozen sections compared to permanent sections, as well as the associations among STAS, tumor grade, and recurrence-free survival (RFS) after sublobar resection. A total of 163 stage I lung adenocarcinoma resections with frozen sections were identified retrospectively. For each case, and for frozen and permanent sections separately, the presence or absence of STAS, as well as the tumor grade, were recorded. Compared to permanent sections, STAS detection on frozen sections had low sensitivity (55%), low positive predictive value (48%), and fair agreement (K = 0.34), whereas there was higher specificity (80%) and negative predictive value (85%). Accuracy was 74%. Tumor grade assessment on frozen sections showed higher sensitivity (77%), positive predictive value (90%), agreement (K = 0.72), specificity (94%), and accuracy (87%), and the same negative predictive value (85%). High-grade histology on frozen sections was associated with shorter RFS (p = 0.02), whereas STAS on frozen sections was not (p = 0.47). Our results suggest that the intraoperative detection of STAS has low sensitivity and positive predictive value. False-positive results may lead to overtreatment of patients with lung cancer. The determination of tumor grade on frozen sections offers better sensitivity and specificity, plus it is associated with RFS, whereas STAS on frozen sections is not. Further study is needed to explore the utility of assessing tumor grade on frozen sections.

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Fig. 1: Example of artifact.
Fig. 2: Concordant case.
Fig. 3: Discordant case.
Fig. 4: Discordant case.
Fig. 5: Comparison of diagnostic performance.
Fig. 6: Grade versus STAS.
Fig. 7: Recurrence-free survival (RFS, days) in patients who underwent sublobar resection.


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The authors would like to thank Benjamin A. Levinson, PhD (Department of Population Health, Division of Biostatistics, NYU Langone Health) for his statistical advice; the Center for Biospecimen Research and Development (CBRD) for logistical support; and NIH NCI Cancer Center support grant P30 CA016087-39 (ALM). MM-K is partially supported by the National Institutes of Health (R01CA240317).

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Study concept and design: FZ, NN, ALM. Methodology development: FZ, ALM. Data acquisition, analysis, and interpretation: FZ, JAV, TMSS, MM-K, HP, ALM. Writing: FZ, NN, MM-K, ALM. All authors read and approved the final paper.

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Correspondence to Fang Zhou.

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The study was approved by each respective Institution Review Board and performed according to HIPAA regulations.

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Zhou, F., Villalba, J.A., Sayo, T.M.S. et al. Assessment of the feasibility of frozen sections for the detection of spread through air spaces (STAS) in pulmonary adenocarcinoma. Mod Pathol (2021).

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