Clinicopathological Features and Survival Outcomes of Primary Pulmonary Invasive Mucinous Adenocarcinoma

SIMPLE SUMMARY: Pulmonary invasive mucinous adenocarcinoma (IMA) is a recognized variant of lung adenocarcinoma (ADC) that has unique histological patterns. Comprehensively clinical studies and pathological analyses on IMAs have been limited because IMA is rarely diagnosed compared with other subtypes. We compared the clinical characteristics, pathological features, and survival outcomes of 77 IMA patients with 520 non-IMA-type ADC patients. Currently, IMAs lack a simple pathological prognostic grading system to predict survival. We therefore proposed a simple two-tier grading system, which was modified from the low- and high-grade PanIN grading system, to evaluate its prognostic value. We found that IMAs have more distinct clinicopathological characteristics compared to non-IMA-type ADCs. For patients with stage I–IIIA IMA, a new two-tier grading system might be useful in predicting recurrence-free survival. We demonstrated that stage I and II IMAs have better overall survival compared with non-IMA-type ADCs. ABSTRACT: Pulmonary invasive mucinous adenocarcinoma (IMA) has unique histological patterns. This study aimed to comprehensively evaluate the clinicopathological features, prognosis, and survival outcomes of IMAs. We retrospectively identified 77 patients with pulmonary IMA and reviewed their clinical and pathological features. Another 520 patients with non-IMA-type ADC were retrieved for comparison with patients with IMA. A new two-tier grading system (high-grade and low-grade IMAs) modified from the pancreatic intraepithelial neoplasia classification system was used for survival analyses. Compared to patients with non-IMA-type ADC, patients with IMA tended to have never smoked (p = 0.01) and had early-stage IMA at initial diagnosis (p < 0.001). For stage I–II diseases, the five-year overall survival (OS) rates were 76% in IMAs and 50% in non-IMA-type ADCs, and a longer OS was observed in patients with IMA (p = 0.002). KRAS mutations were the most commonly detected driver mutations, which occurred in 12 of the 28 (43%) patients. High-grade IMAs were associated with a shorter recurrence-free survival (RFS) for stage I–IIIA diseases (p = 0.010) than low-grade IMAs but not for OS. In conclusion, patients with stage I and II IMA had better OS than those with non-IMA-type ADC. A new two-tier grading system might be useful for predicting RFS in stage I–IIIA IMAs.