Research report: Clinicopathological and molecular correlates of micropapillary/solid and lepidic patterns in lung adenocarcinoma

In a retrospective study of 73 Chinese patients with invasive non-mucinous lung adenocarcinoma, tumors containing micropapillary/solid components were associated with a higher proportion of men and patients with a smoking history, while tumors containing lepidic components had a lower Ki-67 proliferation index. The findings suggest that these histological components can mark biologically distinct features of the disease even when they are not the predominant pattern in a tumor. Researchers evaluated micropapillary/solid and lepidic components irrespective of whether either was dominant, focusing on their associations with pathological features, genomic alterations and perioperative circulating tumor DNA, or ctDNA.

Most of the cohort had early-stage disease: 52 of 73 patients, or 71.2%, had stage I disease, comprising 37 classified as stage IA and 15 as stage IB. The other 21 patients, representing 28.8%, had stage II–IV disease. The investigators used definitive histological subtyping and next-generation sequencing data to compare tumor characteristics.

Men accounted for 55.2% of patients whose tumors contained micropapillary/solid components, compared with 22.7% of those whose tumors did not, a difference associated with a P value of 0.006. Patients with a smoking history made up 44.8% of the micropapillary/solid-positive group, versus 20.5% of the negative group, with P = 0.037. Histological combinations further separated the groups by proliferative activity.

Tumors that were micropapillary/solid positive and lepidic negative had the highest Ki-67 expression, at 30%, and differed significantly from tumors that were micropapillary/solid negative and lepidic positive, for which the reported P value was 0.037. Exploratory genomic analyses of this micropapillary/solid-positive, lepidic-negative subgroup also showed numerical enrichment of KRAS, MET, STK11 and CDKN2A alterations, alongside a lower EGFR alteration rate. None of these genomic differences reached statistical significance, so the findings do not establish a mutation-defined subtype.

The study also used individualized tumor-informed ctDNA detection to examine changes around surgery. Detectable ctDNA was found before surgery in 7 of 31 patients and after surgery in 5 of 28 patients with available samples. All detections occurred among patients whose tumors lacked a lepidic component, but this association was not statistically significant.

Overall, the analysis associates micropapillary/solid and lepidic components with distinct clinical and proliferative characteristics, while the possible genomic and ctDNA relationships remain signals that warrant further investigation.

Subject of Research: Histological and molecular correlates of micropapillary/solid and lepidic patterns in invasive non-mucinous lung adenocarcinoma

Article Title: Clinicopathological and molecular correlates of micropapillary/solid and lepidic patterns in lung adenocarcinoma

Article References: Fang, X., Zhang, L., Li, J., Li, S., Wang, H., Zhu, T., Lu, Y., & Xia, H. (2026). Clinicopathological and molecular correlates of micropapillary/solid and lepidic patterns in lung adenocarcinoma. BMC Cancer. https://doi.org/10.1186/s12885-026-16913-3

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16913-3

Keywords: lung adenocarcinoma, micropapillary/solid pattern, lepidic pattern, Ki-67, next-generation sequencing, circulating tumor DNA, tumor genomics, retrospective cohort, proliferation, molecular residual disease, Clinicopathological, molecular