Excellent Prognosis of Patients with Invasive Lung Adenocarcinomas Intraoperatively Misdiagnosed as AAH/AIS/MIA by Frozen Section

Background: Our previous study revealed that intraoperative frozen section (FS) could accurately differentiate invasive lung adenocarcinoma (LUAD) from pre-invasive lesions. However, few articles analyzed the clinical impact of FS errors such as underestimation of invasive adenocarcinomas, and whether complementary therapy was needed remains controversial.

Research question: This study aims to investigate the prognosis of patients undergoing limited resection for invasive LUAD misdiagnosed as atypical adenomatous hyperplasia (AAH)/adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA) by intraoperative FS.

Study design and methods: From 2012 to 2018, data on 3031 patients undergoing sublobar resection of AAH/AIS/MIA diagnosed by FS were collected. The concordance rate between FS and final pathology (FP) was evaluated. To assess the clinical significance of FS/FP discrepancy, patients with invasive adenocarcinomas in final pathology were identified for prognostic evaluation.

Results: When AAH, AIS and MIA were classified together as a group, the overall concordance rate between FS and FP was 93.7%, and 192 (6.3%) patients got an upgraded diagnosis from the FP. Misdiagnosed invasive adenocarcinomas consisted of 94 (48.9%) lepidic predominant adenocarcinoma, 77 (40.1%) acinar predominant adenocarcinoma, 19 (9.9%) papillary predominant adenocarcinoma, one solid predominant pattern and one invasive mucinous adenocarcinoma. Among these patients, no positive N1, N2 lymph node was found. Moreover, the 5-year recurrence-free survival was still 100% even the final pathology turned out to be invasive adenocarcinoma.

Interpretation: Patients undergoing limited resection of invasive LUAD misdiagnosed as AAH/AIS/MIA by FS had excellent prognosis. Sublobar resection guided by FS diagnosis would be adequate for these underestimated invasive LUAD.

Keywords: frozen section; prognosis; sublobar resection; upgrade.