Family History Associates With Micropapillary Pattern in Lung Adenocarcinoma ≤1.0 cm

Risk factors for micropapillary pattern (MPP) in early-stage lung adenocarcinoma (LUAD) remains poorly elucidated, and subcentimeter LUADs with MPP, although rare, have been seldom investigated. We hypothesized that a family history of cancer may play a role; thus we quantify the effect of family history of malignancy on MPP in invasive LUAD ≤20 mm, and further the effect of EGFR mutation in LUAD with MPP ≤10 mm in this study. Clinical data of pathologically verified invasive LUAD ≤20 mm patients between January 2013 and July 2018 were retrospectively collected. Patients were divided into 2 groups: family history (FH) group and no family history (NFH) group. Propensity score matching was applied to eliminate the bias of tumor length and demographic difference. Clinicopathologic characteristics were compared between matched cohorts. A total of 1026 cases were included, 1:2 propensity score matching was performed, and there remained 64 patients in FH and 127 in NFH. In the 0.5-1.0 cm subgroup, FH increased the incidence of MPP (29.4% vs 3.7%; odds ratio [OR], 10.8; 95% confidence interval [CI], 1.14-103.1; P = .016) compared with NFH, but there was no difference in the 1.1-1.5 cm subgroup (24.1% vs 18.5%; OR, 0.72; 95% CI, 0.28-2.24; P = .563) and 1.6-2.0 subgroup (29.4% vs 3.7%; OR, 1.64; 95% CI, 0.55-4.87; P = .374). A total of 19 FH patients had MPP, of which 16 had mutation examination for EGFR and KRAS. Of 5 FH patients with MPP with tumor length ≤1.0 cm, 1 harbored EGFR mutation and 1 had KRAS mutation (Figure 1). Analysis stratified by lesion length showed that family history of malignancy was positively associated with occurrence of MPP in subcentimeter LUAD ≤10 mm. For 5 cases in which tumor length was ≤1.0 cm, EGFR mutation rate was only 20%, indicating that EGFR mutation might not relate to occurrence of MPP in subcentimeter LUAD. As the tumor grows larger, the percentage of MPP of FH and NFH gradually become similar. This study helped emphasize the importance of early surgical intervention for patients with FH, because this group is likelier to include MPP with poorer prognosis.