Morphological and Molecular Characteristics in Low Grade Fetal Adenocarcinoma of the Lung: Two Case Reports and Literature Review.

Background: Low-grade fetal adenocarcinoma of the lung is a rare pulmonary tumor resembling fetal lung histologically. Due to its rarity, there is limited information regarding the pathogenesis and biological characteristics of low-grade fetal adenocarcinoma of the lung. Here, we describe two cases of low-grade fetal adenocarcinoma of the lung treated at our hospital and summarize cases of low-grade fetal adenocarcinoma of the lung reported in the literature. Case presentation: We examined two cases (one woman and one man; 30 and 67 years old, respectively). Histologically, tumor tissues from both cases had a complex glandular component with clear cuboidal and columnar cells that resembled the histological features of fetal lung. In some areas, squamous morules were prominent. Immunohistochemically, nuclear/cytoplasmic expression of β-catenin was detected in both cases. Mutation analysis revealed a CTNNB1 mutation in both cases and a DICER1 mutation in 1 case. No mutations in EGFR , BRAF , KRAS , or PIK3CA were found. Conclusions: Low-grade fetal adenocarcinoma of the lung showed a high frequency of CTNNB1 mutations and low frequencies of EGFR , KRAS , BRAF , and PIK3CA mutations in our examined cases and in previous studies. This rare tumor has unique clinicopathological characteristics with specific genetic aberrations involving the Wnt pathway. These results provide a molecular basis for development of new therapies to treat these tumors.