Excellent Prognosis of Patients With Invasive Lung Adenocarcinomas During Surgery Misdiagnosed as Atypical Adenomatous Hyperplasia, Adenocarcinoma In Situ, or Minimally Invasive Adenocarcinoma by Frozen Section

Chest. 2021 Mar;159(3):1265-1272. doi: 10.1016/j.chest.2020.10.076. Epub 2020 Nov 14.


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

Research question: What is the prognosis of patients undergoing limited resection for invasive LUAD misdiagnosed as atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), or minimally invasive adenocarcinoma (MIA) by intraoperative FS analysis?

Study design and methods: From 2012 through 2018, data on 3031 patients undergoing sublobar resection of AAH, AIS, or MIA diagnosed by FS analysis were collected. The concordance rate between FS analysis and final pathologic results was evaluated. To assess the clinical significance of a discrepancy between FS and final pathologic results, patients with final pathologic results of IAC were identified for prognostic evaluation.

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

Interpretation: Patients undergoing limited resection of invasive LUAD misdiagnosed as AAH, AIS, or MIA by FS analysis showed excellent prognoses. Sublobar resection guided by FS diagnosis would be adequate for these underestimated cases of invasive LUAD.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma in Situ / diagnosis
  • Adenocarcinoma of Lung* / diagnosis
  • Adenocarcinoma of Lung* / pathology
  • Adenocarcinoma of Lung* / surgery
  • Adenomatosis, Pulmonary / diagnosis
  • China / epidemiology
  • Diagnostic Errors / statistics & numerical data
  • Female
  • Frozen Sections / methods*
  • Humans
  • Intraoperative Care / methods*
  • Lung Neoplasms* / diagnosis
  • Lung Neoplasms* / pathology
  • Lung Neoplasms* / surgery
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Pneumonectomy* / methods
  • Pneumonectomy* / statistics & numerical data
  • Precancerous Conditions / diagnosis*
  • Prognosis
  • Tomography, X-Ray Computed / methods