# Three Cases of Resection of Alpha-Fetoprotein-Positive High-Grade Fetal Adenocarcinoma of the Lung From a Single Institution

## TL;DR

This paper reports three cases of a rare lung cancer type, showing that high alpha-fetoprotein levels and low PD-L1 are linked to poor outcomes, suggesting new treatment strategies.

## Contribution

The study provides new insights into the role of AFP in tumor immunity and proposes a combination therapy for AFP-positive lung adenocarcinoma.

## Key findings

- High AFP expression and low PD-L1 levels are associated with poor prognosis in fetal lung adenocarcinoma.
- AFP may promote regulatory T-cell differentiation, helping tumors evade immune responses.
- Early detection and complete resection improved survival in one case, highlighting the importance of timely intervention.

## Abstract

We describe three cases of resection of embryonal lung adenocarcinoma, along with a literature review and immunohistochemical analyses of alpha-fetoprotein (AFP) levels. Generally, embryonal lung adenocarcinoma has a poor prognosis, which can be attributed to low programmed death-ligand 1 (PD-L1) expression, limiting the efficacy of immune checkpoint inhibitors. The cases showed varying intensities of AFP staining in the tumor tissues. Case 1 was initially negative for AFP, but positive at low levels upon re-staining; Case 2 was positive in a relatively small subset of cells; and Case 3 was intensely positive. Further, Case 3 showed elevated serum levels of AFP. Only Case 2 was positive for PD-L1 at relatively low levels. Patient 1 achieved >50-month overall survival, which can be attributed to early detection and complete resection. Cases 2 and 3 showed a poor prognosis. Our findings suggested that low or absent PD-L1 and moderate-to-high AFP expression may contribute to poor prognosis. AFP may train dendritic cells to promote differentiation of naïve T-cells to regulatory T-cells in the tumor microenvironment, which protects the tumor from adaptive immune responses. Therefore, combination therapy involving an AFP-targeted drug and an immune checkpoint inhibitor may be a viable treatment strategy for AFP-positive fetal lung adenocarcinoma.