Identification of high-grade subtypes of lung adenocarcinoma by cryobiopsy as a postoperative prognostic predictor

Lung adenocarcinoma (LAD), including high-grade subtypes (i.e., micropapillary (MIP) and/or solid (SOL)), is known to have a poor postoperative prognosis. Although it has been almost impossible to identify MIP in biopsy specimens, we reported that cryobiopsy (CB) offers a potential solution (Lung Cancer. 2021;162:147-153.). We aimed to follow up the patients from the study to clarify whether preoperative identification of high-grade subtypes predicts postoperative prognosis. Patients diagnosed with LAD by CB at our hospital from 2017 to 2019 were extracted. Of them, those who underwent surgery at clinical stage IA were included. Presences of high-grade subtypes in the CB and resected specimens were assessed separately. For each high-grade subtype, associations with 5-year disease-free survival (5-DFS) and overall survival (5-OS) were evaluated using the Kaplan-Meier and long-rank tests. Of the total 115 patients, MIP, SOL, and MIP/SOL were identified in the CB specimens in 16 (14.0%), 6 (5.2%), and 1 (0.8%), respectively, while none in 92 (80.0%). In contrast, 35 (30.4%) of the resected specimens proved to have high-grade subtypes. As previously reported, such high-grade LAD had significantly worse 5-DFS (87.8% vs 58.4%, <italic>p</italic>=0.004) and 5-OS (97.3% vs. 81.8%, <italic>p</italic>=0.024) than the others. Meanwhile, only 5-DFS was significantly worse in cases with high-grade subtypes in the CB specimens (84.4% vs 56.1%, <italic>p</italic>=0.024), but it was also associated with worse 5-OS when subdivided into the presence of MIP (94.6% vs 79.0%, <italic>p</italic>=0.042). In conclusion, the identification of high-grade subtypes, especially MIP, by CB would be useful in predicting the postoperative prognosis of LAD.