High Frequency of CTNNB1 Mutation in Low Grade Fetal Adenocarcinoma of the Lung: Two Case Series and Literature Review

Abstract

Background Low-grade fetal adenocarcinoma of the lung (L-FLAC) is a rare pulmonary tumor resembling fetal lung histologically. Due to its rarity, there is limited information about L-FLAC pathogenesis and biological characteristics. Here, we describe two cases of L-FLAC treated at our hospital and summarize L-FLAC cases reported in the literature. Case presentation: We examined one woman and one man who were 30-years-old and 67-years-old, respectively. Histologically, tumor tissue from both cases had a complex glandular component with clear cuboidal and columnar cells that resembled 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, PIK3CA mutation were found. Conclusions L-FLAC showed a high frequency of CTNNB1 mutation and low frequency of EGFR, KRAS, BRAF and PIK3CA mutation 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.